| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Acetic acid | 64-19-7 | 82 | 1977 | 1 | 184.1005 |
SCOGS Opinion:
Acetates are common constituents of plant and animal tissues. They are normal metabolic intermediates produced in relatively large quantities during the digestion and metabolism of foods.
Although the Select Committee is not aware of any long-term feeding studies of acetic acid or the acetates, short term studies have revealed no untoward effects at concentrations far exceeding those consumed in the normal diet and do not suggests that adverse effects might be revealed by longer term studies.
No data on carcinogenic evaluation of acetic acid and the acetate salts have come to the attention of the Select Committee. Limited data indicate that acetic acid is not teratogenic in vivo; sodium acetate is not mutagenic and acetic acid is probably not mutagenic in vitro.
No reports of biological studies on sodium diacetate have been found, but since this substance dissociates in the body to sodium acetate and acetic acid, neither of which elicits adverse effects under current conditions of use, the Select Committee beleives that use of sodium diacetate can be considered to be without adverse effects.
In light of these considerations, the Select Committee concludes that: There is no evidence in the available information on acetic acid, sodium acetate, and sodium diacetate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American diet, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added food
ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Acid hydrolyzed proteins | There is no ID Code | 37b | 1980 | 1 | There is no CFR citation. |
SCOGS Opinion:
The average level of consumption of protein hydrolyzates for flavoring purposes is less than 3 mg per kg per day. Protein hydrolyzates are not used for flavoring purposes in commercially processed baby foods wich formerly may have contained about 2 percent by weight. The Select Committee was unable to locate reports of experimentally demostrable adverse effects of high concentrations of glutamate in dietary mixtures.
In light of the above, and assuming that appropriate product specifications are adopted, the Select Commitee concludes that:
There is no evidence in the available information on acid hydrolyzed proteins, enzymatically hydrolyzed protein, yeast autolysates, and soy sauces, that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used as flavoring agents at levels that are now current or that might reasonably be expected in the future.
The situation is different regarding the use of enzymatic casein hydrolyzates as nutrients. These hydrolyzates are consumed or administered in much higher doses, frequently as the sole source of dietary protein in products that are used as special dietary foods.
Decades of clinical experience have revealed no reports of untoward effects when casein hydrolyzates are administered orally in combination with other nutrients such as glucose. Adverse effects of the dicarboxylic amino acid components have been reported only in rodents under unusual conditions of administration (e.g., gavage or subcutaneous injection) and are not considered relevant to the use of casein hydrolyzates by humans.
The Select Commitee therefore concludes that: There is no evidence in the available information on enzymatically hydrolyzed casein that demostrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used as a nutrient in special dietary foods at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Acid Modified Starch | 65996-63-6 | 115 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Aconitic Acid | 499-12-7 | 41 | 1974 | 1 | 184.1007 |
SCOGS Opinion:
The limited data on trans-aconitic acid indicate it to be less toxic than citric acid. Trans-aconitate salts appear to be excreted readily by the kidneys. There is no direct evidence that trans-aconitic acid is utilized as is the cis-aconitic acid isomer in mammalian metabolism although non-specific oxidation probably occurs. The Select Committee has weighed all of the foregoing and concludes that: There is no evidence in the available information on aconitic acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Adipic acid | 124-04-9 | 80 | 1976 | 1 | 184.1009 |
SCOGS Opinion:
Investigations on animals and humans show that adipic acid is readily absorbed from the alimentary tract. Much of the absorbed compound is rapidly excreted in the urine but a substantial portion is oxidized to carbon dioxide. The intermediate products formed indicate that it is metabolized by the same route as the fatty acids.
The tolerance of animals to adipic acid is comparable to that of certain normal metabolites such as citric acid. Adipic acid caused no harmful effects in animals in long-term tests in which it was added to the diet in amounts up to at least 1 percent (500mg per kg body weight per day). This is over 500 times the daily per capita intake estimated from the poundage reported to be used in food in 1970. The available evidence suggests that the metabolism of adipic acid in man is comparable to that of laboratory animals.
In view of the foregoing, the Select Committee concludes that: There is no evidence in the available information on adipic acid that demonstrates , or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Agar-agar | 9002-18-0 | 23 | 1973 | 2 | 184.1115 |
SCOGS Opinion:
Agar-agar has relatively little effect when added to the diets of animals in amounts considerably greater than those present in the human diet. The observed increases in intestinal weight and length in animals appear to be related to the bulking and hydrocolloidal properties of the material, and these changes occur only at relatively high concentrations of agar-agar. Although no specific studies of the carcinogenicity or other long-term investigtions of agar-agar have been made, this material has a long history of use as a gelling agent and bulk component of experimental animal diets. Because 2 to 5 percent of this material has been used routinely in control diets in numerous studies witout reported significant effects, it is reasonable to conclude that even at these high levels, agar-agar produces no significant chronic effects. However, there is one report that agar-agar, fed at relatively high levels (400 to 1570 mg per kg per
day), is lethal to many pregnant mice and rabbits but not to pregnant rats and hamsters fed at equivalent levels (650 to 1140 mg per kg per day). Significant numbers of material deaths occurred in pregnant mice and rabbits fed agar-agar at levels 110 fold greater (mice) and 30 fold greater (rabbits), than the maximum level estimated to be consumed by adults (13.2 mg per kg per day) in the daily diet, but no toxic effects were observed in pregnant mice and rabbits fed levels 25 fold greater (mice) and 9 fold greater (rabbits) than the estimated adult human intake level. With respect to these comparisons it should be emphasized that the Select Committee believes the intake estimate of 13.2 mg per kg per day (Table II) is overstated by a considerable margin, which could make the foregoing differences in each case even larger. It is noteworthy that similar toxic effects have been observed in identical tests on a number of other polysacchardies (gum arabic, sterculia gum, carob bean gum,
guar gum, gum ghatti, gum tragacanth, carrageenan, propylene glycol alginate, and methyl cellulose) fed at very high levels. The relative sensitivity of the seveeral animal species to these effects varies depending on the particular polysaccharide tested, but in all cases very large doses are required. Until these effects have been adequately explained, it appears to be inappropriate to conclude that unrestricted use of such substances in food would be without harzard. Agar-agar is a product extracted from marine algae. The possibility exists that harmful concentrations of certain metals such as mercury, may be accumulated in the commercial product if algae are harvested from coastal waters contaminated with significant levels of such heavy metals (26). Current specifications for food grade agar-agar (4) place a limitation on the content of "heavy metals as lead." Because modern methods of analysis are capable of distinguishing between and measuring the amounts of the several metal
elements, it would appear advisable to make the specifications for agar-agar more specific with respoect to allowable concentrations of potentially toxic heavy metals, such as mercury. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on agar-agar that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current and in the manner now practiced. However, it is not possible to determine without additional data, whether a significant increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
Tocopherols are a natural constituent of many foods. The average daily dietary intake of tocopherols in the United States is approximately 5 to 20 mg. The quantity of tocopherols added to foods as antioxidants is estimated to be equivalent to an average adult daily intake of 0.6 mg. The several tocopherols used in foods as antioxidants are readily absorbed and metabolized. They are relatively non-toxic. LD50 values for acute oral toxicity of several animal species are in excess of 2000 mg per kg. Hypervitaminosis E has been reported in humans only at oral dosage levels in excess of 400 mg per day. Investigations on mutagenic, carcinogenic, and teratogenic effects of tocopherols have not revealed any deleterious or pathologic alterations, although some reproductive system effects have been observed in young animals fed or administered dosage levels that exceed by manyfold, the quantitites added to food or present in the daily
diet. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on tocopherols and alpha-tocopheryl acetate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| alpha-Tocopherols | 59-02-9 | 36 | 1975 | 1 | 184.1890 |
SCOGS Opinion:
Tocopherols are a natural constituent of many foods. The average daily dietary intake of tocopherols in the United States is approximately 5 to 20 mg. The quantity of tocopherols added to foods as antioxidants is estimated to be equivalent to an average adult daily intake of 0.6 mg. The several tocopherols used in foods as antioxidants are readily absorbed and metabolized. They are relatively non-toxic. LD50 values for acute oral toxicity of several animal species are in excess of 2000 mg per kg. Hypervitaminosis E has been reported in humans only at oral dosage levels in excess of 400 mg per day. Investigations on mutagenic, carcinogenic, and teratogenic effects of tocopherols have not revealed any deleterious or pathologic alterations, although some reproductive system effects have been observed in young animals fed or administered dosage levels that exceed by manyfold, the quantitites added to food or present in the daily
diet. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on tocopherols and alpha-tocopheryl acetate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
SCOGS Opinion:
Silicon dioxide and various silicates occur abundantly in the earth's crust, are present in practically all natural waters,animals, and plants, and are part of the normal human diet. The question of whether or not silicon is an essential human nutrient remains unresolved. Silicon compounds consumed as added food ingredients contribute only a minor proportion of the total dietary silicon intake. The estimated possible human intake of sodium aluminosilicate, the predominant silicate added to foods in this country, is approximately 0.3mg per kg body weight per day. Silicon compounds that are GRAS for use as direct food ingredient, except potassium and sodium silicates, are insoluble or very slightly soluble in water and appear to be biologically inert. The water-soluble silicates are also of low acute toxicity. The acute oral LD50 in rats of sodium aluminosilicate is >1g per kg. No significant tissue accumulation, pathology, or
toxicity has been reported from the ingestion of those insoluble or very slightly soluble GRAS silicon compounds for which data are available. Of the five substances that were reported as added to foods in the NRC survey, biologic effects and safety data are available for all except sodium calcium aluminosilicate, and there is no reason to suspect that the toxicity of the latter would differ from those for which there are data. The results of two studies (1967-1970) in which various silicon compounds were fed to laboratory animals for 1 mo at a level of 0.8g per kg body weight (as silicon dioxide) and for 3 mo at levels of 6 to 30 mg per kg body weight suggests there may be a species-related susceptibility to renal damage from ingestion of sodium silicate, magnesium trisilicate, and finely ground quartz. No substantiating reports of these effects have appeared. Magnesium trisilicate was recognized as safe for prolonged use in human ingestion in large amount as a component of antacid
preparations by the Advisory Review Panel on Over-the-Counter Drugs, and the available evidence on the acute toxicity of sodium silicate indicates that it is low. Consumption data are lacking for aluminium calcium silicate and tricalcium silicate, two compounds that are listed as GRAS for use as anticaking agents. However, their use in keeping with good manufacturing practice and in currently regulated amounts would be of the same order of magnitude as the other GRAS silicates. In addition, the Select Committee has limited information on the amounts of talc that are currently used in foods. However a major food use of talc is in the coating of rice. Assuming package label statements are ignored and coated rice is not washed prior to cooking and no other losses occur, maximun per capita intake of talc from this source appears to be 0.5g per day. With respect to paper and cotton food- packaging products, the possibility is remote that biologically significant amounts of talc,
diatomaceous earth, or sodium silicate migrate to food from packaging, materials containing these substances. Perlite, a naturally occuring polysilicate substance, has an oral LD50 in the rat of >10g per kg body weight. Estimates of the maximun quantities of minerals that might be extracted from perlite and diatomaceous earth used as filteraids in food processing indicates no hazard to public health. There are no food grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc. Such specifications for the substances used in foods are desirable. Specification for food grade talc should limit the content of asbestos fibers even though the potential hazard of ingested asbestos fibers even though the potential hazard of ingested asbestos is not clearly established. The Food and Drug Administration is sponsoring the development of an assay method for asbestos fibers. An upper limit for cadmium should be added to the specifications for food-grade perlite, and
consideration should be given to the need for limitation of cadmium content of other silicates. In the light of all of the foregoing, the Select Committee concludes that: It is essential to establish food-grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc, with provision for an upper limit of asbestos fibers in talc. There is no evidence in the available information on aluminum calcium silicate, calcium silicate, magnesium silicate, potassium silicate, sodium silicate, sodium aluminosilicate, sodium calcium aluminosilicate, tricalcium silicate, silica aerogel, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on diatomaceous earth, silicon dioxides, sodium silicate, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the
public when they are used as ingredients of paper and paperboard products used in food packaging in accordance with current practice. There is no evidence in the available information on sodium silicate and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of cotton and cotton fabrics used in dry food packaging in accordance with current practice. There is no evidence in the available information on diatomaceous earth and perlite that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used as filteraids in food processing at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Aluminum hydroxide | 21645-51-2 | 43 | 1975 | 1 | 184.1139 |
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Aluminum sulfate | 10043-01-3 | 43 | 1975 | 1 | 182.1125 |
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
SCOGS Opinion:
Orally administered licorice and licorice derivatives are absorbed to some extent and the principal metabolic products are excreted through the bile, but most of an ingested dose is hydrolyzed in the digestive tract and the products excreted through the feces. Acute and short-term substances of a very low order of toxicity, capable of eliciting a variety of pharmacological effects but only at levels considerably higher than are likely to be achieved in usual diets. None of these effects suggests cause for convern at current or foreseeable dietary levels of consumption. However, the capacity of licorice and licorice derivatives to elicit transitory hypertensive effects, at higher dosage levels in animals and man, requires more definitive clarification as far as its practical implications are concerned. This would be particularly important for the unknown number but probably few individuals who may indulge themselves with excessive
intakes of licorice-containing candies and/or beverages. The Select Committee has found no long-term toxicological data on licorice-related products administered to animals or man. Until the long-term as well as the acute dose relationships of the hypertensive effect are clarified, it appears inappropriate to conclude that unrestricted use of licorice and licorice derivatives in food would be without hazard to consumers in general. In the light of the foregoing and the information elsewhere in this report, the Select Committee concludes that: There is no evidence in the available information on licorice, glycyrrhiza, and ammoniated glycyrrhizin that demonstrates or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ammonium alginate | 9005-34-9 | 24 | 1973 | 2 | 184.1133 |
SCOGS Opinion:
The available information on the alginates reveals no significant adverse toxicological effects from oral administration in non-pregnant animals or humans in daily amounts greatly exceeding those currently consumed in the diet. However, in pregnant mice, very large doses of propylene glycol alginate, while not teratogenic, cause a significant increase in maternal mortality. Such increased maternal toxicity does not occur at a dose of propylene glycol alginate which is 26-fold or more greater than that estimated to be the average daily adult dietary intake. No respect but studies of propylene glycol, made by the same investigators and is without maternal toxicity even at very large doses. This indicates that the adverse effects reported for propylene glycol alginate may be due to the alginate moiety. It is noteworthy that similar toxic effects have been observed in identical tests on a large number of other polysaccarides (gum
arabic, sterculia gum, carob bean gum, guar gum, gum ghatti, gum tragacanth, carrageenan, methyl cellulose, and agar-agar) fed at very high levels. The relative sensitivity of the several animal species to these effects, varies depending on the particular polysaccaride tested, but in all cases very large doses are required. Until these effects have been adequately explained, it appears to be inappropriate to conclude that unrestricted use of such substances in food would be withou hazard. The Select Committee has weighed all of the foregoing and concludes that: There is no evidence in the available information on ammonium, calcium, potassium, sodium, and propylene glycol alginates that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption of these substances would
constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ammonium bicarbonate | 1066-33-7 | 34 | 1974 | 1 | There is no CFR citation. |
SCOGS Opinion:
Ammonia and the ammonium ion are integral components of normal metabolic processes and play an essential role in the physiology of man. Although there have been no significant feeding studies specifically designed to ascertain the safety threshold of ammonium compounds as food ingredients, numerous metabolic studies have been reported in the scientific literature. Extrapolation of these findings to the concentrations of ammonium compounds normally present in foods does not suggest that there would be untoward effects at such levels. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ammonium bicarbonate, ammonium carbonate, ammonium chloride, ammonium hydroxide, mono and dibasic ammonium phosphate, and ammonium sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that
might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ammonium carbonate | 8000-73-5 | 34 | 1974 | 1 | 184.1137 |
SCOGS Opinion:
Ammonia and the ammonium ion are integral components of normal metabolic processes and play an essential role in the physiology of man. Although there have been no significant feeding studies specifically designed to ascertain the safety threshold of ammonium compounds as food ingredients, numerous metabolic studies have been reported in the scientific literature. Extrapolation of these findings to the concentrations of ammonium compounds normally present in foods does not suggest that there would be untoward effects at such levels. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ammonium bicarbonate, ammonium carbonate, ammonium chloride, ammonium hydroxide, mono and dibasic ammonium phosphate, and ammonium sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that
might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ammonium chloride | 12125-02-9 | 34 | 1974 | 1 | 184.1138 |
SCOGS Opinion:
Ammonia and the ammonium ion are integral components of normal metabolic processes and play an essential role in the physiology of man. Although there have been no significant feeding studies specifically designed to ascertain the safety threshold of ammonium compounds as food ingredients, numerous metabolic studies have been reported in the scientific literature. Extrapolation of these findings to the concentrations of ammonium compounds normally present in foods does not suggest that there would be untoward effects at such levels. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ammonium bicarbonate, ammonium carbonate, ammonium chloride, ammonium hydroxide, mono and dibasic ammonium phosphate, and ammonium sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that
might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ammonium citrate | 7632-50-0 | 84 | 1977 | 1 | 184.1140 |
SCOGS Opinion:
The citrate ion is widely distributed in plants and animals and is a naturally occurring component of the diet. It is a common metabolite in oxidative metabolism and an important component of bone. Exogenous citrate administered to infants and adults as a component of commonly consumed diets is considered completely metabolizable. The addition of citric acid to foods is considered equivalent to adding citrate salts except in foods of very high acidity. The amount of citrate added to foods by foods processors is about 500mg per person per day. This amount occurs naturally in 2 ounces of orange juice and does not constitute a significant addition to the total body load. Although data on acute and chronic effects of orally administered sodium citrate, calcium citrate and potassium citrate are limited, no biological effects of the citrate-containing substances evaluated in this report cause concern about the safety of these GRAS
substances used in reasonable amounts and in accordance with prescribed tolerances and limitations.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on citric acid, sodium citrate, potassium citrate, calcium citrate, ammonium citrate, isopropyl citrate, stearyl citrate, and triethyl citrate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ammonium hydroxide | 1336-21-6 | 34 | 1974 | 1 | 184.1139 |
SCOGS Opinion:
Ammonia and the ammonium ion are integral components of normal metabolic processes and play an essential role in the physiology of man. Although there have been no significant feeding studies specifically designed to ascertain the safety threshold of ammonium compounds as food ingredients, numerous metabolic studies have been reported in the scientific literature. Extrapolation of these findings to the concentrations of ammonium compounds normally present in foods does not suggest that there would be untoward effects at such levels. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ammonium bicarbonate, ammonium carbonate, ammonium chloride, ammonium hydroxide, mono and dibasic ammonium phosphate, and ammonium sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that
might reasonably be expected in future.
SCOGS Opinion:
Ammonia and the ammonium ion are integral components of normal metabolic processes and play an essential role in the physiology of man. Although there have been no significant feeding studies specifically designed to ascertain the safety threshold of ammonium compounds as food ingredients, numerous metabolic studies have been reported in the scientific literature. Extrapolation of these findings to the concentrations of ammonium compounds normally present in foods does not suggest that there would be untoward effects at such levels. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ammonium bicarbonate, ammonium carbonate, ammonium chloride, ammonium hydroxide, mono and dibasic ammonium phosphate, and ammonium sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that
might reasonably be expected in future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
SCOGS Opinion:
Ammonia and the ammonium ion are integral components of normal metabolic processes and play an essential role in the physiology of man. Although there have been no significant feeding studies specifically designed to ascertain the safety threshold of ammonium compounds as food ingredients, numerous metabolic studies have been reported in the scientific literature. Extrapolation of these findings to the concentrations of ammonium compounds normally present in foods does not suggest that there would be untoward effects at such levels. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ammonium bicarbonate, ammonium carbonate, ammonium chloride, ammonium hydroxide, mono and dibasic ammonium phosphate, and ammonium sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that
might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ammonium sulfate | 7783-20-2 | 34 | 1974 | 1 | 184.1143 |
SCOGS Opinion:
Ammonia and the ammonium ion are integral components of normal metabolic processes and play an essential role in the physiology of man. Although there have been no significant feeding studies specifically designed to ascertain the safety threshold of ammonium compounds as food ingredients, numerous metabolic studies have been reported in the scientific literature. Extrapolation of these findings to the concentrations of ammonium compounds normally present in foods does not suggest that there would be untoward effects at such levels. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ammonium bicarbonate, ammonium carbonate, ammonium chloride, ammonium hydroxide, mono and dibasic ammonium phosphate, and ammonium sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that
might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Arrowroot Starch | 977000-09-1 | 115 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
SCOGS Opinion:
L-ascorbic acid, vitamin C, occurs in nutritionally significant amounts as a natural constituent of many fruits, vegetables, berries, and melons. As a vitamin it is needed in the diet of all age groups. L-ascorbic acid and its sodium salt are antioxidants and they are extensively used as preservatives, color stabilizers and for related functions in various foods and beverages. Calcium ascorbate and ascorbyl palmitate, a derivative of ascorbic acid having greater fat solubility, also are anti-oxidants, but appear not to have significant use in processed foods. In addition to their use in foods as antioxidants, L-ascorbic acid and its salts are added to some foods as a source of vitamin C. These sources constitute a significant proportion of the total ascorbate intake of the general population. Erythorbic acid (D-isoascorbic acid), a stereoisomer of L-ascorbic acid, and its sodium salt, also are effective antioxidants and are used
for this purpose in a number of food products. The quantities used in 1970 were substantially less than for the ascorbates. The vitamin activity of erythorbates is only one -twentieth that of ascorbic acid, and their anti-oxidant effectiveness is not greater than for the ascorbates. For this reason, it would seem desirable, where possible, to use L-ascorbic acid rather than erythorbic acid as an antioxidant. From studies in guinea pigs and man it can be concluded that although erythorbic acid shares the same absorption and tissue uptake system as ascorbic acid it has little antiscorbutic activity. Although competition between ascorbic acid and erythorbic acid has been demosntrated at a biochemical level, there is no firm evidence that such competition will produce a scorbutic state. Whether this biochemical interaction could result in a clinically significant depletion of ascorbic acid remains to be established. Both short- and long-term toxicity studies have demonstrated tolerance
without adverse effects for large amounts of orally administered L-ascorbic acid, sodium L-ascorbate, and erythorbic acid in several species including mice, rats, guinea pigs, rabbits, and dogs. A substantial number of short-term experiments with human subjects ingesting 1 to 4 g of ascorbate daily have generally not revealed any harmful effects. Some subjects have received higher amounts, up to at least 8 to 10 g per day. In most instances no untoward results have been noted. But there is marked paucity of such studies that were well controlled and in which inquiring attention was given to possible harmful effects. In due course, such studies would be desirable. In the various studies on the effect of ingesting excessive amounts of ascorbates, attention has been focused on questions including oxalate excretion and renal tract stones, effets on the utilization of copper, iron, and other metals, need for vitamin B12, blood coagulation,and reproductive performance. The findings indicate
that the tolerance to excessive amounts of ascorbic acid and its sodium salt is high. Several investigators have reported the development of dependency in animals and human after ingestion of large amounts of ascorbates for extended time periods; however, the levels of ascorbates added to foods by 1 to 3 orders of magnitude. It is notable that no data have been found concerning the possible effects of ascorbyl palmitate and calcium ascorbate in humans, and there is practically no information regarding the latter in animals. Information concerning ascorbyl palmitate in animals is almost as limited. The few meaningful experiments suggest that ascorbyl palmitate is tolerated about the same as ascorbic acid and sodium ascorbate. This should be expected. It is reasonable to assume that the tolerance to calcium ascorbate is approximately the same as for sodium ascorbate and this is a high level. In view of the foregoing, The Select Committee concludes that: There is no evidence in the
available information on L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, ascorbyl palmitate (palmitoyl L-ascorbic), erythorbic acid (D-isoascorbic acid), and sodium erythorbate (sodium D-isoascorbate) that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used as food ingredients at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
There is a paucity of experimental data on the digestion, absortion, metabolism, and short-term or long-term toxicity of beeswax after oral intake by humans or animals; but as a component of comb honey, beeswax has been ingested since ancient times without evidence of harm. Although the composition of beeswax is not digested or absorbed from the alimentary tract in most animals or man. Beeswax containing pollens or oleoresins may be allergenic to sensitive individuals but beeswax alone has not been reported to be allergenic. No studies designed to show teratogenic effects of beeswax have been reported. Numerous injections of beeswax as a vehicle for drugs have nor led to reports of tumors at the injection site. Relatively little comb honey is used as a food in the U.S. The use of beeswax in processed food products decreased fourfold in the decade from 1960-1970 and presently is very small, amounting to an average estimated per
capita daily intake of about 0.16mg. On the basis of the above considerations the Select Commitee concludes that: There is no evidence in the available information on beeswax (yellow or white) that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Bentonite | 1302-78-9 | 90 | 1977 | 1 | 184.1155 |
SCOGS Opinion:
Bentonite and clay (kaolin) are readily hydratable aluminium silicates. Bentonite is used to assist in the clarification of juices, beverages, and other food products, as a binding agent for the preparation of pelleted animal feeds, and as an ingredient of coatings and adhesives for food packaging materials. The Select Committee is not aware of any instance in current practice where use of bentonite in the processing or packaging of foods for human consumption results in the retention of more than minute amounts in the final product and assumes the current practice will continue. Nevertheless, food grade standards for bentonite should be established, particularly with respect to soluble constituents and heavy metal cations that may be present in commercial products.
Clay (kaolin) is GRAS only as an ingredient of paper and paperboard products used in food packaging. There are no data available concerning the amounts of clay (kaolin) that might migrate to foods from this source but the Select Committee believes the amounts can only be very small.
Apparently, very little, if any, bentonite is absorbed after oral administration and as much as 3 percent in the diet has no observable adverse effects on experimental animals. Diets containing 10 to 25 percent can cause growth retardation both because of dilution of the diet and the tendency of some bentonites to adsorb vitamin A in mixed diets and otherwise interfere with the absortion of this vitamin in the intestinal tract.
Very little, if any, kaolin is absorbed after oral administration. Bowel obstruction occurs at very high doses, about 100g per kg body weight in rats being fatal to 1 percent, about 150 per kg being fatal to 50 percent.
No adverse effects have been observed at dietary levels as high as 12 percent in experimental animals. The human therapeutic dose for diarrhea is about 250 to 1,000 mg per kg.
It is noted that clay (kaolin) administered under conditions that damage mucosal tissues, tends to produce granulomatous lesion. However, the generally high tolerance for kaolin under normal conditions makes it improbable that such effects could result as it is currently used.
Based upon consideration of the data presented in this report and assuming the establishment of appropriate food grade standards fro bentonite, the Select Committee concludes that:
There is no evidence in the available information on bentonite that demonstrates or suggests reasonable grounds to suspect, a hazard to the public when it is used in the manner now practiced or that might reasonably be expected in the future.
There is no evidence in the available information on clay (kaolin) that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used as an ingredient of food packaging materials in the manner now practiced or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Benzoic Acid | 65-85-0 | 7 | 1973 | 1 | 184.1021 |
SCOGS Opinion:
There are extensive metabolic data on benzoic acid and sodium benzoate in experimental animals and man. It appears that the rat and human have similar metabolic pathways. Short- and long-term feeding studies, as well as teratological investigations, have also been reported in the rat. Interpolation of the rat data and consumer exposure data indicates that the highest no effect level reported in the long-term laboratory feeding study of sodim benzoate is approximately 180 fold the amount usually present in man's daily diet. The highest no effect level reported in laboratoy animal feeding is approximately 90 fold the amount that would be consumed if an individual's diet were to consist only of those foods containng the greatest amoutns of sodium benzoate in current usage. In the light of the foregoing the Select Committee concludes that: There is no evidence in the available information to show that benzoic acid and sodium benzoate
as food ingredients constitute a hazard to the general public when used at levels that are now current or that might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Biotin | 58-85-5 | 92 | 1978 | 1 | 182.8159 |
SCOGS Opinion:
Biotin, one of the B complex vitamins, is an essential nutrient functioning as a part of the enzyme systems of the human body that are involved in carboxylation and decarboxylation reactions. It is present in many foods and usual diets of adults probably supply an average of 30 to 40mg daily, with large variation. The difficulty of producing biotin deficiency in mammals without the use of avidin indicates that the usual intakes are in excess of those required for normal maintenance and growth.
Currently the only food use of biotin is in milk-free infant formulas and certain special formulas used in the management of older subjects. Infant formulas are likely to provide approximately 95 mg of biotin per day for a 4 month old (about 20 mg per kg body weight) and an adult receiving 2000 kcal in the form of foods for special dietary use under medical supervision could receive up to 300 mg biotin per day (about 5mg per kg body weight). Considerably larger doses (up to 2mg per kg body weight) have been administered without untoward effects in attempts at treating several disease conditions.
Although adverse effects of biotin administration on reproductive performance have been reported in limited experimenys in rats, the effective doses have been extremely large (about 50mg of biotin per kg of body weight).
Such doses are orders of magnitude greater than those to which humans could conceivably be exposed by consumption of processed foods containing added biotin.
The Select Committee concludes that:
There is no evidence in the available information on biotin that demonstrates, or suggests reasonable grounds to suspect a hazard to the public when it is added to foods at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Bleached Starch | 9005-25-8 | 115 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Brown algae | 977161-38-8 | 38 | 1973 | 1 | 184.1120 |
SCOGS Opinion:
The term, "algae", is too ill-defined to be a meaningful term in the context of the GRAS list. The uncertainty with respect to the source and the nature of these materials makes it imprecise to attempt to evaluate the health aspects of the use of substances that simply bear the designation brown algae, red algae, or algae. This is particularly pertinent because of the variation in the chemical constituency of the several species of algae that have been reported to be used in food. In addition, the fact that there are no data available on the usage or consuption of algae, kelp and dulse, raises a question as to whether or not any of these materials are now being used in foods in the United States.
The Select Commitee believes that the extent of actual use of algae, kelp, and dulse in food should be ascertained. If they are found to be used to any considerable extent, it would be advisable to identify them more definitely for regulatory purposes. Further, in view of the probable absortion of metals by algae from pollutes waters, permissible levels of mercury and other heavy metals should be specified for the materials so identified.
However, within this context, and in the light of available biological data, an interim conclusion can be drawn. The biological information available with respect to algae, dulse, and kelp and certain substances derived from the, is limited to studies on laminine monocitatrate and laminarin sulfate, and to feeding trials involving fooder containing dehydrated algal meals and dried seaweed prepared from several species of brown and red algae. These investigations, involving several animals species have revealed no evidence of adverse effects from the feeding the algal species tested or their derived products at levels that are orders of magnitude above those presumed to be used in foods in this country as ingredients of spices, seasonings, and flavorings.
The Select Commitee has weighed the foregoing and concludes that: There is no evidence in the available information on the brown algae (Laminaria sp. and Nereocystis sp.), also referred to as kelp, and the red algae, Porphyra sp. and Rhodymenia palmata (L.)Grev., also referred to as dulse, and the materials derived from these species, that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that now seem to be current or that might reasonably be expected in future if their use is confined to ingredients of spices, seasonings, and flavorings as is now stated in the Code of Federal Regulations.
SCOGS Opinion:
The absorption and metabolism of BHA by several animal species and by man are well documented. Man excretes a minute quantity of BHA as the free phenol and an ethereal sulfate while the major portion is conjugated with glucoronic acid. In the rat, a larger percentage of administered doses is excreted as the free phenol and an ethereal sulfate. In rats, dogs, monkeys, and man, none of the metabolic products of BHA are antioxidants while in these species, metabolic products of BHT have antioxidant properties. The acute toxicity (LD 5 0) of BHA is about 2g per kg for mice, rats, and rabbits. The no-effect level for short-term effects in the rat has been estimated at 25mg per kg. If this value should be approximately applicable to man, it is 125 to 500 times the estimated daily intake of 0.05 to 0.2mg per kg. Doses of the order of 50 mg per kg or more when fed chronically to animals produced significant liver hypertrophy accompanied by proliferation of endoplasmic reticulum and a
nonspecific stimilation of the synthesis of drug-metabolizing systems. Such effects disappeared on cessation of BHA intake but remained as long as the compound continued to be ingested. Two monkeys fed BHA at the 50mg per kg level had marginal proliferation of the endoplasmic reticulum and stimulation of mixed function oxidases. It was noteworthy that at both the 50mg and 500mg per kg level BHA had a more pronounced effect on liver weight in monkeys than BHT. It is not clear that liver hypertrophy per se is a manifestation of microsomal enzyme induction. Liver hypertrophy is a gross measure of enzyme induction, but its absence may not necessarily mean that enzyme induction is absent. In addition, the findings from studies with rats, monkeys, and man suggest that BHA metabolism may vary among animal species. Recent studies show that BHA action on enzyme systems in vitro occurs at very low concentrations. BHA can conceivably affect drug metabolizing enzymes in vivo which are the natural
effectors of steroid hydroxylations and prostaglandin synthetases. In addition, there are reports that very low concentrations of BHA interfere with the action of bradykinin and prostaglandin synthesis. It would be desirable to determine whether BHA tissue levels resulting from chronic intake affect metabolic rates of natural substrates such as androgenic, progestational and adrenal steroids, pyridine nucleotides and cytochromes. In addition, the effects on metabolism of common drugs and oral contraceptives should be investigated. In man single doses of BHA requires 10 days for elimination probably due to the solubility and retention of the compound in fat. Thus, with a typical American diet which provides a regular intake of BHA, the chronic tissue level should be determined for man. The evidence indicates that BHA is not mutagenic. While there are teratogenic effects of BHA in the avian embryo test system, several investigations using three mammalian species have failed to establish
any teratogenic or embryotoxic potential when BHA is fed to young or adult and pregnant animals at dosages that greatly exceed estimates of human consumption. Data from several studies indicate that BHA is not a carcinogenic substance. There is evidence that BHA may interfere with synthesis of natural carcinogens and suppress or retard growth of tumors induced by known chemical carcinogens. The Select Committee in its report on BHT identified areas of concern regarding the properties of BHT and indicated that additional studies are needed. Although the concentrations at which these responses occur are generally lower with BHA than with BHT, the qualitative effects are comparable. Concern was expressed about the possible enzyme inductive properties of BHT in extrahepatic tissues, particularly the intestine. Questions were also raised regarding the effect of induction of hepatic enzymes on the metabolism of steroids. The long-term effects of continuously maintained liver hypertrophy from
multiple stimuli were also raised. This is a part of the general problem of adaptive responses of the liver which develop after the ingestion of many foreign substances including drugs, hormone analogues, insecticides, alkaloids, and carcinogenic polycyclic hydrocarbons. While available data suggest that BHA in food is ingested at levels many times below that which produces short-term effects, several of these questions remain. The Select Committee concludes that studies on the tissue levels of BHA attained in man by chronic ingestion and the contribution of BHA to the general problem of enzyme induction should be assessed. Finally, chronic feeding studies with BHA at dosages equivalent to human exposure and use levels should be conducted in primates to determine the long-term effects of BHA on liver mixed function oxidase systems. The Select Committee regards these questions as less urgent for BHA than for BHT and concludes that: While no evidence in the available information on
butylated hydroxyanisole (BHA) demonstrates a hazard to the public when it is used at levels that are now current and in the manner now practiced, uncertaintied exist requiring that additional studies be conducted.
SCOGS Opinion:
The information on the metabolism and toxicology of BHT is extensive. There is ample evidence of efficacy of this compound as an antioxidant. It has been suggested that BHT in fatty tissue may even have some effect similar to that of vitamin E. There are some data to indicate that BHT in diets reduces the incidence of certain tumors and the rate of absorption in the rat. The available evidence does not support the view that BHT interferes in any specific way with cellular metabolism. There is no evidence that demonstrates that BHT causes frank biochemical lesions in the liver; moreover, it is obvious that high doses of BHT are needed to induce biochemical alterations. With 0.1% BHT in the diet in rats there are differening data in the literature concerning the effect of such treatment on liver growth and liver enzymes. At 0.05 % in the dit, no toxic effects are discernible. This "no-effect level" is equivalent to 50 mg per kg per
day. However, BHT increases the level of microsomal enzymes in the liver. The significance of this increase raises certain questions. The liver weight of animals fed BHT is increased and some interpret this enlargement as hypertrophy which is fully reversible and without apparent toxicological significance. But a point could occur at which adaptation fails, a new condition is created, and injury commences. It does not appear that "fully adapted" livers have been challenged by additional doses of BHT or, more importantly, other chemicals. In view of the widespread use, for example, of oral contraceptives, it is felt that informatoin should be available on the effect of challenging fully adapted livers with compounds which are themselves metabolized by microsomal hydroxylases. Therefore, there is the need to determine the effects of BHT at levels now present in foods under conditions where steroid hormones or oral contraceptives are being ingested. Other tissues such as lung and the
gastrointestinal mucosa, in addition to liver, can respond to enzyme inducing agents. More information is required on the inducing properties of BHT on extra hepatic organs. If induction should be found to occur, it would be necessary to determine the effect of such enzymes on the conversion of other ingeted materials into toxic substances or carcinogens. The Select Committee has weighed the foregoring and concludes that: While no evidence in the available information on BHT demonstrates a hazard to the public when it is used at levels that are now current and in the manner now practiced, uncertainties exist requiring that additional studies should be conducted.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Caffeine | 58-08-2 | 89 | 1978 | 3,4 | 182.1180 |
SCOGS Opinion:
Caffeine has been consumed by man for centuries in coffee and tea. This opinion is not concerned with such naturally ocurring caffeine in foods. It is addressed solely to caffeine as commercially added to food commodities. Cola beverages comprise the largest and only significant source of caffeine in this latter group. Such beverages have been in use for decades.
The Select Committe's opinion on the health aspects of caffeine as a commercially-added food ingredients rests primarily upon the integrated interpretation of a cluster of eight factors. These are:
1. Levels of consumption of caffeine as a commercially-added food ingredient: Three points of reference have been used: (a) the total amount of caffeine added to foods in the United States supplies about 0.2 mg per kg per day for the population as a whole; (b) most cola drinkers consume about 0.3 mg of caffeine per kg per day from this source with a few in the 1 to 5 years range consuming as much as 1.8 mg per kg per day; (c) the consumption of a 12-ounce container of cola beverage containing 0.01 percent caffeine represents a dose of about 0.9 mg per kg for a 40kg child, for example, or about 0.6 mg per kg for an adult. It is to be noted that these figures represent the amount of caffeine solely form cola drinks. They, therefore, represent the minimum levels of caffeine consumption on the part of individuals consuming a range of caffeine-containing foods and beverages.
2. History of cola consumption: Despite widespread human consumption of cola beverages over many years, the literature contains no definitive studies of possible long-term effects.
3. Mutagenicity: Caffeine causes chromosomal damage in certain microbial and other non-mammalian test systems, and caffeine has similar effects at high concentrations on mammalian cells in culture in several in vitro tests. However, in vivo tests utilizing mice and rats have failed to demonstrate mutagenic effects of caffeine.
4. Teratogenicity: Many animal tests showed that teratogenic effects are generally absent at caffeine doses up to 50 mg per kg body weight. At doses up to 75 mg per kg of body weight, teratogenic effects of caffeine are neither striking nor consistently demonstrated. At bolus doses greater than 75 mg per kg terratogenic effects are apparent. Two retrospective studies of more than 14,000 mothers on whom caffeine consumption histories were obtained, revealed no association between caffeine intakes and abnormalities in offspring.
5. Carcinogenicity: A very recent and as yet unpublished report has indicated that rats given caffeine orally at daily doses of 150 to 250 mg per kg for 15 months develop cancer of several organs. Epidemiological studies suggest that there is no casual relationship between drinking coffee or the caffeine contained in it and cancer.
6. Long term feeding studies
Two to four generation studies with rats intubated daily with up to 30 mg per kg body weight of caffeine or supplied the same dosage in drinking water, showed no consistent dose-related effects. Mice given 250 mg caffeine per kg body weight daily in drinking water throughout life, continued to breed satisfactorily. Fertility of eggs from pullets fed 80mg caffeine per kg per day was not impaired but embryonic losses were about 16 percent compared to 5 percent in controls. Marked but reversible reduction in sperm output and concentration was found in roosters after 3 weeks feeding of 160mg caffeine per kg per day.
7.Dose effects in humans. The pharmacological dose of caffeine used to stimulate central nervous system activity in humans is about 3 mg per kg and is observable at about 2 mg per kg. The acute human fatal dose of caffeine appears to be greater than 170 mg per kg. Oral administration of caffeine (4 mg per kg) has been found to increase blood pressure in fasted individuals.
8. Behavioral effects on children: Concerns with respect to behavioral effects are less for adults, particularly when the amount of caffeine consumed as cola beverages is compared to that consumed in coffee, tea or other natural sources of caffeine, than for children where there can be chronic consumption of caffeine in colatype beverages during the period of brain growth and development. It is during this period of plasticity that the developing central nervous system is most sensitive to the effects of all aspects of the environment. The estimated levels of caffeine intake at these ages are near those levels that are known to cause central nervous system effects in adults. A few short-term human studies suggest that infants (treated neonatally with caffeine for apnea) were not more sensitive than adults to caffeine, that neonatal caffeine treatment did not predispose to neurological or intellectual residua when the children were evaluated 2 years post-treatment, and that caffeine had
no observable behavioral effects on either normal or hyperactive school aged children. Other studies indicate that children may be more sensitive than adults to the stimulant effect of caffeine. In mice, rats and monkeys noticeable behavioral effects have been elicited at dose levels as low as 1 to 2 mg of caffeine per kg, with definite effects apparent at doses upward of 10 mg per kg.
In addition to considering these eight factors, the Select Committee views with concern the continued addition of caffeine to cola-type beverages, representing as it does a unique addition to food of a pharmacologically active central nervous system stimulant. The amount of caffeine consumed as cola type beverages borders on the dose known to produce central nervous system stimulation in animals and man. Whether such stimulation constitutes an adverse effect or whether a potential hazard may exist for the segment of the population, particularly children, that is exposed chronically to stimulating doses of caffeine, cannot be answered on the basis of the evidence now available. Despite the long history of use and absence of definitive evidence of toxicity in mammalian in vivo test systems, there is a possibility that behavioral effects in children from the consumption of caffeine from infancy through adolescence exist, even though these potential effects are neither adequately documents
nor are their consequences clear.
The Select Committe is well aware that caffeine in cola-type beverages is not the only dietary source of this substance. However, based on the evidence available in May 1978, the Committee believes it is not appropriate to continue to consider caffeine as a generally recognized as safe substance for addition to cola-type beverages. A series of rigorously controlled chronic studies in appropriate species, including fetal, neonatal, and growing animals, of the immediate and ultimate behavioral and cardiovascular effects of caffeine added to the diet and given in cola-type beverages, would reduce areas of speculation in this regard. Such animal studies should include doses equivalent to the present estimated daily intakes of caffeine due to consumption of cola-type beverages containing 0.01 percent caffeine, and multiples of that dosage. In addition, appropriate pharmacokinetic studies (acute and chronic) in human subjects appear to be essential in order to establish patterns of
absortion, biotransformation and excretion of caffeine. Such studies should consider caffeine as it occurs in cola-type beverages, as it occurs in natural sources, and in combinations of the two in common use by the general population, in order to study the effects of ranges of total body loads. Such data would be useful in providing a sounder basis for interpreting the possible long term health implications of caffeine consumption.
In light of these considerations, the Select Committee concludes that:
A. While no evidence in the available information on caffeine demosntrates a hazard to the public when it is used in cola type beverages at levels that are now current and in the manner now practiced, uncertainties exist requiring that additional studies be conducted.
B. It is inappropriate to include caffeine among the substances generally recognized as safe (GRAS). At current levels of consumption of cola-type beverages, the dose of caffeine can approximate that known to induce such pharmacological effects as central nervous system stimulation.
A minority report of Select Committee member R.G.H. Siu appears as an appendix to this report.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Calcium acetate | 62-54-4 | 45 | 1975 | 1 | 184.1185 |
SCOGS Opinion:
Extensive studies have been made to determine the nutritional significance of calcium and its salts. Calcium and the acetate, chloride, by the normal metabolic processes in man. Phytic acid is a naturally occurring constituent of foodstuffs of plant origin. The very limited use of calcium phytate appears insignificant in light of the natural occurrence of phytic acid. A review of the concentrations of calcium compounds normally present in or added to foods provides no evidence that suggests possible untoward effects at these levels. No evidence in the available information on calcium acetate, calcium chloride, calcium gluconate, and calcium phytate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Calcium alginate | 9005-35-0 | 24 | 1973 | 2 | 184.1187 |
SCOGS Opinion:
The available information on the alginates reveals no significant adverse toxicological effects from oral administration in non-pregnant animals or humans in daily amounts greatly exceeding those currently consumed in the diet. However, in pregnant mice, very large doses of propylene glycol alginate, while not teratogenic, cause a significant increase in maternal mortality. Such increased maternal toxicity does not occur at a dose of propylene glycol alginate which is 26-fold or more greater than that estimated to be the average daily adult dietary intake. No respect but studies of propylene glycol, made by the same investigators and is without maternal toxicity even at very large doses. This indicates that the adverse effects reported for propylene glycol alginate may be due to the alginate moiety. It is noteworthy that similar toxic effects have been observed in identical tests on a large number of other polysaccarides (gum
arabic, sterculia gum, carob bean gum, guar gum, gum ghatti, gum tragacanth, carrageenan, methyl cellulose, and agar-agar) fed at very high levels. The relative sensitivity of the several animal species to these effects, varies depending on the particular polysaccaride tested, but in all cases very large doses are required. Until these effects have been adequately explained, it appears to be inappropriate to conclude that unrestricted use of such substances in food would be withou hazard. The Select Committee has weighed all of the foregoing and concludes that: There is no evidence in the available information on ammonium, calcium, potassium, sodium, and propylene glycol alginates that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption of these substances would
constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Calcium carbonate | 471-34-1 | 26 | 1975 | 1 | 184.1191 |
SCOGS Opinion:
The Select committee is not aware of any long-term experimental studies on chronic administration of any of the carbonate salts. The results of acute toxicity and short-term feeding experiments are not readily extrapolated in determining toxic levels for carbonate salts consumed by humans. Treatment of gastric or peptic ulcers in patients with large amounts of carbonate salts in various forms has been utilized for many years and only rarely have deleterious results of changes of acid-base balance been reported. When the human respiratory and renal functions are normal, the mechanisms for disposing of bicarbonate intake in large amounts through excretion appear to be highly efficient. Studies of mice suggest that large intakes of calcium carbonate may interfere with reproductive performance. Such effects could be indirectly attributable to certain trace nutrient deficiences. Comparable intake levels of calcium may occur when
calcium carbonate is used for therapeutic purposes but the amounts added to foods in normal manufacturing processes are not high enough to be harmful. While the Select Committee is not aware of any studies on sodium sequicarbonate per se, reasoned judgment suggests its biochemical conversion and metabolism would be similar to that of sodium carbonate and bicarbonate. On the consideration of the foregoing, the Select Committee concludes that: There is no evidence in the available information on calcium carbonate, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, or sodium sesquicarbonate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Calcium caseinate | 9005-43-0 | 96 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
Casein in milk and milk products has been a major component of the diet of man for centuries. Long term animal feeding studies have shown that extremely high dietary levels of casein, in common with other food proteins, may be injurious to the kidneys. However, per capita daily consumption of casein and caseinates added to foods is less than 0.2g and represents a minor contribution to the total average daily intake of protein, about 99g, by the U.S. population.
Heating casein under strongly alkaline conditions at 90°C or autoclaving at higher temperature under near neutral conditions has been shown to result in the formation of lysinoalanine as a component of the protein molecule. Lysinoalanine has been reported in commercial samples of casein, calcium caseinate, and sodium caseinate. Lysinoalanine also has been detected at relatively low concentration in a number of commercial food products and in home-cooked frankfurters, chicken, and egg white.
Sensitivity to lysinoalanine differs among animals species and is dependent on the protein nature of the diet; feeding free lysinoalanine at dietary levels of 1000 ppm to five mammalian species other than the rat, including subhuman primates, failed to produce renal cytomegalic changes. Renal cytomegalic changes have been demonstrated in rats fed free lysinoalanine, or alkalitreated soy protein isolate, lactalbumin or casein containing bound lysinoalanine. The alkali-treated proteins were fed as the sole source of protein at dietary levels of 20 to 30 percent; cytomegaly did not occur or was markedly reduced in rats fed diets in which alkali-treated protein was supplemented with an untreated protein, suggesting that the renal syndrome was caused by protein bound lysinoalanine in diets deficient or imbalanced with respect to one or more amino acids. Although the available information indicates that the present consumption levels of casein and caseinates, less than 0.2g per capita as
currently used, pose no hazard to the consumer,a limitation with respect to lysinoalanine content in specifications for food grade products would avoid possible future problems in this regard.
A small proportion of infants and lesser numbers of children and adults experience untoward reactions to casein and other milk proteins. Casein is only mildly antigenic but the presence of whey proteins in commercial casein may increase the frequency of hypersensitivity reactions. However, the relatively low consumption of casein, sodium and calcium caseinates added to processed foods, as compared to consumption of casein in milk, cheese, other dairy products, and foods containing dairy products as an ingredient, does not appear to significantly exposure to this antigen.
Although few nitrite analyses of caseinates dried in direct fired spray driers were available to the Select Committee, the available data and the finding of nitrite in samples of other products dried in similar equipment indicates that nitrite can occur at low levels in spray-dried products. According to available information, casein and some caseinates are dried in indirectly heated driers and would not be exposed to nitrite from the drying gases. Nitrite content is of concern because of its toxicity, per se, and because it can react with other nitrogen containing compounds to produce nitrosamines, many of which have been shown to be carcinogenic in experimental animals. It is important to ensure that preformed nitrosamines are not present in caseinates and are not formed in processed foods containing caseinates.
Consideration must be given to the potential for nitrosamine formation in vivo from ingestion of foods containing nitrite, and the latter reacting with other nitrogen containing compounds in foods, drugs, and endogenous amines, must be considered. Many natural and processed foods, including spraydried products, contribute to the total human intake of nitrite even though bacterial reduction of nitrate to nitrate in saliva is the mejor source of nitrite entering the stomach.
It has been reported from recent unpublished work with rats fed nitrite that the frequency of lymphoreticular tumor was increased. The possibility that nitrite has a direct adverse effect of this type raises questions about the total body burden of nitrite and the relative contributions from food, saliva, and the estimated larger amount produced by bacteria in the intestinal tract. A study of these sources and their relative importance is required for individuals of different age groups and dietary habits to obtain reliable figures. Specifications should be developed for food grade caseinates which limit the content of nitrite and nitrosamines.
Caseinates appear to contribute a minor quantity of nitrite to total human exposure. Preliminary estimates of per capita exposure indicate they account for less than 0.2 percent of that taken in as an ingredient of food and present in saliva, and less than 0.005 percent of the total taken in as food ingredient, present in the saliva, and generated in the intestinal tract. From the standpoint of relative contributions to the controllable nitrite load and/or total body burden, caseinates do not appear to be cause for concern at this time. Nevertheless, the possible adverse effects of nitrite call for more explicit knowledge and actions for maintaining a low level of the compound in the commercial product and for continued monitoring of its relative contributions, with adjustments as necessary, as the major sources of commercially added nitrites are progressively decreased through regulatory procedures underway.
The Select Committee has weighed the foregoing information and concludes that: It is essential that food grade specifications for casein, sodium caseinate, and calcium caseinate be established including provisions for acceptable levels of lysinoalanine, nitrite, and nitrosamines.
Assuming that acceptable levels of lysinoalanine, nitrite, and nitrosamine are established, there is no evidence in the available information on casein, sodium caseinate, or clacium caseinate that demonstrates or suggest reasonable grounds to suspect a hazard when they are used at levels that are now current or that may reasonably be expected in the future.
There is no evidence in the available information on casein that demonstrates or suggests reasonable grounds to suspect a hazard when it is used in paper and paperboard products for food packaging at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Calcium chloride | 10035-04-8 | 45 | 1975 | 1 | 184.1193 |
SCOGS Opinion:
Extensive studies have been made to determine the nutritional significance of calcium and its salts. Calcium and the acetate, chloride, by the normal metabolic processes in man. Phytic acid is a naturally occurring constituent of foodstuffs of plant origin. The very limited use of calcium phytate appears insignificant in light of the natural occurrence of phytic acid. A review of the concentrations of calcium compounds normally present in or added to foods provides no evidence that suggests possible untoward effects at these levels. No evidence in the available information on calcium acetate, calcium chloride, calcium gluconate, and calcium phytate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Calcium citrate | 813-94-5 | 84 | 1977 | 1 | 184.1195 |
SCOGS Opinion:
The citrate ion is widely distributed in plants and animals and is a naturally occurring component of the diet. It is a common metabolite in oxidative metabolism and an important component of bone. Exogenous citrate administered to infants and adults as a component of commonly consumed diets is considered completely metabolizable. The addition of citric acid to foods is considered equivalent to adding citrate salts except in foods of very high acidity. The amount of citrate added to foods by foods processors is about 500mg per person per day. This amount occurs naturally in 2 ounces of orange juice and does not constitute a significant addition to the total body load. Although data on acute and chronic effects of orally administered sodium citrate, calcium citrate and potassium citrate are limited, no biological effects of the citrate-containing substances evaluated in this report cause concern about the safety of these GRAS
substances used in reasonable amounts and in accordance with prescribed tolerances and limitations.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on citric acid, sodium citrate, potassium citrate, calcium citrate, ammonium citrate, isopropyl citrate, stearyl citrate, and triethyl citrate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Calcium gluconate | 299-28-5 | 45 | 1975 | 1 | 184.1199 |
SCOGS Opinion:
Extensive studies have been made to determine the nutritional significance of calcium and its salts. Calcium and the acetate, chloride, and gluconate anions are common constituents of food and are metabolized by the normal metabolic processes in man. Phytic acid is a naturally occurring constitutent of foods stuffs of plant origin. The very limited use of calcium phytate appears insignificant in light of the natural occurrence of phytic acid. A review of the concentrations of calcium compounds normally present in or added to foods provides no evidence that suggests possible untoward effects at these levels. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available inforamtion on calcium acetate, calcium chloride, calcium gluconate, and calcium phytate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now
current or that might reasonably be expected in the future.
SCOGS Opinion:
The glycerophosphate salts that are considered to be GRAS could provide absorbable sources of glycerol, phosphate, and their respective cations. However, glycerophosphates are not now widely used in foods. The Select Committee believes that the level of consumer exposure is very low and that use under limitations as a nutrient or dietary supplement will nor present a hazard to the public. In previous evaluations of glycerol and certain phosphates no evidence was found of a hazard to the public from the hydrolysis products of the glycerophosphates.
In light of the information reviewed and reported herein, the Select Committee concludes that: There is no evidence in the available information on calcium glycerophosphate, potassium glycerophosphate and manganese glycerophosphate that demonstrates or suggests reasonable grounds to suspect a hazars to the public when they are used as nutrient supplements or as they might reasonably be expected to be so used in the future. There is no evidence in the available information on calcium glycerophosphate and magnesium glycerophosphate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used in food packaging materials as now practiced or as they might be expected to be used for such purposes in the future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Calcium hydroxide | 1305-62-0 | 72 | 1975 | 1 | 184.1205 |
SCOGS Opinion:
Calcium oxide and calcium hydroxide as used in foods contribute to the total biologically available dietary calcium. No evidence has been found that demonstrates these compounds have adverse nutritional implications in the overall dietary intake of cations. Thus, normal physiological mechanisms that control calcium metabolism allow man to utilize these sources of calcium. In light of these considerations, the Select Committee concludes that: There is no evidence in the available information on calcium oxide and calcium hydroxide that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as direct or indirect food ingredients at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Calcium hypophosphite | 7789-79-9 | 73 | 1977 | 1 | There is no CFR citation. |
SCOGS Opinion:
The hypophosphites do not appear to be currently used as ingredients in foods as indicated by a survey of the food industry conducted by a National Research Council subcommittee in 1970 and more recent information obtained from industry by the Select Committee. They had limited medical use many years ago in tonics and as therapeutic agents but appear to be no longer used for these purposes.
The acute toxicity of hypophosphites is relatively low; injected intraperitoneally in mice, the LD50 (30days) for the sodium salt was 1.6g per kg body weight. Calcium and sodium hypophosphites given orally or parenterally to experimental animals and man are rapidly excreted as hypophosphite in the urine. It is the opinion on the Select Committee that potassium hypophosphite is comparable to the sodium salt in excretion and toxicity.
Although animal feeding experiments indicate that the phosphorus in hypophosphites is not biologically available, no adverse effects were reported in young rats fed diets containing calcium hypophosphite (up to 4.3g per kg). Growth and calcium assimilation were as good as observed on diets containing salts recognized as good sources of calcium.
Although no reports were available on the biological effects of manganese hypophosphite, an evaluation of the health aspects of other manganous salts by the Select Committee has found no evidence that would indicate a hazard from manganous hypophosphite if used as a nutrient or dietary supplement.
In view of the foregoing the Select Committee concludes that: There is no evidence in the available information on manganous, calcium, potassium or sodium hypophosphite that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used in the manner now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Calcium iodate | 7789-80-2 | 39 | 1975 | 1 | 184.1206 |
SCOGS Opinion:
Iodine occurs widely and is present in most human foods. While the quantity of iodine in specific foods is highly variable, the average diet usually contains sufficient iodine to supply man's requirement for this essential element. In addition to the iodine in foods, iodine-containing compounds are ingested in the form of dietary supplements, food processing adjuncts, food colors, sanitizing agents, and pharmaceuticals. While no comprehensive consumption data are available for any iodine consumed dialy by individuals has increased in the past several years. Potassium iodide, potassium iodate, and calcium iodate are only three of the many iodine-containing substances including iodates are converted to iodides in food processing or often consumption. Therefore, the Select Committee has limited its evaluations in this report to potassium iodide, potassium iodate and calcium iodate. This is, in effect, evaluating the health aspects
of adding iodide ion to certain foods. Available biological information shows that ingested potassium iodide and other iodides are readily absorbed and utilized to the extent required for nutritional needs, the excess being excreted primarily in the urine. There is no evidence in the studies on experimental animals and man available to the Committee that indicates acute or chronic toxic effects, including mutagenic, teratogenic, and carcinogenic effects, resulting from the consumption of potassium iodide by euthyroid individuals in amounts that are several orders of magnitude greater than those now being consumbed in the daily diet. Based upon consideration of the available data, the Select Committee concludes that: There is no evidence in the available information on potassium iodide, potassium iodate, or calcium iodate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced,
or those which might reasonably be expected in the future under existing limitations.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Calcium Lactate | 814-80-2 | 116 | 1978 | 1 | 184.1207 |
SCOGS Opinion:
Lactic acid is produced in varying amounts by most living tissues as a normal metabolic intermediate. The lactate turnover rate in man has been estimated to be of the order of 2g per kg per day.
An additional load of up to 1 mg per kg per day of lactic acid as the free acid or as calcium lactate contained in commercially prepared food commodities would not appreciably modify the normal metabolic processes. None of the limited toxicity data available raises any suspicion of adverse effects in adults at doses orders of magnitude above the estimated levels of human consumption. There is no indication that the per capita intake of lactate from processed foods will be substantially increased in the foreseeable future.
There is no evidence of potential toxicity of the L-isomer for individuals of any age. However, premature infants fed formulas acidified with DL-lactic acid (or, in one instance, D(-) lactic acid), have reported to develop metabolic acidosis and growth retardation. Results of studies of full-term infants are conflicting and difficult to interpret. Resolution of this conflict is needed even though, as far as the Select Committee is aware, lactic acid acidification of infant formulas is not currently being practiced in the United States except in products designed for special dietary or therapeutic purposes which are not being evaluated in this report.
In the light of these considerations, the Select Committee concludes that:
There is no evidence in the available information on L(+) calcium lactate that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on either of the isomers of lactic acid, their calcium salts, and their racemates that demonstrates or suggests reasonable ground to suspect a hazard to individuals beyond infancy when they are used at levels that are now current or thar might reasonably be expected in the future.
There evidence on D(-)-lactic acid, DL-lactic acid and their calcium salts is insufficient to determine that the adverse effects reported would not be deleterious to infants should they be used in infant formulas. Lactic acid acidification of generally available infant formulas is not now being practiced in the United States.
SCOGS Opinion:
L-ascorbic acid, vitamin C, occurs in nutritionally significant amounts as a natural constituent of many fruits, vegetables, berries, and melons. As a vitamin it is needed in the diet of all age groups. L-ascorbic acid and its sodium salt are antioxidants and they are extensively used as preservatives, color stabilizers and for related functions in various foods and beverages. Calcium ascorbate and ascorbyl palmitate, a derivative of ascorbic acid having greater fat solubility, also are anti-oxidants, but appear not to have significant use in processed foods. In addition to their use in foods as antioxidants, L-ascorbic acid and its salts are added to some foods as a source of vitamin C. These sources constitute a significant proportion of the total ascorbate intake of the general population. Erythorbic acid (D-isoascorbic acid), a stereoisomer of L-ascorbic acid, and its sodium salt, also are effective antioxidants and are used
for this purpose in a number of food products. The quantities used in 1970 were substantially less than for the ascorbates. The vitamin activity of erythorbates is only one -twentieth that of ascorbic acid, and their anti-oxidant effectiveness is not greater than for the ascorbates. For this reason, it would seem desirable, where possible, to use L-ascorbic acid rather than erythorbic acid as an antioxidant. From studies in guinea pigs and man it can be concluded that although erythorbic acid shares the same absorption and tissue uptake system as ascorbic acid it has little antiscorbutic activity. Although competition between ascorbic acid and erythorbic acid has been demosntrated at a biochemical level, there is no firm evidence that such competition will produce a scorbutic state. Whether this biochemical interaction could result in a clinically significant depletion of ascorbic acid remains to be established. Both short- and long-term toxicity studies have demonstrated tolerance
without adverse effects for large amounts of orally administered L-ascorbic acid, sodium L-ascorbate, and erythorbic acid in several species including mice, rats, guinea pigs, rabbits, and dogs. A substantial number of short-term experiments with human subjects ingesting 1 to 4 g of ascorbate daily have generally not revealed any harmful effects. Some subjects have received higher amounts, up to at least 8 to 10 g per day. In most instances no untoward results have been noted. But there is marked paucity of such studies that were well controlled and in which inquiring attention was given to possible harmful effects. In due course, such studies would be desirable. In the various studies on the effect of ingesting excessive amounts of ascorbates, attention has been focused on questions including oxalate excretion and renal tract stones, effets on the utilization of copper, iron, and other metals, need for vitamin B12, blood coagulation,and reproductive performance. The findings indicate
that the tolerance to excessive amounts of ascorbic acid and its sodium salt is high. Several investigators have reported the development of dependency in animals and human after ingestion of large amounts of ascorbates for extended time periods; however, the levels of ascorbates added to foods by 1 to 3 orders of magnitude. It is notable that no data have been found concerning the possible effects of ascorbyl palmitate and calcium ascorbate in humans, and there is practically no information regarding the latter in animals. Information concerning ascorbyl palmitate in animals is almost as limited. The few meaningful experiments suggest that ascorbyl palmitate is tolerated about the same as ascorbic acid and sodium ascorbate. This should be expected. It is reasonable to assume that the tolerance to calcium ascorbate is approximately the same as for sodium ascorbate and this is a high level. In view of the foregoing, The Select Committee concludes that: There is no evidence in the
available information on L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, ascorbyl palmitate (palmitoyl L-ascorbic), erythorbic acid (D-isoascorbic acid), and sodium erythorbate (sodium D-isoascorbate) that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used as food ingredients at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Calcium oxide | 1305-78-8 | 72 | 1975 | 1 | 184.1210 |
SCOGS Opinion:
Calcium oxide and calcium hydroxide as used in foods contribute to the total biologically available dietary calcium. No evidence has been found that demonstrates these compounds have adverse nutritional implications in the overall dietary intake of cations. Thus, normal physiological mechanisms that control calcium metabolism allow man to utilize these sources of calcium. In light of these considerations, the Select Committee concludes that: There is no evidence in the available information on calcium oxide and calcium hydroxide that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as direct or indirect food ingredients at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Calcium phytate | 3615-82-5 | 45 | 1975 | 1 | 582.6219 |
SCOGS Opinion:
Extensive studies have been made to determine the nutritional significance of calcium and its salts. Calcium and the acetate, chloride, by the normal metabolic processes in man. Phytic acid is a naturally occurring constituent of foodstuffs of plant origin. The very limited use of calcium phytate appears insignificant in light of the natural occurrence of phytic acid. A review of the concentrations of calcium compounds normally present in or added to foods provides no evidence that suggests possible untoward effects at these levels. No evidence in the available information on calcium acetate, calcium chloride, calcium gluconate, and calcium phytate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Calcium propionate | 4075-81-4 | 79 | 1979 | 1 | 184.1221 |
SCOGS Opinion:
Propionic acid occurs naturally in various foods including butter and cheese. Its absorption and metabolism are demonstrated in experimental animals and humans where it is a normal intermediary metabolite. As incorporated in foods as its sodium or calcium salt or as the free acid, propionic acid does not occur at the concentrations or under the conditions that are necessary to produce signs of mucosal damage in experimental animals. Propionic acid, sodium propionate, and calcium propinate have demonstrated low acute toxicity after oral administration to mice or rats. The adverse effects observed in chicken embryos occurred only after injection of large amounts of calcium propionate or sodium propionate into the yolk sac, and the reversions observed in a host-mediated assay of calcium propionate were unrelated to dose. These results in chickenembryos and the host-mediated assay must be viewed in the light of other microbial
assays and animal studies that demonstrate no adverse effects and the fact that propionate is a normal intermediary metabolite. Microbial assays for mutagenicity of propionic acid and calcium and sodium propionate were negative. Investigations of the teratogenicity of calcium propionate in four mammalian systems also were negative. Short-term feeding tests show the most sensitive animals tested, young and vitamin B12-deficient animals, experience adverse effects on weight gain only when propionate intakes are many orders of magnitude greater than the estimate of human dietary intake of propionate used as a food ingredient, about 1 mg per kg per day. Long-term feeding studies of propionic acid and calcium propionate have not been reported. However, a long-term feeding study of sodium propionate showed no adverse effects in rats. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on propionic acid, calcium propionate, and
sodium propionate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Calcium silicate | 1344-95-2 | 61 | 1979 | 1 | 182.2227 |
SCOGS Opinion:
Silicon dioxide and various silicates occur abundantly in the earth's crust, are present in practically all natural waters,animals, and plants, and are part of the normal human diet. The question of whether or not silicon is an essential human nutrient remains unresolved. Silicon compounds consumed as added food ingredients contribute only a minor proportion of the total dietary silicon intake. The estimated possible human intake of sodium aluminosilicate, the predominant silicate added to foods in this country, is approximately 0.3mg per kg body weight per day. Silicon compounds that are GRAS for use as direct food ingredient, except potassium and sodium silicates, are insoluble or very slightly soluble in water and appear to be biologically inert. The water-soluble silicates are also of low acute toxicity. The acute oral LD50 in rats of sodium aluminosilicate is >1g per kg. No significant tissue accumulation, pathology, or
toxicity has been reported from the ingestion of those insoluble or very slightly soluble GRAS silicon compounds for which data are available. Of the five substances that were reported as added to foods in the NRC survey, biologic effects and safety data are available for all except sodium calcium aluminosilicate, and there is no reason to suspect that the toxicity of the latter would differ from those for which there are data. The results of two studies (1967-1970) in which various silicon compounds were fed to laboratory animals for 1 mo at a level of 0.8g per kg body weight (as silicon dioxide) and for 3 mo at levels of 6 to 30 mg per kg body weight suggests there may be a species-related susceptibility to renal damage from ingestion of sodium silicate, magnesium trisilicate, and finely ground quartz. No substantiating reports of these effects have appeared. Magnesium trisilicate was recognized as safe for prolonged use in human ingestion in large amount as a component of antacid
preparations by the Advisory Review Panel on Over-the-Counter Drugs, and the available evidence on the acute toxicity of sodium silicate indicates that it is low. Consumption data are lacking for aluminium calcium silicate and tricalcium silicate, two compounds that are listed as GRAS for use as anticaking agents. However, their use in keeping with good manufacturing practice and in currently regulated amounts would be of the same order of magnitude as the other GRAS silicates. In addition, the Select Committee has limited information on the amounts of talc that are currently used in foods. However a major food use of talc is in the coating of rice. Assuming package label statements are ignored and coated rice is not washed prior to cooking and no other losses occur, maximun per capita intake of talc from this source appears to be 0.5g per day. With respect to paper and cotton food- packaging products, the possibility is remote that biologically significant amounts of talc,
diatomaceous earth, or sodium silicate migrate to food from packaging, materials containing these substances. Perlite, a naturally occuring polysilicate substance, has an oral LD50 in the rat of >10g per kg body weight. Estimates of the maximun quantities of minerals that might be extracted from perlite and diatomaceous earth used as filteraids in food processing indicates no hazard to public health. There are no food grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc. Such specifications for the substances used in foods are desirable. Specification for food grade talc should limit the content of asbestos fibers even though the potential hazard of ingested asbestos fibers even though the potential hazard of ingested asbestos is not clearly established. The Food and Drug Administration is sponsoring the development of an assay method for asbestos fibers. An upper limit for cadmium should be added to the specifications for food-grade perlite, and
consideration should be given to the need for limitation of cadmium content of other silicates. In the light of all of the foregoing, the Select Committee concludes that: It is essential to establish food-grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc, with provision for an upper limit of asbestos fibers in talc. There is no evidence in the available information on aluminum calcium silicate, calcium silicate, magnesium silicate, potassium silicate, sodium silicate, sodium aluminosilicate, sodium calcium aluminosilicate, tricalcium silicate, silica aerogel, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on diatomaceous earth, silicon dioxides, sodium silicate, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the
public when they are used as ingredients of paper and paperboard products used in food packaging in accordance with current practice. There is no evidence in the available information on sodium silicate and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of cotton and cotton fabrics used in dry food packaging in accordance with current practice. There is no evidence in the available information on diatomaceous earth and perlite that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used as filteraids in food processing at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Calcium sorbate | 7492-55-9 | 57 | 1975 | 1 | 182.3225 |
SCOGS Opinion:
Sorbic acid and its salts demonstrate very low acute or chronic toxicity for experimental animals. In animals sorbate is metabolized by the normal fatty acid pathway. Although no metabolic or toxicological studies have been conducted in man, the similarity on the pathway of fatty acid metabolism in man and animals suggests that no deleterious effects are to be expected from sorbic acid in the diet even in amounts many times greater than those at which it appears to be used. Based on these considerations the Select Committee concludes that: There is no evidence in the available information on sorbic acid and its sodium, potassium and calcium salts that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Calcium stearate | 1592-23-0 | 54 | 1975 | 1 | 181.129, 184.1229 |
SCOGS Opinion:
Tallow and stearic acid, one of its chemical components, are consumed as part of normal human diets primarily in meats and in smaller quantities as ingredients of shortening and oleomargarine. Calcium stearate appears to be a normal product of digestion of diets containing calcium and stearic acid. Hydrogenated tallow, including tallow flakes, is used to some extent in the manufacture of shortening. Feeding tests with animals show a high utilization of tallow as an energy source, but a relatively low digestibility of hydrogenated tallow, stearic acid, and calcium stearate. None of the feeding tests involving amounts of these substances comparable to those estimated to be consumed as food additives showed any toxic effects. Furthermore, the toxicity of stearic acid at very high concentrations is markedly reduced by the presence in the diet of glycerides of substantially lower melting point, such as those containing unsaturated fatty acids. Carcinogenicity test of stearic acid have shown
negative results. This report is directed toward the GRAS status of tallow, hydrogenated tallow, and stearic acid as given in the Code of Federal Regulations 121.101(i) as substances migrating to food from cotton and cotton fabrics used in dry food packaging and calcium stearate as a GRAS substance (unpublished). Even at the levels estimated as being consumed by man from all added sources of these substances there is no evidence to demonstrate a hazard to the public. In light of these observations, the Select Committee concludes that: As a substances that may migrate to foods from cotton or cotton fabrics, there is no evidence in the available information on tallow, hydrogenated tallow, or stearic acid that demonstrates, or suggests reasonably grounds to suspect, a hazard to the public, when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on calcium stearate that demonstrates, or suggests
reasonable grounds to suspect a hazard to the public, when it is used as a direct food additive at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Caprylic Acid | 124-07-2 | 29 | 1974 | 1 | 184.1025 |
SCOGS Opinion:
Caprylic acid, a naturally occuring constituent of many foods, is absorbed and metabolized by man. Triblycerides containing this fatty acid are hydrolyzed in the intestinal mucosa and the liberated fatty acids are transported in the portal ciculation and are almost completely oxidzed in the liver. Significant oxidation also appears to occur in the intestinal mucosa. Little caprylic acid is stored, and long-term feeding at high levels results in decreased overall fat storage that is indicative of nutritional utilization. thus caprylic acid is a fatty acid nutritionally utilizable by man and animals. Based upon consideration of the data presented in this report the Select Committee concludes that: There is no evidence in the available information on caprylic acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in
future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Caramel | 8028-89-5 | 20 | 1973 | 1 | 182.1235 |
SCOGS Opinion:
Interpolation of data from long-term feeding studies in the rat and from consumer exposure data indicates that the highest no-effect level reported in laboratory animal feeding of caramel is approximately 130-fold the usual level of man's daily intake. The highest no-effect level reported in laboratory animal feeding is approximately 50-fold the intake level if an individual's diet were to consist only of those foods contaiing the greatest amounts of caramel. Based on the one published experiment in man, the corresponding figures are approximately 15-fold and 6-fold. The Select Committee believes that the level of heterocyclic nitrogen-containing compounds in caramel colors should not be left to chance. While all available information indicates that the levels of nitrogen-containing heterocyclic compounds in commercial caramel colors as currently used is well below that which could be toxic to the consumer, a limitation with
respect to nitrogen-containing compounds in the specification for food grade caramel would avoid possible future problems in this regard. The Select Committee has weighed the foregoing and concludes that: The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information to show that caramel as a food ingredient constitues a hazard to the general public when used at levels that are now current or might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Carbon dioxide | 124-38-9 | 117 | 1979 | 1 | 184.1240 |
SCOGS Opinion:
SCOGS OPINION :
The Select Committee could find no data relating directly to the safety of carbon dioxide as a food ingredient. However, there is substantial evidence that the amount of carbon dioxide ingested with foods is negligible compared with that produced normally by the body. Carbon dioxide also has been administered experimentally without ill effects in amount orders of magnitude greater than from possible food sources.
Under resting conditions, an average adult will produce in excess of 500 g of carbon dioxide daily, approximately 2000 times the estimated intake from foods. During moderate or heavy activity, considerably greater amounts of carbon dioxide would be produced. The official occupational standard for the workroom atmosphere is 5000 ppm, equivalent to the inhalation during an 8-hour work day of about 30 g of carbon dioxide. Human subjects have been exposed to 1.5 percent carbon dioxide (a daily inhalation of over 200g) continually for 42 days without serious or lasting ill effects.
The amount of bicarbonate that could be produced from the ingested carbon dioxide is far less than the amounts routinely ingested in food or used without ill effects as an antacid.
The Select Committee is not aware of any study on the mutagenicity of carbon dioxide. Carcinogenic actions have been reported only after repeated application of the solid form to the skin. Teratogenic effects were produced after inhalation of carbon dioxide at levels far higher than could be obtained from foods.
In considerations of these factors, the Select Committee concludes that: There is no evidence in the available information on carbon dioxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Carbonyl Iron | 7439-89-6 | 35 | 1980 | 2 | 184.1375 |
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk of
developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an increase
in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report. Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to determination of the acute toxicity and bioavailability of specific
iron forms. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecdotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled chronic feeding studies with most of the individual compounds, before confident appraisal can be made of their relative merts or hazards.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
In the light of the above considerations, the Select Committee concludes that: There is no evidence in the available information on reduced, electrolytic, and carbonyl iron, ferrous ascorbate, ferrous carbonate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric citrate, ferric phosphate, or ferric pyrophosphate, that suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or in the manner now practiced., or if deemed necessary at somewhat higher levels to meet nutritional needs. However, it is not possible to determine without additional data whether a major increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk of
developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an increase
in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report. Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to determination of the acute toxicity and bioavailability of specific
iron forms. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecdotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled chronic feeding studies with most of the individual compounds, before confident appraisal can be made of their relative merts or hazards.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
In the light of the above considerations, the Select Committee concludes that: There is no evidence in the available information on reduced, electrolytic, and carbonyl iron, ferrous ascorbate, ferrous carbonate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric citrate, ferric phosphate, or ferric pyrophosphate, that suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or in the manner now practiced., or if deemed necessary at somewhat higher levels to meet nutritional needs. However, it is not possible to determine without additional data whether a major increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
Cellulose is a major constituent of many foods of plant origin. As such it is a significant portion of the diet, but is neither degraded nor absorbed. Cellulose derivatives considered in this report are virtually unabsorbed and little or no degradation of absorbed and little or no degradation of absorbable products occurs in the human digestive tract. In man, consumption of large amounts appears to have no effect other than providing dietary bulk, reducing the nutritive value of such foodstuffs and possibly exerting a laxative effect. However, the existence of certain data and the different categorization of cellulose and the several cellulose derivatives on the GRAS list suggest that the Select Committee should render a separate opinion on each substance considered in this report.
A. CELLULOSE, MICROCRYSTALLINE CELLULOSE
Although pure cellulose and regenerated cellulose, including microcrystalline cellulose are not on the GRAS list, there is nothing in the available information to suggest that such forms of cellulose have significantly different biological properties that distinguish these forms of cellulose from those currently considered as GRAS or from naturally occurring cellulose. In view of the foregoing, the Select Committee concludes that: There is no evidence in the available information on pure and regenerated cellulose, including microcrystalline cellulose, that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current, or that might reasonably be expected in future.
B. METHYL CELLULOSE
In humans, virtually 100 percent of orally ingested methyl cellulose can be recovered in the feces withihn four days, indicating that absorption does not occur. However, in pregnant mice, very high doses of methyl cellulose, while not teratogenic, cause a significant increase in maternal mortality and retardation of fetal maturation. Such increased maternal and fetal toxicity does not occur at a dose of methyl cellulose which is 26-fold (or more) greater than that estimated to be the average daily adult dietary intake. It is noteworthy in this regard that similar toxic effects have been observed in identical tests performed by the same investigators on a large number of other polysaccharides fed at very high doses. The relative sensitivity of the several animal species to these effects varies, depending on the particular polysaccharide tested, but in all cases very large doses are required. Until these effects have been adequately explained, it appears to be inappropriate to conclude
that unrestricted use of such substances in food would be without hazard. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on methyl cellulose that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
C. CARBOXYMETHYL CELLULOSE
Carboxymethyl cellulose is converted spontaneously to a salt in alkaline solution, and it is probable that the distinction between carboxymethyl cellulose and its salts is artificial. However, carboxymethyl cellulose is liested as GRAS as a substance migrating to food from cotton or cotton fabrice used in dry foods packaging, while its sodium salt is listed as GRAS as a miscellaneous or general purpose food additive. In view of the separate listing of carboxymethyl cellulose, the Select Committee concludes that: There is no evidence in the available information on carboxymethyl cellulose that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used in dry food packaing materials originating from cotton or cotton fabrics as now practed or as it might reasonably be expected to be used for such purposes in future.
D. SODIUM CARBOXYMETHYL CELLULOSE
Despite the probable lack of distinction between sodium carboxy methyl cellulose and its parent compound, carboxymethyl cellulose, only the sodium carboxymethyl cellulose is GRAS as a miscellaneous and general purpose food additive. As such, there are no data that suggest it reacts differently than pure and regenerated cellulose or carboxymethyl cellulose. In view of the foregoing the Select Committee concludes that: There is no evidence in the available information on sodium carboxymethyl cellulose that demonstrtes, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in future.
E. HYDROXYPROPYLMETHYL CELLULOSE
Hydroxypropylmethyl cellulose is not listed as GRAS. It is a food additive used as a thickening agent, stabilizer and emulsifier. Hydroxypropylmethyl cellulose is sinthesized from methyl cellulose by the action of alkali and propylene oxide. There are no data available to suggest that hydroxypropylmethyl cellulose possesses adverse health effects; however, teratology studies dimilar to those conducted with mehtyl cellulose are not available for its hydroxypropyl derivative. Therefore, it is suggested that, in due course, appropriate studies should be conducted with hydroxypropylmethyl cellulose. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on hydroxypropylmethyl cellulose that demonstrates, or suggested reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current and in the manner now practiced (21 CFR 121.1021)
F. ETHYL CELLULOSE AND CELLULOSE ACETATE
There is a paucity of data concerning possible adverse health effects of ethyl cellulose and cellulose acetate. both are included in the GRAS list as substances migrating to food from paper or paperboard products used in food packaging. According to the NRC survey (6), very small amounts of ethyl cellulose also appear to be used in hard candy and chewing gum. In the GRAS context, the quantity of ethyl cellulose or cellulose acetate migrating to foods from packaging would be orders of magnitude below the levels of cellulose and cellulose derivaties now known to occur in foods. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ethyl cellulose and cellulose acetate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used in food packaging materials as now practiced or as they might be expeccted to be used for such purposes in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Carnauba wax | 8015-86-9 | 47 | 1975 | 5 | 184.1978 |
SCOGS Opinion:
Carnauba wax is a substance of plant origin that is used at a low level of addition in a limited number of food products. The per capita adult daily intake has been estimated to be about 1.2mg. Despite its use in food since 1900, an extensive search of the literature has revealed no information on its absortion, metabolism or excretion by animals, acute or chronic toxicity, or its teratogenic or carcinogenic properties. In view of the almost complete lack of biological studies, the Select Committee has insufficient data upon which to evaluate the safety of carnauba wax as a miscellaneous or general purpose food additive.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Carob Bean Gum | 9000-40-2 | 3 | 1972 | 2 | 184.1343 |
SCOGS Opinion:
The available information reveals that there are no short-term toxicological consequences in chicks, rats, mice, hamsters, rabbits, and man in the normal diet of the U.S. population. There is no evidence that consumption of carob bean gum by man since 1925, when it was first used in the United States, has had adverse effects. It is to be noted, however, that no long-term feeding studies of carob bean gum have been reported. While the available information does not suggest long-term toxicity, it may be advisable in due course to conduct adequate feeding studies in several animal species, including pregnant animals, at dosage levels that approximate and exceed the current estimated maximum daily load in humans. Carob bean gum, fed at relatively high levels, is reported to be toxic to pregnant animals of some species. Because the toxic levels reported are well in excess of the highest levels now consumed by man, the Select Committee
is of the opinion that there are no adverse health aspects of consuming carob bean gum at current levels. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard. The Select Committee has weight the foregoing and concludes that: The available information contains no evidence demonstrating that carob bean gum constitutes a hazard to the public when used in the manner and quantity now practiced.
SCOGS Opinion:
Carotene is a general term describing certain polyene hydrocarbons containing 40 carbon atoms. Three of these, a- , b- , and g-carotene, as well as some closely related oxygen-containing carotenoids, exhibit provitamin A activity. b-carotene is the most active of the carotenes and the only one which is available commercially. It is added to food, chiefly margarine, both as a coloring agent, and for its vitamin A potential. Early studies of the health aspects of "carotene" were performed with preparations of uncertain composition and purity. However, it is apparent from the sources of carotene utilized and the purification procedures adopted, that the active principle in these studies was largely b - carotene, so that the results are relevant to the present review. Since the development or synthetic b - carotene for commercial use in 1954, nearly all research on "carotene" has employed a crystalline and well-defined product.
The average daily intake of carotene from natural sources is estimated to be about 2mg per day which is equivalent to approximately 3300 IU of vitamin A. Substantially larger amounts may be ingested in diets rich in colored vegetables. The Recommended Dietary Allowance of vitamin A from all sources is 5000 IU for adults. Consumption information from various sources, suggests that the per capita daily intake of b - carotene added to foods is 0.2 to 0.3mg.
Doses several orders of magnitude greater than would conceivably be used as additives in food have proved nontoxic to various animal species given b- carotene orally in acute, short and long term studies. A single study suggested some impairment in neonatal skeletal development when 180 mg per kg or more of carotene were administered, daily to rats, but this study has not been confirmed.
When given in moderate amounts, carotene is readily converted to vitamin A. However, this conversion is limited when large amounts of carotene are administered. The regulatory mechanism has not been elucidated. Doses of 180 mg (300,000 IU) daily for 2 or more years have been taken orally by patients suffering from certain types of photosensitivity with no evidence of hypervitaminosis A or other harmful effects.
In the light of these considerations, the Select Committee concludes that: There is no evidence in the available information on carotene (b - carotene) that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Carrageenan | 9000-07-1 | 6 | 1973 | 3 | 172.620 |
SCOGS Opinion:
The available information on the oral administration of undegraded carrageenan at levels greatly exceeding the daily human intake, reveals evidence of possible adverse effects on the gastrointestinal epithelium. Extensive recent investigations of carrageenan and the pathogenesis of gastrointestinal changes indicates the susceptibility of the guinea pig to ulcerative colitis when fed relatively high levels of carrageenan in the diet. The work suggests that the occurrance of ulcers in the large bowl of animals is a species-specific phenomenon where feeding of carrageenan can induce ulceration in the caecum and proximal colon of the guinea pig which to date, does nto appear to occur n the rat, mouse, hamster, pig, squirrel monkey, or man. Recent reports on the oral administration of undegraded sodium and calcium carrageenan of known quality to pregnant animals reveals fetotoxic effects, with or without frank teratogenic effects, in
some species at levels that do not greatly exceed the average daily human rate of intake. There effects appear to be dose-dependent. While carrageenan exhibites no mutagenic effects as measured by the host-mediated and dominant lethal assay procedures, significant abnormalities appear to be induced in the anaphase figures of human embryoic lung cells in tissue culture at dosages that are slightly above average daily human intake. It is of further concern that parenterally administered carrageenan is reported to inhibit the activity of complement, excert cytotoxic effects on macrophases, suppress delayed hypersensitivity reactions in some tuberculin sensitive animals, activate factors causing procoagulant activity in human blood platelets, increase vascular permeabiltiy, and liberate kinin in vitro, all of which point to the possibility of the generation of toxic effects that could cause adverse responses followint the oral consumption of carrageenan if, during pregnancy or in the
presence of infectious challenge or metabolic disorder, appropriate amounts of carrageenan should be absorbed from the gastrointestinal tract. The Select committee has been informed that additional animal feeding and teratologic studis are soon to be initiated on commercial carrageenan and on several of the separated polysaccharide components of carrageenan. The Committee's opinion should be reviewed once the results of these studie become available. The Selct Committee has weighed the foregoing and concludes that: While no evidence in the available information on undegraded carrageenan demonstrates a hazard to the public when it is used at levels that are now current and in the manner now practiced, uncertainties exist requiring that additional studies should be conducted.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Casein | 9000-71-9 | 96 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
Casein in milk and milk products has been a major component of the diet of man for centuries. Long term animal feeding studies have shown that extremely high dietary levels of casein, in common with other food proteins, may be injurious to the kidneys. However, per capita daily consumption of casein and caseinates added to foods is less than 0.2g and represents a minor contribution to the total average daily intake of protein, about 99g, by the U.S. population.
Heating casein under strongly alkaline conditions at 90°C or autoclaving at higher temperature under near neutral conditions has been shown to result in the formation of lysinoalanine as a component of the protein molecule. Lysinoalanine has been reported in commercial samples of casein, calcium caseinate, and sodium caseinate. Lysinoalanine also has been detected at relatively low concentration in a number of commercial food products and in home-cooked frankfurters, chicken, and egg white.
Sensitivity to lysinoalanine differs among animals species and is dependent on the protein nature of the diet; feeding free lysinoalanine at dietary levels of 1000 ppm to five mammalian species other than the rat, including subhuman primates, failed to produce renal cytomegalic changes. Renal cytomegalic changes have been demonstrated in rats fed free lysinoalanine, or alkalitreated soy protein isolate, lactalbumin or casein containing bound lysinoalanine. The alkali-treated proteins were fed as the sole source of protein at dietary levels of 20 to 30 percent; cytomegaly did not occur or was markedly reduced in rats fed diets in which alkali-treated protein was supplemented with an untreated protein, suggesting that the renal syndrome was caused by protein bound lysinoalanine in diets deficient or imbalanced with respect to one or more amino acids. Although the available information indicates that the present consumption levels of casein and caseinates, less than 0.2g per capita as
currently used, pose no hazard to the consumer,a limitation with respect to lysinoalanine content in specifications for food grade products would avoid possible future problems in this regard.
A small proportion of infants and lesser numbers of children and adults experience untoward reactions to casein and other milk proteins. Casein is only mildly antigenic but the presence of whey proteins in commercial casein may increase the frequency of hypersensitivity reactions. However, the relatively low consumption of casein, sodium and calcium caseinates added to processed foods, as compared to consumption of casein in milk, cheese, other dairy products, and foods containing dairy products as an ingredient, does not appear to significantly exposure to this antigen.
Although few nitrite analyses of caseinates dried in direct fired spray driers were available to the Select Committee, the available data and the finding of nitrite in samples of other products dried in similar equipment indicates that nitrite can occur at low levels in spray-dried products. According to available information, casein and some caseinates are dried in indirectly heated driers and would not be exposed to nitrite from the drying gases. Nitrite content is of concern because of its toxicity, per se, and because it can react with other nitrogen containing compounds to produce nitrosamines, many of which have been shown to be carcinogenic in experimental animals. It is important to ensure that preformed nitrosamines are not present in caseinates and are not formed in processed foods containing caseinates.
Consideration must be given to the potential for nitrosamine formation in vivo from ingestion of foods containing nitrite, and the latter reacting with other nitrogen containing compounds in foods, drugs, and endogenous amines, must be considered. Many natural and processed foods, including spraydried products, contribute to the total human intake of nitrite even though bacterial reduction of nitrate to nitrate in saliva is the mejor source of nitrite entering the stomach.
It has been reported from recent unpublished work with rats fed nitrite that the frequency of lymphoreticular tumor was increased. The possibility that nitrite has a direct adverse effect of this type raises questions about the total body burden of nitrite and the relative contributions from food, saliva, and the estimated larger amount produced by bacteria in the intestinal tract. A study of these sources and their relative importance is required for individuals of different age groups and dietary habits to obtain reliable figures. Specifications should be developed for food grade caseinates which limit the content of nitrite and nitrosamines.
Caseinates appear to contribute a minor quantity of nitrite to total human exposure. Preliminary estimates of per capita exposure indicate they account for less than 0.2 percent of that taken in as an ingredient of food and present in saliva, and less than 0.005 percent of the total taken in as food ingredient, present in the saliva, and generated in the intestinal tract. From the standpoint of relative contributions to the controllable nitrite load and/or total body burden, caseinates do not appear to be cause for concern at this time. Nevertheless, the possible adverse effects of nitrite call for more explicit knowledge and actions for maintaining a low level of the compound in the commercial product and for continued monitoring of its relative contributions, with adjustments as necessary, as the major sources of commercially added nitrites are progressively decreased through regulatory procedures underway.
The Select Committee has weighed the foregoing information and concludes that: It is essential that food grade specifications for casein, sodium caseinate, and calcium caseinate be established including provisions for acceptable levels of lysinoalanine, nitrite, and nitrosamines.
Assuming that acceptable levels of lysinoalanine, nitrite, and nitrosamine are established, there is no evidence in the available information on casein, sodium caseinate, or clacium caseinate that demonstrates or suggest reasonable grounds to suspect a hazard when they are used at levels that are now current or that may reasonably be expected in the future.
There is no evidence in the available information on casein that demonstrates or suggests reasonable grounds to suspect a hazard when it is used in paper and paperboard products for food packaging at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Cellulose acetate | 9004-35-7 | 25 | 1973 | 2 | 182.90 |
SCOGS Opinion:
Cellulose is a major constituent of many foods of plant origin. As such it is a significant portion of the diet, but is neither degraded nor absorbed. Cellulose derivatives considered in this report are virtually unabsorbed and little or no degradation of absorbed and little or no degradation of absorbable products occurs in the human digestive tract. In man, consumption of large amounts appears to have no effect other than providing dietary bulk, reducing the nutritive value of such foodstuffs and possibly exerting a laxative effect. However, the existence of certain data and the different categorization of cellulose and the several cellulose derivatives on the GRAS list suggest that the Select Committee should render a separate opinion on each substance considered in this report.
A. CELLULOSE, MICROCRYSTALLINE CELLULOSE
Although pure cellulose and regenerated cellulose, including microcrystalline cellulose are not on the GRAS list, there is nothing in the available information to suggest that such forms of cellulose have significantly different biological properties that distinguish these forms of cellulose from those currently considered as GRAS or from naturally occurring cellulose. In view of the foregoing, the Select Committee concludes that: There is no evidence in the available information on pure and regenerated cellulose, including microcrystalline cellulose, that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current, or that might reasonably be expected in future.
B. METHYL CELLULOSE
In humans, virtually 100 percent of orally ingested methyl cellulose can be recovered in the feces withihn four days, indicating that absorption does not occur. However, in pregnant mice, very high doses of methyl cellulose, while not teratogenic, cause a significant increase in maternal mortality and retardation of fetal maturation. Such increased maternal and fetal toxicity does not occur at a dose of methyl cellulose which is 26-fold (or more) greater than that estimated to be the average daily adult dietary intake. It is noteworthy in this regard that similar toxic effects have been observed in identical tests performed by the same investigators on a large number of other polysaccharides fed at very high doses. The relative sensitivity of the several animal species to these effects varies, depending on the particular polysaccharide tested, but in all cases very large doses are required. Until these effects have been adequately explained, it appears to be inappropriate to conclude
that unrestricted use of such substances in food would be without hazard. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on methyl cellulose that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
C. CARBOXYMETHYL CELLULOSE
Carboxymethyl cellulose is converted spontaneously to a salt in alkaline solution, and it is probable that the distinction between carboxymethyl cellulose and its salts is artificial. However, carboxymethyl cellulose is liested as GRAS as a substance migrating to food from cotton or cotton fabrice used in dry foods packaging, while its sodium salt is listed as GRAS as a miscellaneous or general purpose food additive. In view of the separate listing of carboxymethyl cellulose, the Select Committee concludes that: There is no evidence in the available information on carboxymethyl cellulose that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used in dry food packaing materials originating from cotton or cotton fabrics as now practed or as it might reasonably be expected to be used for such purposes in future.
D. SODIUM CARBOXYMETHYL CELLULOSE
Despite the probable lack of distinction between sodium carboxy methyl cellulose and its parent compound, carboxymethyl cellulose, only the sodium carboxymethyl cellulose is GRAS as a miscellaneous and general purpose food additive. As such, there are no data that suggest it reacts differently than pure and regenerated cellulose or carboxymethyl cellulose. In view of the foregoing the Select Committee concludes that: There is no evidence in the available information on sodium carboxymethyl cellulose that demonstrtes, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in future.
E. HYDROXYPROPYLMETHYL CELLULOSE
Hydroxypropylmethyl cellulose is not listed as GRAS. It is a food additive used as a thickening agent, stabilizer and emulsifier. Hydroxypropylmethyl cellulose is sinthesized from methyl cellulose by the action of alkali and propylene oxide. There are no data available to suggest that hydroxypropylmethyl cellulose possesses adverse health effects; however, teratology studies dimilar to those conducted with mehtyl cellulose are not available for its hydroxypropyl derivative. Therefore, it is suggested that, in due course, appropriate studies should be conducted with hydroxypropylmethyl cellulose. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on hydroxypropylmethyl cellulose that demonstrates, or suggested reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current and in the manner now practiced (21 CFR 121.1021)
F. ETHYL CELLULOSE AND CELLULOSE ACETATE
There is a paucity of data concerning possible adverse health effects of ethyl cellulose and cellulose acetate. both are included in the GRAS list as substances migrating to food from paper or paperboard products used in food packaging. According to the NRC survey (6), very small amounts of ethyl cellulose also appear to be used in hard candy and chewing gum. In the GRAS context, the quantity of ethyl cellulose or cellulose acetate migrating to foods from packaging would be orders of magnitude below the levels of cellulose and cellulose derivaties now known to occur in foods. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ethyl cellulose and cellulose acetate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used in food packaging materials as now practiced or as they might be expeccted to be used for such purposes in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Cholic acid | 81-25-4 | 44 | 1975 | 1 | There is no CFR citation. |
SCOGS Opinion:
The amounts of the bile acids ingested as constituents of ox bile extract used as a food additive are relatively insignificant, compared to the amounts normally present in the bile of man. The available information indicates that orally administered cholic acid, desoxycholic acid, glycocholic acid, and taurocholic acid are readily absorbed and excreted without accumulation. They exhibit a relatively low toxicity for several animal species tested. The Select Commitee has no information to indicate that the individual bile acids or their salts are used in foods. However, the intake estimates available for ox bile extract, of which bile acids and their salts are major constituents, indicate that average daily consumption of ox bile extract added to foods is small, amounting to 0.1 mg or less. The intake of individuals bile acids or their salts would be, commensurately, very small. Such biological effects as have been reported in
animal studies, have been elicited at levels of administration that are several orders of magnitude greater that the levels to which man is now exposed in his daily diet. In the light of the information contained in this report, the Select Commitee concludes that: There is no evidence in the available information on ox bile extraxt, or its constituents cholic acid, desoxycholic acid. glycocholic acid, and taurocholic acid- that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Choline Bitartrate | 87-67-2 | 42 | 1975 | 1 | 182.8250 |
SCOGS Opinion:
Despite the significant endogenous synthesis of choline, it is an important dietary constituent for normal growth and well-being in all of the species that have been studied. Its metabolic role in fat transport is established. In addition, it is a contributor of methyl groups in essential transmethylation reactions in the animal body. However, the precise nutritional significance of dietary choline for man is not clear. In evaluating the possible effects of choline salts as added food ingredients, particularly on the infant which is the largest consumer of these supplements, the Select Committee recognizes the approximate nature of current estimates of total daily intake and the scarcity of chronic toxicity data. The latter information might be supplied by studies on preweanling animals. However, the available evidence raises no suspicion that choline chloride and choline bitartrate have harmful effects at dosage levels that are
several orders of magnitude greater than the most generous current estimates of human intake. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on choline chloride and choline bitartrate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Choline Chloride | 67-48-1 | 42 | 1975 | 1 | 182.8252 |
SCOGS Opinion:
Despite the significant endogenous synthesis of choline, it is an important dietary constituent for normal growth and well-being in all of the species that have been studied. Its metabolic role in fat transport is established. In addition, it is a contributor of methyl groups in essential transmethylation reactions in the animal body. However, the precise nutritional significance of dietary choline for man is not clear. In evaluating the possible effects of choline salts as added food ingredients, particularly on the infant which is the largest consumer of these supplements, the Select Committee recognizes the approximate nature of current estimates of total daily intake and the scarcity of chronic toxicity data. The latter information might be supplied by studies on preweanling animals. However, the available evidence raises no suspicion that choline chloride and choline bitartrate have harmful effects at dosage levels that are
several orders of magnitude greater than the most generous current estimates of human intake. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on choline chloride and choline bitartrate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Citric acid | 77-92-9 | 84 | 1977 | 1 | 184.1033 |
SCOGS Opinion:
The citrate ion is widely distributed in plants and animals and is a naturally occurring component of the diet. It is a common metabolite in oxidative metabolism and an important component of bone. Exogenous citrate administered to infants and adults as a component of commonly consumed diets is considered completely metabolizable. The addition of citric acid to foods is considered equivalent to adding citrate salts except in foods of very high acidity. The amount of citrate added to foods by foods processors is about 500mg per person per day. This amount occurs naturally in 2 ounces of orange juice and does not constitute a significant addition to the total body load. Although data on acute and chronic effects of orally administered sodium citrate, calcium citrate and potassium citrate are limited, no biological effects of the citrate-containing substances evaluated in this report cause concern about the safety of these GRAS
substances used in reasonable amounts and in accordance with prescribed tolerances and limitations.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on citric acid, sodium citrate, potassium citrate, calcium citrate, ammonium citrate, isopropyl citrate, stearyl citrate, and triethyl citrate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Bentonite and clay (kaolin) are readily hydratable aluminium silicates. Bentonite is used to assist in the clarification of juices, beverages, and other food products, as a binding agent for the preparation of pelleted animal feeds, and as an ingredient of coatings and adhesives for food packaging materials. The Select Committee is not aware of any instance in current practice where use of bentonite in the processing or packaging of foods for human consumption results in the retention of more than minute amounts in the final product and assumes the current practice will continue. Nevertheless, food grade standards for bentonite should be established, particularly with respect to soluble constituents and heavy metal cations that may be present in commercial products.
Clay (kaolin) is GRAS only as an ingredient of paper and paperboard products used in food packaging. There are no data available concerning the amounts of clay (kaolin) that might migrate to foods from this source but the Select Committee believes the amounts can only be very small.
Apparently, very little, if any, bentonite is absorbed after oral administration and as much as 3 percent in the diet has no observable adverse effects on experimental animals. Diets containing 10 to 25 percent can cause growth retardation both because of dilution of the diet and the tendency of some bentonites to adsorb vitamin A in mixed diets and otherwise interfere with the absortion of this vitamin in the intestinal tract.
Very little, if any, kaolin is absorbed after oral administration. Bowel obstruction occurs at very high doses, about 100g per kg body weight in rats being fatal to 1 percent, about 150 per kg being fatal to 50 percent.
No adverse effects have been observed at dietary levels as high as 12 percent in experimental animals. The human therapeutic dose for diarrhea is about 250 to 1,000 mg per kg.
It is noted that clay (kaolin) administered under conditions that damage mucosal tissues, tends to produce granulomatous lesion. However, the generally high tolerance for kaolin under normal conditions makes it improbable that such effects could result as it is currently used.
Based upon consideration of the data presented in this report and assuming the establishment of appropriate food grade standards fro bentonite, the Select Committee concludes that:
There is no evidence in the available information on bentonite that demonstrates or suggests reasonable grounds to suspect, a hazard to the public when it is used in the manner now practiced or that might reasonably be expected in the future.
There is no evidence in the available information on clay (kaolin) that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used as an ingredient of food packaging materials in the manner now practiced or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Clove Bud Extract | 8000-34-8 | 19 | 1973 | 1 | 184.1257 |
SCOGS Opinion:
The available information indicates that orally administered eugenol, the principal ingredient of cloves and products derived from them, is readily absorbed and excreted without accumulation. Eugenol exhibits a low degree of toxicity for the several animal species tested, and only at levels far greater than those occurring in foods, does it appear to be able under some conditions to produce irritation of the squamous epithelium of the gastrointestinal tract. It is to be noted that cloves, clove oils and eugenol have long been used topically as analgesics, germicides, and for other purposes. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on cloves, clove oils and their principal constituents, eugenol, that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be
expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Clove Bud Oil | 8000-34-8 | 19 | 1973 | 1 | 184.1257 |
SCOGS Opinion:
The available information indicates that orally administered eugenol, the principal ingredient of cloves and products derived from them, is readily absorbed and excreted without accumulation. Eugenol exhibits a low degree of toxicity for the several animal species tested, and only at levels far greater than those occurring in foods, does it appear to be able under some conditions to produce irritation of the squamous epithelium of the gastrointestinal tract. It is to be noted that cloves, clove oils and eugenol have long been used topically as analgesics, germicides, and for other purposes. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on cloves, clove oils and their principal constituents, eugenol, that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be
expected in the future.
SCOGS Opinion:
The available information indicates that orally administered eugenol, the principal ingredient of cloves and products derived from them, is readily absorbed and excreted without accumulation. Eugenol exhibits a low degree of toxicity for the several animal species tested, and only at levels far greater than those occurring in foods, does it appear to be able under some conditions to produce irritation of the squamous epithelium of the gastrointestinal tract. It is to be noted that cloves, clove oils and eugenol have long been used topically as analgesics, germicides, and for other purposes. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on cloves, clove oils and their principal constituents, eugenol, that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be
expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Clove Leaf Oil | 8000-34-8 | 19 | 1973 | 1 | 184.1257 |
SCOGS Opinion:
The available information indicates that orally administered eugenol, the principal ingredient of cloves and products derived from them, is readily absorbed and excreted without accumulation. Eugenol exhibits a low degree of toxicity for the several animal species tested, and only at levels far greater than those occurring in foods, does it appear to be able under some conditions to produce irritation of the squamous epithelium of the gastrointestinal tract. It is to be noted that cloves, clove oils and eugenol have long been used topically as analgesics, germicides, and for other purposes. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on cloves, clove oils and their principal constituents, eugenol, that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be
expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Clove Stem Oil | 8000-34-8 | 19 | 1973 | 1 | 184.1257 |
SCOGS Opinion:
The available information indicates that orally administered eugenol, the principal ingredient of cloves and products derived from them, is readily absorbed and excreted without accumulation. Eugenol exhibits a low degree of toxicity for the several animal species tested, and only at levels far greater than those occurring in foods, does it appear to be able under some conditions to produce irritation of the squamous epithelium of the gastrointestinal tract. It is to be noted that cloves, clove oils and eugenol have long been used topically as analgesics, germicides, and for other purposes. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on cloves, clove oils and their principal constituents, eugenol, that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be
expected in the future.
SCOGS Opinion:
Coconut oil, peanut oil, oleic acid, and linoleic acid have been used as foods or as food components by man for many years. These two oils and the fatty acids are rapidly absorbed after oral administration, metabolized, and the metabolic products are utilized and excreted. None of the available biological information indicates that these substances are hazardous to man or animals even when consumed at levels that are orders of magnitude greater than could result form their use for the purposes covered in this report. The evidence now available indicates that linoleic acid is not being used by the food industry as a nutrient or dietary supplement. Based on these considerations, the Select Commitee concludes that: There is no evidence in the available information on coconut oil, peanut oil, and oleic acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public as they are now used in paper and cotton
packaging material for food at levels now current or as they might reasonably be expected to be used for such purposes in the future. There is no evidence in the available information on linoleic acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used as a nutruient or dietary supplement at levels now current or that might reasonably be expected in the future.
SCOGS Opinion:
Copper is an essential trace element for most plant and animal species, including man. Its deficiency is characterized by specific biochemical and pathological lesions. The customary adult daily diet provides adequate copper to prevent signs of deficiency. Both copper deficiency and chronic copper intoxication are relatively rare.
The absortion of copper is limited to about one third to one half of that ingested under usual circumstances. When large amounts of copper are ingested, the absorptive mechanism becomes saturated and much of the copper remains unabsorbed. Further limitations are imposed by competition for absortion with cadmium and zinc, by organic complexing with ascorbic acid, and by the alkalinity of intestinal contents. Much of the copper that is absorbed is later excreted in the bile so that more than 90 percent of ingested copper is found in feces.
Cupric gluconate, cupric sulfate and cuprous iodode are GRAS in foods for specified purposes: cupric gluconate as a nutrient and/or dietary supplement; cupric sulfate in paper and paperboard products used in food packaging; and cuprous iodide as a source of dietary iodine in table salt.
About 2mg copper per day is required by the average adult with an acceptable daily intake of 0.5mg per kg body weight or about 30mg recommended by international authorities. About 2 to 4mg copper per day are supplied as natural ingredients in the normal diet. Copper added to food in the form of cupric gluconate is estimated to be about 0.005mg per capita daily. The amounts added as cupric sulfate or cuprous iodide are unknown but are believed to be less than that from cupric gluconate. Thus, the normal diet supplies several hundred times the amount of copper added to foods. The amount of anions ingested form copper salts added to foods is negligible compared with that produced physiologically or found in normal diets.
Animal toxicity with copper salts was observed only with quantities several orders of magnitude greater than that used as food supplements.
Cupric gluconate, cupric sulfate and cuprous iodide were all nonmutagenic in various microbial tests.
Cupric gluconate and sulfate, as well as other copper salts tested, were noncarcinogenic when given by mouth or parenterally. No reports of carcinogenicity studies on cuprous iodide were available to the Select Committee.
Cupric gluconate produced teratogenic effects in the chick embryo, but not in mice or rats. Cupric sulfate was embryotoxic and teratogenic when injected in large amounts into pregnant hamsters.
In light of these considerations, the Select Committee concludes that: There is no evidence in the available information on copper (cupric) gluconate or copper (cupric) sulfate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on cuprous iodide that demonstrates or suggests reasonable grounds to suspect a hazard to the public should it be used at the level and in the manner now uthorized.
There is no evidence in the available information on copper (cupric) sulfate that demonstrates or suggests reasonable grounds to suspect a hazard when it is used as an ingredient of paper and paperboard materials in food packaging at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Copper is an essential trace element for most plant and animal species, including man. Its deficiency is characterized by specific biochemical and pathological lesions. The customary adult daily diet provides adequate copper to prevent signs of deficiency. Both copper deficiency and chronic copper intoxication are relatively rare.
The absortion of copper is limited to about one third to one half of that ingested under usual circumstances. When large amounts of copper are ingested, the absorptive mechanism becomes saturated and much of the copper remains unabsorbed. Further limitations are imposed by competition for absortion with cadmium and zinc, by organic complexing with ascorbic acid, and by the alkalinity of intestinal contents. Much of the copper that is absorbed is later excreted in the bile so that more than 90 percent of ingested copper is found in feces.
Cupric gluconate, cupric sulfate and cuprous iodode are GRAS in foods for specified purposes: cupric gluconate as a nutrient and/or dietary supplement; cupric sulfate in paper and paperboard products used in food packaging; and cuprous iodide as a source of dietary iodine in table salt.
About 2mg copper per day is required by the average adult with an acceptable daily intake of 0.5mg per kg body weight or about 30mg recommended by international authorities. About 2 to 4mg copper per day are supplied as natural ingredients in the normal diet. Copper added to food in the form of cupric gluconate is estimated to be about 0.005mg per capita daily. The amounts added as cupric sulfate or cuprous iodide are unknown but are believed to be less than that from cupric gluconate. Thus, the normal diet supplies several hundred times the amount of copper added to foods. The amount of anions ingested form copper salts added to foods is negligible compared with that produced physiologically or found in normal diets.
Animal toxicity with copper salts was observed only with quantities several orders of magnitude greater than that used as food supplements.
Cupric gluconate, cupric sulfate and cuprous iodide were all nonmutagenic in various microbial tests.
Cupric gluconate and sulfate, as well as other copper salts tested, were noncarcinogenic when given by mouth or parenterally. No reports of carcinogenicity studies on cuprous iodide were available to the Select Committee.
Cupric gluconate produced teratogenic effects in the chick embryo, but not in mice or rats. Cupric sulfate was embryotoxic and teratogenic when injected in large amounts into pregnant hamsters.
In light of these considerations, the Select Committee concludes that: There is no evidence in the available information on copper (cupric) gluconate or copper (cupric) sulfate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on cuprous iodide that demonstrates or suggests reasonable grounds to suspect a hazard to the public should it be used at the level and in the manner now uthorized.
There is no evidence in the available information on copper (cupric) sulfate that demonstrates or suggests reasonable grounds to suspect a hazard when it is used as an ingredient of paper and paperboard materials in food packaging at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The dextrines covered by this report are those produced by the dry heating of unmodified starch under the range of conditions specified in the body of the report as representative of commercial practice for this class of products. Included are the white dextrines, yellow or canary dextrins and the British gums. The dextrines are similar to their parent starches in that they are composed principally of ?-D-anhydroglucose units joined through 1,4-linkages; they differ in that dextrinization reduces the molecular weight and, particularly in case of the yellow or canary dextrines and the British gums, increases branching in the molecules. Dextrinization slightly reduces the digestibility of corn and wheat starch, probably attibutable to the more highly branched structure of the dextrins.
Animal feeding studies have shown dextrins to be digested and metabolized to a limited degree without toxic effects when fed at levels many times greater than those present from use of these products as a direct food additive, or at levels that are orders of magnitude greater than might occur by migration from food packaging materials containing dextrins. The Select Committee concludes that: There is no evidence in the available information on dextrins and corn dextrin that demonstrates or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might be reasonably expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Corn silk | 977000-79-5 | 87 | 1977 | 5 | 184.1262 |
SCOGS Opinion:
The silk of corn contains a wide variety of compounds, many present in very small amounts; included are sugars, tannins, saponins, flavones, glucosides, fats, alkaloids, and various aromatic components of the essential oil fraction. The composition of the commercial product (corn silk) that is added to foods will obviously depend on the procedures used for extraction of the silk of corn and the subsequent concentration and fractionation of the extract. The Select Committee has not been able to obtain any information concerning the method of preparation of the commercial product or its composition, or to find any reports of biological studies on the commercial product. In the absence of such information, it is not possible to relate the few reported biological studies on corn silk extracts and components to the possible consequences of using corn silk as a food ingredient.
There are no known specifications for food-grade corn silk. Considering the origin of the product, specifications are needed to establish limits for possible variations in its composition and for the presence of incidental contaminants such as pesticidal chemicals.
In light of the foregoing, and in spite of the fact that the amount of corn silk consumed as a result of its addition to foods is extremely small, the Select Committee concludes that: In view of the lack of information on the identity of the product used in foods and of relevant biological studies concerning it, the Select Committee has insufficient data upon which to base an evaluation of corn silk when it is used as a food ingredient.
SCOGS Opinion:
Corn sugar, commonly referred to as dextrose, is crystalline ?-D-glucose. Glucose is widely distributed in nature both in the free state and in various combined forms, including starch and sucrose. Glucose-yielding carbohydrates constitute one of the main sources of energy in the typical North American diet. Fructose, produced along with glucose in the hydrolysis of sucrose to invert sugar and by isomerization of dextrose, also is a significant calorie source. The absorption and metabolism of these sugars are well established. Biological studies have shown that these substances are devoid of toxic effects at dosage levels well in excess of those that exist in the American diet and, accordingly, at levels that are orders of magnitude higher than those which might occur from the migration of these substances from paper and paperboard products.
Glucose syrup, also called corn syrup when made by the hydrolysis of corn starch, contains in addition to glucose, maltose, and higher saccharides in proportions that depend on the degree of hydrolysis of the starch. The higher conversion syrups may also contain small amounts of disaccharides formed by the recombination of glucose through glucosidic linkages not present in starch. Animal feeding studies have shown that glucose syrups are readily digested and metabolized and have given no evidence of toxic effects.
Fructose-dextrose mixtures have been observed to have hyperlipemic effects when fed at high levels in fat-free diets to adult males and postmenopausal women. There is no evidence, however, that the levels of invert sugar and high-fructose corn syrup in the average diet cause significant elevations in blood lipids and it is unlikely that the consumption of fructose or glucose, ingested as monosaccharides, has a role in coronary heart disease. Although glucose and fructose as well as sucrose have been demonstrated to be cariogenic in animal experiments, epidemiological studies of dietary habits and controlled diets in institutional feeding indicate that the cariogenicity of sucrose and other foods is affected by several factors and not necessarily by the total amount consumed. These factors include the frequency eating, duration of exposure, and the form and physical properties of the food in which the sugar is ingested. Between-meal eating has been demonstrated to be significantly
correlated with frequency and severity of caries in both children and adults. Thus, protection is facilitated by limitation of the frequency of consumption of sugar and sugared foods.
Consumption of dextrose and corn syrup has increased markedly in recent years and represented about 21 percent of the sweetener marker in 1974 as compared to about 15 percent in 1970. A major part of the increase resulted from the introduction of high-fructose corn syrup produced the enzymatic isomerization of dextrose in starch hydrolyzates. Level of fructose as the monosaccharide in the diet has increased accordingly but 1974 per capita daily consumption of this monosaccharide from all sources was only 6g and no higher than in 1925-29, when apples provided a larger contribution than at present. High-fructose corn syrups are predicted to increase in production and to replace sucrose and invert sugar in up to 30 percent of their applications by 1980-85, based largely on relative costs. There is no evidence that such replacement, per se, would have an adverse effect on public health. However, the Select Committee has expressed concern in its report on sucrose (73) that is this sugar
contributes to dental caries in the public at current consumption levels as used in the manner now practiced. It is questionable that replacement of sucrose by syrups and sugars derived from starch would greatly change the cariogenicity of foods containing these sugars. Informing the consumer of the sugar content of foods by appropriate labeling could lead to judicious use of sweetened foods. Choices could be made easier with a greater selection of less sugared foods in the market place. The Select Committee has weighed all of the foregoing and concludes that: Evidence exists that simple sugars, including glucose and fructose [and, therefore, corn sugar(dextrose), corn syrup including high-fructose corn syrup, and invert sugars] are cariogenic. However, in the quantities that these simple sugars are now consumed in processed foods, their contribution to formation of dental caries should be relatively small. If increased usage should occur, as seems likely, the contribution of these
sugars to the occurrence of dental caries might become more important. Other than the contribution made to dental caries, there is no evidence in the available information on corn sugar(dextrose), corn syrup, and invert sugar that demonstrated a hazard to the public when they are used at levels that are now current and in the manner now practiced. however, it is not possible to determine without additional data, whether an increase in consumption-that would result if there were a significant increase in the total of corn sugar, corn syrup, invert sugar and sucrose added to foods-would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Corn Syrup | 8029-43-4 | 50 | 1976 | 2 | 184.1865 |
SCOGS Opinion:
Corn sugar, commonly referred to as dextrose, is crystalline ?-D-glucose. Glucose is widely distributed in nature both in the free state and in various combined forms, including starch and sucrose. Glucose-yielding carbohydrates constitute one of the main sources of energy in the typical North American diet. Fructose, produced along with glucose in the hydrolysis of sucrose to invert sugar and by isomerization of dextrose, also is a significant calorie source. The absorption and metabolism of these sugars are well established. Biological studies have shown that these substances are devoid of toxic effects at dosage levels well in excess of those that exist in the American diet and, accordingly, at levels that are orders of magnitude higher than those which might occur from the migration of these substances from paper and paperboard products.
Glucose syrup, also called corn syrup when made by the hydrolysis of corn starch, contains in addition to glucose, maltose, and higher saccharides in proportions that depend on the degree of hydrolysis of the starch. The higher conversion syrups may also contain small amounts of disaccharides formed by the recombination of glucose through glucosidic linkages not present in starch. Animal feeding studies have shown that glucose syrups are readily digested and metabolized and have given no evidence of toxic effects.
Fructose-dextrose mixtures have been observed to have hyperlipemic effects when fed at high levels in fat-free diets to adult males and postmenopausal women. There is no evidence, however, that the levels of invert sugar and high-fructose corn syrup in the average diet cause significant elevations in blood lipids and it is unlikely that the consumption of fructose or glucose, ingested as monosaccharides, has a role in coronary heart disease. Although glucose and fructose as well as sucrose have been demonstrated to be cariogenic in animal experiments, epidemiological studies of dietary habits and controlled diets in institutional feeding indicate that the cariogenicity of sucrose and other foods is affected by several factors and not necessarily by the total amount consumed. These factors include the frequency eating, duration of exposure, and the form and physical properties of the food in which the sugar is ingested. Between-meal eating has been demonstrated to be significantly
correlated with frequency and severity of caries in both children and adults. Thus, protection is facilitated by limitation of the frequency of consumption of sugar and sugared foods.
Consumption of dextrose and corn syrup has increased markedly in recent years and represented about 21 percent of the sweetener marker in 1974 as compared to about 15 percent in 1970. A major part of the increase resulted from the introduction of high-fructose corn syrup produced the enzymatic isomerization of dextrose in starch hydrolyzates. Level of fructose as the monosaccharide in the diet has increased accordingly but 1974 per capita daily consumption of this monosaccharide from all sources was only 6g and no higher than in 1925-29, when apples provided a larger contribution than at present. High-fructose corn syrups are predicted to increase in production and to replace sucrose and invert sugar in up to 30 percent of their applications by 1980-85, based largely on relative costs. There is no evidence that such replacement, per se, would have an adverse effect on public health. However, the Select Committee has expressed concern in its report on sucrose (73) that is this sugar
contributes to dental caries in the public at current consumption levels as used in the manner now practiced. It is questionable that replacement of sucrose by syrups and sugars derived from starch would greatly change the cariogenicity of foods containing these sugars. Informing the consumer of the sugar content of foods by appropriate labeling could lead to judicious use of sweetened foods. Choices could be made easier with a greater selection of less sugared foods in the market place. The Select Committee has weighed all of the foregoing and concludes that: Evidence exists that simple sugars, including glucose and fructose [and, therefore, corn sugar(dextrose), corn syrup including high-fructose corn syrup, and invert sugars] are cariogenic. However, in the quantities that these simple sugars are now consumed in processed foods, their contribution to formation of dental caries should be relatively small. If increased usage should occur, as seems likely, the contribution of these
sugars to the occurrence of dental caries might become more important. Other than the contribution made to dental caries, there is no evidence in the available information on corn sugar(dextrose), corn syrup, and invert sugar that demonstrated a hazard to the public when they are used at levels that are now current and in the manner now practiced. however, it is not possible to determine without additional data, whether an increase in consumption-that would result if there were a significant increase in the total of corn sugar, corn syrup, invert sugar and sucrose added to foods-would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Cornstarch | 977050-51-3 | 115 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Cuprous iodide | 7681-65-4 | 98 | 1979 | 1 | 184.1265 |
SCOGS Opinion:
Copper is an essential trace element for most plant and animal species, including man. Its deficiency is characterized by specific biochemical and pathological lesions. The customary adult daily diet provides adequate copper to prevent signs of deficiency. Both copper deficiency and chronic copper intoxication are relatively rare.
The absortion of copper is limited to about one third to one half of that ingested under usual circumstances. When large amounts of copper are ingested, the absorptive mechanism becomes saturated and much of the copper remains unabsorbed. Further limitations are imposed by competition for absortion with cadmium and zinc, by organic complexing with ascorbic acid, and by the alkalinity of intestinal contents. Much of the copper that is absorbed is later excreted in the bile so that more than 90 percent of ingested copper is found in feces.
Cupric gluconate, cupric sulfate and cuprous iodode are GRAS in foods for specified purposes: cupric gluconate as a nutrient and/or dietary supplement; cupric sulfate in paper and paperboard products used in food packaging; and cuprous iodide as a source of dietary iodine in table salt.
About 2mg copper per day is required by the average adult with an acceptable daily intake of 0.5mg per kg body weight or about 30mg recommended by international authorities. About 2 to 4mg copper per day are supplied as natural ingredients in the normal diet. Copper added to food in the form of cupric gluconate is estimated to be about 0.005mg per capita daily. The amounts added as cupric sulfate or cuprous iodide are unknown but are believed to be less than that from cupric gluconate. Thus, the normal diet supplies several hundred times the amount of copper added to foods. The amount of anions ingested form copper salts added to foods is negligible compared with that produced physiologically or found in normal diets.
Animal toxicity with copper salts was observed only with quantities several orders of magnitude greater than that used as food supplements.
Cupric gluconate, cupric sulfate and cuprous iodide were all nonmutagenic in various microbial tests.
Cupric gluconate and sulfate, as well as other copper salts tested, were noncarcinogenic when given by mouth or parenterally. No reports of carcinogenicity studies on cuprous iodide were available to the Select Committee.
Cupric gluconate produced teratogenic effects in the chick embryo, but not in mice or rats. Cupric sulfate was embryotoxic and teratogenic when injected in large amounts into pregnant hamsters.
In light of these considerations, the Select Committee concludes that: There is no evidence in the available information on copper (cupric) gluconate or copper (cupric) sulfate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on cuprous iodide that demonstrates or suggests reasonable grounds to suspect a hazard to the public should it be used at the level and in the manner now uthorized.
There is no evidence in the available information on copper (cupric) sulfate that demonstrates or suggests reasonable grounds to suspect a hazard when it is used as an ingredient of paper and paperboard materials in food packaging at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Pantothenates occur in all tissues of the body and are essential for normal metabolic function. Daily consumption of calcium pantothenate added to foods by processors in the United States appears to be less than 0.08mg per capita (1.3mg per kg), a value that probably also represents total per capita daily consumption of pantothenates added to foods since sodium pantothenate and pantothenyl alcohol do not appear to be used by food processors.
It is estimated that the usual adult diet provides approximately 5 to 19mg (83 to 316mg per kg) of naturally occuring pantothenates daily. Animals of several species given 100 mg per kg or more of calcium pantothenate daily for several months showed no evidence of toxicity. Adult patients with disseminated or discoid lupus erythematosus receiving doses of 1g or more daily (16.6mg per kg) for several months manifested no evidence of toxicity. Although the evidence is scanty, there appears to be no reason to suspect teratogenicity, fetotoxicity or carcinogenicity from intakes considerably greater than those likely to be obtained from foods.
There is little information concerning the metabolism of L-pantothenic acid or its salts, although animals and human studies of administration of racemic mixtures of calcium or sodium pantothenate demonstrate no untoward effects at doses considerably higher than could be reasonably expected from pantothenates added to food.
There are no specifications listed for food grade sodium pantothenate. The Select Committee believes such specifications should be developed even though there appears to be no current use of sodium pantothenate.
The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on D-pantothenyl alcohol, D- or DL- calcium pantothenate or D- or DL-sodium-pantothenate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| D(-)-lactic acid | 10326-41-7 | 116 | 1978 | 1,4 | There is no CFR citation. |
SCOGS Opinion:
Lactic acid is produced in varying amounts by most living tissues as a normal metabolic intermediate. The lactate turnover rate in man has been estimated to be of the order of 2g per kg per day.
An additional load of up to 1 mg per kg per day of lactic acid as the free acid or as calcium lactate contained in commercially prepared food commodities would not appreciably modify the normal metabolic processes. None of the limited toxicity data available raises any suspicion of adverse effects in adults at doses orders of magnitude above the estimated levels of human consumption. There is no indication that the per capita intake of lactate from processed foods will be substantially increased in the foreseeable future.
There is no evidence of potential toxicity of the L-isomer for individuals of any age. However, premature infants fed formulas acidified with DL-lactic acid (or, in one instance, D(-) lactic acid), have reported to develop metabolic acidosis and growth retardation. Results of studies of full-term infants are conflicting and difficult to interpret. Resolution of this conflict is needed even though, as far as the Select Committee is aware, lactic acid acidification of infant formulas is not currently being practiced in the United States except in products designed for special dietary or therapeutic purposes which are not being evaluated in this report.
In the light of these considerations, the Select Committee concludes that:
There is no evidence in the available information on L(+) calcium lactate that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on either of the isomers of lactic acid, their calcium salts, and their racemates that demonstrates or suggests reasonable ground to suspect a hazard to individuals beyond infancy when they are used at levels that are now current or thar might reasonably be expected in the future.
There evidence on D(-)-lactic acid, DL-lactic acid and their calcium salts is insufficient to determine that the adverse effects reported would not be deleterious to infants should they be used in infant formulas. Lactic acid acidification of generally available infant formulas is not now being practiced in the United States.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Desoxycholic acid | 83-44-3 | 44 | 1975 | 1 | There is no CFR citation. |
SCOGS Opinion:
The amounts of the bile acids ingested as constituents of ox bile extract used as a food additive are relatively insignificant, compared to the amounts normally present in the bile of man. The available information indicates that orally administered cholic acid, desoxycholic acid, glycocholic acid, and taurocholic acid are readily absorbed and excreted without accumulation. They exhibit a relatively low toxicity for several animal species tested. The Select Commitee has no information to indicate that the individual bile acids or their salts are used in foods. However, the intake estimates available for ox bile extract, of which bile acids and their salts are major constituents, indicate that average daily consumption of ox bile extract added to foods is small, amounting to 0.1 mg or less. The intake of individuals bile acids or their salts would be, commensurately, very small. Such biological effects as have been reported in
animal studies, have been elicited at levels of administration that are several orders of magnitude greater that the levels to which man is now exposed in his daily diet. In the light of the information contained in this report, the Select Commitee concludes that: There is no evidence in the available information on ox bile extraxt, or its constituents cholic acid, desoxycholic acid. glycocholic acid, and taurocholic acid- that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Dextran | 9004-54-0 | 83 | 1975 | 2 | 186.1275 |
SCOGS Opinion:
Dextrans are polysaccharides composed of ?-D-glucopyranose units and are commercially prepared by the action of bacterial enzymes on sucrose. They occur naturally in small amounts in such foods as refined crystalline sugar, maple syrup, sauerkraut juice and honey and also as a component of dental plaque.
No use of dextran in food was reported in the 1970 survey of food processors conducted by a NRC subcommittee and the Select Committee concludes that any undisclosed use was probably small. More recently, however, one company has marketed a beverage product containing dextran. Current distribution and use of this product also appear to be small.
Oral ingestion studies in animals and man have shown that dextran is broken down by intestinal enzymes and is absorbed from the gastrointestinal enzymes and is absorbed from the gastrointestinal tract. Intravenously administered dextran also is metabolized in animals and man. Weight gain of rats fed diets containing 15 percent dextran in short-term test was comparable to that on a glucose supplemented diet indicating good utilization of dextran as an energy source. No adverse physiological effects were noted in these test nor were any reported in acute toxicity tests.
The absence of evidence of harm in the limited biological test that have been conducted and the extensive use of dextran as a blood volume expander without untoward effects, except for reaction of an allergic type in a low percentage of patients, support the opinion of the Select Committee that the use of dextrain in food at present levels poses no problem. However, there is no long history of use of dextran as an ingredient of food products. Should the level of use be increased, particularly as a beverage product in which dextran is a major component, the existing scientific data are insuficient for judgment as to possible health hazards.
In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on dextran that demonstrates a hazard to the public when it is used at levels that are now current and in the manner now practiced. However, it is not possible to determine without additional data, whether a significant increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Dextrins | 9004-53-9 | 75 | 1975 | 1 | 184.1277 |
SCOGS Opinion:
The dextrines covered by this report are those produced by the dry heating of unmodified starch under the range of conditions specified in the body of the report as representative of commercial practice for this class of products. Included are the white dextrines, yellow or canary dextrins and the British gums. The dextrines are similar to their parent starches in that they are composed principally of ?-D-anhydroglucose units joined through 1,4-linkages; they differ in that dextrinization reduces the molecular weight and, particularly in case of the yellow or canary dextrines and the British gums, increases branching in the molecules. Dextrinization slightly reduces the digestibility of corn and wheat starch, probably attibutable to the more highly branched structure of the dextrins.
Animal feeding studies have shown dextrins to be digested and metabolized to a limited degree without toxic effects when fed at levels many times greater than those present from use of these products as a direct food additive, or at levels that are orders of magnitude greater than might occur by migration from food packaging materials containing dextrins. The Select Committee concludes that: There is no evidence in the available information on dextrins and corn dextrin that demonstrates or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might be reasonably expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Diacetyl | 431-03-8 | 94 | 1980 | 1 | 184.1278 |
SCOGS Opinion:
Diacetyl is added to some foods for flavoring purposes. It is metabolized in mammals, is of low acute toxicity, and the no-adverse-effect level, based on a 90-day study in rats, is approximately 90 mg per kg body weight. The per capita daily intake of diacetyl added to food, both as a component of starter distillate and as diacetyl itself , is estimated to be less than 0.3mg.
Available studies of the biological effects of commercial starter distillate consist of two report; the one showed that starter distillate exhibited no mutagenic activity in in vitro test systems; the other showed that it was without teratogenic activity when administered orally in doses as high as 1600mg per kg body weight to pregnant mice, rats, hamsters, and rabbits.
The per capita daily intake of starter distillate is about 5mg or about 0.1mg on an anhydrous basis. Diacetyl and acetic acid are major components of starter distillate; total daily per capita intake of all organic components of starter distillate, other than diacetyl and acetic acid, is estimated to be less than 0.08 mg per body weight. Based on the nature of the starting material and the process used to produce starter distillate, the Select Committee has no grounds to suspect that the small amount of unidentified ingredients poses a hazard. It would appear that the possibility of hazard from the addition of starter distillate is minimal. However, no food grade standars exist for starter distillate. It is a mixture of many substances, not all of which have been identified, whose qualitiative and quantitative composition may vary depending on the combinations of microorganism used in the starter culture, and on the conditions of steam distillation. Hence, there is need for
establishing practical food grade standards for starter distillate specifying acceptable limits of variability.
In light of these considerations the Select Committee concludes that: There is no evidence in the available information on diacetyl or starter distillate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Silicon dioxide and various silicates occur abundantly in the earth's crust, are present in practically all natural waters,animals, and plants, and are part of the normal human diet. The question of whether or not silicon is an essential human nutrient remains unresolved. Silicon compounds consumed as added food ingredients contribute only a minor proportion of the total dietary silicon intake. The estimated possible human intake of sodium aluminosilicate, the predominant silicate added to foods in this country, is approximately 0.3mg per kg body weight per day. Silicon compounds that are GRAS for use as direct food ingredient, except potassium and sodium silicates, are insoluble or very slightly soluble in water and appear to be biologically inert. The water-soluble silicates are also of low acute toxicity. The acute oral LD50 in rats of sodium aluminosilicate is >1g per kg. No significant tissue accumulation, pathology, or
toxicity has been reported from the ingestion of those insoluble or very slightly soluble GRAS silicon compounds for which data are available. Of the five substances that were reported as added to foods in the NRC survey, biologic effects and safety data are available for all except sodium calcium aluminosilicate, and there is no reason to suspect that the toxicity of the latter would differ from those for which there are data. The results of two studies (1967-1970) in which various silicon compounds were fed to laboratory animals for 1 mo at a level of 0.8g per kg body weight (as silicon dioxide) and for 3 mo at levels of 6 to 30 mg per kg body weight suggests there may be a species-related susceptibility to renal damage from ingestion of sodium silicate, magnesium trisilicate, and finely ground quartz. No substantiating reports of these effects have appeared. Magnesium trisilicate was recognized as safe for prolonged use in human ingestion in large amount as a component of antacid
preparations by the Advisory Review Panel on Over-the-Counter Drugs, and the available evidence on the acute toxicity of sodium silicate indicates that it is low. Consumption data are lacking for aluminium calcium silicate and tricalcium silicate, two compounds that are listed as GRAS for use as anticaking agents. However, their use in keeping with good manufacturing practice and in currently regulated amounts would be of the same order of magnitude as the other GRAS silicates. In addition, the Select Committee has limited information on the amounts of talc that are currently used in foods. However a major food use of talc is in the coating of rice. Assuming package label statements are ignored and coated rice is not washed prior to cooking and no other losses occur, maximun per capita intake of talc from this source appears to be 0.5g per day. With respect to paper and cotton food- packaging products, the possibility is remote that biologically significant amounts of talc,
diatomaceous earth, or sodium silicate migrate to food from packaging, materials containing these substances. Perlite, a naturally occuring polysilicate substance, has an oral LD50 in the rat of >10g per kg body weight. Estimates of the maximun quantities of minerals that might be extracted from perlite and diatomaceous earth used as filteraids in food processing indicates no hazard to public health. There are no food grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc. Such specifications for the substances used in foods are desirable. Specification for food grade talc should limit the content of asbestos fibers even though the potential hazard of ingested asbestos fibers even though the potential hazard of ingested asbestos is not clearly established. The Food and Drug Administration is sponsoring the development of an assay method for asbestos fibers. An upper limit for cadmium should be added to the specifications for food-grade perlite, and
consideration should be given to the need for limitation of cadmium content of other silicates. In the light of all of the foregoing, the Select Committee concludes that: It is essential to establish food-grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc, with provision for an upper limit of asbestos fibers in talc. There is no evidence in the available information on aluminum calcium silicate, calcium silicate, magnesium silicate, potassium silicate, sodium silicate, sodium aluminosilicate, sodium calcium aluminosilicate, tricalcium silicate, silica aerogel, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on diatomaceous earth, silicon dioxides, sodium silicate, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the
public when they are used as ingredients of paper and paperboard products used in food packaging in accordance with current practice. There is no evidence in the available information on sodium silicate and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of cotton and cotton fabrics used in dry food packaging in accordance with current practice. There is no evidence in the available information on diatomaceous earth and perlite that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used as filteraids in food processing at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Magnesium is a dietary essential. It is involved in myriad metabolic reactions and is necessary for the activity of many intracellular enzymes. Also, with certain other cations, it is important in electrolyte balance. Magnesium is present in fruits, vegetables, grains, milk, meat and fish and the natural content of these foods is the major source of the current dietary intake. The Food and Nutrition Board, NRC, has recommended that cereal grain products be fortified with magnesium in view of potential risk of deficiency among significant segments of the population. The usual adult intake is about 300mg or less per day from all sources and the contribution of food additives to total magnesium intake is very small. The administration of magnesium sulfate in very high doses to humans occasionally has resulted in severe and even fatal episodes, especially in the presence of pre-existing disease. These occurrences should not be prejudicial to the use of magnesium salts as foods ingredients
since the dosages given were orders of magnitude greater than the daily intake of magnesium added to food. While chronic toxicity data are lacking, the status of magnesium as a ubiquitous and essential dietary ingredient for the maintenance of homeostatic and bioenergetic mechanisms leads to the opinion that none of the available evidence suggests any probable hazard when any of the GRAS compounds of magnesium is used as a food ingredient. In view of the foregoing, The Select Committee concludes that: There is no evidence in the available information on magnesium carbonate, magnesium chloride, magnesium sulfate, magnesium hydroxide, magnesium oxide, magnesium stearate, dibasic magnesium phosphate and tribasic magnesium phosphate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced, or which might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Dietary Iron | 7439-89-6 | PB-218 836 | 1972 | There is no conclusion type. | There is no CFR citation. |
SCOGS Opinion:
OPINION OF THE CONSULTANTS:
1. Majority opinion
The majority of the ad hoc group members agreed that the proposed increase in iron enrichment will not jeopardize the health of U.S. males who have normal iron metabolism. They noted that adult males have always consumed more dietary iron than required to meet their nutritional needs. It is difficult to conceive of any combination of foods, in amounts consumed to meet caloric requirements, that would not provide more iron than the adult male requires. It is believed by some that in the past, beacuse of gretaer physical activity and consumption of greater quantities of food, the average daily intake of iron exceeded that presently proposed (Finch and Monsen, 1972).
If it is accepted that hemochromatosis is an inborn error of metabolism, then it may be concluded that the propsed increase in the iron content of the general diet will not affect the number of individuals who have the inborn error. In addition, the majority of the consultants agreed that the incidence of hemochromatosis will not be increased. The consultants were aware of the published opinions that the rate of accumulation of iron in the latent hemochromatosis may be accelerated and presumably this would result iin an increase in the severity of the clinical manifestations. This opinion is plausible but there is no substantial evidence to prove or disprove it. Thus, it would appear that the proposed increase in the iron content of enriched flour and related products should have little or no untoward effects on iron accumulation of individuals with latent iron storage disorders. However, the consultants acknowledged that all these opinions where based on informed judgment rather than
direct experimental evidence and that additional resaerch would be required to resolve conclusively the significance of the amount of dietary iron on iron accumulation. The majority of the consultants indicated that it would be desirable to perform such research algon with implementation of any regulation increasing the iron enrichment of flour and related cereal products. They stated that if and when the proposed regulation is implemented, continuous careful surveillance of representative segments of the U.S. population will be needed not only to evaluate efficacy in the prevention of iron deficiency, but also to provide information as to whether or not there is any effect on the incidence and severity of iron storage disorders.
SCOGS Opinion:
A survey of industry indicated thiodipropionic acid and dilauryl thiodipropionate were not added to processed foods in 1970. There might be some quantity of these compounds in antioxidant formulations in use today that the Select Committee has not been able to identify. If so, it is most likely to be small. In any case, it may be advisable that this value be ascertained. These substances are of limited value as antioxidants in food systems but may be of greater importance in food packaging films.If thiodipropionic acid and dilauryl thiodipropionate are added to food, present limitations require that the total content of antioxidants may not exceed 0.02 percent of fat or oil content, including essential (volatile) oil content of the food. When used in food packaging, the resulting level of addition to the packaged food must be less than 0.005 percent.
Thiodipropionic acid and dilauryl thiodipropionate are of low acute toxicity when orally administered to experimental animals. Doses of 100 mg per kg administered to rats were absorbed and largely excreted in the urine within a few days as thiodipropionic acid or an acid labile-conjugate. Apparently less than 10 percent is otherwise metabolized, and in the case of the ester, evidence of some incorporation into fat depots was detected. No studies of the disposition of these compounds in humans or subhuman primates are available for review. Test of the teratogenic and mutagenic effects of both compounds did not suggest cause for concern. The only reports of feeding studies are unpublished and of limited thoroughness. The unpublished feeding studies on thiodipropionic acid in rats and guinea pigs presented no adverse effects as measured by growth rate or mortality. However, in unpublished long term studies, the investigators noted increased mortality in groups of rats fed dilauryl
thiodipropionate as 0.5 and 3 percent of the diet and as a mixture with thiodipropionic acid as 1.1 percent of the diet. It would seem advisable to conduct adequate long term feeding studies on thiodipropionic acid and dilauryl thiodipropionate should it be ascertained that significant amounts are currently being used.
In light of these considerations, the Select Commitee concludes that: There is no evidence in the available information on thiodipropionic acid and dilauryl thiodipropionate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard. There is no evidence in the available information on thiodipropionic acid and dilauryl thiodipropionate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients in food packaging materials at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Distarch Glycerol | 58944-89-1 | 115 | 1979 | 4 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Distarch Oxypropanol | 977043-57-4 | 115 | 1979 | 3 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Distarch Propanol | There is no ID Code | 115 | 1979 | 2 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| DL-sodium-pantothenate | 867-81-2 | 93 | 1978 | 1 | There is no CFR citation. |
SCOGS Opinion:
Pantothenates occur in all tissues of the body and are essential for normal metabolic function. Daily consumption of calcium pantothenate added to foods by processors in the United States appears to be less than 0.08mg per capita (1.3mg per kg), a value that probably also represents total per capita daily consumption of pantothenates added to foods since sodium pantothenate and pantothenyl alcohol do not appear to be used by food processors.
It is estimated that the usual adult diet provides approximately 5 to 19mg (83 to 316mg per kg) of naturally occuring pantothenates daily. Animals of several species given 100 mg per kg or more of calcium pantothenate daily for several months showed no evidence of toxicity. Adult patients with disseminated or discoid lupus erythematosus receiving doses of 1g or more daily (16.6mg per kg) for several months manifested no evidence of toxicity. Although the evidence is scanty, there appears to be no reason to suspect teratogenicity, fetotoxicity or carcinogenicity from intakes considerably greater than those likely to be obtained from foods.
There is little information concerning the metabolism of L-pantothenic acid or its salts, although animals and human studies of administration of racemic mixtures of calcium or sodium pantothenate demonstrate no untoward effects at doses considerably higher than could be reasonably expected from pantothenates added to food.
There are no specifications listed for food grade sodium pantothenate. The Select Committee believes such specifications should be developed even though there appears to be no current use of sodium pantothenate.
The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on D-pantothenyl alcohol, D- or DL- calcium pantothenate or D- or DL-sodium-pantothenate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Pantothenates occur in all tissues of the body and are essential for normal metabolic function. Daily consumption of calcium pantothenate added to foods by processors in the United States appears to be less than 0.08 mg per capita (1.3mg per kg), a value that probably also represents total per capita daily consumption of pantothenates added to foods since sodium pantothenate and pantothenyl alcohol do not appear to be used by food processors.
It is estimated that the usual adult diet provides approximately 5 to 19 mg (83 to 316mg per kg) of naturally occuring pantothenates daily. Animals of several species given 100 mg per kg or more of calcium pantothenate daily for several months showed no evidence of toxicity. Adult patients with disseminated or discoid lupus erythematosus receiving doses of 1 g or more daily (16.6mg per kg) for several months manifested no evidence of toxicity. Although the evidence is scanty, there appears to be no reason to suspect teratogenicity, fetotoxicity or carcinogenicity from intakes considerably greater than those likely to be obtained from foods.
There is little information concerning the metabolism of L-pantothenic acid or its salts, although animals and human studies of administration of racemic mixtures of calcium or sodium pantothenate demonstrate no untoward effects at doses considerably higher than could be reasonably expected from pantothenates added to food.
There are no specifications listed for food grade sodium pantothenate. The Select Committee believes such specifications should be developed even though there appears to be no current use of sodium pantothenate.
The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on D-pantothenyl alcohol, D- or DL- calcium pantothenate or D- or DL-sodium-pantothenate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| D-sodium-pantothenate | 867-81-2 | 93 | 1978 | 1 | There is no CFR citation. |
SCOGS Opinion:
Pantothenates occur in all tissues of the body and are essential for normal metabolic function. Daily consumption of calcium pantothenate added to foods by processors in the United States appears to be less than 0.08mg per capita (1.3mg per kg), a value that probably also represents total per capita daily consumption of pantothenates added to foods since sodium pantothenate and pantothenyl alcohol do not appear to be used by food processors.
It is estimated that the usual adult diet provides approximately 5 to 19mg (83 to 316mg per kg) of naturally occuring pantothenates daily. Animals of several species given 100 mg per kg or more of calcium pantothenate daily for several months showed no evidence of toxicity. Adult patients with disseminated or discoid lupus erythematosus receiving doses of 1g or more daily (16.6mg per kg) for several months manifested no evidence of toxicity. Although the evidence is scanty, there appears to be no reason to suspect teratogenicity, fetotoxicity or carcinogenicity from intakes considerably greater than those likely to be obtained from foods.
There is little information concerning the metabolism of L-pantothenic acid or its salts, although animals and human studies of administration of racemic mixtures of calcium or sodium pantothenate demonstrate no untoward effects at doses considerably higher than could be reasonably expected from pantothenates added to food.
There are no specifications listed for food grade sodium pantothenate. The Select Committee believes such specifications should be developed even though there appears to be no current use of sodium pantothenate.
The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on D-pantothenyl alcohol, D- or DL- calcium pantothenate or D- or DL-sodium-pantothenate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Electrolytic Iron | 7439-89-6 | 35 | 1980 | 2 | 184.1375 |
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk of
developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an increase
in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report. Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to determination of the acute toxicity and bioavailability of specific
iron forms. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecdotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled chronic feeding studies with most of the individual compounds, before confident appraisal can be made of their relative merts or hazards.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
In the light of the above considerations, the Select Committee concludes that: There is no evidence in the available information on reduced, electrolytic, and carbonyl iron, ferrous ascorbate, ferrous carbonate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric citrate, ferric phosphate, or ferric pyrophosphate, that suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or in the manner now practiced., or if deemed necessary at somewhat higher levels to meet nutritional needs. However, it is not possible to determine without additional data whether a major increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report. Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to determination of the acute toxicity and bioavailability of
specific iron forms. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecdotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled chronic feeding studies with most of the individual compounds, before confident appraisal can be made of their relative merts or hazards.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
In the light of the above considerations, the Select Committee concludes that: There is no evidence in the available information on reduced, electrolytic, and carbonyl iron, ferrous ascorbate, ferrous carbonate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric citrate, ferric phosphate, or ferric pyrophosphate, that suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or in the manner now practiced., or if deemed necessary at somewhat higher levels to meet nutritional needs. However, it is not possible to determine without additional data whether a major increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
The average level of consumption of protein hydrolyzates for flavoring purposes is less than 3 mg per kg per day. Protein hydrolyzates are not used for flavoring purposes in commercially processed baby foods wich formerly may have contained about 2 percent by weight. The Select Committee was unable to locate reports of experimentally demostrable adverse effects of high concentrations of glutamate in dietary mixtures.
In light of the above, and assuming that appropriate product specifications are adopted, the Select Commitee concludes that:
There is no evidence in the available information on acid hydrolyzed proteins, enzymatically hydrolyzed protein, yeast autolysates, and soy sauces, that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used as flavoring agents at levels that are now current or that might reasonably be expected in the future.
The situation is different regarding the use of enzymatic casein hydrolyzates as nutrients. These hydrolyzates are consumed or administered in much higher doses, frequently as the sole source of dietary protein in products that are used as special dietary foods.
Decades of clinical experience have revealed no reports of untoward effects when casein hydrolyzates are administered orally in combination with other nutrients such as glucose. Adverse effects of the dicarboxylic amino acid components have been reported only in rodents under unusual conditions of administration (e.g., gavage or subcutaneous injection) and are not considered relevant to the use of casein hydrolyzates by humans.
The Select Commitee therefore concludes that: There is no evidence in the available information on enzymatically hydrolyzed casein that demostrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used as a nutrient in special dietary foods at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The average level of consumption of protein hydrolyzates for flavoring purposes is less than 3 mg per kg per day. Protein hydrolyzates are not used for flavoring purposes in commercially processed baby foods wich formerly may have contained about 2 percent by weight. The Select Committee was unable to locate reports of experimentally demostrable adverse effects of high concentrations of glutamate in dietary mixtures.
In light of the above, and assuming that appropriate product specifications are adopted, the Select Commitee concludes that:
There is no evidence in the available information on acid hydrolyzed proteins, enzymatically hydrolyzed protein, yeast autolysates, and soy sauces, that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used as flavoring agents at levels that are now current or that might reasonably be expected in the future.
The situation is different regarding the use of enzymatic casein hydrolyzates as nutrients. These hydrolyzates are consumed or administered in much higher doses, frequently as the sole source of dietary protein in products that are used as special dietary foods.
Decades of clinical experience have revealed no reports of untoward effects when casein hydrolyzates are administered orally in combination with other nutrients such as glucose. Adverse effects of the dicarboxylic amino acid components have been reported only in rodents under unusual conditions of administration (e.g., gavage or subcutaneous injection) and are not considered relevant to the use of casein hydrolyzates by humans.
The Select Commitee therefore concludes that: There is no evidence in the available information on enzymatically hydrolyzed casein that demostrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used as a nutrient in special dietary foods at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
L-ascorbic acid, vitamin C, occurs in nutritionally significant amounts as a natural constituent of many fruits, vegetables, berries, and melons. As a vitamin it is needed in the diet of all age groups. L-ascorbic acid and its sodium salt are antioxidants and they are extensively used as preservatives, color stabilizers and for related functions in various foods and beverages. Calcium ascorbate and ascorbyl palmitate, a derivative of ascorbic acid having greater fat solubility, also are anti-oxidants, but appear not to have significant use in processed foods. In addition to their use in foods as antioxidants, L-ascorbic acid and its salts are added to some foods as a source of vitamin C. These sources constitute a significant proportion of the total ascorbate intake of the general population. Erythorbic acid (D-isoascorbic acid), a stereoisomer of L-ascorbic acid, and its sodium salt, also are effective antioxidants and are used
for this purpose in a number of food products. The quantities used in 1970 were substantially less than for the ascorbates. The vitamin activity of erythorbates is only one -twentieth that of ascorbic acid, and their anti-oxidant effectiveness is not greater than for the ascorbates. For this reason, it would seem desirable, where possible, to use L-ascorbic acid rather than erythorbic acid as an antioxidant. From studies in guinea pigs and man it can be concluded that although erythorbic acid shares the same absorption and tissue uptake system as ascorbic acid it has little antiscorbutic activity. Although competition between ascorbic acid and erythorbic acid has been demosntrated at a biochemical level, there is no firm evidence that such competition will produce a scorbutic state. Whether this biochemical interaction could result in a clinically significant depletion of ascorbic acid remains to be established. Both short- and long-term toxicity studies have demonstrated tolerance
without adverse effects for large amounts of orally administered L-ascorbic acid, sodium L-ascorbate, and erythorbic acid in several species including mice, rats, guinea pigs, rabbits, and dogs. A substantial number of short-term experiments with human subjects ingesting 1 to 4 g of ascorbate daily have generally not revealed any harmful effects. Some subjects have received higher amounts, up to at least 8 to 10 g per day. In most instances no untoward results have been noted. But there is marked paucity of such studies that were well controlled and in which inquiring attention was given to possible harmful effects. In due course, such studies would be desirable. In the various studies on the effect of ingesting excessive amounts of ascorbates, attention has been focused on questions including oxalate excretion and renal tract stones, effets on the utilization of copper, iron, and other metals, need for vitamin B12, blood coagulation,and reproductive performance. The findings indicate
that the tolerance to excessive amounts of ascorbic acid and its sodium salt is high. Several investigators have reported the development of dependency in animals and human after ingestion of large amounts of ascorbates for extended time periods; however, the levels of ascorbates added to foods by 1 to 3 orders of magnitude. It is notable that no data have been found concerning the possible effects of ascorbyl palmitate and calcium ascorbate in humans, and there is practically no information regarding the latter in animals. Information concerning ascorbyl palmitate in animals is almost as limited. The few meaningful experiments suggest that ascorbyl palmitate is tolerated about the same as ascorbic acid and sodium ascorbate. This should be expected. It is reasonable to assume that the tolerance to calcium ascorbate is approximately the same as for sodium ascorbate and this is a high level. In view of the foregoing, The Select Committee concludes that: There is no evidence in the
available information on L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, ascorbyl palmitate (palmitoyl L-ascorbic), erythorbic acid (D-isoascorbic acid), and sodium erythorbate (sodium D-isoascorbate) that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used as food ingredients at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ethyl cellulose | 9004-57-3 | 25 | 1973 | 2 | 182.90 |
SCOGS Opinion:
Cellulose is a major constituent of many foods of plant origin. As such it is a significant portion of the diet, but is neither degraded nor absorbed. Cellulose derivatives considered in this report are virtually unabsorbed and little or no degradation of absorbed and little or no degradation of absorbable products occurs in the human digestive tract. In man, consumption of large amounts appears to have no effect other than providing dietary bulk, reducing the nutritive value of such foodstuffs and possibly exerting a laxative effect. However, the existence of certain data and the different categorization of cellulose and the several cellulose derivatives on the GRAS list suggest that the Select Committee should render a separate opinion on each substance considered in this report.
A. CELLULOSE, MICROCRYSTALLINE CELLULOSE
Although pure cellulose and regenerated cellulose, including microcrystalline cellulose are not on the GRAS list, there is nothing in the available information to suggest that such forms of cellulose have significantly different biological properties that distinguish these forms of cellulose from those currently considered as GRAS or from naturally occurring cellulose. In view of the foregoing, the Select Committee concludes that: There is no evidence in the available information on pure and regenerated cellulose, including microcrystalline cellulose, that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current, or that might reasonably be expected in future.
B. METHYL CELLULOSE
In humans, virtually 100 percent of orally ingested methyl cellulose can be recovered in the feces withihn four days, indicating that absorption does not occur. However, in pregnant mice, very high doses of methyl cellulose, while not teratogenic, cause a significant increase in maternal mortality and retardation of fetal maturation. Such increased maternal and fetal toxicity does not occur at a dose of methyl cellulose which is 26-fold (or more) greater than that estimated to be the average daily adult dietary intake. It is noteworthy in this regard that similar toxic effects have been observed in identical tests performed by the same investigators on a large number of other polysaccharides fed at very high doses. The relative sensitivity of the several animal species to these effects varies, depending on the particular polysaccharide tested, but in all cases very large doses are required. Until these effects have been adequately explained, it appears to be inappropriate to conclude
that unrestricted use of such substances in food would be without hazard. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on methyl cellulose that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
C. CARBOXYMETHYL CELLULOSE
Carboxymethyl cellulose is converted spontaneously to a salt in alkaline solution, and it is probable that the distinction between carboxymethyl cellulose and its salts is artificial. However, carboxymethyl cellulose is liested as GRAS as a substance migrating to food from cotton or cotton fabrice used in dry foods packaging, while its sodium salt is listed as GRAS as a miscellaneous or general purpose food additive. In view of the separate listing of carboxymethyl cellulose, the Select Committee concludes that: There is no evidence in the available information on carboxymethyl cellulose that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used in dry food packaing materials originating from cotton or cotton fabrics as now practed or as it might reasonably be expected to be used for such purposes in future.
D. SODIUM CARBOXYMETHYL CELLULOSE
Despite the probable lack of distinction between sodium carboxy methyl cellulose and its parent compound, carboxymethyl cellulose, only the sodium carboxymethyl cellulose is GRAS as a miscellaneous and general purpose food additive. As such, there are no data that suggest it reacts differently than pure and regenerated cellulose or carboxymethyl cellulose. In view of the foregoing the Select Committee concludes that: There is no evidence in the available information on sodium carboxymethyl cellulose that demonstrtes, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in future.
E. HYDROXYPROPYLMETHYL CELLULOSE
Hydroxypropylmethyl cellulose is not listed as GRAS. It is a food additive used as a thickening agent, stabilizer and emulsifier. Hydroxypropylmethyl cellulose is sinthesized from methyl cellulose by the action of alkali and propylene oxide. There are no data available to suggest that hydroxypropylmethyl cellulose possesses adverse health effects; however, teratology studies dimilar to those conducted with mehtyl cellulose are not available for its hydroxypropyl derivative. Therefore, it is suggested that, in due course, appropriate studies should be conducted with hydroxypropylmethyl cellulose. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on hydroxypropylmethyl cellulose that demonstrates, or suggested reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current and in the manner now practiced (21 CFR 121.1021)
F. ETHYL CELLULOSE AND CELLULOSE ACETATE
There is a paucity of data concerning possible adverse health effects of ethyl cellulose and cellulose acetate. both are included in the GRAS list as substances migrating to food from paper or paperboard products used in food packaging. According to the NRC survey (6), very small amounts of ethyl cellulose also appear to be used in hard candy and chewing gum. In the GRAS context, the quantity of ethyl cellulose or cellulose acetate migrating to foods from packaging would be orders of magnitude below the levels of cellulose and cellulose derivaties now known to occur in foods. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ethyl cellulose and cellulose acetate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used in food packaging materials as now practiced or as they might be expeccted to be used for such purposes in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ethyl formate | 109-94-4 | 71 | 1976 | 1 | 184.1295 |
SCOGS Opinion:
Formic acid is a natural constituent of many foods. It is a metabolite in normal intermediary metabolism, and is a precursor in the biosynthesis of several body constituents. The tolerance of the body to large amounts is relatively high. For example, 160mg of formic acid per kg of body weight orally was tolerated by rats; men reportedly 8 mg of formic acid per kg per day orally for a period of four weeks; and no adverse effects were reported in rats that received 730mg of sodium formate per kg in their diet for one and a half years. Average daily intake of ethyl formate and formic acid is about 1 mg per kg or less as formic acid. Although formic acid appears to be moderately mutagenic in E.coli and Drosophila, ethyl formate is not mutagenic toward strain D4 of Saccharomyces cerevisiae or to three strains of Salmonella typhimurium. No adverse effects attibutable to formate were found in five successive generations of rats given
up to 200 mg of calcium formate per kg of body weight daily. Based on these considerations, the Select Committee concludes that: There is no evidence in the available information on formic acid and sodium formate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of paper and paperboard food packaging materials, or as they might reasonably be expected to be used for such purposes in the future. There is no evidence in the available information on ethyl formate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when it is used at levels that are now current and in the manner now practiced or that might reasonably be expected in the future.
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
In the light of the above considerations, the Select Committee concludes that: There is no evidence in the available information on reduced, electrolytic, and carbonyl iron, ferrous ascorbate, ferrous carbonate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric citrate, ferric phosphate, or ferric pyrophosphate, that suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or in the manner now practiced., or if deemed necessary at somewhat higher levels to meet nutritional needs. However, it is not possible to determine without additional data whether a major increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ferric chloride | 7705-08-0 | 35 | 1980 | 1 | 184.1297 |
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report. Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to determination of the acute toxicity and bioavailability of
specific iron forms. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecdotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled chronic feeding studies with most of the individual compounds, before confident appraisal can be made of their relative merts or hazards.
Several iron compounds are used in the preparation of paper and paperboard materials contacting foods or as ingredients used to hasten the drying of films used in coating the inner surface of food cans. Neither the amounts used for these purposes nor the extent to which they might migrate to foods are known to the Select Committee. However, the extent of their migration to food is believed to be very slight. The Select Committee concludes that: There is no evidence in the available information on elemental irion, ferrous sulfate, ferric chloride, ferric oxide, ferric sulfate, iron caprylate, iron linoleate, iron tallate, or the oxides of iron that dmonstrates, or suggests reasonably grounds to suspect, a hazard to the public when they are used as ingredients of paper and paperboard materials or in films coating the inner surface of cans in the manner now practiced or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ferric citrate | 2338-05-8 | 35 | 1980 | 2 | 184.1307c |
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
In the light of the above considerations, the Select Committee concludes that: There is no evidence in the available information on reduced, electrolytic, and carbonyl iron, ferrous ascorbate, ferrous carbonate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric citrate, ferric phosphate, or ferric pyrophosphate, that suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or in the manner now practiced., or if deemed necessary at somewhat higher levels to meet nutritional needs. However, it is not possible to determine without additional data whether a major increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ferric oxide | 1309-37-1 | 35 | 1980 | 5 | 186.1300 |
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
Serious deficiences exist in the experimental data or clinical experience with a number of iron compounds employed or suggested as iron fortifying agents for foods. The Select Committee concludes that: In view of the deficiency of relevant biological studies, it has insufficient data upon which to base an evaluation of ferric oxide, iron peptonate, iron polyvinyl pyrrolidone, sodium ferric EDTA, sodium ferricitropyrophosphate, or ferric sodium pyrophosphate when it is used as a food ingredient.
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report. Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to determination of the acute toxicity and bioavailability of
specific iron forms. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecdotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled chronic feeding studies with most of the individual compounds, before confident appraisal can be made of their relative merts or hazards.
Several iron compounds are used in the preparation of paper and paperboard materials contacting foods or as ingredients used to hasten the drying of films used in coating the inner surface of food cans. Neither the amounts used for these purposes nor the extent to which they might migrate to foods are known to the Select Committee. However, the extent of their migration to food is believed to be very slight. The Select Committee concludes that: There is no evidence in the available information on elemental irion, ferrous sulfate, ferric chloride, ferric oxide, ferric sulfate, iron caprylate, iron linoleate, iron tallate, or the oxides of iron that dmonstrates, or suggests reasonably grounds to suspect, a hazard to the public when they are used as ingredients of paper and paperboard materials or in films coating the inner surface of cans in the manner now practiced or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ferric phosphate | 10045-86-0 | 35 | 1980 | 2 | 184.1301 |
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
In the light of the above considerations, the Select Committee concludes that: There is no evidence in the available information on reduced, electrolytic, and carbonyl iron, ferrous ascorbate, ferrous carbonate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric citrate, ferric phosphate, or ferric pyrophosphate, that suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or in the manner now practiced., or if deemed necessary at somewhat higher levels to meet nutritional needs. However, it is not possible to determine without additional data whether a major increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
In the light of the above considerations, the Select Committee concludes that: There is no evidence in the available information on reduced, electrolytic, and carbonyl iron, ferrous ascorbate, ferrous carbonate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric citrate, ferric phosphate, or ferric pyrophosphate, that suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or in the manner now practiced., or if deemed necessary at somewhat higher levels to meet nutritional needs. However, it is not possible to determine without additional data whether a major increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
Serious deficiences exist in the experimental data or clinical experience with a number of iron compounds employed or suggested as iron fortifying agents for foods. The Select Committee concludes that: In view of the deficiency of relevant biological studies, it has insufficient data upon which to base an evaluation of ferric oxide, iron peptonate, iron polyvinyl pyrrolidone, sodium ferric EDTA, sodium ferricitropyrophosphate, or ferric sodium pyrophosphate when it is used as a food ingredient.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ferric sulfate | 10028-22-5 | 35 | 1980 | 1 | 184.1307 |
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report. Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to determination of the acute toxicity and bioavailability of
specific iron forms. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecdotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled chronic feeding studies with most of the individual compounds, before confident appraisal can be made of their relative merts or hazards.
Several iron compounds are used in the preparation of paper and paperboard materials contacting foods or as ingredients used to hasten the drying of films used in coating the inner surface of food cans. Neither the amounts used for these purposes nor the extent to which they might migrate to foods are known to the Select Committee. However, the extent of their migration to food is believed to be very slight. The Select Committee concludes that: There is no evidence in the available information on elemental irion, ferrous sulfate, ferric chloride, ferric oxide, ferric sulfate, iron caprylate, iron linoleate, iron tallate, or the oxides of iron that dmonstrates, or suggests reasonably grounds to suspect, a hazard to the public when they are used as ingredients of paper and paperboard materials or in films coating the inner surface of cans in the manner now practiced or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ferrous ascorbate | 7439-89-6 | 35 | 1980 | 2 | 184.1307a |
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
In the light of the above considerations, the Select Committee concludes that: There is no evidence in the available information on reduced, electrolytic, and carbonyl iron, ferrous ascorbate, ferrous carbonate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric citrate, ferric phosphate, or ferric pyrophosphate, that suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or in the manner now practiced., or if deemed necessary at somewhat higher levels to meet nutritional needs. However, it is not possible to determine without additional data whether a major increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ferrous carbonate | 563-71-3 | 35 | 1980 | 2 | 184.1307b |
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
In the light of the above considerations, the Select Committee concludes that: There is no evidence in the available information on reduced, electrolytic, and carbonyl iron, ferrous ascorbate, ferrous carbonate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric citrate, ferric phosphate, or ferric pyrophosphate, that suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or in the manner now practiced., or if deemed necessary at somewhat higher levels to meet nutritional needs. However, it is not possible to determine without additional data whether a major increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ferrous citrate | 7439-89-6 | 35 | 1980 | 2 | 184.1307c |
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
In the light of the above considerations, the Select Committee concludes that: There is no evidence in the available information on reduced, electrolytic, and carbonyl iron, ferrous ascorbate, ferrous carbonate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric citrate, ferric phosphate, or ferric pyrophosphate, that suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or in the manner now practiced., or if deemed necessary at somewhat higher levels to meet nutritional needs. However, it is not possible to determine without additional data whether a major increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ferrous fumarate | 141-01-5 | 35 | 1980 | 2 | 184.1307d |
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
In the light of the above considerations, the Select Committee concludes that: There is no evidence in the available information on reduced, electrolytic, and carbonyl iron, ferrous ascorbate, ferrous carbonate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric citrate, ferric phosphate, or ferric pyrophosphate, that suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or in the manner now practiced., or if deemed necessary at somewhat higher levels to meet nutritional needs. However, it is not possible to determine without additional data whether a major increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ferrous gluconate | 6047-12-7 | 35 | 1980 | 2 | 184.1308 |
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
In the light of the above considerations, the Select Committee concludes that: There is no evidence in the available information on reduced, electrolytic, and carbonyl iron, ferrous ascorbate, ferrous carbonate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric citrate, ferric phosphate, or ferric pyrophosphate, that suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or in the manner now practiced., or if deemed necessary at somewhat higher levels to meet nutritional needs. However, it is not possible to determine without additional data whether a major increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ferrous lactate | 5905-52-2 | 35 | 1980 | 2 | 184.1311 |
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
In the light of the above considerations, the Select Committee concludes that: There is no evidence in the available information on reduced, electrolytic, and carbonyl iron, ferrous ascorbate, ferrous carbonate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric citrate, ferric phosphate, or ferric pyrophosphate, that suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or in the manner now practiced., or if deemed necessary at somewhat higher levels to meet nutritional needs. However, it is not possible to determine without additional data whether a major increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ferrous sulfate | 7720-78-7 | 35 | 1980 | 2 | 184.1315 |
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
In the light of the above considerations, the Select Committee concludes that: There is no evidence in the available information on reduced, electrolytic, and carbonyl iron, ferrous ascorbate, ferrous carbonate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric citrate, ferric phosphate, or ferric pyrophosphate, that suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or in the manner now practiced., or if deemed necessary at somewhat higher levels to meet nutritional needs. However, it is not possible to determine without additional data whether a major increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report. Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to determination of the acute toxicity and bioavailability of
specific iron forms. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecdotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled chronic feeding studies with most of the individual compounds, before confident appraisal can be made of their relative merts or hazards.
Several iron compounds are used in the preparation of paper and paperboard materials contacting foods or as ingredients used to hasten the drying of films used in coating the inner surface of food cans. Neither the amounts used for these purposes nor the extent to which they might migrate to foods are known to the Select Committee. However, the extent of their migration to food is believed to be very slight. The Select Committee concludes that: There is no evidence in the available information on elemental irion, ferrous sulfate, ferric chloride, ferric oxide, ferric sulfate, iron caprylate, iron linoleate, iron tallate, or the oxides of iron that dmonstrates, or suggests reasonably grounds to suspect, a hazard to the public when they are used as ingredients of paper and paperboard materials or in films coating the inner surface of cans in the manner now practiced or that might reasonably be expected in the future.
SCOGS Opinion:
On the basis of the evidence reviewed, the amount of hydrogenated fish oil migrating to food from cotton and cotton fabrics used in dry food packaging, or form paper and paperboard packaging used with dry, aqueous, and fatty acids, is not great enough to be harmful to humans. Even a moderate amount of partially hydrogenated fish oil in the diet would have no adverse health effects if adequate sources of essential fatty acids and vitamin E were present and the manufacturing and handling practices were satisfactory. In view of the foregoing, the Select Committee concludes that: There is no evidence in the available informartion on hydrogenated fish oil that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used in food packaging materials as now practiced or as it might be expected to be used for such purposes in the future.
SCOGS Opinion:
Formic acid is a natural constituent of many foods. It is a metabolite in normal intermediary metabolism, and is a precursor in the biosynthesis of several body constituents. The tolerance of the body to large amounts is relatively high. For example, 160 mg of formic acid per kg of body weight orally was tolerated by rats; men reportedly 8 mg of formic acid per kg per day orally for a period of four weeks; and no adverse effects were reported in rats that received 730mg of sodium formate per kg in their diet for one and a half years. Average daily intake of ethyl formate and formic acid is about 1 mg per kg or less as formic acid. Although formic acid appears to be moderately mutagenic in E.coli and Drosophila, ethyl formate is not mutagenic toward strain D4 of Saccharomyces cerevisiae or to three strains of Salmonella typhimurium. No adverse effects attibutable to formate were found in five successive generations of rats given
up to 200 mg of calcium formate per kg of body weight daily. Based on these considerations, the Select Committee concludes that: There is no evidence in the available information on formic acid and sodium formate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of paper and paperboard food packaging materials, or as they might reasonably be expected to be used for such purposes in the future. There is no evidence in the available information on ethyl formate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when it is used at levels that are now current and in the manner now practiced or that might reasonably be expected in the future.
SCOGS Opinion:
The long history of the use of garlic in food and acute, chronic and inhalation studies, although limited, reveal no credible adverse biological effects even at concentrations which are of orders of magnitude greater than the levels reported to be currently consumed in man's daily diet. In view of the foregoing, the Select Committee concludes that: There is no evidence in the available information on garlic or oil of garlic that demonstrates a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Gelatin | 9000-70-8 | 58 | 1975 | 1 | There is no CFR citation. |
SCOGS Opinion:
Gelatin is a hydrolyzate of naturally occurring collagen, an ingredient of commonly consumed foods of animal origin. It has been used for over 125 years as an ingredient in the manufacture of various foodstuffs.There is no documented evidence of a deleterious nature to humans from the ingestion of gelatin, other than a rare allergenic response, when the diet has provided an adequate amount of the amino acid tryptophan and is deficient in several others, and thus is of low nutritive value. Gelatin is used in various pharmaceutical formulations. The incidence of tumors in experimental animals (mice) injected subcutaneously with gelatin in various strength solutions, did not differ from that in untreated control animals. No significant adverse findings other than rare hypersensitivity have been found in the examination of data from feeding and biochemical experiments. Thus, there is no evidence to demonstrate a hazard to the public
at the level gelatin is consumed as a food or a food ingredient. Based on these considerations, the Select Committee concludes that: There is no evidence in the available information on gelatin that demonstrates or suggests reasonable grounds to suspect a hazard to the public when it is used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
1. Mono- and diglycerides of edible fat-forming fatty acids Although mono- and diglycerides of edible fat-forming fatty acids are found naturally, those that are used as food additives are usually prepared synthetically. Mono-, di- and triglycerides are metabolized by the same mechanisms. The biological effects of glycerides are either those of the entire molecule or of the metabolic products, fatty acids and glycerin. Triglyceride fats are a major source of calories in the diet of many people. Mono- and diglycerides are minor components of natural fats. They are intermediate metabolic products of ingested triglycerides. There is no evidence that the mono- and diglycerides of edible fat-forming fatty acids behave differently from triglycerides upon ingestion. There is evidence that ingestion of excesses of saturated fats and cholesterol promotes arteriosclerosis and cardiovascular disease. Continuation of research in this area
may refine relationships of the various fatty acids to the point where harmfulness may become an impelling consideration. However, because a reasonable estimate of the consumption of all added mono- and diglycerides is of the order of 1 to 10 g per person per day, only a fraction of which contains saturated fatty acids, it can hardly be concluded that they make a sufficient contribution to any hazard associated with normal ingestion of saturated fatty acids in fatty foods to justify limitation of the level of their current use. In light of the scientific information available, the Select Committee concludes that: There is no evidence in the available information on mono- and diglycerides of fat-formaing fatty acids that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future. 2. Diacetyl tartaric acid esters of mono- and diglycerides The diacetyl tartaric acid
esters of mixed mono- and diglycerides have been found to be without toxic effects in long-term feeding experiments with rats and dogs at levels that were orders of magnitude greater than those to which consumers are exposed. In light of these data, the Select Committee concludes that: There is no evidence in the available information on the diacetyl tartaric acid esters of mono- and diglycerdies that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future. 3. Triacetin, acettooleins, acetostearins Triacetin and two types of acetooleins have been found to be without toxic effects in long-term feeding tests in rats at levels that were several orders of magnitude greater than those to which consumers are exposed. Three types of acetostearins have been found to be without toxic effects in long-term feeding tests in rats at levels up to 5 g per kg per day. This
contrasts with an estimated human consumption of a fraction of a milligram per kg per day. It is recognized that at an even higher feeding level (10 g per kg per day) male rats developed testicular atrophy and female rats, uterine discoloration. However, such a level which would amount to 50 g or more for an infant and 600 g for an adult per day, is vastly higher than would be possible in the consumption of foods to which acetostearins are added for functional purposes. In light of the available scientific information the Select Committee concludes that: There is no evidence in the available information on triacetin, acetooleins, and acetostearins that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future. 4. Glyceryl lactopalmitate, glyceryl lactooleate have been found to be without toxic effects in long-term feeding tests with rats at levels that were orders of
magnitude greater than those to which consumers are exposed. In light of the available scientific information the Select Committee concludes that: There is no evidence in the available information on glyceryl lactopalmitate and glyceryl lactooleate that demonstrates or suggests reasonable grounds to suspect a hazard to the pulbic when they are used at levels that are now current or that might reasonably be expected in the future. 5. Oxystearins In the only chronic study of the oxystearins available to the Select Committee, levels as high as 7.5 g per kg per day for two years elicited no chronic toxic effects. However, Leydig cell adenomas of the testes were observed. It is recognized that the investigators noted that it was only remotely possible that appearance of these adenomas was related to the oxystearins in the diet and that the dietary level at which they appeared was several orders of magnitude greater than could occur practically. Nevertheless, until this effect has been
adequately explained it is inappropriate to conclude that unrestricted use of oxystearins in food would be without hazard. The Select Committee also recognizes the need for establishing the identity of the substances now referred to as the "oxystearins" since the oxidative processes by which they now are prepared would be expected to produce a number of products, such as peroxides, of varying nature and amount. In light of the scientific information available, the Select Committee concludes that: While no evidence in the available information on oxystearins demonstrates a hazard to the public when they are used at levels that are now current and in the manner now practiced, uncertainties exist requiring that additional studies should be conducted.
6. Other glycerides
Opinions and conclusions concerning the sulfoacetate derivatives of mono- and diglycerides, the monosodium phosphate derivatives of mono- and diglycerides and monoglyceride citrate cannot be provided due to the absence or inadequacy of biological data. While chronic feeding studies of a product called succistearin revealed no evidence of toxic effects at levels that were orders of magnitude greater than those to which consumers are exposed, the product fed was a mixture whose primary constituent (stearoyl propylene glycol hydrogen succinate) is not a glyceride. Therefore, a conclusion with respect to succistearin is not included in this report.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Glycocholic acid | 475-31-0 | 44 | 1975 | 1 | There is no CFR citation. |
SCOGS Opinion:
The amounts of the bile acids ingested as constituents of ox bile extract used as a food additive are relatively insignificant, compared to the amounts normally present in the bile of man. The available information indicates that orally administered cholic acid, desoxycholic acid, glycocholic acid, and taurocholic acid are readily absorbed and excreted without accumulation. They exhibit a relatively low toxicity for several animal species tested. The Select Commitee has no information to indicate that the individual bile acids or their salts are used in foods. However, the intake estimates available for ox bile extract, of which bile acids and their salts are major constituents, indicate that average daily consumption of ox bile extract added to foods is small, amounting to 0.1 mg or less. The intake of individuals bile acids or their salts would be, commensurately, very small. Such biological effects as have been reported in
animal studies, have been elicited at levels of administration that are several orders of magnitude greater that the levels to which man is now exposed in his daily diet. In the light of the information contained in this report, the Select Commitee concludes that: There is no evidence in the available information on ox bile extraxt, or its constituents cholic acid, desoxycholic acid. glycocholic acid, and taurocholic acid- that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Glycyrrhiza | 68916-91-6 | 28 | 1974 | 2 | 184.1408 |
SCOGS Opinion:
Orally administered licorice and licorice derivatives are absorbed to some extent and the principal metabolic products are excreted through the bile, but most of an ingested dose is hydrolyzed in the digestive tract and the products excreted through the feces. Acute and short-term substances of a very low order of toxicity, capable of eliciting a variety of pharmacological effects but only at levels considerably higher than are likely to be achieved in usual diets. None of these effects suggests cause for convern at current or foreseeable dietary levels of consumption. However, the capacity of licorice and licorice derivatives to elicit transitory hypertensive effects, at higher dosage levels in animals and man, requires more definitive clarification as far as its practical implications are concerned. This would be particularly important for the unknown number but probably few individuals who may indulge themselves with excessive
intakes of licorice-containing candies and/or beverages. The Select Committee has found no long-term toxicological data on licorice-related products administered to animals or man. Until the long-term as well as the acute dose relationships of the hypertensive effect are clarified, it appears inappropriate to conclude that unrestricted use of licorice and licorice derivatives in food would be without hazard to consumers in general. In the light of the foregoing and the information elsewhere in this report, the Select Committee concludes that: There is no evidence in the available information on licorice, glycyrrhiza, and ammoniated glycyrrhizin that demonstrates or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Guar Gum | 9000-30-0 | 13 | 1973 | 2 | 184.1339 |
SCOGS Opinion:
The available information reveals that there are no adverse short-term toxicological consequences in animals of consuming guar gum in amounts exceeding those currently consumed in the normal diet of the U.S. population. In addition, there is no evidence that consumption of guar gum by man has had adverse effects in India or Pakistan, where it has long been used as food, or in the U.S., where it has been used in foods since 1949. However, it should be noted that no long-term animal feeding studies of guar gum have been reported. While the available information does not suggest long-term toxicity, it may be advisable in due course to conduct adequate feeding studies in several species, including pregnant animals, at dosage levels that approximate and exceed the current estimated maximum daily human intakes. Guar gum, fed at relatively high levels, is reported to be toxic to pregnant mice. Because these toxic levels reported are
well in excess of the highest levels now consumed by man, the Select Committee is of the opinion that there are no adverse health aspects of consuming guar gum at current levels. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on guar gum that demonstrates a hazard to the public when it is used at levels that are now current and in the manner now practiced.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Gum Arabic | 9000-01-5 | 1 | 1973 | 2 | 184.1330 |
SCOGS Opinion:
In common with many other food ingredients of natural origin, commercial gum arabic is a relatively crude and undefined material. In view of the demonstrated indications that sensitization is due to the gum polysaccharide itself, it becomes important to know, nevertheless, to what extent extraneous contaminants such as protein may be contained in the commercial product. The Select Committee suggests consideration of revising the specifications for gum arabic to establish limits for the content of materials such as protein that may possibly be associated with some of the observed biological effects of the commercial gum. In view of the prevalence of allergies to gum arabic, and its increasing use in a wide variety of food products, additional experiments should be undertaken to evaluate the significance of its allergenicity in the population as a whole. An epidemiological survey might determine whether significant numbers of
persons are being placed in a state of receptiveness to cross-reactive allergies based upon daily lifelong exposures to gum arabic and two other gums allerged to be allergenic-gum tragacanth and karaya gum. Gum arabic, fed at relatively high levels, is reported to be toxic to pregnant animals of one species, hence it may be advisable, in due course, to conduct feeding studies in several animal species, includingpregnant animals, at dosage levels that approximate and exceed the current maximum daily human intake. The Select Committee has weighted the foregoing and concludes that: There is no evidence in the available information on gum arabic that demonstrates a hazard to the public when it is used at levels that are now current and in the manner now practiced. However, it is not possible to determine without additional data, whether a significant increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Gum Ghatti | 9000-28-6 | 12 | 1973 | 2 | 184.1333 |
SCOGS Opinion:
There is no evidence that consumption of gum ghatti by man has has adverse effects when used at present levels. However, this presumption of lack of hazard is based primarily on the absence of evidence of human toxicity, rather than on substantive evidence supporting this conclusion. In view of the sparseness of toxicity data, the Select Committee attaches greater possible significance to the preliminary evidence indicating the maternal toxicity of gum ghatti at very high oral doses to pregnant rats and rabbits than it might otherwise accord these few data. It may be advisable, in due course, to conduct feeding studies in several animal species, including pregnant animals, at dosage levels that approximate and exceed the current estimated maximum daily human intake. The Select Committee has weighed the foregoing and concludes that: There is no evidence in available information on gum ghatti that demonstrates a hazard to the
public when it is used at levels that are now current and in the manner now practiced.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Gum guaiac | 9000-29-7 | 64 | 1975 | 1 | There is no CFR citation. |
SCOGS Opinion:
The literature on the biological activity of gum guaiac indicates that it is a substance of very low acute toxicity. A number of short- and long-term feeding studies in experimental animals at levels orders of magnitude greater than those to which humans might be exposed indicate the abscence of chronic effects. Daily ingestion by human subjects for nearly four years resulted in no observable adverse effects. The Select Committee has found no indication that gum guaiac is currently used as a food ingredient. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on gum guaiac that demonstrates, or suggests seasonable grounds to suspect, a hazard to the public if it is used as an antioxidant at levels compatible with current limitations.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Gum Tragacanth | 9000-65-1 | 4 | 1972 | 2 | 184.1351 |
SCOGS Opinion:
Since uncertainties exist with respect to the prevalence of allergies to gum tragacanth, additional experiments should be undertaken to evaluate the significance of its allergenic effects. A statistically-significant survey, conducted by practicing allergists, would help to determine whether significant numbers of persons are being placed in a state of receptiveness to cross -reactive allergies based upon lifelong daily exposures to gum tragacanth and the other two gums alleged to be allergenic-gum arabic and karaya gum. Gum tragacanth, fed at relatively high levels, is reorted to be toxic to pregnant animals of some species; hence, it may be advisable, in due course, to conduct feeding studies in several animal species, including pregnant animals, at dosage levels that approximate and exceed the current estimated maximum daily human intake. The Select Committee has weighed the foregoing and concludes that: The available
information contains no evidence demonstrating that gum tragacanth constitues a hazard to the public when used in the manner and quantity now practiced.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Helium gas | 7440-59-7 | 112 | 1979 | 1 | 184.1355 |
SCOGS Opinion:
The NRC survey did not identify any use of helium gas as a commercially added food ingredient; however, one manufacturer has reported that is was used during food processing to detect leaks from aerosol cannisters. Considering its low solubility in water and fats, its chemical inertness, and its high diffusion coefficient, the amounts of helium consumed from foods exposed to it would be minute. Although no feeding tests on foods exposed to helium have been reported, the negative results from many inhalation studies involving high concentrations and pressures of the gas with both man and animals, and other studies on tissue cultures, suggest that no adverse physiological effects would result, even from consumption of foods saturated with helium during commercial processing and storage. There are no food grade specifications for helium and storage. There are no food grade specifications for helium gas; it is suggested that such
standards should be developed.
In the light of these considerations, the Select Committee concludes that:
There is no evidence in the available information on helium gas that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| High Amylose Cornstarch | 9005-25-8 | 115 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Hydrochloric acid | 7647-01-0 | 99 | 1979 | 1 | 182.1057 |
SCOGS Opinion:
Hydrochloric acid in concentated form is a strongly corrosive agent and the consequences of exposure to it are well known. However, as it is used in food processing, or as a food additive to adjust the pH, hydrochloric acid is neutralized or buffered by the food to which it is added. Thus, human consumption is not of the acid, but of the chloride ion in the salts formed in the neutralization process. The small amounts of hydrochloric acid that may persist in foods or drinks, would, in turn, be neutralized and buffered during ingestion and digestion, or after absortion. Hydrochloric acid is also a natural secretory product of the stomach of animals, including man (about 0.5 percent concentration in the gastric juice). The normal production of hydrochloric acid by the stomach exceeds manyfold the amounts that could be derived from foods.
Animal experiments have not revealed untoward effects of hydrochloric acid consumption in amouts greatly exceeding those that can be reasonably expected to result from consumption of foods treated with hydrochloric acid.
Based on these considerations, the Select Committee concludes that: There is no evidence in the available information on hydrochloric acid that demonstrates or suggests reasonable grounds to suspect a hazard to the public when it is used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Hydrogen peroxide | 7722-84-1 | 113 | 1979 | 2 | 184.1366 |
SCOGS Opinion:
Hydrogen peroxide is GRAS when used as a bleaching agent in foods and in cotton and cotton fabrics for dry food packaging. It is considered GRAS by the Department of the Treasury in the treatment of wines. It is used as an antimicrobial agent in cheese manufacturing under standards of identity and also in whey processing.
Consumer exposure data indicate only 8 mg per capita per day are used by food manufacturers and much of this would be destroyed or dissipated during processing. Toxic effects in animals by all routes studies ocurred only at levels several orders of magnitude greater than man's possible exposure from food sources or packaging materials. There is no evidence that hydrogen peroxide is carcinogenic, teratogenic, or mutagenic at levels present in foods treated with hydrogen peroxide during processing.
Vigorous treatment of foods with hydrogen peroxide may cause some destruction of ascorbic acid, methionine, and cystine. Under the conditions normally employed, the Select Committee believes their loss to be nutritionally insignificant.
Various oxidation products of normal food constituents are formed by the action of hydrogen peroxide. It is possible that such products might include epoxides or peroxides of unsaturated fatty acids and sterols, some of which are suspected of being carcinogenic or atherogenic under specialized conditions. However, none of the oxidation products thus far tested has proved carcinogenic when given by mouth, even at levels many times greater than any reasonable intake in food. Angiotoxicity has been produced only with amounts of sterol oxidation products several orders of magnitude greater than would be produced under conditions currently practices. There is no evidence that such products are, in fact, produced under current conditions of hydrogen peroxide usage. Because of the vulnerability of epoxides and peroxides to gastrointestinal action, only a small fraction of the amount ingested would be absorbed and this in turn would be subjected to hydrolysis by liver enzymes.
Although there is no evidence that the present usage of hydrogen peroxide in foods poses a hazard to consumers, insufficient data are available to ensure a lack of hazard with all foods or when more rigorous treatments are employed, using higher concentrations, prolonged exposure, or elevated temperatures.
In the light of the foregoing considerations, the Select Committee concludes that:
There is no evidence in the available information on hydrogen peroxide that demonstrates or suggests reasonable grounds to suspect a hazard to the public when it is used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
There is no evidence in the available information on hydrogen peroxide that demonstrates or suggests reasonable grounds to suspect a hazard to the public when it is used in cotton and cotton fabrics for dry food packaging at levels that are now current or might reasonably be expected in the future.
SCOGS Opinion:
Hydrogenated soybean oil as a major food fat in the American dietary. Food uses of hydrogenated soybean oil are in the production of margarine, shortening, and salad and cooking oils. These products are not formulated from completely hydrogenated vegetable oils; soybean oils for margarines and salad and cooking oils are only partially hydrogenated and the saturated fatty acid content is increased little by the process. The content of polyunsaturates in a soft tub margarine or salad and cooking oil may be two to three times that of the saturated fatty acids. Shortenings of the plastic type have a higher saturated fatty acids content than margarines but are no higher in this respect than the animal fats they have replaced, and generally have a higher content of polyunsaturated fatty acids.
Geometric and position isomers of the unsaturated fatty acids formed in hydrogenation have physical properties different from the isomers present in the natural oil. Presence of these unnatural isomers has led to extensive investigation of their nutritional and biological properties. The major geometric isomer formed is elaidic acid, the trans-isomer of oleic acid, although cis, trans-dienoic acids also are produced. It is estimated that the trans fatty acids content of the fat in the average American diet, largely contributed by hydrogenated vegetable oil products, is about 8 percent.
Digestibility of partially hydrogenated soybean oils is high and comparable to that of the unhydrogenated oil. No difference has been found in the intestinal absortion and rates of disappearance from the plasma of the trans-isomers of oleic and linoleic acid as compared to the cis-isomers. Rates of excretion as respiratory carbon dioxide are essentially the same for the trans- and cis-isomers.
The trans-isomers of linoleic acid do not have essential fatty acid activity, but the content of the cis- cis- isomer in hydrogenated soybean oil products is as high or higher than is found in butter fat, lard or tallow. Presence of either the trans-isomer of oleic acid or the trans-isomers of linoleic acid does not interfere with the utilization of linoleic acid as an essential fatty acid deficiency posed to consumers of commercial hydrogenated soybean oil products.
Many animal studies have demonstrated that the deposition of dietary trans-fatty acids in tissues and tissue lipids is selective. In vitro studies with liver mitochondrial and microsomal enzymes have demonstrated selectivity of action among fatty acids geometric and position isomers in the synthesis and hydrolysis of phospholipids and cholesterol esters. In a human subject labeled oleic and elaidic acids were rapidly exchanged with the fatty acids in the serum lipids. Analysis of human tissues at autopsy reflected the presence of trans- fatty acids in the diet.
In vitro experiments indicate that membrane functions can be affected by the incorporation of trans- fatty acids in experimental diets. Liver mitochondria isolated from rats fed elaidic acid exhibited two to threefold greater initial rates of swelling in hypotonic swelling media compared to those from control rats. Erythrocytes containing trans-fatty acids hemolyzed at a rate five times greater than that of control cells when incubated with ?- lecithinase. However, a long-term rat feeding test of a hydrogenated soybean-cottonseed oil containing 35 percent trans- acids showed no histopathology attributable to diet. Feeding hydrogenated oil of this composition to rats for 60 generations produced no adverse effects on fertility, litter, size, weight at weaning, growth at 90 days, and longevity. A two-year rat feeding test of a hydrogenated soybean cooking oil and a control soybean oil revealed no differences in histopathology attributable to diet.
Considerable experimental evidence shows that polyunsaturated fatty acids in dietary fat as triglycerids from natural sources have a hypocholesterolemic effect, monounsaturated fatty acids are neutral and saturated fatty acids, particularly those 12 to 16 carbons in chain lengh, are hypercholesterolemic when they replace mixed carbohydrates on an isocaloric basis. Soy bean oil, however, contains only traces of the 12 to 16 carbon unsaturated acids which can be converted to the corresponding saturated acids by hydrogenation, and it is only some of the industrial shortening that the stearic acid content is increases by hydrogenation. Although results of studies on the effect of trans-isomers on serum lipid levels in human are not definitive, the weight of evidence indicates that trans-monoenoic acids, the principal geometric isomers present in hydrogenated soybean oil, are not hypercholesterolemic. Similarly, the results of animal experimentation indicate that trans-acids of hydrogenated
soybean oil are not atherogenic at normal dietary levels.
In the light of the foregoing, the Select Commmittee concludes that: There is no evidence in the available information on hydrogenated soybean oil that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used as a direct or indirect food ingredient at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Tallow and stearic acid, one of its chemical components, are consumed as part of normal human diets primarily in meats and in smaller quantities as ingredients of shortening and oleomargarine. Calcium stearate appears to be a normal product of digestion of diets containing calcium and stearic acid. Hydrogenated tallow, including tallow flakes, is used to some extent in the manufacture of shortening. Feeding tests with animals show a high utilization of tallow as an energy source, but a relatively low digestibility of hydrogenated tallow, stearic acid, and calcium stearate. None of the feeding tests involving amounts of these substances comparable to those estimated to be consumed as food additives showed any toxic effects. Furthermore, the toxicity of stearic acid at very high concentrations is markedly reduced by the presence in the diet of glycerides of substantially lower melting point, such as those containing unsaturated fatty acids. Carcinogenicity test of stearic acid have shown
negative results. This report is directed toward the GRAS status of tallow, hydrogenated tallow, and stearic acid as given in the Code of Federal Regulations 121.101(i) as substances migrating to food from cotton and cotton fabrics used in dry food packaging and calcium stearate as a GRAS substance (unpublished). Even at the levels estimated as being consumed by man from all added sources of these substances there is no evidence to demonstrate a hazard to the public. In light of these observations, the Select Committee concludes that: As a substances that may migrate to foods from cotton or cotton fabrics, there is no evidence in the available information on tallow, hydrogenated tallow, or stearic acid that demonstrates, or suggests reasonably grounds to suspect, a hazard to the public, when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on calcium stearate that demonstrates, or suggests
reasonable grounds to suspect a hazard to the public, when it is used as a direct food additive at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Hydroxypropyl Starch | 9049-76-7 | 115 | 1979 | 3 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
SCOGS Opinion:
Cellulose is a major constituent of many foods of plant origin. As such it is a significant portion of the diet, but is neither degraded nor absorbed. Cellulose derivatives considered in this report are virtually unabsorbed and little or no degradation of absorbed and little or no degradation of absorbable products occurs in the human digestive tract. In man, consumption of large amounts appears to have no effect other than providing dietary bulk, reducing the nutritive value of such foodstuffs and possibly exerting a laxative effect. However, the existence of certain data and the different categorization of cellulose and the several cellulose derivatives on the GRAS list suggest that the Select Committee should render a separate opinion on each substance considered in this report.
A. CELLULOSE, MICROCRYSTALLINE CELLULOSE
Although pure cellulose and regenerated cellulose, including microcrystalline cellulose are not on the GRAS list, there is nothing in the available information to suggest that such forms of cellulose have significantly different biological properties that distinguish these forms of cellulose from those currently considered as GRAS or from naturally occurring cellulose. In view of the foregoing, the Select Committee concludes that: There is no evidence in the available information on pure and regenerated cellulose, including microcrystalline cellulose, that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current, or that might reasonably be expected in future.
B. METHYL CELLULOSE
In humans, virtually 100 percent of orally ingested methyl cellulose can be recovered in the feces withihn four days, indicating that absorption does not occur. However, in pregnant mice, very high doses of methyl cellulose, while not teratogenic, cause a significant increase in maternal mortality and retardation of fetal maturation. Such increased maternal and fetal toxicity does not occur at a dose of methyl cellulose which is 26-fold (or more) greater than that estimated to be the average daily adult dietary intake. It is noteworthy in this regard that similar toxic effects have been observed in identical tests performed by the same investigators on a large number of other polysaccharides fed at very high doses. The relative sensitivity of the several animal species to these effects varies, depending on the particular polysaccharide tested, but in all cases very large doses are required. Until these effects have been adequately explained, it appears to be inappropriate to conclude
that unrestricted use of such substances in food would be without hazard. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on methyl cellulose that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
C. CARBOXYMETHYL CELLULOSE
Carboxymethyl cellulose is converted spontaneously to a salt in alkaline solution, and it is probable that the distinction between carboxymethyl cellulose and its salts is artificial. However, carboxymethyl cellulose is liested as GRAS as a substance migrating to food from cotton or cotton fabrice used in dry foods packaging, while its sodium salt is listed as GRAS as a miscellaneous or general purpose food additive. In view of the separate listing of carboxymethyl cellulose, the Select Committee concludes that: There is no evidence in the available information on carboxymethyl cellulose that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used in dry food packaing materials originating from cotton or cotton fabrics as now practed or as it might reasonably be expected to be used for such purposes in future.
D. SODIUM CARBOXYMETHYL CELLULOSE
Despite the probable lack of distinction between sodium carboxy methyl cellulose and its parent compound, carboxymethyl cellulose, only the sodium carboxymethyl cellulose is GRAS as a miscellaneous and general purpose food additive. As such, there are no data that suggest it reacts differently than pure and regenerated cellulose or carboxymethyl cellulose. In view of the foregoing the Select Committee concludes that: There is no evidence in the available information on sodium carboxymethyl cellulose that demonstrtes, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in future.
E. HYDROXYPROPYLMETHYL CELLULOSE
Hydroxypropylmethyl cellulose is not listed as GRAS. It is a food additive used as a thickening agent, stabilizer and emulsifier. Hydroxypropylmethyl cellulose is sinthesized from methyl cellulose by the action of alkali and propylene oxide. There are no data available to suggest that hydroxypropylmethyl cellulose possesses adverse health effects; however, teratology studies dimilar to those conducted with mehtyl cellulose are not available for its hydroxypropyl derivative. Therefore, it is suggested that, in due course, appropriate studies should be conducted with hydroxypropylmethyl cellulose. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on hydroxypropylmethyl cellulose that demonstrates, or suggested reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current and in the manner now practiced (21 CFR 121.1021)
F. ETHYL CELLULOSE AND CELLULOSE ACETATE
There is a paucity of data concerning possible adverse health effects of ethyl cellulose and cellulose acetate. both are included in the GRAS list as substances migrating to food from paper or paperboard products used in food packaging. According to the NRC survey (6), very small amounts of ethyl cellulose also appear to be used in hard candy and chewing gum. In the GRAS context, the quantity of ethyl cellulose or cellulose acetate migrating to foods from packaging would be orders of magnitude below the levels of cellulose and cellulose derivaties now known to occur in foods. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ethyl cellulose and cellulose acetate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used in food packaging materials as now practiced or as they might be expeccted to be used for such purposes in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Indian Dill Seed | 8006-75-5 | 22 | 1973 | 1 | 184.1282 |
SCOGS Opinion:
The Select Committee estimates that daily consumption of dill probably does not exceed the equivalent of 1 mg of dill oil per capita, or about 0.017 mg per kg per day in adults and about twice that level in children. The oil's most plentiful constituent, carvone, present to the extent of about 60 percent of the oil, elicits toxic responses only at levels much greater than those that might be present in the diet. Other constituents, present in some oils in lesser to trace amounts, such as apiole, dillapiole, and myristicin have not been shown to produce toxic effects on feeding at levels many times those that could exist in man's diet. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on dill and dill oils that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably
be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Inositol | 87-89-8 | 51 | 1975 | 1 | 184.1370 |
SCOGS Opinion:
Inositol is a naturally-occurring substance that is widely distributed in plant and animal tissues and synthesized in animals and man. Orally administered inositol is absorbed slowly and is metabolized. The available information form toxicological studies in animals suggests no adverse effects associated with consumption of inositol at levels considerably in excess of those now consumed by humans.
Despite the demonstration of signs of inositol deficiency in several animal species, no requirement for dietary inositol in man has been established. The high inositol concentration of human milk, and the relatively low concentration in cow's milk, together with the inadequate understanding of inositol metabolism and utilization during neonatal development in animals and man, suggest the possibility that basic infant formulas, particularly milk-free preparations, may contain less inositol than is necessary for optimal growth and development. The rationale for adding inositol to certain infant formulas is based on an assumption that the greater intake insures against a possible deficiency of inositol during early growth and development, when the need for dietary sources of inositol might be maximal. However, if future investigations should clearly demonstrate a need for additional inositol in infant formulas, and if that need should be greater than the amount now added, it is unlikely
that the recommended level of intake would exceed that supplied by human milk. The Select Commitee has considered the foregoing and concludes that: There is no evidence in the available information on inositol that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Invert Sugar | 57-50-1 | 50 | 1976 | 2 | 184.1859 |
SCOGS Opinion:
Corn sugar, commonly referred to as dextrose, is crystalline ?-D-glucose. Glucose is widely distributed in nature both in the free state and in various combined forms, including starch and sucrose. Glucose-yielding carbohydrates constitute one of the main sources of energy in the typical North American diet. Fructose, produced along with glucose in the hydrolysis of sucrose to invert sugar and by isomerization of dextrose, also is a significant calorie source. The absorption and metabolism of these sugars are well established. Biological studies have shown that these substances are devoid of toxic effects at dosage levels well in excess of those that exist in the American diet and, accordingly, at levels that are orders of magnitude higher than those which might occur from the migration of these substances from paper and paperboard products.
Glucose syrup, also called corn syrup when made by the hydrolysis of corn starch, contains in addition to glucose, maltose, and higher saccharides in proportions that depend on the degree of hydrolysis of the starch. The higher conversion syrups may also contain small amounts of disaccharides formed by the recombination of glucose through glucosidic linkages not present in starch. Animal feeding studies have shown that glucose syrups are readily digested and metabolized and have given no evidence of toxic effects.
Fructose-dextrose mixtures have been observed to have hyperlipemic effects when fed at high levels in fat-free diets to adult males and postmenopausal women. There is no evidence, however, that the levels of invert sugar and high-fructose corn syrup in the average diet cause significant elevations in blood lipids and it is unlikely that the consumption of fructose or glucose, ingested as monosaccharides, has a role in coronary heart disease. Although glucose and fructose as well as sucrose have been demonstrated to be cariogenic in animal experiments, epidemiological studies of dietary habits and controlled diets in institutional feeding indicate that the cariogenicity of sucrose and other foods is affected by several factors and not necessarily by the total amount consumed. These factors include the frequency eating, duration of exposure, and the form and physical properties of the food in which the sugar is ingested. Between-meal eating has been demonstrated to be significantly
correlated with frequency and severity of caries in both children and adults. Thus, protection is facilitated by limitation of the frequency of consumption of sugar and sugared foods.
Consumption of dextrose and corn syrup has increased markedly in recent years and represented about 21 percent of the sweetener marker in 1974 as compared to about 15 percent in 1970. A major part of the increase resulted from the introduction of high-fructose corn syrup produced the enzymatic isomerization of dextrose in starch hydrolyzates. Level of fructose as the monosaccharide in the diet has increased accordingly but 1974 per capita daily consumption of this monosaccharide from all sources was only 6g and no higher than in 1925-29, when apples provided a larger contribution than at present. High-fructose corn syrups are predicted to increase in production and to replace sucrose and invert sugar in up to 30 percent of their applications by 1980-85, based largely on relative costs. There is no evidence that such replacement, per se, would have an adverse effect on public health. However, the Select Committee has expressed concern in its report on sucrose (73) that is this sugar
contributes to dental caries in the public at current consumption levels as used in the manner now practiced. It is questionable that replacement of sucrose by syrups and sugars derived from starch would greatly change the cariogenicity of foods containing these sugars. Informing the consumer of the sugar content of foods by appropriate labeling could lead to judicious use of sweetened foods. Choices could be made easier with a greater selection of less sugared foods in the market place. The Select Committee has weighed all of the foregoing and concludes that: Evidence exists that simple sugars, including glucose and fructose [and, therefore, corn sugar(dextrose), corn syrup including high-fructose corn syrup, and invert sugars] are cariogenic. However, in the quantities that these simple sugars are now consumed in processed foods, their contribution to formation of dental caries should be relatively small. If increased usage should occur, as seems likely, the contribution of these
sugars to the occurrence of dental caries might become more important. Other than the contribution made to dental caries, there is no evidence in the available information on corn sugar(dextrose), corn syrup, and invert sugar that demonstrated a hazard to the public when they are used at levels that are now current and in the manner now practiced. however, it is not possible to determine without additional data, whether an increase in consumption-that would result if there were a significant increase in the total of corn sugar, corn syrup, invert sugar and sucrose added to foods-would constitute a dietary hazard.
SCOGS Opinion:
LSRO RESUME: It is apparent that in the United States the iron enrich ment of foods is accomplished almost entirely through the use of four compounds: ferrous sulfate, reduced iron (so-called), ferric orthophosphate, and sodium iron pyrophosphate. In the regulation establishing the original flour and bread enrichment program, the iron to be added was described only as "harmless and assimilable." Considering the assay values which have been determined for either ferric orthophosphate or sodium iron pyrophosphate, it would be difficult to interpret "assimilable" in a manner which would include either compound. The former has a value of 25 to 30 percent that of ferrous sulfate; the latter a value of 5 to 10 percent. It seems obvious that, from the point of view of the consumer, the addition of ferric orthophosphate to a cereal food is a very minor nutritional benefit, and the addition of sodium iron pyrophosphate is essentially
futile. Therefore, it would seem wise to examine each present use of these salts in the hope that an iron compound of greater bioavailablity might be substituted. Some of our consultants were firmly of the opinion that fullest use was not being made of ferrous sulfate at the present time; particularly so at the bakery level. The Iron Committee has stated that "the use of ferrous sulfate at the bakery level appears to create no problems," but, for reasons of convenience or reluctance to change, other forms of iron are still used. The belief was expressed that if allenrichment of bread and other baked goods were carried out at the bakery this would promote a greater use of ferrous sulfate. As noted in Table 2 when enrichment is done at the flour mill the iron added is preponderantly reduced iron. A development of great potential for extending the use of ferrous sulfate in the enrichment program would be the commercial availability of a stabilized form of this salt. The objective is to
treat the compound in some manner so that its untoward effects on flour or other food during storage is inhibited while its good absorption from the digestive tract is retained. The problem is under active investigation and there is reason to believe that it will be solved in some degree. The most important iron source in the enrichment of foods is, by present estimates of use, reduced iron. In an addendum to this report (Appendix A), Patrick has provided valuable and much-needed information on the seveal iron powders which are collectively referred to as "reduced iron" in the food industry. He describes the process by which each is manufactured and suggests how this may influence the presence of impurities, particle size distribution, and biological activity. It is obvious that the extent to which the particles of iron dissolve in the acid of the stomach must be a very important determinant of bioavailability, but it is indicated that not only the size of the particle but also its
shape, surface area and density influence the speed with which it dissolves. The differences in the latter properties are suggested in the illustrations. The possible effect of the method of manufacture on the biological properties of iron powders would suggest that distinctive names should be applied to each. The Food Chemicals Codex (1972) contains monographs of "Iron, Electrolytic" and "Iron, Reduced" but none on iron prepared by the carbonyl method. This could indicated that no carbonyl iron owder is used in the enrichment of foods in this country, but because of the present imprecise designation, "reduced iron," this assumption might be wrong. This situation should be clarified.
The excellent absorption of iron reduced by hydrogen observed by Cook et al (1973) in human subjects was ascribed, in large part, to the very small particles achived in milling the small radiolabeled sample. These authors reported that more than 95 percent of the particles ranged in size from 5-10 microns, which they acknowledged was smaller than is commercially available. Even though it would be unrealistic economically, and, according to Patrick, perhaps hazardous to attempt the commercial production of such extremely fine iron powders, efforts in this direction should be considered. Certainly, in the use of iron powders for food enrichment, average particle size distributin must be an important specification. Cook et al. (1973) have listed the size distribution in the better commercial products.
In Appendix B certain comments and suggestions have been made in the hope of expediting the development of an official assay method for assessing the bioavailability of the iron in different sources. There is urgent need for an official well-designed assay. Without it there is little hope that the widely divergent values, that have been reported on the same products, can be resolved, or that further progress can be made in solving the remaining problems of the enrichment program.
SCOGS Opinion:
LSRO STAFF CONCLUSIONS:
The primary objective of this study was to determine the feasibility of developing protocols of clinical reearch which might answer the question: Will the proposed change in iron enrichment increase the prevalence or enhance the severity of iron storage disorders? We may now ask if the two experiments outlined in Protocols A and B are likely to answer that question. We conclude that neither will give a direct answer.
The experiment outlined in Protocol A is designed to permit the measuremetn of any difference in iron absorption, over a 10-day period, from two diets, identical except for the two breads with different levels of iron enrichment. The subjects will be mainly individuals with diagnosed diseases which are known, or believed,k to have some derangement of iron metabolism. However, there is no factual information that iron per se is the basic cause of the diseases listed in Protocol A. It is only when body stores of iron become excessive that they influence the clinical managemetn of patients with these diseases. Under present dietary conditions, clinicians manage this disorder by phlebotomy. We see no way of interpreting any increase in the absorptino of iron over a 10-day period in terms of ultimate accumulation of iron stores.
The objective of the experiment outlined in Protocol B is to acquire information on the response of healthy, adult males over a long period of time to different levels of dietary iron provided in bread or other four-containing items. The effects of this extra dietary iron on the accumulation of body stores will be of particular intererst. The possibility that an iron storage disease, such as hemochromatosis, might be precipitated by any of the levels of iron intake is considered extremely remote. Finally, if it is possible to conduct the clinical studies outlined in Protocol B it is highly unlikely that the basic question will be answered.
However, these two proposed experiments have scientific merit. They will supply information that is a prerequisite to a further understanding of the mechanisms regulating iron absorption and storage.
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report. Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to determination of the acute toxicity and bioavailability of
specific iron forms. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecdotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled chronic feeding studies with most of the individual compounds, before confident appraisal can be made of their relative merts or hazards.
Several iron compounds are used in the preparation of paper and paperboard materials contacting foods or as ingredients used to hasten the drying of films used in coating the inner surface of food cans. Neither the amounts used for these purposes nor the extent to which they might migrate to foods are known to the Select Committee. However, the extent of their migration to food is believed to be very slight. The Select Committee concludes that: There is no evidence in the available information on elemental irion, ferrous sulfate, ferric chloride, ferric oxide, ferric sulfate, iron caprylate, iron linoleate, iron tallate, or the oxides of iron that dmonstrates, or suggests reasonably grounds to suspect, a hazard to the public when they are used as ingredients of paper and paperboard materials or in films coating the inner surface of cans in the manner now practiced or that might reasonably be expected in the future.
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report. Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to determination of the acute toxicity and bioavailability of
specific iron forms. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecdotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled chronic feeding studies with most of the individual compounds, before confident appraisal can be made of their relative merts or hazards.
Several iron compounds are used in the preparation of paper and paperboard materials contacting foods or as ingredients used to hasten the drying of films used in coating the inner surface of food cans. Neither the amounts used for these purposes nor the extent to which they might migrate to foods are known to the Select Committee. However, the extent of their migration to food is believed to be very slight. The Select Committee concludes that: There is no evidence in the available information on elemental irion, ferrous sulfate, ferric chloride, ferric oxide, ferric sulfate, iron caprylate, iron linoleate, iron tallate, or the oxides of iron that dmonstrates, or suggests reasonably grounds to suspect, a hazard to the public when they are used as ingredients of paper and paperboard materials or in films coating the inner surface of cans in the manner now practiced or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Iron naphthenate | 1338-14-3 | 35 | 1980 | 5 | There is no CFR citation. |
SCOGS Opinion:
The body content of iron is regulated primarily by a controlled absorption from the intestinal tract. This absorptive mechanism normally adapts itself to the body's need for iron, thus protecting against an accumulation of iron, even when moderately excessive amounts are ingested. However, in individuals with latent or overt hemochromatosis, the normal intestinal control is defective, and iron in excess of bodily needs may accumulate in the tissues. The incidence of this rare metabolic disorder is not known. Because iron deficiency is a leading nutritional deficiency disorder in the United States and because iron fortification of foods constitues an important public health measure in correcting iron deficiency, the use of forms of irion of low bioavailability seems inappropriate for food fortification. It is evident that use of iron of low bioavailability, no matter how safe, will not satisfy the intended purpose of
fortification. For this reason, the Select Committee believes that food should be forified with iron forms of reasonably adequate bioavailability, meaning those that demonstrate by some standardized assay at least 50 percent of the bioavailability of ferrous sulfate. The avoidance of iron overload from fortified foods might be approached by limiting both the amont of added iron and the foods to which it is added. However, overall questions of iron overload are not answered in this report and deserve separate study, with due consideration for the various forms and amounts of iron intake from all sources, including vitamin-mineral supplements. Regular monitoring of the iron nutritional status of the population is essential in this connection. Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited
relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
No information is available on the metabolism or toxicity of the various substances included under the term iron naphthenate. The Select Committee concludes that: In view of the deficieny of relevant biological studies, it has insufficient data upon which to base an evaluation of iron naphthenate when it is used as an ingredient food can coating films.
SCOGS Opinion:
The body content of iron is regulated primarily by a controlled absorption from the intestinal tract. This absorptive mechanism normally adapts itself to the body's need for iron, thus protecting against an accumulation of iron, even when moderately excessive amounts are ingested. However, in individuals with latent or overt hemochromatosis, the normal intestinal control is defective, and iron in excess of bodily needs may accumulate in the tissues. The incidence of this rare metabolic disorder is not known. Because iron deficiency is a leading nutritional deficiency disorder in the United States and because iron fortification of foods constitues an important public health measure in correcting iron deficiency, the use of forms of irion of low bioavailability seems inappropriate for food fortification. It is evident that use of iron of low bioavailability, no matter how safe, will not satisfy the intended purpose of
fortification. For this reason, the Select Committee believes that food should be forified with iron forms of reasonably adequate bioavailability, meaning those that demonstrate by some standardized assay at least 50 percent of the bioavailability of ferrous sulfate. The avoidance of iron overload from fortified foods might be approached by limiting both the amont of added iron and the foods to which it is added. However, overall questions of iron overload are not answered in this report and deserve separate study, with due consideration for the various forms and amounts of iron intake from all sources, including vitamin-mineral supplements. Regular monitoring of the iron nutritional status of the population is essential in this connection. Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited
relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
Several iron compounds are used in the preparation of paper and paperboard materials contacting foods or as ingredients used to hasten the drying of films used in coating the inner surface of food cans. Neither the amounts used for these purposes nor the extent to which they might migrate to foods are known to the Select Committee. However, the extent of their migration to food is believed to be very slight. The Select committee concludes that: There is no evidence in the available information on elemental iron, ferrous sulfate, ferric chloride, ferric oxide, ferric sulfate, iron caprylate, iron linoleate, iron tallate, or the oxides of iron that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of paper and paperboard materials or in films coating the inner surface of cans in the manner now practiced or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Iron peptonate | 977009-72-5 | 35 | 1980 | 5 | There is no CFR citation. |
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report. Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to determination of the acute toxicity and bioavailability of
specific iron forms. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecdotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled chronic feeding studies with most of the individual compounds, before confident appraisal can be made of their relative merts or hazards.
Serious deficiences exist in the experimental data or clinical experience with a number of iron compounds employed or suggested as iron fortifying agents for foods. The Select Committee concludes that: In view of the deficiency of relevant biological studies, it has insufficient data upon which to base an evaluation of ferric oxide, iron peptonate, iron polyvinyl pyrrolidone, sodium ferric EDTA, sodium ferricitropyrophosphate, or ferric sodium pyrophosphate when it is used as a food ingredient.
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
Serious deficiences exist in the experimental data or clinical experience with a number of iron compounds employed or suggested as iron fortifying agents for foods. The Select Committee concludes that: In view of the deficiency of relevant biological studies, it has insufficient data upon which to base an evaluation of ferric oxide, iron peptonate, iron polyvinyl pyrrolidone, sodium ferric EDTA, sodium ferricitropyrophosphate, or ferric sodium pyrophosphate when it is used as a food ingredient.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Iron tallate | 61788-81-6 | 35 | 1980 | 1 | There is no CFR citation. |
SCOGS Opinion:
The body content of iron is regulated primarily by a controlled absorption from the intestinal tract. This absorptive mechanism normally adapts itself to the body's need for iron, thus protecting against an accumulation of iron, even when moderately excessive amounts are ingested. However, in individuals with latent or overt hemochromatosis, the normal intestinal control is defective, and iron in excess of bodily needs may accumulate in the tissues. The incidence of this rare metabolic disorder is not known. Because iron deficiency is a leading nutritional deficiency disorder in the United States and because iron fortification of foods constitues an important public health measure in correcting iron deficiency, the use of forms of irion of low bioavailability seems inappropriate for food fortification. It is evident that use of iron of low bioavailability, no matter how safe, will not satisfy the intended purpose of
fortification. For this reason, the Select Committee believes that food should be forified with iron forms of reasonably adequate bioavailability, meaning those that demonstrate by some standardized assay at least 50 percent of the bioavailability of ferrous sulfate. The avoidance of iron overload from fortified foods might be approached by limiting both the amont of added iron and the foods to which it is added. However, overall questions of iron overload are not answered in this report and deserve separate study, with due consideration for the various forms and amounts of iron intake from all sources, including vitamin-mineral supplements. Regular monitoring of the iron nutritional status of the population is essential in this connection. Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited
relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
Several iron compounds are used in the preparation of paper and paperboard materials contacting foods or as ingredients used to hasten the drying of films used in coating the inner surface of food cans. Neither the amounts used for these purposes nor the extent to which they might migrate to foods are known to the Select Committee. However, the extent of their migration to food is believed to be very slight. The Select committee concludes that: There is no evidence in the available information on elemental iron, ferrous sulfate, ferric chloride, ferric oxide, ferric sulfate, iron caprylate, iron linoleate, iron tallate, or the oxides of iron that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of paper and paperboard materials or in films coating the inner surface of cans in the manner now practiced or that might reasonably be expected in the future.
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report. Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to determination of the acute toxicity and bioavailability of
specific iron forms. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecdotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled chronic feeding studies with most of the individual compounds, before confident appraisal can be made of their relative merts or hazards.
Several iron compounds are used in the preparation of paper and paperboard materials contacting foods or as ingredients used to hasten the drying of films used in coating the inner surface of food cans. Neither the amounts used for these purposes nor the extent to which they might migrate to foods are known to the Select Committee. However, the extent of their migration to food is believed to be very slight. The Select Committee concludes that: There is no evidence in the available information on elemental irion, ferrous sulfate, ferric chloride, ferric oxide, ferric sulfate, iron caprylate, iron linoleate, iron tallate, or the oxides of iron that dmonstrates, or suggests reasonably grounds to suspect, a hazard to the public when they are used as ingredients of paper and paperboard materials or in films coating the inner surface of cans in the manner now practiced or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Isopropyl citrate | 39413-05-3 | 84 | 1977 | 1 | 184.1386 |
SCOGS Opinion:
The citrate ion is widely distributed in plants and animals and is a naturally occurring component of the diet. It is a common metabolite in oxidative metabolism and an important component of bone. Exogenous citrate administered to infants and adults as a component of commonly consumed diets is considered completely metabolizable. The addition of citric acid to foods is considered equivalent to adding citrate salts except in foods of very high acidity. The amount of citrate added to foods by foods processors is about 500mg per person per day. This amount occurs naturally in 2 ounces of orange juice and does not constitute a significant addition to the total body load. Although data on acute and chronic effects of orally administered sodium citrate, calcium citrate and potassium citrate are limited, no biological effects of the citrate-containing substances evaluated in this report cause concern about the safety of these GRAS
substances used in reasonable amounts and in accordance with prescribed tolerances and limitations.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on citric acid, sodium citrate, potassium citrate, calcium citrate, ammonium citrate, isopropyl citrate, stearyl citrate, and triethyl citrate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Japan wax is a substance of plant origin which is generally recognized as safe (GRAS) as a substance migrating to food from cotton and cotton fabrics used in dry food packaging. However, the Select Committee has found no information on the acute toxicity of this substance, or reports of long-term feeding studies, or studies of its carcinogenicity or teratogenicity. In view of the almost complete lack of biological studies, the Select Committee has insufficient data upon which to evaluate the safety of Japan max as a substance migrating to food from cotton and cotton fabrics used in dry foods packaging.
SCOGS Opinion:
Tartrates occur naturally in many fruits and high concentrations are found in wine. Consumer exposure data suggest that about 6mg each of tartaric acid and potassium acid tartrate added to foods are ingested daily per capita (a total of about 0.2mg per kg in an adult). The literature indicates that there are no differences in the biological effects of the several tartrates added to food and that their toxicity is dose related. Studies using modern tracer techniques would be helpful in ascertaining the extent of absortion and metabolic fate of ingested tartrates.
Tartrates are reported to elicit nephritic lesions in several animal species, but ususally only after parenteral injection of very large doses. Daily ingestion of 2.3g per kg of body weight per day for 150 days produced no ill effects in rabbits. No toxicity was found in rats ingesting up to 1.2g per kg of body weight of tartaric acid in the diet daily for 2 years. The daily intake of tartrates added to foods is orders of magnitude below that which could be expected to cause toxicity in man.
In light of the above, the Select Committe concludes that: There is no evidence in the available information on L(+) potassium acid tartrate, L(+) sodium potassium tartrate acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current, or that might reasonably be expected in the future.
SCOGS Opinion:
Tartrates occur naturally in many fruits and high concentrations are found in wine. Consumer exposure data suggest that about 6mg each of tartaric acid and potassium acid tartrate added to foods are ingested daily per capita (a total of about 0.2mg per kg in an adult). The literature indicates that there are no differences in the biological effects of the several tartrates added to food and that their toxicity is dose related. Studies using modern tracer techniques would be helpful in ascertaining the extent of absortion and metabolic fate of ingested tartrates.
Tartrates are reported to elicit nephritic lesions in several animal species, but ususally only after parenteral injection of very large doses. Daily ingestion of 2.3g per kg of body weight per day for 150 days produced no ill effects in rabbits. No toxicity was found in rats ingesting up to 1.2g per kg of body weight of tartaric acid in the diet daily for 2 years. The daily intake of tartrates added to foods is orders of magnitude below that which could be expected to cause toxicity in man.
In light of the above, the Select Committe concludes that: There is no evidence in the available information on L(+) potassium acid tartrate, L(+) sodium potassium tartrate acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current, or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| L(+) tartaric acid | 87-69-4 | 107 | 1979 | 1 | 184.1099 |
SCOGS Opinion:
Tartrates occur naturally in many fruits and high concentrations are found in wine. Consumer exposure data suggest that about 6mg each of tartaric acid and potassium acid tartrate added to foods are ingested daily per capita (a total of about 0.2mg per kg in an adult). The literature indicates that there are no differences in the biological effects of the several tartrates added to food and that their toxicity is dose related. Studies using modern tracer techniques would be helpful in ascertaining the extent of absortion and metabolic fate of ingested tartrates.
Tartrates are reported to elicit nephritic lesions in several animal species, but ususally only after parenteral injection of very large doses. Daily ingestion of 2.3g per kg of body weight per day for 150 days produced no ill effects in rabbits. No toxicity was found in rats ingesting up to 1.2g per kg of body weight of tartaric acid in the diet daily for 2 years. The daily intake of tartrates added to foods is orders of magnitude below that which could be expected to cause toxicity in man.
In light of the above, the Select Committe concludes that: There is no evidence in the available information on L(+) potassium acid tartrate, L(+) sodium potassium tartrate acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current, or that might reasonably be expected in the future.
SCOGS Opinion:
Lactic acid is produced in varying amounts by most living tissues as a normal metabolic intermediate. The lactate turnover rate in man has been estimated to be of the order of 2g per kg per day.
An additional load of up to 1 mg per kg per day of lactic acid as the free acid or as calcium lactate contained in commercially prepared food commodities would not appreciably modify the normal metabolic processes. None of the limited toxicity data available raises any suspicion of adverse effects in adults at doses orders of magnitude above the estimated levels of human consumption. There is no indication that the per capita intake of lactate from processed foods will be substantially increased in the foreseeable future.
There is no evidence of potential toxicity of the L-isomer for individuals of any age. However, premature infants fed formulas acidified with DL-lactic acid (or, in one instance, D(-) lactic acid), have reported to develop metabolic acidosis and growth retardation. Results of studies of full-term infants are conflicting and difficult to interpret. Resolution of this conflict is needed even though, as far as the Select Committee is aware, lactic acid acidification of infant formulas is not currently being practiced in the United States except in products designed for special dietary or therapeutic purposes which are not being evaluated in this report.
In the light of these considerations, the Select Committee concludes that:
There is no evidence in the available information on L(+) calcium lactate that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on either of the isomers of lactic acid, their calcium salts, and their racemates that demonstrates or suggests reasonable ground to suspect a hazard to individuals beyond infancy when they are used at levels that are now current or thar might reasonably be expected in the future.
There evidence on D(-)-lactic acid, DL-lactic acid and their calcium salts is insufficient to determine that the adverse effects reported would not be deleterious to infants should they be used in infant formulas. Lactic acid acidification of generally available infant formulas is not now being practiced in the United States.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| L(+)-lactic acid | 79-33-4 | 116 | 1978 | 1 | 184.1061 |
SCOGS Opinion:
Lactic acid is produced in varying amounts by most living tissues as a normal metabolic intermediate. The lactate turnover rate in man has been estimated to be of the order of 2g per kg per day.
An additional load of up to 1 mg per kg per day of lactic acid as the free acid or as calcium lactate contained in commercially prepared food commodities would not appreciably modify the normal metabolic processes. None of the limited toxicity data available raises any suspicion of adverse effects in adults at doses orders of magnitude above the estimated levels of human consumption. There is no indication that the per capita intake of lactate from processed foods will be substantially increased in the foreseeable future.
There is no evidence of potential toxicity of the L-isomer for individuals of any age. However, premature infants fed formulas acidified with DL-lactic acid (or, in one instance, D(-) lactic acid), have reported to develop metabolic acidosis and growth retardation. Results of studies of full-term infants are conflicting and difficult to interpret. Resolution of this conflict is needed even though, as far as the Select Committee is aware, lactic acid acidification of infant formulas is not currently being practiced in the United States except in products designed for special dietary or therapeutic purposes which are not being evaluated in this report.
In the light of these considerations, the Select Committee concludes that:
There is no evidence in the available information on L(+) calcium lactate that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on either of the isomers of lactic acid, their calcium salts, and their racemates that demonstrates or suggests reasonable ground to suspect a hazard to individuals beyond infancy when they are used at levels that are now current or thar might reasonably be expected in the future.
There evidence on D(-)-lactic acid, DL-lactic acid and their calcium salts is insufficient to determine that the adverse effects reported would not be deleterious to infants should they be used in infant formulas. Lactic acid acidification of generally available infant formulas is not now being practiced in the United States.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Lactic acid | 598-82-3 | 116 | 1978 | 1,4 | There is no CFR citation. |
SCOGS Opinion:
Lactic acid is produced in varying amounts by most living tissues as a normal metabolic intermediate. The lactate turnover rate in man has been estimated to be of the order of 2g per kg per day.
An additional load of up to 1 mg per kg per day of lactic acid as the free acid or as calcium lactate contained in commercially prepared food commodities would not appreciably modify the normal metabolic processes. None of the limited toxicity data available raises any suspicion of adverse effects in adults at doses orders of magnitude above the estimated levels of human consumption. There is no indication that the per capita intake of lactate from processed foods will be substantially increased in the foreseeable future.
There is no evidence of potential toxicity of the L-isomer for individuals of any age. However, premature infants fed formulas acidified with DL-lactic acid (or, in one instance, D(-) lactic acid), have reported to develop metabolic acidosis and growth retardation. Results of studies of full-term infants are conflicting and difficult to interpret. Resolution of this conflict is needed even though, as far as the Select Committee is aware, lactic acid acidification of infant formulas is not currently being practiced in the United States except in products designed for special dietary or therapeutic purposes which are not being evaluated in this report.
In the light of these considerations, the Select Committee concludes that:
There is no evidence in the available information on L(+) calcium lactate that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on either of the isomers of lactic acid, their calcium salts, and their racemates that demonstrates or suggests reasonable ground to suspect a hazard to individuals beyond infancy when they are used at levels that are now current or thar might reasonably be expected in the future.
There evidence on D(-)-lactic acid, DL-lactic acid and their calcium salts is insufficient to determine that the adverse effects reported would not be deleterious to infants should they be used in infant formulas. Lactic acid acidification of generally available infant formulas is not now being practiced in the United States.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Lard (packaging) | 61789-99-9 | 91 | 1976 | 1 | 182.70 |
SCOGS Opinion:
Lard has been consumed in pork, as an ingredient in foods, or has been added to food as the result of frying, for centuries. Aside from the implication of all animal fats as contributors to atherosclerosis, no deleterious effects have been recorded. Some adverse effects observed in experimental animals can be ascribed to very high levels of fat in the diet rather than to specific effects of lard. Such high dietary levels of lard or lard oil are unlikely to occur in the diet of man. Moreover, the amount of lard or lard oil , is obviously minute compared to the amounts of lard ingested in food.
In the light of these considerations, the Select Committee concludes that: There is no evidence in the available information on lard and lard oil that demonstrates, or suggests reasonable grounds to suspect a hazard to the public when they are used in cotton and cotton fabric dry food packaging materials as now practiced or as they might reasonably be expected to be used for such purposes in the future.
SCOGS Opinion:
Lard has been consumed in pork, as an ingredient in foods, or has been added to food as the result of frying, for centuries. Aside from the implication of all animal fats as contributors to atherosclerosis, no deleterious effects have been recorded. Some adverse effects observed in experimental animals can be ascribed to very high levels of fat in the diet rather than to specific effects of lard. Such high dietary levels of lard or lard oil are unlikely to occur in the diet of man. Moreover, the amount of lard or lard oil , is obviously minute compared to the amounts of lard ingested in food.
In the light of these considerations, the Select Committee concludes that: There is no evidence in the available information on lard and lard oil that demonstrates, or suggests reasonable grounds to suspect a hazard to the public when they are used in cotton and cotton fabric dry food packaging materials as now practiced or as they might reasonably be expected to be used for such purposes in the future
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| L-ascorbic acid | 50-81-7 | 59 | 1979 | 1 | 182.3013, 182.8013 |
SCOGS Opinion:
L-ascorbic acid, vitamin C, occurs in nutritionally significant amounts as a natural constituent of many fruits, vegetables, berries, and melons. As a vitamin it is needed in the diet of all age groups. L-ascorbic acid and its sodium salt are antioxidants and they are extensively used as preservatives, color stabilizers and for related functions in various foods and beverages. Calcium ascorbate and ascorbyl palmitate, a derivative of ascorbic acid having greater fat solubility, also are anti-oxidants, but appear not to have significant use in processed foods. In addition to their use in foods as antioxidants, L-ascorbic acid and its salts are added to some foods as a source of vitamin C. These sources constitute a significant proportion of the total ascorbate intake of the general population. Erythorbic acid (D-isoascorbic acid), a stereoisomer of L-ascorbic acid, and its sodium salt, also are effective antioxidants and are used for this purpose in a number of food products. The
quantities used in 1970 were substantially less than for the ascorbates. The vitamin activity of erythorbates is only one -twentieth that of ascorbic acid, and their anti-oxidant effectiveness is not greater than for the ascorbates. For this reason, it would seem desirable, where possible, to use L-ascorbic acid rather than erythorbic acid as an antioxidant. From studies in guinea pigs and man it can be concluded that although erythorbic acid shares the same absorption and tissue uptake system as ascorbic acid it has little antiscorbutic activity. Although competition between ascorbic acid and erythorbic acid has been demosntrated at a biochemical level, there is no firm evidence that such competition will produce a scorbutic state. Whether this biochemical interaction could result in a clinically significant depletion of ascorbic acid remains to be established. Both short- and long-term toxicity studies have demonstrated tolerance without adverse effects for large amounts of orally
administered L-ascorbic acid, sodium L-ascorbate, and erythorbic acid in several species including mice, rats, guinea pigs, rabbits, and dogs. A substantial number of short-term experiments with human subjects ingesting 1 to 4 g of ascorbate daily have generally not revealed any harmful effects. Some subjects have received higher amounts, up to at least 8 to 10 g per day. In most instances no untoward results have been noted. But there is marked paucity of such studies that were well controlled and in which inquiring attention was given to possible harmful effects. In due course, such studies would be desirable. In the various studies on the effect of ingesting excessive amounts of ascorbates, attention has been focused on questions including oxalate excretion and renal tract stones, effets on the utilization of copper, iron, and other metals, need for vitamin B12, blood coagulation,and reproductive performance. The findings indicate that the tolerance to excessive amounts of ascorbic
acid and its sodium salt is high. Several investigators have reported the development of dependency in animals and human after ingestion of large amounts of ascorbates for extended time periods; however, the levels of ascorbates added to foods by 1 to 3 orders of magnitude. It is notable that no data have been found concerning the possible effects of ascorbyl palmitate and calcium ascorbate in humans, and there is practically no information regarding the latter in animals. Information concerning ascorbyl palmitate in animals is almost as limited. The few meaningful experiments suggest that ascorbyl palmitate is tolerated about the same as ascorbic acid and sodium ascorbate. This should be expected. It is reasonable to assume that the tolerance to calcium ascorbate is approximately the same as for sodium ascorbate and this is a high level. In view of the foregoing, The Select Committee concludes that: There is no evidence in the available information on L-ascorbic acid, sodium
L-ascorbate, calcium L-ascorbate, ascorbyl palmitate (palmitoyl L-ascorbic), erythorbic acid (D-isoascorbic acid), and sodium erythorbate (sodium D-isoascorbate) that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used as food ingredients at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Lecithin | 8002-43-5 | 106 | 1979 | 1 | 184.1400 |
SCOGS Opinion:
Food grade lecithin is a complex mixture of substances derived from the processing of soybean, corn, or safflower oil. Almost all of the lecithin of commerce is derived from soybeans. Phosphoglycerides, the major constituents of lecithin, are present throughout the body as chief components of cell membranes; significant amounts are also present in bile and plasma. The major phosphoglycerides found in soy lecithin can be catabolized and also synthesized de novo in mammalian systems. Commercial lecithin may contain up to 35 percent triglycerides; these compounds occur naturally in the diet and are also catabolized and synthesized in man. The average daily consumption of lecithin added to foods by manufacturers in 1970, based on the total amount reported to be used, was 92mg, amounting to about 1.5mg per kg body weight for adults. The corresponding figure for lecithin bleached with hydrogen peroxide was probably less than 4mg,
about 0.07mg per kg. Thus, the lecithin added to foods amounts to only 2 to 10 percent of the 1 to 5g of phosphoglycerides consumed daily as natural constituents of the diet. A 2 year feeding study with rats given 1400mg lecithin per kg bodyweight daily (equivalent to a human dose of about 84g daily) showed no adverse effects except for an increased incidence of parathyroid hyperplasia. The parathyroid hyperplasia seen in the rats probably resulted form the increased phosphate load in the diet. No adverse effects have been noted in volunteers taking 20g or more of lecithin daily for several months. The Select Committe is not aware of any animal feeding studies with "food grade" bleached lecithin. Similarly, there appear to be no studies identifying the reaction products of lecithin bleached with hydrogen peroxide. However, in another report,the Select Committee reviewed studies of animals fed compounds which conceivably could form as a result of hydrogen peroxide oxidation of
unsaturated fatty acids. Limited feeding studies indicate these compounds are not carcinogenic when given orally and are toxic only at doses orders of magnitude greater than could be expected from the addition to food of lecithin bleached with hydrogen peroxide.
No specifications are listed in the Food Chemicals Codex for the peroxide value of lecithin bleached with hydrogen peroxide; the Select Committee believes such specifications should be developed.
In the light of these considerations, the Select Committee concludes that: There is no evidence in the available information on lecithin and lecithin bleached with hydrogen peroxide that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Food grade lecithin is a complex mixture of substances derived from the processing of soybean, corn, or safflower oil. Almost all of the lecithin of commerce is derived from soybeans. Phosphoglycerides, the major constituents of lecithin, are present throughout the body as chief components of cell membranes; significant amounts are also present in bile and plasma. The major phosphoglycerides found in soy lecithin can be catabolized and also synthesized de novo in mammalian systems. Commercial lecithin may contain up to 35 percent triglycerides; these compounds occur naturally in the diet and are also catabolized and synthesized in man. The average daily consumption of lecithin added to foods by manufacturers in 1970, based on the total amount reported to be used, was 92mg, amounting to about 1.5mg per kg body weight for adults. The corresponding figure for lecithin bleached with hydrogen peroxide was probably less than 4mg,
about 0.07mg per kg. Thus, the lecithin added to foods amounts to only 2 to 10 percent of the 1 to 5g of phosphoglycerides consumed daily as natural constituents of the diet. A 2 year feeding study with rats given 1400mg lecithin per kg bodyweight daily (equivalent to a human dose of about 84g daily) showed no adverse effects except for an increased incidence of parathyroid hyperplasia. The parathyroid hyperplasia seen in the rats probably resulted form the increased phosphate load in the diet. No adverse effects have been noted in volunteers taking 20g or more of lecithin daily for several months. The Select Committe is not aware of any animal feeding studies with "food grade" bleached lecithin. Similarly, there appear to be no studies identifying the reaction products of lecithin bleached with hydrogen peroxide. However, in another report,the Select Committee reviewed studies of animals fed compounds which conceivably could form as a result of hydrogen peroxide oxidation of
unsaturated fatty acids. Limited feeding studies indicate these compounds are not carcinogenic when given orally and are toxic only at doses orders of magnitude greater than could be expected from the addition to food of lecithin bleached with hydrogen peroxide.
No specifications are listed in the Food Chemicals Codex for the peroxide value of lecithin bleached with hydrogen peroxide; the Select Committee believes such specifications should be developed.
In the light of these considerations, the Select Committee concludes that: There is no evidence in the available information on lecithin and lecithin bleached with hydrogen peroxide that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| L-Glutamic acid | 56-86-0 | 37a | 1980 | 2 | 182.1045 |
SCOGS Opinion:
The Select Committee notes that the new information on long-term oral administration of monosodium glutamate (MSG) is the diet to varios animal species has revealed no adverse effects, while data showing neuropathological lesions in neonatal animals resulting from subcutaneous or forced oral dosing of MSG has thus far been confirmed only in rodents. The administration of protein or carbohydrate products concurrently with MSG has been shown to lower plasma glutamate levels, and in two recent studies, to reduce the incidence of hypothalamic lesions in mice. In pregnant monkeys, glutamate does not appear to readily cross the placental barrier. From comparisons of plasma glutamate levels, healthy term and premature infants have already developed the capability to metabolize glutamates. Ingestion of MSG solutions has been demostrated to cause transient clinical symptoms resembling those of "Chinese Restaurant Syndrome" and there is
evidence that some individuals may respond to relatively small doses. Similar symptoms can be evoked by certain other food substances. The use of MSG in restaurant and/or home-prepared foods not fall within the purview of the Select Committee since it is limited in its considerations to the use of glutamates as ingredients of processed foods. According to industry sources, MGS is not added to infant and junior foods. Because, however, a proportion of the consuming public may be sensitive acute responders, even though the unpleasant symptoms are transient, the Selected Committee believes there should be some constraint placed on the addition of MSG to pocessed foods.
In light of the foregoing studies on the biological effects of monosodium glutamate and the information considered in its previous report on glutamates, the Select Committee concludes that: There is no evidence in the available information on L-glutamic acid, L-glutamic acid hydrochloride, monosodium L-glutamate, monoammonium L-glutamate, and monopotassium L-glutamate that demonstrates, or suggests reasonable grounds to suspects, a hazard to the public when they are used at levels that are now current and in the manner now practices. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
The Select Committee notes that the new information on long-term oral administration of monosodium glutamate (MSG) is the diet to varios animal species has revealed no adverse effects, while data showing neuropathological lesions in neonatal animals resulting from subcutaneous or forced oral dosing of MSG has thus far been confirmed only in rodents. The administration of protein or carbohydrate products concurrently with MSG has been shown to lower plasma glutamate levels, and in two recent studies, to reduce the incidence of hypothalamic lesions in mice. In pregnant monkeys, glutamate does not appear to readily cross the placental barrier. From comparisons of plasma glutamate levels, healthy term and premature infants have already developed the capability to metabolize glutamates. Ingestion of MSG solutions has been demostrated to cause transient clinical symptoms resembling those of "Chinese Restaurant Syndrome" and there is
evidence that some individuals may respond to relatively small doses. Similar symptoms can be evoked by certain other food substances. The use of MSG in restaurant and/or home-prepared foods not fall within the purview of the Select Committee since it is limited in its considerations to the use of glutamates as ingredients of processed foods. According to industry sources, MGS is not added to infant and junior foods. Because, however, a proportion of the consuming public may be sensitive acute responders, even though the unpleasant symptoms are transient, the Selected Committee believes there should be some constraint placed on the addition of MSG to pocessed foods.
In light of the foregoing studies on the biological effects of monosodium glutamate and the information considered in its previous report on glutamates, the Select Committee concludes that: There is no evidence in the available information on L-glutamic acid, L-glutamic acid hydrochloride, monosodium L-glutamate, monoammonium L-glutamate, and monopotassium L-glutamate that demonstrates, or suggests reasonable grounds to suspects, a hazard to the public when they are used at levels that are now current and in the manner now practices. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
Orally administered licorice and licorice derivatives are absorbed to some extent and the principal metabolic products are excreted through the bile, but most of an ingested dose is hydrolyzed in the digestive tract and the products excreted through the feces. Acute and short-term substances of a very low order of toxicity, capable of eliciting a variety of pharmacological effects but only at levels considerably higher than are likely to be achieved in usual diets. None of these effects suggests cause for convern at current or foreseeable dietary levels of consumption. However, the capacity of licorice and licorice derivatives to elicit transitory hypertensive effects, at higher dosage levels in animals and man, requires more definitive clarification as far as its practical implications are concerned. This would be particularly important for the unknown number but probably few individuals who may indulge themselves with excessive
intakes of licorice-containing candies and/or beverages. The Select Committee has found no long-term toxicological data on licorice-related products administered to animals or man. Until the long-term as well as the acute dose relationships of the hypertensive effect are clarified, it appears inappropriate to conclude that unrestricted use of licorice and licorice derivatives in food would be without hazard to consumers in general. In the light of the foregoing and the information elsewhere in this report, the Select Committee concludes that: There is no evidence in the available information on licorice, glycyrrhiza, and ammoniated glycyrrhizin that demonstrates or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Linoleic acid | 60-33-3 | 65 | 1975 | 1 | 184.1065 |
SCOGS Opinion:
Coconut oil, peanut oil, oleic acid, and linoleic acid have been used as foods or as food components by man for many years. These two oils and the fatty acids are rapidly absorbed after oral administration, metabolized, and the metabolic products are utilized and excreted. None of the available biological information indicates that these substances are hazardous to man or animals even when consumed at levels that are orders of magnitude greater than could result form their use for the purposes covered in this report. The evidence now available indicates that linoleic acid is not being used by the food industry as a nutrient or dietary supplement. Based on these considerations, the Select Commitee concludes that: There is no evidence in the available information on coconut oil, peanut oil, and oleic acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public as they are now used in paper and cotton
packaging material for food at levels now current or as they might reasonably be expected to be used for such purposes in the future. There is no evidence in the available information on linoleic acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used as a nutruient or dietary supplement at levels now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| L-malic acid | 617-48-1 | 56 | 1975 | 1 | 184.1069 |
SCOGS Opinion:
In view of the natural occurrence of L-malic acid in a variety of fruits, vegetables, and certain other foods, its important role in intermediary metabolism as a component of the Krebs cycle, rather detailed knowledge of its formation and metabolism in animals and plants, its relatively low toxicity when given orally to animals, and its specialized uses in foods and nonalcoholic beverages as an acidulant or flavoring agent, there is no scientific basis for suspecting that the amounts of L-malic acid now added to foods would be hazardous. There is no indication that malic acid is added to any foods specifically designed for infant feeding. The scientific literature is less satisfactory on D-malic acid, the unnatural isomer, and a co-constituent of the racemic DL-malic acid, which is the form now used as a food additive. Very little is known about the metabolism, absorption, excretion, and biological effects of D-malic acid, or
whether animal species differ in the way they can utilize and tolerate this compound. DL-malic acid was employed in several of the toxicological, reproductive, and teratological studies; results suggests that D-malic acid as a component of DL-malic acid, is not likely to have adverse effects. Some concern has been expressed about the ability of young infants to metabolize D-malic acid, but fortunately, in current practice, this dose not pose a problem since DL-malic acid is not now added to infant foods. The Select Committee has weighed the foregoing and concludes: For individuals beyond the age of infancy, there is no evidence in the available information on L-malic acid and DL-malic acid that demosntrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Magnesium is a dietary essential. It is involved in myriad metabolic reactions and is necessary for the activity of many intracellular enzymes. Also, with certain other cations, it is important in electrolyte balance. Magnesium is present in fruits, vegetables, grains, milk, meat and fish and the natural content of these foods is the major source of the current dietary intake. The Food and Nutrition Board, NRC, has recommended that cereal grain products be fortified with magnesium in view of potential risk of deficiency among significant segments of the population. The usual adult intake is about 300mg or less per day from all sources and the contribution of food additives to total magnesium intake is very small. The administration of magnesium sulfate in very high doses to humans occasionally has resulted in severe and even fatal episodes, especially in the presence of pre-existing disease. These occurrences should not be prejudicial to the use of magnesium salts as foods ingredients
since the dosages given were orders of magnitude greater than the daily intake of magnesium added to food. While chronic toxicity data are lacking, the status of magnesium as a ubiquitous and essential dietary ingredient for the maintenance of homeostatic and bioenergetic mechanisms leads to the opinion that none of the available evidence suggests any probable hazard when any of the GRAS compounds of magnesium is used as a food ingredient. In view of the foregoing, The Select Committee concludes that: There is no evidence in the available information on magnesium carbonate, magnesium chloride, magnesium sulfate, magnesium hydroxide, magnesium oxide, magnesium stearate, dibasic magnesium phosphate and tribasic magnesium phosphate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced, or which might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Magnesium chloride | 7786-30-3 | 60 | 1979 | 1 | 184.1426 |
SCOGS Opinion:
Magnesium is a dietary essential. It is involved in myriad metabolic reactions and is necessary for the activity of many intracellular enzymes. Also, with certain other cations, it is important in electrolyte balance. Magnesium is present in fruits, vegetables, grains, milk, meat and fish and the natural content of these foods is the major source of the current dietary intake. The Food and Nutrition Board, NRC, has recommended that cereal grain products be fortified with magnesium in view of potential risk of deficiency among significant segments of the population. The usual adult intake is about 300mg or less per day from all sources and the contribution of food additives to total magnesium intake is very small. The administration of magnesium sulfate in very high doses to humans occasionally has resulted in severe and even fatal episodes, especially in the presence of pre-existing disease. These occurrences should not be prejudicial to the use of magnesium salts as foods ingredients
since the dosages given were orders of magnitude greater than the daily intake of magnesium added to food. While chronic toxicity data are lacking, the status of magnesium as a ubiquitous and essential dietary ingredient for the maintenance of homeostatic and bioenergetic mechanisms leads to the opinion that none of the available evidence suggests any probable hazard when any of the GRAS compounds of magnesium is used as a food ingredient. In view of the foregoing, The Select Committee concludes that: There is no evidence in the available information on magnesium carbonate, magnesium chloride, magnesium sulfate, magnesium hydroxide, magnesium oxide, magnesium stearate, dibasic magnesium phosphate and tribasic magnesium phosphate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced, or which might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Magnesium gluconate | 3632-91-5 | 78 | 1978 | 1 | There is no CFR citation. |
SCOGS Opinion:
Gluconates are useful as nutritional supplements since their high solubility allows relatively rapid absorption of the cations. Evidence suggests that any possible toxicity is a function of the cation rather than of the gluconate portion of these substances. Thus, the acute toxic responses to the various gluconate salts are comparable with other salts of the same metals and long-term toxicities seem related to the tissue deposition of these metals. These observations could have been anticipated because gluconic acid is a normal metabolic product of glucose. The amount of gluconic acid produced endogenously is many times greater than the largest amounts likely to be consumed from food. Because the toxicological activities of these gluconates appear to be a function of their cationic components, safe and acceptable levels in foods are limited only by the nature of the specific cations. There is no evidence in the available
information on sodium gluconate, potassium gluconate, magnesium gluconate, and zinc gluconate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Magnesium is a dietary essential. It is involved in myriad metabolic reactions and is necessary for the activity of many intracellular enzymes. Also, with certain other cations, it is important in electrolyte balance. Magnesium is present in fruits, vegetables, grains, milk, meat and fish and the natural content of these foods is the major source of the current dietary intake. The Food and Nutrition Board, NRC, has recommended that cereal grain products be fortified with magnesium in view of potential risk of deficiency among significant segments of the population. The usual adult intake is about 300mg or less per day from all sources and the contribution of food additives to total magnesium intake is very small. The administration of magnesium sulfate in very high doses to humans occasionally has resulted in severe and even fatal episodes, especially in the presence of pre-existing disease. These occurrences should not be prejudicial to the use of magnesium salts as foods ingredients
since the dosages given were orders of magnitude greater than the daily intake of magnesium added to food. While chronic toxicity data are lacking, the status of magnesium as a ubiquitous and essential dietary ingredient for the maintenance of homeostatic and bioenergetic mechanisms leads to the opinion that none of the available evidence suggests any probable hazard when any of the GRAS compounds of magnesium is used as a food ingredient. In view of the foregoing, The Select Committee concludes that: There is no evidence in the available information on magnesium carbonate, magnesium chloride, magnesium sulfate, magnesium hydroxide, magnesium oxide, magnesium stearate, dibasic magnesium phosphate and tribasic magnesium phosphate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced, or which might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Magnesium oxide | 1309-48-4 | 60 | 1979 | 1 | 184.1431 |
SCOGS Opinion:
Magnesium is a dietary essential. It is involved in myriad metabolic reactions and is necessary for the activity of many intracellular enzymes. Also, with certain other cations, it is important in electrolyte balance. Magnesium is present in fruits, vegetables, grains, milk, meat and fish and the natural content of these foods is the major source of the current dietary intake. The Food and Nutrition Board, NRC, has recommended that cereal grain products be fortified with magnesium in view of potential risk of deficiency among significant segments of the population. The usual adult intake is about 300mg or less per day from all sources and the contribution of food additives to total magnesium intake is very small. The administration of magnesium sulfate in very high doses to humans occasionally has resulted in severe and even fatal episodes, especially in the presence of pre-existing disease. These occurrences should not be prejudicial to the use of magnesium salts as foods ingredients
since the dosages given were orders of magnitude greater than the daily intake of magnesium added to food. While chronic toxicity data are lacking, the status of magnesium as a ubiquitous and essential dietary ingredient for the maintenance of homeostatic and bioenergetic mechanisms leads to the opinion that none of the available evidence suggests any probable hazard when any of the GRAS compounds of magnesium is used as a food ingredient. In view of the foregoing, The Select Committee concludes that: There is no evidence in the available information on magnesium carbonate, magnesium chloride, magnesium sulfate, magnesium hydroxide, magnesium oxide, magnesium stearate, dibasic magnesium phosphate and tribasic magnesium phosphate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced, or which might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Magnesium silicate | 1343-88-0 | 61 | 1979 | 1 | 182.2437 |
SCOGS Opinion:
Silicon dioxide and various silicates occur abundantly in the earth's crust, are present in practically all natural waters,animals, and plants, and are part of the normal human diet. The question of whether or not silicon is an essential human nutrient remains unresolved. Silicon compounds consumed as added food ingredients contribute only a minor proportion of the total dietary silicon intake. The estimated possible human intake of sodium aluminosilicate, the predominant silicate added to foods in this country, is approximately 0.3mg per kg body weight per day. Silicon compounds that are GRAS for use as direct food ingredient, except potassium and sodium silicates, are insoluble or very slightly soluble in water and appear to be biologically inert. The water-soluble silicates are also of low acute toxicity. The acute oral LD50 in rats of sodium aluminosilicate is >1g per kg. No significant tissue accumulation, pathology, or
toxicity has been reported from the ingestion of those insoluble or very slightly soluble GRAS silicon compounds for which data are available. Of the five substances that were reported as added to foods in the NRC survey, biologic effects and safety data are available for all except sodium calcium aluminosilicate, and there is no reason to suspect that the toxicity of the latter would differ from those for which there are data. The results of two studies (1967-1970) in which various silicon compounds were fed to laboratory animals for 1 mo at a level of 0.8g per kg body weight (as silicon dioxide) and for 3 mo at levels of 6 to 30 mg per kg body weight suggests there may be a species-related susceptibility to renal damage from ingestion of sodium silicate, magnesium trisilicate, and finely ground quartz. No substantiating reports of these effects have appeared. Magnesium trisilicate was recognized as safe for prolonged use in human ingestion in large amount as a component of antacid
preparations by the Advisory Review Panel on Over-the-Counter Drugs, and the available evidence on the acute toxicity of sodium silicate indicates that it is low. Consumption data are lacking for aluminium calcium silicate and tricalcium silicate, two compounds that are listed as GRAS for use as anticaking agents. However, their use in keeping with good manufacturing practice and in currently regulated amounts would be of the same order of magnitude as the other GRAS silicates. In addition, the Select Committee has limited information on the amounts of talc that are currently used in foods. However a major food use of talc is in the coating of rice. Assuming package label statements are ignored and coated rice is not washed prior to cooking and no other losses occur, maximun per capita intake of talc from this source appears to be 0.5g per day. With respect to paper and cotton food- packaging products, the possibility is remote that biologically significant amounts of talc,
diatomaceous earth, or sodium silicate migrate to food from packaging, materials containing these substances. Perlite, a naturally occuring polysilicate substance, has an oral LD50 in the rat of >10g per kg body weight. Estimates of the maximun quantities of minerals that might be extracted from perlite and diatomaceous earth used as filteraids in food processing indicates no hazard to public health. There are no food grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc. Such specifications for the substances used in foods are desirable. Specification for food grade talc should limit the content of asbestos fibers even though the potential hazard of ingested asbestos fibers even though the potential hazard of ingested asbestos is not clearly established. The Food and Drug Administration is sponsoring the development of an assay method for asbestos fibers. An upper limit for cadmium should be added to the specifications for food-grade perlite, and
consideration should be given to the need for limitation of cadmium content of other silicates. In the light of all of the foregoing, the Select Committee concludes that: It is essential to establish food-grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc, with provision for an upper limit of asbestos fibers in talc. There is no evidence in the available information on aluminum calcium silicate, calcium silicate, magnesium silicate, potassium silicate, sodium silicate, sodium aluminosilicate, sodium calcium aluminosilicate, tricalcium silicate, silica aerogel, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on diatomaceous earth, silicon dioxides, sodium silicate, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the
public when they are used as ingredients of paper and paperboard products used in food packaging in accordance with current practice. There is no evidence in the available information on sodium silicate and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of cotton and cotton fabrics used in dry food packaging in accordance with current practice. There is no evidence in the available information on diatomaceous earth and perlite that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used as filteraids in food processing at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Magnesium stearate | 557-04-0 | 60 | 1979 | 1 | 184.1440 |
SCOGS Opinion:
Magnesium is a dietary essential. It is involved in myriad metabolic reactions and is necessary for the activity of many intracellular enzymes. Also, with certain other cations, it is important in electrolyte balance. Magnesium is present in fruits, vegetables, grains, milk, meat and fish and the natural content of these foods is the major source of the current dietary intake. The Food and Nutrition Board, NRC, has recommended that cereal grain products be fortified with magnesium in view of potential risk of deficiency among significant segments of the population. The usual adult intake is about 300mg or less per day from all sources and the contribution of food additives to total magnesium intake is very small. The administration of magnesium sulfate in very high doses to humans occasionally has resulted in severe and even fatal episodes, especially in the presence of pre-existing disease. These occurrences should not be prejudicial to the use of magnesium salts as foods ingredients
since the dosages given were orders of magnitude greater than the daily intake of magnesium added to food. While chronic toxicity data are lacking, the status of magnesium as a ubiquitous and essential dietary ingredient for the maintenance of homeostatic and bioenergetic mechanisms leads to the opinion that none of the available evidence suggests any probable hazard when any of the GRAS compounds of magnesium is used as a food ingredient. In view of the foregoing, The Select Committee concludes that: There is no evidence in the available information on magnesium carbonate, magnesium chloride, magnesium sulfate, magnesium hydroxide, magnesium oxide, magnesium stearate, dibasic magnesium phosphate and tribasic magnesium phosphate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced, or which might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Magnesium sulfate | 10034-99-8 | 60 | 1979 | 1 | 184.1443 |
SCOGS Opinion:
Magnesium is a dietary essential. It is involved in myriad metabolic reactions and is necessary for the activity of many intracellular enzymes. Also, with certain other cations, it is important in electrolyte balance. Magnesium is present in fruits, vegetables, grains, milk, meat and fish and the natural content of these foods is the major source of the current dietary intake. The Food and Nutrition Board, NRC, has recommended that cereal grain products be fortified with magnesium in view of potential risk of deficiency among significant segments of the population. The usual adult intake is about 300mg or less per day from all sources and the contribution of food additives to total magnesium intake is very small. The administration of magnesium sulfate in very high doses to humans occasionally has resulted in severe and even fatal episodes, especially in the presence of pre-existing disease. These occurrences should not be prejudicial to the use of magnesium salts as foods ingredients
since the dosages given were orders of magnitude greater than the daily intake of magnesium added to food. While chronic toxicity data are lacking, the status of magnesium as a ubiquitous and essential dietary ingredient for the maintenance of homeostatic and bioenergetic mechanisms leads to the opinion that none of the available evidence suggests any probable hazard when any of the GRAS compounds of magnesium is used as a food ingredient. In view of the foregoing, The Select Committee concludes that: There is no evidence in the available information on magnesium carbonate, magnesium chloride, magnesium sulfate, magnesium hydroxide, magnesium oxide, magnesium stearate, dibasic magnesium phosphate and tribasic magnesium phosphate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced, or which might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| malic acid | 97-67-6 | 56 | 1975 | 1 | 184.1069 |
SCOGS Opinion:
In view of the natural occurrence of L-malic acid in a variety of fruits, vegetables, and certain other foods, its important role in intermediary metabolism as a component of the Krebs cycle, rather detailed knowledge of its formation and metabolism in animals and plants, its relatively low toxicity when given orally to animals, and its specialized uses in foods and nonalcoholic beverages as an acidulant or flavoring agent, there is no scientific basis for suspecting that the amounts of L-malic acid now added to foods would be hazardous. There is no indication that malic acid is added to any foods specifically designed for infant feeding. The scientific literature is less satisfactory on D-malic acid, the unnatural isomer, and a co-constituent of the racemic DL-malic acid, which is the form now used as a food additive. Very little is known about the metabolism, absorption, excretion, and biological effects of D-malic acid, or
whether animal species differ in the way they can utilize and tolerate this compound. DL-malic acid was employed in several of the toxicological, reproductive, and teratological studies; results suggests that D-malic acid as a component of DL-malic acid, is not likely to have adverse effects. Some concern has been expressed about the ability of young infants to metabolize D-malic acid, but fortunately, in current practice, this dose not pose a problem since DL-malic acid is not now added to infant foods. The Select Committee has weighed the foregoing and concludes: For individuals beyond the age of infancy, there is no evidence in the available information on L-malic acid and DL-malic acid that demosntrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The glycerophosphate salts that are considered to be GRAS could provide absorbable sources of glycerol, phosphate, and their respective cations. However, glycerophosphates are not now widely used in foods. The Select Committee believes that the level of consumer exposure is very low and that use under limitations as a nutrient or dietary supplement will nor present a hazard to the public. In previous evaluations of glycerol and certain phosphates no evidence was found of a hazard to the public from the hydrolysis products of the glycerophosphates.
In light of the information reviewed and reported herein, the Select Committee concludes that: There is no evidence in the available information on calcium glycerophosphate, potassium glycerophosphate and manganese glycerophosphate that demonstrates or suggests reasonable grounds to suspect a hazars to the public when they are used as nutrient supplements or as they might reasonably be expected to be so used in the future. There is no evidence in the available information on calcium glycerophosphate and magnesium glycerophosphate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used in food packaging materials as now practiced or as they might be expected to be used for such purposes in the future.
SCOGS Opinion:
The glycerophosphate salts that are considered to be GRAS could provide absorbable sources of glycerol, phosphate, and their respective cations. However, glycerophosphates are not now widely used in foods. The Select Committee believes that the level of consumer exposure is very low and that use under limitations as a nutrient or dietary supplement will nor present a hazard to the public. In previous evaluations of glycerol and certain phosphates no evidence was found of a hazard to the public from the hydrolysis products of the glycerophosphates.
In light of the information reviewed and reported herein, the Select Committee concludes that: There is no evidence in the available information on calcium glycerophosphate, potassium glycerophosphate and manganese glycerophosphate that demonstrates or suggests reasonable grounds to suspect a hazars to the public when they are used as nutrient supplements or as they might reasonably be expected to be so used in the future. There is no evidence in the available information on calcium glycerophosphate and magnesium glycerophosphate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used in food packaging materials as now practiced or as they might be expected to be used for such purposes in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Manganous chloride | 7773-01-5 | 67 | 1979 | 5 | There is no CFR citation. |
SCOGS Opinion:
The conclusions in the opinion are limited to the use of manganous salts in foods for human consumption and do not concern the use of manganese in animal feeds.
The available information indicates that a wide margin exists between present intake levels of manganese as manganous salts and those levels that have been reported to produce harmful effects. Manganese is an essential nutrient that is required for the optimal functioning of several metabolic systems largely through its role as a prosthetic group or as essential cofactor. Divalent manganese is among the least toxic of the trace elements. As was indicated in the review of the experiments involving manganous chloride and manganous sulfate, the oral toxicity of manganese is low largely because of restricted absorption and the existence of a relatively efficient mechanism regulating intestinal excretion.
Manganese interacts metabolically with several other minerals including calcium, phosphorous, iron, and copper. Under most conditions, however, it is unlikely that the ratio of manganese to these elements is distorted enough to produce an adverse effect.
The only manganese salts known by the Select Committe to be in use as ingredients of foods for human consumption are the chloride and the sulfate. Despite the nearly complete lack of scientific reports on the biologic effects of manganous citrate and gluconate, the relatively low toxicity of the manganous ion and the innocuous nature of citrates and gluconates when used as food ingredients suggest that no health hazard would result from similar uses of manganous citrate and gluconate.
While there is good evidence of the short-term tolerance of manganous oxide as an added feed ingredient for poultry and livestock, no acute oral toxicity studies or long-term feeding studies of manganous oxide have been reported. In addition, the Select Committee has no information on the amounts of manganous oxide, if any, that may be use in food for human consumption in this country.
The Select Committe has weighed the foregoing data and concludes that: There is no evidence in the availble information on manganous citrate, chloride, gluconate, and sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonable be expected in the future. In view of the deficiency of relevant biological studies and information on consumer exposure, the Select Committee has insufficient data upon which to base an evaluation of manganous oxide when it is used in food for human consumption.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Manganous citrate | 10024-66-5 | 67 | 1979 | 5 | 184.1449 |
SCOGS Opinion:
The conclusions in the opinion are limited to the use of manganous salts in foods for human consumption and do not concern the use of manganese in animal feeds.
The available information indicates that a wide margin exists between present intake levels of manganese as manganous salts and those levels that have been reported to produce harmful effects. Manganese is an essential nutrient that is required for the optimal functioning of several metabolic systems largely through its role as a prosthetic group or as essential cofactor. Divalent manganese is among the least toxic of the trace elements. As was indicated in the review of the experiments involving manganous chloride and manganous sulfate, the oral toxicity of manganese is low largely because of restricted absorption and the existence of a relatively efficient mechanism regulating intestinal excretion.
Manganese interacts metabolically with several other minerals including calcium, phosphorous, iron, and copper. Under most conditions, however, it is unlikely that the ratio of manganese to these elements is distorted enough to produce an adverse effect.
The only manganese salts known by the Select Committe to be in use as ingredients of foods for human consumption are the chloride and the sulfate. Despite the nearly complete lack of scientific reports on the biologic effects of manganous citrate and gluconate, the relatively low toxicity of the manganous ion and the innocuous nature of citrates and gluconates when used as food ingredients suggest that no health hazard would result from similar uses of manganous citrate and gluconate.
While there is good evidence of the short-term tolerance of manganous oxide as an added feed ingredient for poultry and livestock, no acute oral toxicity studies or long-term feeding studies of manganous oxide have been reported. In addition, the Select Committee has no information on the amounts of manganous oxide, if any, that may be use in food for human consumption in this country.
The Select Committe has weighed the foregoing data and concludes that: There is no evidence in the availble information on manganous citrate, chloride, gluconate, and sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonable be expected in the future. In view of the deficiency of relevant biological studies and information on consumer exposure, the Select Committee has insufficient data upon which to base an evaluation of manganous oxide when it is used in food for human consumption.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Manganous gluconate | 6485-39-8 | 67 | 1979 | 5 | There is no CFR citation. |
SCOGS Opinion:
The conclusions in the opinion are limited to the use of manganous salts in foods for human consumption and do not concern the use of manganese in animal feeds.
The available information indicates that a wide margin exists between present intake levels of manganese as manganous salts and those levels that have been reported to produce harmful effects. Manganese is an essential nutrient that is required for the optimal functioning of several metabolic systems largely through its role as a prosthetic group or as essential cofactor. Divalent manganese is among the least toxic of the trace elements. As was indicated in the review of the experiments involving manganous chloride and manganous sulfate, the oral toxicity of manganese is low largely because of restricted absorption and the existence of a relatively efficient mechanism regulating intestinal excretion.
Manganese interacts metabolically with several other minerals including calcium, phosphorous, iron, and copper. Under most conditions, however, it is unlikely that the ratio of manganese to these elements is distorted enough to produce an adverse effect.
The only manganese salts known by the Select Committe to be in use as ingredients of foods for human consumption are the chloride and the sulfate. Despite the nearly complete lack of scientific reports on the biologic effects of manganous citrate and gluconate, the relatively low toxicity of the manganous ion and the innocuous nature of citrates and gluconates when used as food ingredients suggest that no health hazard would result from similar uses of manganous citrate and gluconate.
While there is good evidence of the short-term tolerance of manganous oxide as an added feed ingredient for poultry and livestock, no acute oral toxicity studies or long-term feeding studies of manganous oxide have been reported. In addition, the Select Committee has no information on the amounts of manganous oxide, if any, that may be use in food for human consumption in this country.
The Select Committe has weighed the foregoing data and concludes that: There is no evidence in the availble information on manganous citrate, chloride, gluconate, and sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonable be expected in the future. In view of the deficiency of relevant biological studies and information on consumer exposure, the Select Committee has insufficient data upon which to base an evaluation of manganous oxide when it is used in food for human consumption.
SCOGS Opinion:
The hypophosphites do not appear to be currently used as ingredients in foods as indicated by a survey of the food industry conducted by a National Research Council subcommittee in 1970 and more recent information obtained from industry by the Select Committee. They had limited medical use many years ago in tonics and as therapeutic agents but appear to be no longer used for these purposes.
The acute toxicity of hypophosphites is relatively low; injected intraperitoneally in mice, the LD50 (30days) for the sodium salt was 1.6g per kg body weight. Calcium and sodium hypophosphites given orally or parenterally to experimental animals and man are rapidly excreted as hypophosphite in the urine. It is the opinion on the Select Committee that potassium hypophosphite is comparable to the sodium salt in excretion and toxicity.
Although animal feeding experiments indicate that the phosphorus in hypophosphites is not biologically available, no adverse effects were reported in young rats fed diets containing calcium hypophosphite (up to 4.3g per kg). Growth and calcium assimilation were as good as observed on diets containing salts recognized as good sources of calcium.
Although no reports were available on the biological effects of manganese hypophosphite, an evaluation of the health aspects of other manganous salts by the Select Committee has found no evidence that would indicate a hazard from manganous hypophosphite if used as a nutrient or dietary supplement.
In view of the foregoing the Select Committee concludes that: There is no evidence in the available information on manganous, calcium, potassium or sodium hypophosphite that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used in the manner now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Manganous oxide | 1317-35-7 | 67 | 1979 | 5 | There is no CFR citation. |
SCOGS Opinion:
The conclusions in the opinion are limited to the use of manganous salts in foods for human consumption and do not concern the use of manganese in animal feeds.
The available information indicates that a wide margin exists between present intake levels of manganese as manganous salts and those levels that have been reported to produce harmful effects. Manganese is an essential nutrient that is required for the optimal functioning of several metabolic systems largely through its role as a prosthetic group or as essential cofactor. Divalent manganese is among the least toxic of the trace elements. As was indicated in the review of the experiments involving manganous chloride and manganous sulfate, the oral toxicity of manganese is low largely because of restricted absorption and the existence of a relatively efficient mechanism regulating intestinal excretion.
Manganese interacts metabolically with several other minerals including calcium, phosphorous, iron, and copper. Under most conditions, however, it is unlikely that the ratio of manganese to these elements is distorted enough to produce an adverse effect.
The only manganese salts known by the Select Committe to be in use as ingredients of foods for human consumption are the chloride and the sulfate. Despite the nearly complete lack of scientific reports on the biologic effects of manganous citrate and gluconate, the relatively low toxicity of the manganous ion and the innocuous nature of citrates and gluconates when used as food ingredients suggest that no health hazard would result from similar uses of manganous citrate and gluconate.
While there is good evidence of the short-term tolerance of manganous oxide as an added feed ingredient for poultry and livestock, no acute oral toxicity studies or long-term feeding studies of manganous oxide have been reported. In addition, the Select Committee has no information on the amounts of manganous oxide, if any, that may be use in food for human consumption in this country.
The Select Committe has weighed the foregoing data and concludes that: There is no evidence in the availble information on manganous citrate, chloride, gluconate, and sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonable be expected in the future. In view of the deficiency of relevant biological studies and information on consumer exposure, the Select Committee has insufficient data upon which to base an evaluation of manganous oxide when it is used in food for human consumption.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Manganous sulfate | 7785-87-7 | 67 | 1979 | 5 | There is no CFR citation. |
SCOGS Opinion:
The conclusions in the opinion are limited to the use of manganous salts in foods for human consumption and do not concern the use of manganese in animal feeds.
The available information indicates that a wide margin exists between present intake levels of manganese as manganous salts and those levels that have been reported to produce harmful effects. Manganese is an essential nutrient that is required for the optimal functioning of several metabolic systems largely through its role as a prosthetic group or as essential cofactor. Divalent manganese is among the least toxic of the trace elements. As was indicated in the review of the experiments involving manganous chloride and manganous sulfate, the oral toxicity of manganese is low largely because of restricted absorption and the existence of a relatively efficient mechanism regulating intestinal excretion.
Manganese interacts metabolically with several other minerals including calcium, phosphorous, iron, and copper. Under most conditions, however, it is unlikely that the ratio of manganese to these elements is distorted enough to produce an adverse effect.
The only manganese salts known by the Select Committe to be in use as ingredients of foods for human consumption are the chloride and the sulfate. Despite the nearly complete lack of scientific reports on the biologic effects of manganous citrate and gluconate, the relatively low toxicity of the manganous ion and the innocuous nature of citrates and gluconates when used as food ingredients suggest that no health hazard would result from similar uses of manganous citrate and gluconate.
While there is good evidence of the short-term tolerance of manganous oxide as an added feed ingredient for poultry and livestock, no acute oral toxicity studies or long-term feeding studies of manganous oxide have been reported. In addition, the Select Committee has no information on the amounts of manganous oxide, if any, that may be use in food for human consumption in this country.
The Select Committe has weighed the foregoing data and concludes that: There is no evidence in the availble information on manganous citrate, chloride, gluconate, and sulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonable be expected in the future. In view of the deficiency of relevant biological studies and information on consumer exposure, the Select Committee has insufficient data upon which to base an evaluation of manganous oxide when it is used in food for human consumption.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Mannitol | 69-65-8 | 10 | 1972 | 1 | 180.25 |
SCOGS Opinion:
The available evidence reveals no short-term toxicological consequences in mice, rats, hamsters, or man when mannitol is fed in amounts exceeding those currently consumed in man's daily diet. There is no evidence that consumption of mannitol in the United States since 1950, when it was first used, has had adverse effects. It is recognized that mannitol exerts a laxative effect at levels that are from 5 to 10 times the estimated average adult intake level and about 2 to 3 times the maximum adult intake level. Children in the age groups 6-11 months and 12-23 months are now estimated to be consuming mannitol in amounts close to or in excess of those capable of exerting a laxative effect. Recognizing this and also that the reported average and maximum intake levels are generous over estimates, it is the opinion of the Select Committee that the use of mannitol in food in the present or reasonably foreseeable amounts poses no problem
in this regard. The lack of experimentla data on long-term studies, carcinogenicity, mutagenicity, or effects on reproduction mertis special attention. This is pertinent because ofthe repidly increasing use of mannitol in food products. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available literature to show that mannitol constitues a hazard to the public when used at levels that are now current, or that might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Methyl Paraben | 99-76-3 | 8 | 1972 | 1 | 184.1490 |
SCOGS Opinion:
The available information reveals that there are no short-term toxicological consequences in the rat, rabbit, cat, dog, or man and no long-term toxicological consequences in rats, of consuming the parabens in amounts greatly exceeding those currently consumed in the normal diet of the U.S. population. There is no evidence that consumption of the parabens as food ingredients has had an adverse effect on man in the 40 years they have been so used in the United States. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on the two parabens, methyl and proyl p-hydroxy-benzoic acid, that demonstrates a hazard to the public when they are used at levels that are now current or that might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Methylcellulose | 9004-67-5 | 25 | 1973 | 2 | 182.1480 |
SCOGS Opinion:
Cellulose is a major constituent of many foods of plant origin. As such it is a significant portion of the diet, but is neither degraded nor absorbed. Cellulose derivatives considered in this report are virtually unabsorbed and little or no degradation of absorbed and little or no degradation of absorbable products occurs in the human digestive tract. In man, consumption of large amounts appears to have no effect other than providing dietary bulk, reducing the nutritive value of such foodstuffs and possibly exerting a laxative effect. However, the existence of certain data and the different categorization of cellulose and the several cellulose derivatives on the GRAS list suggest that the Select Committee should render a separate opinion on each substance considered in this report.
A. CELLULOSE, MICROCRYSTALLINE CELLULOSE
Although pure cellulose and regenerated cellulose, including microcrystalline cellulose are not on the GRAS list, there is nothing in the available information to suggest that such forms of cellulose have significantly different biological properties that distinguish these forms of cellulose from those currently considered as GRAS or from naturally occurring cellulose. In view of the foregoing, the Select Committee concludes that: There is no evidence in the available information on pure and regenerated cellulose, including microcrystalline cellulose, that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current, or that might reasonably be expected in future.
B. METHYL CELLULOSE
In humans, virtually 100 percent of orally ingested methyl cellulose can be recovered in the feces withihn four days, indicating that absorption does not occur. However, in pregnant mice, very high doses of methyl cellulose, while not teratogenic, cause a significant increase in maternal mortality and retardation of fetal maturation. Such increased maternal and fetal toxicity does not occur at a dose of methyl cellulose which is 26-fold (or more) greater than that estimated to be the average daily adult dietary intake. It is noteworthy in this regard that similar toxic effects have been observed in identical tests performed by the same investigators on a large number of other polysaccharides fed at very high doses. The relative sensitivity of the several animal species to these effects varies, depending on the particular polysaccharide tested, but in all cases very large doses are required. Until these effects have been adequately explained, it appears to be inappropriate to conclude
that unrestricted use of such substances in food would be without hazard. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on methyl cellulose that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
C. CARBOXYMETHYL CELLULOSE
Carboxymethyl cellulose is converted spontaneously to a salt in alkaline solution, and it is probable that the distinction between carboxymethyl cellulose and its salts is artificial. However, carboxymethyl cellulose is liested as GRAS as a substance migrating to food from cotton or cotton fabrice used in dry foods packaging, while its sodium salt is listed as GRAS as a miscellaneous or general purpose food additive. In view of the separate listing of carboxymethyl cellulose, the Select Committee concludes that: There is no evidence in the available information on carboxymethyl cellulose that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used in dry food packaing materials originating from cotton or cotton fabrics as now practed or as it might reasonably be expected to be used for such purposes in future.
D. SODIUM CARBOXYMETHYL CELLULOSE
Despite the probable lack of distinction between sodium carboxy methyl cellulose and its parent compound, carboxymethyl cellulose, only the sodium carboxymethyl cellulose is GRAS as a miscellaneous and general purpose food additive. As such, there are no data that suggest it reacts differently than pure and regenerated cellulose or carboxymethyl cellulose. In view of the foregoing the Select Committee concludes that: There is no evidence in the available information on sodium carboxymethyl cellulose that demonstrtes, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in future.
E. HYDROXYPROPYLMETHYL CELLULOSE
Hydroxypropylmethyl cellulose is not listed as GRAS. It is a food additive used as a thickening agent, stabilizer and emulsifier. Hydroxypropylmethyl cellulose is sinthesized from methyl cellulose by the action of alkali and propylene oxide. There are no data available to suggest that hydroxypropylmethyl cellulose possesses adverse health effects; however, teratology studies dimilar to those conducted with mehtyl cellulose are not available for its hydroxypropyl derivative. Therefore, it is suggested that, in due course, appropriate studies should be conducted with hydroxypropylmethyl cellulose. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on hydroxypropylmethyl cellulose that demonstrates, or suggested reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current and in the manner now practiced (21 CFR 121.1021)
F. ETHYL CELLULOSE AND CELLULOSE ACETATE
There is a paucity of data concerning possible adverse health effects of ethyl cellulose and cellulose acetate. both are included in the GRAS list as substances migrating to food from paper or paperboard products used in food packaging. According to the NRC survey (6), very small amounts of ethyl cellulose also appear to be used in hard candy and chewing gum. In the GRAS context, the quantity of ethyl cellulose or cellulose acetate migrating to foods from packaging would be orders of magnitude below the levels of cellulose and cellulose derivaties now known to occur in foods. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ethyl cellulose and cellulose acetate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used in food packaging materials as now practiced or as they might be expeccted to be used for such purposes in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Milo Starch | 9004-53-9 | 115 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
SCOGS Opinion:
The Select Committee notes that the new information on long-term oral administration of monosodium glutamate (MSG) is the diet to varios animal species has revealed no adverse effects, while data showing neuropathological lesions in neonatal animals resulting from subcutaneous or forced oral dosing of MSG has thus far been confirmed only in rodents. The administration of protein or carbohydrate products concurrently with MSG has been shown to lower plasma glutamate levels, and in two recent studies, to reduce the incidence of hypothalamic lesions in mice. In pregnant monkeys, glutamate does not appear to readily cross the placental barrier. From comparisons of plasma glutamate levels, healthy term and premature infants have already developed the capability to metabolize glutamates. Ingestion of MSG solutions has been demostrated to cause transient clinical symptoms resembling those of "Chinese Restaurant Syndrome" and there is
evidence that some individuals may respond to relatively small doses. Similar symptoms can be evoked by certain other food substances. The use of MSG in restaurant and/or home-prepared foods not fall within the purview of the Select Committee since it is limited in its considerations to the use of glutamates as ingredients of processed foods. According to industry sources, MGS is not added to infant and junior foods. Because, however, a proportion of the consuming public may be sensitive acute responders, even though the unpleasant symptoms are transient, the Selected Committee believes there should be some constraint placed on the addition of MSG to pocessed foods.
In light of the foregoing studies on the biological effects of monosodium glutamate and the information considered in its previous report on glutamates, the Select Committee concludes that: There is no evidence in the available information on L-glutamic acid, L-glutamic acid hydrochloride, monosodium L-glutamate, monoammonium L-glutamate, and monopotassium L-glutamate that demonstrates, or suggests reasonable grounds to suspects, a hazard to the public when they are used at levels that are now current and in the manner now practices. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
The amounts of monomeric and polymeric methyl and ethyl acrylates that may migrate to foods from paper and paperboard used in food packaging are limited by regulation. Measurements made under severest conditions of extraction, show that human exposure to these substances from food packaged in materials containing them is less than 1 mg per kg body weight per day, and is probably considerably less than this figure under usual conditions.
While it has been shown that both monomers are absorbed from the gastrointestinal and respiratory tracts and from the skin, no absortion studies of the polymers have been made and the metabolic fate of the monomers and polymers has not been elucidated. However, no adverse effects have been observed and no pathological changes encountered in animals consuming up to 23 mg per kg of the methyl monomer for 33 days, or up to 280 mg per kg of the ethyl monomer for two years.
Polyethyl acrylate, but not polymethyl acrylate, has been fed for eight weeks at dose of 5.5g per kg body weight and a formulation containing both polyethyl acrylate and polymethacrylate has been fed for six months at a dose of 2.5 g per kg body weight without appearance of toxic or pathological effects.
The biological data on the monomers and on polyethyl acrylate, when related to estimates of human exposure that might occur due to migration of these substances from packaging materials, raise no concern about the safety of current practices. However, no biological studies upon which evaluation of the methyl polymer can be based have been reported.
In light of these considerations, the Select Committee concludes that: There is no evidence in the available information on monomeric ethyl acrylate, monomeric methyl acrylate, or polymeric ethyl acrylate that demonstrates or suggests reasonable grounds to suspect, a hazard to the public when they are used in paper and paperboard food packaging materials as now practiced, or as they might be expexted to be used for such purposes in the future.
In view of the deficiency of relevant biological studies, the Select Committee has insufficient data upon which to base an evaluation of polymeric methyl acrylate when it is used as an ingredient of food packaging materials.
SCOGS Opinion:
The amounts of monomeric and polymeric methyl and ethyl acrylates that may migrate to foods from paper and paperboard used in food packaging are limited by regulation. Measurements made under severest conditions of extraction, show that human exposure to these substances from food packaged in materials containing them is less than 1 mg per kg body weight per day, and is probably considerably less than this figure under usual conditions.
While it has been shown that both monomers are absorbed from the gastrointestinal and respiratory tracts and from the skin, no absortion studies of the polymers have been made and the metabolic fate of the monomers and polymers has not been elucidated. However, no adverse effects have been observed and no pathological changes encountered in animals consuming up to 23 mg per kg of the methyl monomer for 33 days, or up to 280mg per kg of the ethyl monomer for two years.
Polyethyl acrylate, but not polymethyl acrylate, has been fed for eight weeks at dose of 5.5g per kg body weight and a formulation containing both polyethyl acrylate and polymethacrylate has been fed for six months at a dose of 2.5 g per kg body weight without appearance of toxic or pathological effects.
The biological data on the monomers and on polyethyl acrylate, when related to estimates of human exposure that might occur due to migration of these substances from packaging materials, raise no concern about the safety of current practices. However, no biological studies upon which evaluation of the methyl polymer can be based have been reported.
In light of these considerations, the Select Committee concludes that: There is no evidence in the available information on monomeric ethyl acrylate, monomeric methyl acrylate, or polymeric ethyl acrylate that demonstrates or suggests reasonable grounds to suspect, a hazard to the public when they are used in paper and paperboard food packaging materials as now practiced, or as they might be expexted to be used for such purposes in the future.
In view of the deficiency of relevant biological studies, the Select Committee has insufficient data upon which to base an evaluation of polymeric methyl acrylate when it is used as an ingredient of food packaging materials.
SCOGS Opinion:
The Select Committee notes that the new information on long-term oral administration of monosodium glutamate (MSG) is the diet to varios animal species has revealed no adverse effects, while data showing neuropathological lesions in neonatal animals resulting from subcutaneous or forced oral dosing of MSG has thus far been confirmed only in rodents. The administration of protein or carbohydrate products concurrently with MSG has been shown to lower plasma glutamate levels, and in two recent studies, to reduce the incidence of hypothalamic lesions in mice. In pregnant monkeys, glutamate does not appear to readily cross the placental barrier. From comparisons of plasma glutamate levels, healthy term and premature infants have already developed the capability to metabolize glutamates. Ingestion of MSG solutions has been demostrated to cause transient clinical symptoms resembling those of "Chinese Restaurant Syndrome" and there is
evidence that some individuals may respond to relatively small doses. Similar symptoms can be evoked by certain other food substances. The use of MSG in restaurant and/or home-prepared foods not fall within the purview of the Select Committee since it is limited in its considerations to the use of glutamates as ingredients of processed foods. According to industry sources, MGS is not added to infant and junior foods. Because, however, a proportion of the consuming public may be sensitive acute responders, even though the unpleasant symptoms are transient, the Selected Committee believes there should be some constraint placed on the addition of MSG to pocessed foods.
In light of the foregoing studies on the biological effects of monosodium glutamate and the information considered in its previous report on glutamates, the Select Committee concludes that: There is no evidence in the available information on L-glutamic acid, L-glutamic acid hydrochloride, monosodium L-glutamate, monoammonium L-glutamate, and monopotassium L-glutamate that demonstrates, or suggests reasonable grounds to suspects, a hazard to the public when they are used at levels that are now current and in the manner now practices. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
The Select Committee notes that the new information on long-term oral administration of monosodium glutamate (MSG) is the diet to varios animal species has revealed no adverse effects, while data showing neuropathological lesions in neonatal animals resulting from subcutaneous or forced oral dosing of MSG has thus far been confirmed only in rodents. The administration of protein or carbohydrate products concurrently with MSG has been shown to lower plasma glutamate levels, and in two recent studies, to reduce the incidence of hypothalamic lesions in mice. In pregnant monkeys, glutamate does not appear to readily cross the placental barrier. From comparisons of plasma glutamate levels, healthy term and premature infants have already developed the capability to metabolize glutamates. Ingestion of MSG solutions has been demostrated to cause transient clinical symptoms resembling those of "Chinese Restaurant Syndrome" and there is
evidence that some individuals may respond to relatively small doses. Similar symptoms can be evoked by certain other food substances. The use of MSG in restaurant and/or home-prepared foods not fall within the purview of the Select Committee since it is limited in its considerations to the use of glutamates as ingredients of processed foods. According to industry sources, MGS is not added to infant and junior foods. Because, however, a proportion of the consuming public may be sensitive acute responders, even though the unpleasant symptoms are transient, the Selected Committee believes there should be some constraint placed on the addition of MSG to pocessed foods.
In light of the foregoing studies on the biological effects of monosodium glutamate and the information considered in its previous report on glutamates, the Select Committee concludes that: There is no evidence in the available information on L-glutamic acid, L-glutamic acid hydrochloride, monosodium L-glutamate, monoammonium L-glutamate, and monopotassium L-glutamate that demonstrates, or suggests reasonable grounds to suspects, a hazard to the public when they are used at levels that are now current and in the manner now practices. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Monostarch Phosphate | 11120-02-8 | 115 | 1979 | 2 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
SCOGS Opinion:
The two mustards (brown and yellow) commonly used in the United States are derived from two Braassica species that differ with respoect to the major chemical constituents of their essential oils. The available information shows that the characteristic isothiocyanates, other known constituents, and decomposition products of the essential oils of both mustards, have low orders of oral toxicity in experimental animals. Further, there is no reported evidence that orally administered doses of these constituents are carcinogenic, teratogenic, or mutagenic. However, interpretation of the available information suffers from a general lack of specificity on the part of investigators concerning the identity of the particular mustard used in their experiments, and from the fact that the major constituents of the essential oils are either very volatile or unstabel, making it speculative how much of each of these substances was actually
present in the preparation tested. The industrial practice of using mextures of mustards to impart desired flavors compounds the problem of relating the results of toxicological studies to conditions that may exist in foods. For the same reasons, the amounts of the essential mustard oil constituents actually present in foods at the time of consumption are unpredictably variable, but must be less than the amounts calculated from the reported daily human intake levels of mustard. The Select Committee has made an exhaustive search for information relevant to the health aspects of mustard and mustard oils as food ingredients and is confident that the literature evaluated in this report is representative and significant as a basis for judgement. However, because of the long history of use of the mustards in or on foods without apparent adverse effects on man, and because, as a consequence, they have been generally recognized as safe, there have been few well-defined toxicological studies.
The Select Committee is of the opinion that the mustards are examples of substances where more definitive toxicological studes on representative samples of the products actually used by the food industry would be useful in confirming the apparent absence of adverse health effects when they are used in or on foods. Moreover, in products like the mustards, which consist of variable mixtures of mustard seeds containing several chemical entities, the toxicological study of the products as actually used, at levels that approximate or exceed those now in current use, would be of greater significane and usefulness than the separate study of constituents known or assumed to be present. The Select Committee has weighed the foregoing data and concludes that: There is no evidence in the available inforatmion on allyl isothiocyanate, p-hydroxybenzyl isothiocyanate, and brown and yellow mustard that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used
at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The term niacin as adopted by the American Institute of Nutrition, is a generic form including both nicotinic acid and its amide, nicotinamide (or niacinamide), to which it is readily converted in the body. However, niacin as employed by the Code of Federal Regulations refers only to nicotinic acid. Nicotinamide is a component of two essential coenzymes, nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate. The body is also able to form nicotinamide from tryptophan (60mf of tryptophan provide 1mg of niacin equivalent) and much of the total niacin equivalents of the diet are supplied in this manner.
Disappearance data suggest that per capita daily intakes of nicotinic acid and nicotinamide added to foods are less than 7.5 and 2.2mg, respectively. Thus the amount added to foods (about 0.15mg per kg body weight) is approximately one half the total dietary intake of these substances from both added and natural sources. The LD50 for various laboratory animals given the substances parenterally has generally been found to be more than 1g per kg per day. Limited data on oral ingestion by mice and rats suggest that the LD50 may be more than 4g per kg per day. Young laboratory animals fed diets containing 1 or 2 percent nicotinic acid or nicotinamide (1 to 2 g per kg body weight per day) have demonstrated growth depression in some but not all studies. At levels of 0.1 percent in the diet, fatty livers may occur, reflecting an induced choline deficiency.
Because large doses of nicotinic acid are known to reduce serum concentration of cholesterol, administration of nicotinic acid has been employed in management of patients with hypercholesterolemia. Dosage commonly employed is 3 to 9g daily (50 to 150 mg per kg). Initially experienced side effects, including cutaneous flushing, pruritis, and nausea, usually subside with continued therapy and the great majority of subjects then appear to experience no adverse effects. However, abnormal values in liver function test have been detected rather frequently and at least a few subjects have developed jaundice. These manifestations generally subside promptly after discontinuation of treatment. Pathologic changes in the liver, possibly irreversible, have been associated with treatment with large daily doses in a few instances.
Although there have been no short or long term animal studies defining the greatest no adverse effect level of intake of nicotinic and man have been associated with intakes at least a hundredfold greater than those likely to be achieved from fortification of foods.
In the light of these considerations, the Select Committee concludes that:
There is no evidence in the available information on niacin (nicotinic acid) or niacinamide (nicotinamide) that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The term niacin as adopted by the American Institute of Nutrition, is a generic form including both nicotinic acid and its amide, nicotinamide (or niacinamide), to which it is readily converted in the body. However, niacin as employed by the Code of Federal Regulations refers only to nicotinic acid. Nicotinamide is a component of two essential coenzymes, nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate. The body is also able to form nicotinamide from tryptophan (60mf of tryptophan provide 1mg of niacin equivalent) and much of the total niacin equivalents of the diet are supplied in this manner.
Disappearance data suggest that per capita daily intakes of nicotinic acid and nicotinamide added to foods are less than 7.5 and 2.2mg, respectively. Thus the amount added to foods (about 0.15mg per kg body weight) is approximately one half the total dietary intake of these substances from both added and natural sources. The LD50 for various laboratory animals given the substances parenterally has generally been found to be more than 1g per kg per day. Limited data on oral ingestion by mice and rats suggest that the LD50 may be more than 4g per kg per day. Young laboratory animals fed diets containing 1 or 2 percent nicotinic acid or nicotinamide (1 to 2 g per kg body weight per day) have demonstrated growth depression in some but not all studies. At levels of 0.1 percent in the diet, fatty livers may occur, reflecting an induced choline deficiency.
Because large doses of nicotinic acid are known to reduce serum concentration of cholesterol, administration of nicotinic acid has been employed in management of patients with hypercholesterolemia. Dosage commonly employed is 3 to 9g daily (50 to 150 mg per kg). Initially experienced side effects, including cutaneous flushing, pruritis, and nausea, usually subside with continued therapy and the great majority of subjects then appear to experience no adverse effects. However, abnormal values in liver function test have been detected rather frequently and at least a few subjects have developed jaundice. These manifestations generally subside promptly after discontinuation of treatment. Pathologic changes in the liver, possibly irreversible, have been associated with treatment with large daily doses in a few instances.
Although there have been no short or long term animal studies defining the greatest no adverse effect level of intake of nicotinic and man have been associated with intakes at least a hundredfold greater than those likely to be achieved from fortification of foods.
In the light of these considerations, the Select Committee concludes that:
There is no evidence in the available information on niacin (nicotinic acid) or niacinamide (nicotinamide) that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Nickel (elemental) | 7440-02-0 | 97 | 1979 | 1 | 184.1537 |
SCOGS Opinion:
This opinion concerns the only GRAS use of nickel, that as a catalyst in the hydrogenation of edible oils and fats. According to industry, a residue of 0.1 to 1.5 ppm nickel may be present in the hydrogenated oils. There are few data on the amount of nickel actually consumed by humans from this sources, but at the average level of 0.55ppm reported by industry in 1975 it can be estimated that the per capita intake from the residual in hydrogenated oils was about 30 mg. This amount is about an order of magnitude lower than that ingested in the diet from natural sources, which is estimated at 300 to 600mg per day.
Most of the nickel ingested is excreted in the feces; a small proportion is absorbed and excreted in urine and sweat. Nickel and nickel salts when administered orally to various species of animals have relatively low toxicities. Granulocytic hyperplasia of the bone marrow was observed in dogs fed high levels (60mg per kg body weight) of nickel as the sulfate but carcinogenicity has not been reported for nickel and nickel salts administered orally to experimental animals; however, tumors have resulted following parenteral administration. Adverse effects on reproductive performance have been reported in mice fed nickel acetate; daily intake was estimated to be 335mg per kg body weight. Daily ingestion of 9.4 mg nickel as nickel sulfate per kg body weight, has caused infertility in rats. However, no effect on the reproductive performance of rats resulted from feeding up to 100mg per kg body weight of catalytic nickel power. The existence of nickel dermatitis from occupational contract
with nickel or nickel salts as well as in the general population is recognized. No data are available indicating the occurence of allergic reactions to the oral ingestion of nickel and nickel salts.
Based on these considerations, the Select Committee concludes that: There is no evidence in the available information on elemental nickel that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current and in the manner now practiced or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Nutmeg and Mace | 532-27-4 | 18 | 1973 | 3 | 182.10 |
SCOGS Opinion:
The toxic and alleged psychogenic effects of nutmeg and some of its pharmacologically active constituents such as myristicin, elemicin, and safrole are clearly manifested only at doses vastly greater than the usual levels of intake in the human diet. Histoically the toxic effects of massive doses (10 or more grams) of nutmeg when taken as an emmenagogue, abortifacient, or hallucinogen, although distressing, are transient and rarely fatal. However, it is to be recognized that as much as 6 percent of safrole, a weak hepatocarcinogen, is reported to be present in the essential oil of East Indian nutmeg, the major U.S. source. In 1960 FDA prohibited the use of safrole in food. Moreover, the closely related methoxy derivative of safrole, myristicin, is also present in some nutmeg oils in amounts approximating 5 percent. Our calculations (Section III of this report) indicate that the intake level of nutmeg oil and its equivalent in the
form of nutmeg and mace, based on the total imports available annually for use in food in the U.S., is of the order of 0.05 mg per kg per day for adults. Assuming a maximum content of 6 percent safrole in the oil, possible daily intake of safrole would be about 4 mcg per kg per day for an adult and about 5 times this amount for a child 6-11 months of age, who, according to the NRC survey, consumes the largest amounts of nutmeg products per kg of body weight. If myristicin is capable of conversion to safrole in vivo, intakes could be about double these amounts. All of these intake estimates would be low, of course, for any in the population who are particularly heavy consumers of food products containing nutmeg. While there is no evidence that such levels of consumption are capable of eliciting adverse effects, it is the opinion of the Select Committee that the safrole andmyristicin content of nutmeg products, and perhaps the content of such related constitutents as elemicin, eugenol,
and methoxyeugenol, should be further investigated to determine the range of content in both the East and West Indian products and to investigate or reinvestigate their possible mutagenic, teratogenic, and carcinogenic effects. The Select Committee has weighed the foregoing and concludes that: While no evidence in the available information on nutmeg, mace, or their essential oils demonstrates a hazard to the public when they are used in the manner now practiced, uncertainties exist requiring that additional studies should be conducted.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Oil of Rue | 8014-29-7 | 14 | 1973 | 2 | 184.1699 |
SCOGS Opinion:
The data available indicate that the quantity of oil of rue in the diet is minute, probably as little as one microgram per person per day. Adverse effects due to oil of rue from long-term exposure at such a low level in the human diet are not evident in the meager data now available. It is to be noted, however, that oil of rue is a complex of organic substances only a few of which have been identified. Chemical identification of all the substances in the oil could be accomplished with present analystical techniques and would provide positive assurance that oil of rue does not contain components known to be toxic. Moreover, the evidence that oil of rue is absorbed, can pass the placenta and is toxic to fetal tissues at relatively high doses, suggests the desireability, in due course, of conducting teratological and fetal toxicity tests at oral dosages equivalent to the present very low levels of consumption. The Select Committee
recognizes that there is little incentive to develop this kind of information for a substance that is used in the U.S. to the extent of less than 100 pounds per year. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on oil of rue that demonstrates a hazard to the public when it is used at levels that are now current and in the manner now practiced.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Oleic acid (packaging) | 112-80-1 | 65 | 1975 | 1 | There is no CFR citation. |
SCOGS Opinion:
Coconut oil, peanut oil, oleic acid, and linoleic acid have been used as foods or as food components by man for many years. These two oils and the fatty acids are rapidly absorbed after oral administration, metabolized, and the metabolic products are utilized and excreted. None of the available biological information indicates that these substances are hazardous to man or animals even when consumed at levels that are orders of magnitude greater than could result form their use for the purposes covered in this report. The evidence now available indicates that linoleic acid is not being used by the food industry as a nutrient or dietary supplement. Based on these considerations, the Select Commitee concludes that: There is no evidence in the available information on coconut oil, peanut oil, and oleic acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public as they are now used in paper and cotton
packaging material for food at levels now current or as they might reasonably be expected to be used for such purposes in the future. There is no evidence in the available information on linoleic acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used as a nutruient or dietary supplement at levels now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Ox bile extract | 8008-63-7 | 44 | 1975 | 1 | 184.1560 |
SCOGS Opinion:
The amounts of the bile acids ingested as constituents of ox bile extract used as a food additive are relatively insignificant, compared to the amounts normally present in the bile of man. The available information indicates that orally administered cholic acid, desoxycholic acid, glycocholic acid, and taurocholic acid are readily absorbed and excreted without accumulation. They exhibit a relatively low toxicity for several animal species tested. The Select Commitee has no information to indicate that the individual bile acids or their salts are used in foods. However, the intake estimates available for ox bile extract, of which bile acids and their salts are major constituents, indicate that average daily consumption of ox bile extract added to foods is small, amounting to 0.1 mg or less. The intake of individuals bile acids or their salts would be, commensurately, very small. Such biological effects as have been reported in
animal studies, have been elicited at levels of administration that are several orders of magnitude greater that the levels to which man is now exposed in his daily diet. In the light of the information contained in this report, the Select Commitee concludes that: There is no evidence in the available information on ox bile extraxt, or its constituents cholic acid, desoxycholic acid. glycocholic acid, and taurocholic acid- that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Papain | 9001-73-4 | 77 | 1977 | 1 | 184.1585 |
SCOGS Opinion:
No studies of the acute, short-term, or long-term effects from ingestion or oral administration of the pure enzyme papain have been found by the Select Committee. The acute oral LD50 of a commercial preparation of papain has been reported to be more than 10g per kg for mice. The apparent acute oral toxicity is low when compared with the ususal levels of human exposure which appear to be of the order of 2 to 25mg per day. Commercial papains are only standardized for their proteolytic activity and the various methods of preparation may result in the presence of other macromolecules, such as protein and carbohydrate, as well as minerals. The relationship between food grade papain and that used by the investigators in the biological studies evaluated in this report is not known but their gross similarity can be assumed.
The proteolytic activity of papain is destroyed by extremes of pH and by heat. Cooking converts the enzyme to an inactivate protein. Little is known about the nature and properties of the inactivated enzyme, or the other protein and non-protein portions of commercial preparations, but there is no evidence that they produce deleterious effects when ingested with food.
Allergies to papain have been reported but the incidence is low and the slight reactions reported appear to be confined to workers exposed to papain in air-borne dust.
In common with other proteolytic enzymes, papain digests the mucosa and the musculature of tissues in contact with the active enzyme for an appreciable period. Because there is no food use of papain that could result in the enzyme preparation occurring in sufficient amount in foods to produce these effects, this property does not pose a dietary hazard.
In view of the foregoing, the Select Committee concludes that: There is no evidence in the available information on papain that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Peanut oil (packaging) | 8002-03-7 | 65 | 1975 | 1 | There is no CFR citation. |
SCOGS Opinion:
Coconut oil, peanut oil, oleic acid, and linoleic acid have been used as foods or as food components by man for many years. These two oils and the fatty acids are rapidly absorbed after oral administration, metabolized, and the metabolic products are utilized and excreted. None of the available biological information indicates that these substances are hazardous to man or animals even when consumed at levels that are orders of magnitude greater than could result form their use for the purposes covered in this report. The evidence now available indicates that linoleic acid is not being used by the food industry as a nutrient or dietary supplement. Based on these considerations, the Select Commitee concludes that: There is no evidence in the available information on coconut oil, peanut oil, and oleic acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public as they are now used in paper and cotton
packaging material for food at levels now current or as they might reasonably be expected to be used for such purposes in the future. There is no evidence in the available information on linoleic acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used as a nutruient or dietary supplement at levels now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Pectin, amidated | 56645-02-4 | 81 | 1977 | 1 | 184.1588 |
SCOGS Opinion:
Pectin is a constituent of the cell walls of all green land plants. Among food sources, fruits and vegetables have the highest content and may contain 0.5 to 4 percent of pectic substances on a fresh weight basis. Extensive studies on pectins and pectinates demonstrates that they are largely decomposed by the microflora in the colon of man and experimental animals. The breakdown products do not appear to enter metabolic pathways to an appreciable extent because pectin in the diet is not available as a source of energy. Animal feeding studies have shown no toxic effects when pectins and pectinates, including amidated pectines, are fed at levels many times greater than the estimated human intake of pectin added to foods.
In the light of the foregoing , the Select Committee concludes that: There is no evidence in the available information on pectin and pectinates, including amidated pectins, that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Pectin, high ester | 9000-69-5 | 81 | 1977 | 1 | 184.1588 |
SCOGS Opinion:
Pectin is a constituent of the cell walls of all green land plants. Among food sources, fruits and vegetables have the highest content and may contain 0.5 to 4 percent of pectic substances on a fresh weight basis. Extensive studies on pectins and pectinates demonstrates that they are largely decomposed by the microflora in the colon of man and experimental animals. The breakdown products do not appear to enter metabolic pathways to an appreciable extent because pectin in the diet is not available as a source of energy. Animal feeding studies have shown no toxic effects when pectins and pectinates, including amidated pectines, are fed at levels many times greater than the estimated human intake of pectin added to foods.
In the light of the foregoing , the Select Committee concludes that: There is no evidence in the available information on pectin and pectinates, including amidated pectins, that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Pectin, low acid | There is no ID Code | 81 | 1977 | 1 | 184.1588 |
SCOGS Opinion:
Pectin is a constituent of the cell walls of all green land plants. Among food sources, fruits and vegetables have the highest content and may contain 0.5 to 4 percent of pectic substances on a fresh weight basis. Extensive studies on pectins and pectinates demonstrates that they are largely decomposed by the microflora in the colon of man and experimental animals. The breakdown products do not appear to enter metabolic pathways to an appreciable extent because pectin in the diet is not available as a source of energy. Animal feeding studies have shown no toxic effects when pectins and pectinates, including amidated pectines, are fed at levels many times greater than the estimated human intake of pectin added to foods.
In the light of the foregoing , the Select Committee concludes that: There is no evidence in the available information on pectin and pectinates, including amidated pectins, that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Pectinates | 9005-59-8 | 81 | 1977 | 1 | 184.1588 |
SCOGS Opinion:
Pectin is a constituent of the cell walls of all green land plants. Among food sources, fruits and vegetables have the highest content and may contain 0.5 to 4 percent of pectic substances on a fresh weight basis. Extensive studies on pectins and pectinates demonstrates that they are largely decomposed by the microflora in the colon of man and experimental animals. The breakdown products do not appear to enter metabolic pathways to an appreciable extent because pectin in the diet is not available as a source of energy. Animal feeding studies have shown no toxic effects when pectins and pectinates, including amidated pectines, are fed at levels many times greater than the estimated human intake of pectin added to foods.
In the light of the foregoing , the Select Committee concludes that: There is no evidence in the available information on pectin and pectinates, including amidated pectins, that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Pectinic acid | 9046-40-6 | 81 | 1977 | 1 | 184.1588 |
SCOGS Opinion:
Pectin is a constituent of the cell walls of all green land plants. Among food sources, fruits and vegetables have the highest content and may contain 0.5 to 4 percent of pectic substances on a fresh weight basis. Extensive studies on pectins and pectinates demonstrates that they are largely decomposed by the microflora in the colon of man and experimental animals. The breakdown products do not appear to enter metabolic pathways to an appreciable extent because pectin in the diet is not available as a source of energy. Animal feeding studies have shown no toxic effects when pectins and pectinates, including amidated pectines, are fed at levels many times greater than the estimated human intake of pectin added to foods.
In the light of the foregoing , the Select Committee concludes that: There is no evidence in the available information on pectin and pectinates, including amidated pectins, that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Perlite (filter aid) | 93763-70-3 | 61 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
Silicon dioxide and various silicates occur abundantly in the earth's crust, are present in practically all natural waters,animals, and plants, and are part of the normal human diet. The question of whether or not silicon is an essential human nutrient remains unresolved. Silicon compounds consumed as added food ingredients contribute only a minor proportion of the total dietary silicon intake. The estimated possible human intake of sodium aluminosilicate, the predominant silicate added to foods in this country, is approximately 0.3mg per kg body weight per day. Silicon compounds that are GRAS for use as direct food ingredient, except potassium and sodium silicates, are insoluble or very slightly soluble in water and appear to be biologically inert. The water-soluble silicates are also of low acute toxicity. The acute oral LD50 in rats of sodium aluminosilicate is >1g per kg. No significant tissue accumulation, pathology, or
toxicity has been reported from the ingestion of those insoluble or very slightly soluble GRAS silicon compounds for which data are available. Of the five substances that were reported as added to foods in the NRC survey, biologic effects and safety data are available for all except sodium calcium aluminosilicate, and there is no reason to suspect that the toxicity of the latter would differ from those for which there are data. The results of two studies (1967-1970) in which various silicon compounds were fed to laboratory animals for 1 mo at a level of 0.8g per kg body weight (as silicon dioxide) and for 3 mo at levels of 6 to 30 mg per kg body weight suggests there may be a species-related susceptibility to renal damage from ingestion of sodium silicate, magnesium trisilicate, and finely ground quartz. No substantiating reports of these effects have appeared. Magnesium trisilicate was recognized as safe for prolonged use in human ingestion in large amount as a component of antacid
preparations by the Advisory Review Panel on Over-the-Counter Drugs, and the available evidence on the acute toxicity of sodium silicate indicates that it is low. Consumption data are lacking for aluminium calcium silicate and tricalcium silicate, two compounds that are listed as GRAS for use as anticaking agents. However, their use in keeping with good manufacturing practice and in currently regulated amounts would be of the same order of magnitude as the other GRAS silicates. In addition, the Select Committee has limited information on the amounts of talc that are currently used in foods. However a major food use of talc is in the coating of rice. Assuming package label statements are ignored and coated rice is not washed prior to cooking and no other losses occur, maximun per capita intake of talc from this source appears to be 0.5g per day. With respect to paper and cotton food- packaging products, the possibility is remote that biologically significant amounts of talc,
diatomaceous earth, or sodium silicate migrate to food from packaging, materials containing these substances. Perlite, a naturally occuring polysilicate substance, has an oral LD50 in the rat of >10g per kg body weight. Estimates of the maximun quantities of minerals that might be extracted from perlite and diatomaceous earth used as filteraids in food processing indicates no hazard to public health. There are no food grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc. Such specifications for the substances used in foods are desirable. Specification for food grade talc should limit the content of asbestos fibers even though the potential hazard of ingested asbestos fibers even though the potential hazard of ingested asbestos is not clearly established. The Food and Drug Administration is sponsoring the development of an assay method for asbestos fibers. An upper limit for cadmium should be added to the specifications for food-grade perlite, and
consideration should be given to the need for limitation of cadmium content of other silicates. In the light of all of the foregoing, the Select Committee concludes that: It is essential to establish food-grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc, with provision for an upper limit of asbestos fibers in talc. There is no evidence in the available information on aluminum calcium silicate, calcium silicate, magnesium silicate, potassium silicate, sodium silicate, sodium aluminosilicate, sodium calcium aluminosilicate, tricalcium silicate, silica aerogel, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on diatomaceous earth, silicon dioxides, sodium silicate, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the
public when they are used as ingredients of paper and paperboard products used in food packaging in accordance with current practice. There is no evidence in the available information on sodium silicate and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of cotton and cotton fabrics used in dry food packaging in accordance with current practice. There is no evidence in the available information on diatomaceous earth and perlite that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used as filteraids in food processing at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Phosphoric acid | 7664-38-2 | 32 | 1975 | 1 | 182.1073 |
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
SCOGS Opinion:
The amounts of monomeric and polymeric methyl and ethyl acrylates that may migrate to foods from paper and paperboard used in food packaging are limited by regulation. Measurements made under severest conditions of extraction, show that human exposure to these substances from food packaged in materials containing them is less than 1 mg per kg body weight per day, and is probably considerably less than this figure under usual conditions.
While it has been shown that both monomers are absorbed from the gastrointestinal and respiratory tracts and from the skin, no absortion studies of the polymers have been made and the metabolic fate of the monomers and polymers has not been elucidated. However, no adverse effects have been observed and no pathological changes encountered in animals consuming up to 23 mg per kg of the methyl monomer for 33 days, or up to 280mg per kg of the ethyl monomer for two years.
Polyethyl acrylate, but not polymethyl acrylate, has been fed for eight weeks at dose of 5.5g per kg body weight and a formulation containing both polyethyl acrylate and polymethacrylate has been fed for six months at a dose of 2.5 g per kg body weight without appearance of toxic or pathological effects.
The biological data on the monomers and on polyethyl acrylate, when related to estimates of human exposure that might occur due to migration of these substances from packaging materials, raise no concern about the safety of current practices. However, no biological studies upon which evaluation of the methyl polymer can be based have been reported.
In light of these considerations, the Select Committee concludes that: There is no evidence in the available information on monomeric ethyl acrylate, monomeric methyl acrylate, or polymeric ethyl acrylate that demonstrates or suggests reasonable grounds to suspect, a hazard to the public when they are used in paper and paperboard food packaging materials as now practiced, or as they might be expexted to be used for such purposes in the future.
In view of the deficiency of relevant biological studies, the Select Committee has insufficient data upon which to base an evaluation of polymeric methyl acrylate when it is used as an ingredient of food packaging materials.
SCOGS Opinion:
The amounts of monomeric and polymeric methyl and ethyl acrylates that may migrate to foods from paper and paperboard used in food packaging are limited by regulation. Measurements made under severest conditions of extraction, show that human exposure to these substances from food packaged in materials containing them is less than 1 mg per kg body weight per day, and is probably considerably less than this figure under usual conditions.
While it has been shown that both monomers are absorbed from the gastrointestinal and respiratory tracts and from the skin, no absortion studies of the polymers have been made and the metabolic fate of the monomers and polymers has not been elucidated. However, no adverse effects have been observed and no pathological changes encountered in animals consuming up to 23 mg per kg of the methyl monomer for 33 days, or up to 280mg per kg of the ethyl monomer for two years.
Polyethyl acrylate, but not polymethyl acrylate, has been fed for eight weeks at dose of 5.5g per kg body weight and a formulation containing both polyethyl acrylate and polymethacrylate has been fed for six months at a dose of 2.5 g per kg body weight without appearance of toxic or pathological effects.
The biological data on the monomers and on polyethyl acrylate, when related to estimates of human exposure that might occur due to migration of these substances from packaging materials, raise no concern about the safety of current practices. However, no biological studies upon which evaluation of the methyl polymer can be based have been reported.
In light of these considerations, the Select Committee concludes that: There is no evidence in the available information on monomeric ethyl acrylate, monomeric methyl acrylate, or polymeric ethyl acrylate that demonstrates or suggests reasonable grounds to suspect, a hazard to the public when they are used in paper and paperboard food packaging materials as now practiced, or as they might be expexted to be used for such purposes in the future.
In view of the deficiency of relevant biological studies, the Select Committee has insufficient data upon which to base an evaluation of polymeric methyl acrylate when it is used as an ingredient of food packaging materials.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Potassium alginate | 9005-36-1 | 24 | 1973 | 2 | 184.1610 |
SCOGS Opinion:
The available information on the alginates reveals no significant adverse toxicological effects from oral administration in non-pregnant animals or humans in daily amounts greatly exceeding those currently consumed in the diet. However, in pregnant mice, very large doses of propylene glycol alginate, while not teratogenic, cause a significant increase in maternal mortality. Such increased maternal toxicity does not occur at a dose of propylene glycol alginate which is 26-fold or more greater than that estimated to be the average daily adult dietary intake. No respect but studies of propylene glycol, made by the same investigators and is without maternal toxicity even at very large doses. This indicates that the adverse effects reported for propylene glycol alginate may be due to the alginate moiety. It is noteworthy that similar toxic effects have been observed in identical tests on a large number of other polysaccarides (gum
arabic, sterculia gum, carob bean gum, guar gum, gum ghatti, gum tragacanth, carrageenan, methyl cellulose, and agar-agar) fed at very high levels. The relative sensitivity of the several animal species to these effects, varies depending on the particular polysaccaride tested, but in all cases very large doses are required. Until these effects have been adequately explained, it appears to be inappropriate to conclude that unrestricted use of such substances in food would be withou hazard. The Select Committee has weighed all of the foregoing and concludes that: There is no evidence in the available information on ammonium, calcium, potassium, sodium, and propylene glycol alginates that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption of these substances would
constitute a dietary hazard.
SCOGS Opinion:
The Select committee is not aware of any long-term experimental studies on chronic administration of any of the carbonate salts. The results of acute toxicity and short-term feeding experiments are not readily extrapolated in determining toxic levels for carbonate salts consumed by humans. Treatment of gastric or peptic ulcers in patients with large amounts of carbonate salts in various forms has been utilized for many years and only rarely have deleterious results of changes of acid-base balance been reported. When the human respiratory and renal functions are normal, the mechanisms for disposing of bicarbonate intake in large amounts through excretion appear to be highly efficient. Studies of mice suggest that large intakes of calcium carbonate may interfere with reproductive performance. Such effects could be indirectly attributable to certain trace nutrient deficiences. Comparable intake levels of calcium may occur when
calcium carbonate is used for therapeutic purposes but the amounts added to foods in normal manufacturing processes are not high enough to be harmful. While the Select Committee is not aware of any studies on sodium sequicarbonate per se, reasoned judgment suggests its biochemical conversion and metabolism would be similar to that of sodium carbonate and bicarbonate. On the consideration of the foregoing, the Select Committee concludes that: There is no evidence in the available information on calcium carbonate, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, or sodium sesquicarbonate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Potassium chloride | 7447-40-7 | 102 | 1979 | 1 | 184.1622 |
SCOGS Opinion:
Potassium chloride, a major constituent of plant and animal cells, is an essential constituent of the body and is rapidly adjusted to homeostatic levels following ingestion in amounts that can be tolerated without causing nausea and vomiting. The amount of potassium chloride added to food by processors in 1975 was of the order of 20 mg daily on a per capita basis while the amount of potassium in the average diet was equivalent to 4 to 9g of potassium chloride. Review of the available information reveals that under clinical conditions, fatal or serious toxic reactions to potassium chloride rarely occur. An occasional complication from concentrated potassium chloride tablets given orally is ulceration of the small intestine.
The available evidence indicates that in normal individuals potassium chloride is well tolerated, and that metabolism quickly and efficiently adjusts potassium in the body to narrow homeostatic levels. Certain health conditions are known to affect the normal homeostatic control of sodium and potassium metabolism, and patients with these conditions must adjust their diets to avoid proscribed electrolyte intakes.
Water intake, efficiency of the kidney, and the ratio of sodium to potassium in the diet are interrelated factors that must be evaluated in considering the health aspects of changing the relative intakes of sodium chloride and potassium chloride. Potassium chloride could be substituted for sodium chloride in some of its applications; however, the unpleasant taste of substantial amounts of potassium chloride, in the absence of sodium chloride, makes this improbable. Thus, the Select Committee believes that the extensive substitution of potassium chloride, which might increase its per capita usage from 20 mg to 2 g or more, is unlikely. If this degree of substitution were made, the ratio of sodium to potassium in the diet would be reduced from the current value of approximately 1.4 to a value nearer 0.9 in a 2600 kcal diet which would provide about 160mg potassium and 140mg sodium per 100kcal. By replacing some sodium containing ingredients with ingredients that provide other cations and
by increasing the consumption of foods lower in sodium content, it is probable that reduced sodium intakes would be a more important factor than increased consumption of potassium in lowering this ratio. Available data do not provide cause for concern in this regard. Nevertheless, the following conclusion of the Select Committee is premised on the continued monitoring of the sodium and potassium content of the U.S. diet and contingent upon periodic review of the health aspects of using potassium chloride as a food ingredient.
In view of the foregoing, the Select Committee concludes that: There is no evidence in the available information on potassium chloride that demonstrates or suggests reasonable grounds to suspect a hazard to the public when it is used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Potassium citrate | 6100-05-6 | 84 | 1977 | 1 | 184.1625 |
SCOGS Opinion:
The citrate ion is widely distributed in plants and animals and is a naturally occurring component of the diet. It is a common metabolite in oxidative metabolism and an important component of bone. Exogenous citrate administered to infants and adults as a component of commonly consumed diets is considered completely metabolizable. The addition of citric acid to foods is considered equivalent to adding citrate salts except in foods of very high acidity. The amount of citrate added to foods by foods processors is about 500mg per person per day. This amount occurs naturally in 2 ounces of orange juice and does not constitute a significant addition to the total body load. Although data on acute and chronic effects of orally administered sodium citrate, calcium citrate and potassium citrate are limited, no biological effects of the citrate-containing substances evaluated in this report cause concern about the safety of these GRAS
substances used in reasonable amounts and in accordance with prescribed tolerances and limitations.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on citric acid, sodium citrate, potassium citrate, calcium citrate, ammonium citrate, isopropyl citrate, stearyl citrate, and triethyl citrate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Potassium gluconate | 299-27-4 | 78 | 1978 | 1 | There is no CFR citation. |
SCOGS Opinion:
Gluconates are useful as nutritional supplements since their high solubility allows relatively rapid absorption of the cations. Evidence suggests that any possible toxicity is a function of the cation rather than of the gluconate portion of these substances. Thus, the acute toxic responses to the various gluconate salts are comparable with other salts of the same metals and long-term toxicities seem related to the tissue deposition of these metals. These observations could have been anticipated because gluconic acid is a normal metabolic product of glucose. The amount of gluconic acid produced endogenously is many times greater than the largest amounts likely to be consumed from food. Because the toxicological activities of these gluconates appear to be a function of their cationic components, safe and acceptable levels in foods are limited only by the nature of the specific cations. There is no evidence in the available
information on sodium gluconate, potassium gluconate, magnesium gluconate, and zinc gluconate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The glycerophosphate salts that are considered to be GRAS could provide absorbable sources of glycerol, phosphate, and their respective cations. However, glycerophosphates are not now widely used in foods. The Select Committee believes that the level of consumer exposure is very low and that use under limitations as a nutrient or dietary supplement will nor present a hazard to the public. In previous evaluations of glycerol and certain phosphates no evidence was found of a hazard to the public from the hydrolysis products of the glycerophosphates.
In light of the information reviewed and reported herein, the Select Committee concludes that: There is no evidence in the available information on calcium glycerophosphate, potassium glycerophosphate and manganese glycerophosphate that demonstrates or suggests reasonable grounds to suspect a hazars to the public when they are used as nutrient supplements or as they might reasonably be expected to be so used in the future. There is no evidence in the available information on calcium glycerophosphate and magnesium glycerophosphate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used in food packaging materials as now practiced or as they might be expected to be used for such purposes in the future. .
SCOGS Opinion:
The Select Committee has found no data suggesting that the use of sodium or potassium hydroxides, as currently practiced in food processing, is hazardous to consumers. The corrosive effect of ingestion of large amounts of strong alkalis such as sodium and potassium hydroxides has been amply demonstrated. However, these alkalis are not present as such in foods as consumed. The small amounts added for pH adjustment during food processing react rapidly with food acids to form neutral salts. Moreover, any free alkali that might be present in food, either from direct addition or from migration from packaging materials, is rapidly converted to neutral salts in the stomach.
The amounts of sodium and potassium hydroxide used in food processing contribute only 2 to 5 percent of the total sodium and potassium intake from all dietary sources. Accordingly, these alkais, as now used in food processing, do not add significantly to the usual dietary load of sodium and potassium.
In light of the foregoing, and the information elsewhere in this report, the Select Committee concludes that: There is no evidence in the available information on potassium hydroxide or sodium hydroxide that demonstrates, or suggests reasonable grounds to suspect a hazard to the public, when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on sodium hydroxide that demonstrates, or suggests, reasonable grounds to suspect a hazard to the public when it is used as an ingredient of food packaging materials in the manner now practiced or that might reasonably be expected in the future.
SCOGS Opinion:
The hypophosphites do not appear to be currently used as ingredients in foods as indicated by a survey of the food industry conducted by a National Research Council subcommittee in 1970 and more recent information obtained from industry by the Select Committee. They had limited medical use many years ago in tonics and as therapeutic agents but appear to be no longer used for these purposes.
The acute toxicity of hypophosphites is relatively low; injected intraperitoneally in mice, the LD50 (30days) for the sodium salt was 1.6g per kg body weight. Calcium and sodium hypophosphites given orally or parenterally to experimental animals and man are rapidly excreted as hypophosphite in the urine. It is the opinion on the Select Committee that potassium hypophosphite is comparable to the sodium salt in excretion and toxicity.
Although animal feeding experiments indicate that the phosphorus in hypophosphites is not biologically available, no adverse effects were reported in young rats fed diets containing calcium hypophosphite (up to 4.3g per kg). Growth and calcium assimilation were as good as observed on diets containing salts recognized as good sources of calcium.
Although no reports were available on the biological effects of manganese hypophosphite, an evaluation of the health aspects of other manganous salts by the Select Committee has found no evidence that would indicate a hazard from manganous hypophosphite if used as a nutrient or dietary supplement.
In view of the foregoing the Select Committee concludes that: There is no evidence in the available information on manganous, calcium, potassium or sodium hypophosphite that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used in the manner now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Potassium iodate | 7758-05-6 | 39 | 1975 | 1 | 184.1635 |
SCOGS Opinion:
Iodine occurs widely and is present in most human foods. While the quantity of iodine in specific foods is highly variable, the average diet usually contains sufficient iodine to supply man's requirement for this essential element. In addition to the iodine in foods, iodine-containing compounds are ingested in the form of dietary supplements, food processing adjuncts, food colors, sanitizing agents, and pharmaceuticals. While no comprehensive consumption data are available for any iodine consumed dialy by individuals has increased in the past several years. Potassium iodide, potassium iodate, and calcium iodate are only three of the many iodine-containing substances including iodates are converted to iodides in food processing or often consumption. Therefore, the Select Committee has limited its evaluations in this report to potassium iodide, potassium iodate and calcium iodate. This is, in effect, evaluating the health aspects
of adding iodide ion to certain foods. Available biological information shows that ingested potassium iodide and other iodides are readily absorbed and utilized to the extent required for nutritional needs, the excess being excreted primarily in the urine. There is no evidence in the studies on experimental animals and man available to the Committee that indicates acute or chronic toxic effects, including mutagenic, teratogenic, and carcinogenic effects, resulting from the consumption of potassium iodide by euthyroid individuals in amounts that are several orders of magnitude greater than those now being consumbed in the daily diet. Based upon consideration of the available data, the Select Committee concludes that: There is no evidence in the available information on potassium iodide, potassium iodate, or calcium iodate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced,
or those which might reasonably be expected in the future under existing limitations.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Potassium iodide | 7681-11-0 | 39 | 1975 | 1 | 184.1634 |
SCOGS Opinion:
Iodine occurs widely and is present in most human foods. While the quantity of iodine in specific foods is highly variable, the average diet usually contains sufficient iodine to supply man's requirement for this essential element. In addition to the iodine in foods, iodine-containing compounds are ingested in the form of dietary supplements, food processing adjuncts, food colors, sanitizing agents, and pharmaceuticals. While no comprehensive consumption data are available for any iodine consumed dialy by individuals has increased in the past several years. Potassium iodide, potassium iodate, and calcium iodate are only three of the many iodine-containing substances including iodates are converted to iodides in food processing or often consumption. Therefore, the Select Committee has limited its evaluations in this report to potassium iodide, potassium iodate and calcium iodate. This is, in effect, evaluating the health aspects
of adding iodide ion to certain foods. Available biological information shows that ingested potassium iodide and other iodides are readily absorbed and utilized to the extent required for nutritional needs, the excess being excreted primarily in the urine. There is no evidence in the studies on experimental animals and man available to the Committee that indicates acute or chronic toxic effects, including mutagenic, teratogenic, and carcinogenic effects, resulting from the consumption of potassium iodide by euthyroid individuals in amounts that are several orders of magnitude greater than those now being consumbed in the daily diet. Based upon consideration of the available data, the Select Committee concludes that: There is no evidence in the available information on potassium iodide, potassium iodate, or calcium iodate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced,
or those which might reasonably be expected in the future under existing limitations.
SCOGS Opinion:
Based upon chronic toxicity tests in animals, primarily in rats, the no observed adverse effect level of SO2 is estimated to be in the range of 30 to 100 mg of SO2 per kg of body weight per day. These values are considerably higher than the estimated average per capita consumption of about 0.2 mg of SO2 equivalent per kg body weight per day, and well above the estimates of up to 2 mg per kg body weight per day that some individuals may consume if they select foods and beverages relatively high in SO2 content. The margin of only about fifteenfold between the SO2 that may be ingested by high-intake consumers and the lowest estimated no observed adverse effect level is relatively narrow. However, consideration of the significance of this difference should recognize the difficulties in estimating with confidence the components which are the basis of the calculated margin. While the biological effects of sulfiting agents are still
incompletely understood, certain conclusions are warranted. There is no reason to believe the direct, local, irritating effects of sulfite, seen in high-dose acute toxicity tests, constitute a hazard from ingestion of sulfiting agents as they are presently used in foods. Orally administered sulfite is very rapidly oxidized to sulfate in all species studied. The metabolic removal of sulfite appears to be the critical defense mechanism, and this points to the important role of the enzyme, sulfite oxidase. Congenital deficiency of hepatic sulfite oxidase has been described as a rare metabolic disorder in man. There is also paucity of data on the normal development of this enzyme with age in various species, and on the possible effects of dietary factors and disease on sulfite oxidase activity. Moreover, sulfite is capable of deaminating cytosine in vitro and inhibiting several enzymes requiring NAD or pyridoxal as cofactors which suggests that sulfite might be toxic in vivo if sulfite
oxidase activity were sufficiently impaired or this metabolic mechanism were sufficiently overloaded, to prevent rapid oxidation of ingested sulfite to sulfate. Information in these respects would be helpful in assessing any special risk factors that may apply for select subpopulations. Destruction of thiamine can occur as a result of the sulfiting of foods but suffiecient thiamine is present in usual mixed diets, particularly because use of sulfiting agents is prohibited by regulation in foods known to be major sources of the vitamin. While there is no evidence that the sulfiting agents are teratogenic, there is evidence that directly added sulfite produces mutations in bacteria by alteration of nucleic acids. None of the available mammalian in vivo studies confirms these observations. Because the same organisms are not affected in the host-mediated assay, it seems reasonable to infer that rapid destruction of sulfite by the host's sulfite oxidase provides protection. In view of the
foregoing, the Select Committee concludes that: There is no evidence in the available information on potassium bisulfite, potassium metabisulfite, sodium bisulfite, sodium metabisulfite, sodium sulfite, and sulfur dioxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Potassium silicate | 1312-76-1 | 61 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
Silicon dioxide and various silicates occur abundantly in the earth's crust, are present in practically all natural waters,animals, and plants, and are part of the normal human diet. The question of whether or not silicon is an essential human nutrient remains unresolved. Silicon compounds consumed as added food ingredients contribute only a minor proportion of the total dietary silicon intake. The estimated possible human intake of sodium aluminosilicate, the predominant silicate added to foods in this country, is approximately 0.3mg per kg body weight per day. Silicon compounds that are GRAS for use as direct food ingredient, except potassium and sodium silicates, are insoluble or very slightly soluble in water and appear to be biologically inert. The water-soluble silicates are also of low acute toxicity. The acute oral LD50 in rats of sodium aluminosilicate is >1g per kg. No significant tissue accumulation, pathology, or
toxicity has been reported from the ingestion of those insoluble or very slightly soluble GRAS silicon compounds for which data are available. Of the five substances that were reported as added to foods in the NRC survey, biologic effects and safety data are available for all except sodium calcium aluminosilicate, and there is no reason to suspect that the toxicity of the latter would differ from those for which there are data. The results of two studies (1967-1970) in which various silicon compounds were fed to laboratory animals for 1 mo at a level of 0.8g per kg body weight (as silicon dioxide) and for 3 mo at levels of 6 to 30 mg per kg body weight suggests there may be a species-related susceptibility to renal damage from ingestion of sodium silicate, magnesium trisilicate, and finely ground quartz. No substantiating reports of these effects have appeared. Magnesium trisilicate was recognized as safe for prolonged use in human ingestion in large amount as a component of antacid
preparations by the Advisory Review Panel on Over-the-Counter Drugs, and the available evidence on the acute toxicity of sodium silicate indicates that it is low. Consumption data are lacking for aluminium calcium silicate and tricalcium silicate, two compounds that are listed as GRAS for use as anticaking agents. However, their use in keeping with good manufacturing practice and in currently regulated amounts would be of the same order of magnitude as the other GRAS silicates. In addition, the Select Committee has limited information on the amounts of talc that are currently used in foods. However a major food use of talc is in the coating of rice. Assuming package label statements are ignored and coated rice is not washed prior to cooking and no other losses occur, maximun per capita intake of talc from this source appears to be 0.5g per day. With respect to paper and cotton food- packaging products, the possibility is remote that biologically significant amounts of talc,
diatomaceous earth, or sodium silicate migrate to food from packaging, materials containing these substances. Perlite, a naturally occuring polysilicate substance, has an oral LD50 in the rat of >10g per kg body weight. Estimates of the maximun quantities of minerals that might be extracted from perlite and diatomaceous earth used as filteraids in food processing indicates no hazard to public health. There are no food grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc. Such specifications for the substances used in foods are desirable. Specification for food grade talc should limit the content of asbestos fibers even though the potential hazard of ingested asbestos fibers even though the potential hazard of ingested asbestos is not clearly established. The Food and Drug Administration is sponsoring the development of an assay method for asbestos fibers. An upper limit for cadmium should be added to the specifications for food-grade perlite, and
consideration should be given to the need for limitation of cadmium content of other silicates. In the light of all of the foregoing, the Select Committee concludes that: It is essential to establish food-grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc, with provision for an upper limit of asbestos fibers in talc. There is no evidence in the available information on aluminum calcium silicate, calcium silicate, magnesium silicate, potassium silicate, sodium silicate, sodium aluminosilicate, sodium calcium aluminosilicate, tricalcium silicate, silica aerogel, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on diatomaceous earth, silicon dioxides, sodium silicate, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the
public when they are used as ingredients of paper and paperboard products used in food packaging in accordance with current practice. There is no evidence in the available information on sodium silicate and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of cotton and cotton fabrics used in dry food packaging in accordance with current practice. There is no evidence in the available information on diatomaceous earth and perlite that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used as filteraids in food processing at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Potassium sorbate | 24634-61-5 | 57 | 1975 | 1 | 182.3640 |
SCOGS Opinion:
Sorbic acid and its salts demonstrate very low acute or chronic toxicity for experimental animals. In animals sorbate is metabolized by the normal fatty acid pathway. Although no metabolic or toxicological studies have been conducted in man, the similarity on the pathway of fatty acid metabolism in man and animals suggests that no deleterious effects are to be expected from sorbic acid in the diet even in amounts many times greater than those at which it appears to be used. Based on these considerations the Select Committee concludes that: There is no evidence in the available information on sorbic acid and its sodium, potassium and calcium salts that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Potato starch | 977000-07-9 | 115 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Pregelatinized starch | 9005-25-8 | 115 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Propionic acid | 79-09-4 | 79 | 1979 | 1 | 184.1081 |
SCOGS Opinion:
Propionic acid occurs naturally in various foods including butter and cheese. Its absorption and metabolism are demonstrated in experimental animals and humans where it is a normal intermediary metabolite. As incorporated in foods as its sodium or calcium salt or as the free acid, propionic acid does not occur at the concentrations or under the conditions that are necessary to produce signs of mucosal damage in experimental animals. Propionic acid, sodium propionate, and calcium propinate have demonstrated low acute toxicity after oral administration to mice or rats. The adverse effects observed in chicken embryos occurred only after injection of large amounts of calcium propionate or sodium propionate into the yolk sac, and the reversions observed in a host-mediated assay of calcium propionate were unrelated to dose. These results in chickenembryos and the host-mediated assay must be viewed in the light of other microbial
assays and animal studies that demonstrate no adverse effects and the fact that propionate is a normal intermediary metabolite. Microbial assays for mutagenicity of propionic acid and calcium and sodium propionate were negative. Investigations of the teratogenicity of calcium propionate in four mammalian systems also were negative. Short-term feeding tests show the most sensitive animals tested, young and vitamin B12-deficient animals, experience adverse effects on weight gain only when propionate intakes are many orders of magnitude greater than the estimate of human dietary intake of propionate used as a food ingredient, about 1 mg per kg per day. Long-term feeding studies of propionic acid and calcium propionate have not been reported. However, a long-term feeding study of sodium propionate showed no adverse effects in rats. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on propionic acid, calcium propionate, and
sodium propionate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Propyl Gallate | 121-79-9 | 11 | 1973 | 1 | 184.1660 |
SCOGS Opinion:
Although interpretation of some reports is difficult, particularly where propyl gallate has been studied in mextures with other antioxidants, it is evident that the no effect level of propyl gallate for the rat exceeds 100 mg per kg per day, and no effect levels of this order have also been reported for mice, guinea pigs and dogs. The Select Committee regards as reasonable the estimate of the FAO/WHO Expert committee on Food Additives of 100 mg per kg per day as the level of propyl gallate that causes no significant toxicological effect when fed to the rat. Using this estimate and the consumer exposure data in Section III, the highest no effect level of orally administered propyl gallate is more than 1,500 fold that usually present in an adult's daily diet and more than 400 fold that which would obtain if his diet were to consist only of those foods contaiing the maximum amount of propyl gallate. Moreover, the highest no effect
level is some 200 fold the maximum reported levels of consumption of the children who, according to the data in Section III, consume propyl gallate at the highest rates. In light of the foreoging the Select Committee concludes that: There is no evidence in the available information on propyl gallate that demonstrates it to be a hazard to the public when used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Propyl Paraben | 94-13-3 | 8 | 1972 | 1 | 184.1670 |
SCOGS Opinion:
The available information reveals that there are no short-term toxicological consequences in the rat, rabbit, cat, dog, or man and no long-term toxicological consequences in rats, of consuming the parabens in amounts greatly exceeding those currently consumed in the normal diet of the U.S. population. There is no evidence that consumption of the parabens as food ingredients has had an adverse effect on man in the 40 years they have been so used in the United States. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on the two parabens, methyl and proyl p-hydroxy-benzoic acid, that demonstrates a hazard to the public when they are used at levels that are now current or that might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Propylene Glycol | 57-55-6 | 27 | 1973 | 1 | 184.1666 |
SCOGS Opinion:
Propylene glycol is metabolized by animals and can be used as a carbohydrate source. Propylene glycol can be ingested over long periods of time and in substantial quantities (up to 5 percent of the total food intake) without causing frank toxic effects. Propylene glycol monostearate is readily hydrolysed in vivo and the propylene glycol and fatty acid moieties enter their respective metabolic pathways. At lethal or near lethal doses (6 g per kg or more), however, it has been reported to cause kidney damage in several species and toe deformities in chicks. These doses contrast with the few mg per kg per day estimated in Section III of this report to be the human daily dietary intake of propylene glycol. The Select Committee has weighed the available information and concludes that: There is no evidence in the available information on propylene glycol and propylene glycol monostearate that demonstrates, or suggests reason to
suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in future.
SCOGS Opinion:
The available information on the alginates reveals no significant adverse toxicological effects from oral administration in non-pregnant animals or humans in daily amounts greatly exceeding those currently consumed in the diet. However, in pregnant mice, very large doses of propylene glycol alginate, while not teratogenic, cause a significant increase in maternal mortality. Such increased maternal toxicity does not occur at a dose of propylene glycol alginate which is 26-fold or more greater than that estimated to be the average daily adult dietary intake. No respect but studies of propylene glycol, made by the same investigators and is without maternal toxicity even at very large doses. This indicates that the adverse effects reported for propylene glycol alginate may be due to the alginate moiety. It is noteworthy that similar toxic effects have been observed in identical tests on a large number of other polysaccarides (gum
arabic, sterculia gum, carob bean gum, guar gum, gum ghatti, gum tragacanth, carrageenan, methyl cellulose, and agar-agar) fed at very high levels. The relative sensitivity of the several animal species to these effects, varies depending on the particular polysaccaride tested, but in all cases very large doses are required. Until these effects have been adequately explained, it appears to be inappropriate to conclude that unrestricted use of such substances in food would be withou hazard. The Select Committee has weighed all of the foregoing and concludes that: There is no evidence in the available information on ammonium, calcium, potassium, sodium, and propylene glycol alginates that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption of these substances would
constitute a dietary hazard.
SCOGS Opinion:
Propylene glycol is metabolized by animals and can be used as a carbohydrate source. Propylene glycol can be ingested over long periods of time and in substantial quantities (up to 5 percent of the total food intake) without causing frank toxic effects. Propylene glycol monostearate is readily hydrolysed in vivo and the propylene glycol and fatty acid moieties enter their respective metabolic pathways. At lethal or near lethal doses (6 g per kg or more), however, it has been reported to cause kidney damage in several species and toe deformities in chicks. These doses contrast with the few mg per kg per day estimated in Section III of this report to be the human daily dietary intake of propylene glycol. The Select Committee has weighed the available information and concludes that: There is no evidence in the available information on propylene glycol and propylene glycol monostearate that demonstrates, or suggests reason to
suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Pulps (packaging) | 977139-78-8 | 40 | 1973 | 1 | 184.1673 |
SCOGS Opinion:
Since paper and paperboard packaging materials are not food but might be considered possible contaminants in food, it is not surprising that the Food Chemicals Codex does not include specifications for such materials. However, inasmuch as pulp from paper and paperboard can conceivably migrate to foods and thus become a food ingredient, specifications for paper used in connections with food, including limits with respect to source, abradability, and content of heavy metals and other possible toxicants, could be a useful, additional safeguard of food wholesomeness. In the meantime it is assumed that good manufacturing practice and quality control provide for adequate safeguards in the use of "food quality" cellulose and other pulp ingredients in the packaging materials used for food. In light of all the foregoing, the Select Committee concludes that: There is no evidence in the available information on pulps that demonstrates, or
suggests reasonable grounds to suspect, a hazard to the public when they are used in food packaging materials as now practiced or as they might be expected to be used for such purposes in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Pyridoxine | 65-23-6 | 100 | 1977 | 1 | There is no CFR citation. |
SCOGS Opinion:
Vitamin B6 compounds, after conversion to the active coenzyme form, pyridoxal phosphate, function in a variety of enzyme reaction that are metabolically essential. The vitamin is naturally present in a wide variety of foods. The Recommended Dietary Allowance is 2 mg per day for adults and 2.5mg per day during pregnancy, although it has been suggested that an intake as high as 15 to 30mg per day may be desirable for women during pregnancy or those using oral contraceptives. Thus, the daily per capita "intake" of 0.2 mg of pyridoxine hydrochloride per day (0.003mg per kg per day for adults) resulting from its addition to foods may amount to no more than 10 percent of the total intake. Available data are inadequate, because of variations in consumption patterns, for estimating the greatest amounts of pyridoxine hydrochloride added to foods that may be consumed by individuals in various age groups beyond infancy. For infants, such
variations are rare because a large percentage of the food intake may be derived from commercially prepared formulas fortified with pyridoxine hydrochloride. It is estimated that the largest consumption by infants of pyridoxine hydrochloride added to foods will be less than 0.1mg per kg body weight per day.
Oral administration of pyridoxine hydrochloride or pyridoxine base to experimental animals in doses of approximately 10mg per kg per day to more than 100mg per kg per day has not been associated with adverse effects, including effects on reproductive performance. Pyridoxine dependency has not been produced in offspring of animals given high doses of pyridoxine hydrochloride during pregnancy. The acute LD50 in animals generally ranges hydrochloride during pregnancy. The acute LD50 in animals generally ranges from 1000 to 6000mg per kg when administered orally. Patients with homocystinuria and other vitamin B6 dependency states have been given daily doses of 1 to 25 mg per kg per day for months without evidence of adverse reactions.
The Select Committee has no evidence that pyridoxine (ie., pyridoxine base) is added to foods in the United States. Even if it were, its safety threshold appears to be no different than that of pyridoxine hydrochloride.
In the light of these considerations, the Select Committee concludes that: There is no evidence in the available information on pyridoxine hydrochloride or pyridoxine that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Vitamin B6 compounds, after conversion to the active coenzyme form, pyridoxal phosphate, function in a variety of enzyme reaction that are metabolically essential. The vitamin is naturally present in a wide variety of foods. The Recommended Dietary Allowance is 2 mg per day for adults and 2.5mg per day during pregnancy, although it has been suggested that an intake as high as 15 to 30mg per day may be desirable for women during pregnancy or those using oral contraceptives. Thus, the daily per capita "intake" of 0.2 mg of pyridoxine hydrochloride per day (0.003mg per kg per day for adults) resulting from its addition to foods may amount to no more than 10 percent of the total intake. Available data are inadequate, because of variations in consumption patterns, for estimating the greatest amounts of pyridoxine hydrochloride added to foods that may be consumed by individuals in various age groups beyond infancy. For infants, such
variations are rare because a large percentage of the food intake may be derived from commercially prepared formulas fortified with pyridoxine hydrochloride. It is estimated that the largest consumption by infants of pyridoxine hydrochloride added to foods will be less than 0.1mg per kg body weight per day.
Oral administration of pyridoxine hydrochloride or pyridoxine base to experimental animals in doses of approximately 10mg per kg per day to more than 100mg per kg per day has not been associated with adverse effects, including effects on reproductive performance. Pyridoxine dependency has not been produced in offspring of animals given high doses of pyridoxine hydrochloride during pregnancy. The acute LD50 in animals generally ranges hydrochloride during pregnancy. The acute LD50 in animals generally ranges from 1000 to 6000mg per kg when administered orally. Patients with homocystinuria and other vitamin B6 dependency states have been given daily doses of 1 to 25 mg per kg per day for months without evidence of adverse reactions.
The Select Committee has no evidence that pyridoxine (ie., pyridoxine base) is added to foods in the United States. Even if it were, its safety threshold appears to be no different than that of pyridoxine hydrochloride.
In the light of these considerations, the Select Committee concludes that: There is no evidence in the available information on pyridoxine hydrochloride or pyridoxine that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Red algae | 977007-74-1 | 38 | 1973 | 1 | 184.1121 |
SCOGS Opinion:
The term, "algae", is too ill-defined to be a meaningful term in the context of the GRAS list. The uncertainty with respect to the source and the nature of these materials makes it imprecise to attempt to evaluate the health aspects of the use of substances that simply bear the designation brown algae, red algae, or algae. This is particularly pertinent because of the variation in the chemical constituency of the several species of algae that have been reported to be used in food. In addition, the fact that there are no data available on the usage or consuption of algae, kelp and dulse, raises a question as to whether or not any of these materials are now being used in foods in the United States.
The Select Commitee believes that the extent of actual use of algae, kelp, and dulse in food should be ascertained. If they are found to be used to any considerable extent, it would be advisable to identify them more definitely for regulatory purposes. Further, in view of the probable absortion of metals by algae from pollutes waters, permissible levels of mercury and other heavy metals should be specified for the materials so identified.
However, within this context, and in the light of available biological data, an interim conclusion can be drawn. The biological information available with respect to algae, dulse, and kelp and certain substances derived from the, is limited to studies on laminine monocitatrate and laminarin sulfate, and to feeding trials involving fooder containing dehydrated algal meals and dried seaweed prepared from several species of brown and red algae. These investigations, involving several animals species have revealed no evidence of adverse effects from the feeding the algal species tested or their derived products at levels that are orders of magnitude above those presumed to be used in foods in this country as ingredients of spices, seasonings, and flavorings.
The Select Commitee has weighed the foregoing and concludes that: There is no evidence in the available information on the brown algae (Laminaria sp. and Nereocystis sp.), also referred to as kelp, and the red algae, Porphyra sp. and Rhodymenia palmata (L.)Grev., also referred to as dulse, and the materials derived from these species, that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that now seem to be current or that might reasonably be expected in future if their use is confined to ingredients of spices, seasonings, and flavorings as is now stated in the Code of Federal Regulations.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Reduced Iron | 7439-89-6 | 35 | 1980 | 2 | 184.1375 |
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk of
developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an increase
in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report. Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to determination of the acute toxicity and bioavailability of specific
iron forms. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecdotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled chronic feeding studies with most of the individual compounds, before confident appraisal can be made of their relative merts or hazards.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
In the light of the above considerations, the Select Committee concludes that: There is no evidence in the available information on reduced, electrolytic, and carbonyl iron, ferrous ascorbate, ferrous carbonate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric citrate, ferric phosphate, or ferric pyrophosphate, that suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or in the manner now practiced., or if deemed necessary at somewhat higher levels to meet nutritional needs. However, it is not possible to determine without additional data whether a major increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk of
developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an increase
in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report. Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to determination of the acute toxicity and bioavailability of specific
iron forms. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecdotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled chronic feeding studies with most of the individual compounds, before confident appraisal can be made of their relative merts or hazards.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
In the light of the above considerations, the Select Committee concludes that: There is no evidence in the available information on reduced, electrolytic, and carbonyl iron, ferrous ascorbate, ferrous carbonate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric citrate, ferric phosphate, or ferric pyrophosphate, that suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or in the manner now practiced., or if deemed necessary at somewhat higher levels to meet nutritional needs. However, it is not possible to determine without additional data whether a major increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Rennet | 9042-08-4 | 76 | 1977 | 1 | 184.1685 |
SCOGS Opinion:
Rennet is an extract containing the milk-clotting enzime, rennin, that is obtained from edible tissues of animals commonly used for food. It has been used for centuries in the production of cheese. Consumption of cheese, the major source of rennet in the diet, adds to the diet an insignificant amount of rennet protein (0.06mg of which 0.003mg is rennin) and very small amounts (0.1 mg or less per person per day) of preservatives such as sodium benzoate or methyl and propyl parabens, levels at which the Select Committee found no evidence of hazard in previous evaluations. Although rennin is a protease, it is unlikely to exert significant proteolytic activity on the mucosa of the alimentary tract since it is ingested at very low concentrations in the presence of large amounts of substrate and would be rapidly inactivated by digestion. No adverse effects have been reported in infants fed milk coagulated with rennin preparations.
Teratogenicity tests on rennet by the chick embryo method have given negative results. In view of the foregoing, the Select Committee concludes that: There is no evidence in the available information on rennet that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when used at levels that are now current and in the manner now practiced, or those that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Riboflavin | 83-88-5 | 114 | 1979 | 1 | 184.1695 |
SCOGS Opinion:
Riboflavin, an essential nutrient, is a constituent of two coenzymes: riboflavin-5'-phosphate [flavin mononucleotide (FMN)] and flavin adenine dinucleotide (FAD), which are essential components of a number of oxidative enzyme systems. Various foods such as bakery, cereal and pasta products are commonly enriched by the addition of 2 to 5 mg per kg products. Also, many commonly used vitamin supplements contain riboflavin. The amount of riboflavin-5'-phosphate added to food is minuscule.
The Recommended Dietary Allowance of riboflavin is 0.6mg per 1000kcal for persons of all ages with an additional 0.3mg daily for pregnant and 0.5mg for lactating women. A recent U.S. survey of over 20,000 persons, 1 to 74 years of age, revealed a mean average intake of 1.92 and a median of 1.69mg per day.
The acute toxicity in animals of riboflavin or FMN given orally is extremely low, with LD50 values several orders of magnitude greater than the dietary requirements or the estimated addition to food. The relative insolubility of riboflavin limits the absortion when large amounts are ingested. No reports have come to the attention of the Select Committee suggesting carcinogenic, mutagenic, or teratogenic effects of riboflavin. Normal reproductive performance was observed in three generations of rats fed several hundred times their daily requirements. Toxic effects in man have not been reported apart from rare instances of sensitivity.
In light of these considerations, the Select Committee concludes that: There is no evidence in the available information on riboflavin or riboflavin-5'-phosphate that demonstrates or suggest reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Riboflavin, an essential nutrient, is a constituent of two coenzymes: riboflavin-5'-phosphate [flavin mononucleotide (FMN)] and flavin adenine dinucleotide (FAD), which are essential components of a number of oxidative enzyme systems. Various foods such as bakery, cereal and pasta products are commonly enriched by the addition of 2 to 5 mg per kg products. Also, many commonly used vitamin supplements contain riboflavin. The amount of riboflavin-5'-phosphate added to food is minuscule.
The Recommended Dietary Allowance of riboflavin is 0.6mg per 1000kcal for persons of all ages with an additional 0.3mg daily for pregnant and 0.5mg for lactating women. A recent U.S. survey of over 20,000 persons, 1 to 74 years of age, revealed a mean average intake of 1.92 and a median of 1.69mg per day.
The acute toxicity in animals of riboflavin or FMN given orally is extremely low, with LD50 values several orders of magnitude greater than the dietary requirements or the estimated addition to food. The relative insolubility of riboflavin limits the absortion when large amounts are ingested. No reports have come to the attention of the Select Committee suggesting carcinogenic, mutagenic, or teratogenic effects of riboflavin. Normal reproductive performance was observed in three generations of rats fed several hundred times their daily requirements. Toxic effects in man have not been reported apart from rare instances of sensitivity.
In light of these considerations, the Select Committee concludes that: There is no evidence in the available information on riboflavin or riboflavin-5'-phosphate that demonstrates or suggest reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Rice Starch | 977000-08-0 | 115 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Silica aerogel | 977052-02-0 | 61 | 1979 | 1 | 182.1711 |
SCOGS Opinion:
Silicon dioxide and various silicates occur abundantly in the earth's crust, are present in practically all natural waters,animals, and plants, and are part of the normal human diet. The question of whether or not silicon is an essential human nutrient remains unresolved. Silicon compounds consumed as added food ingredients contribute only a minor proportion of the total dietary silicon intake. The estimated possible human intake of sodium aluminosilicate, the predominant silicate added to foods in this country, is approximately 0.3mg per kg body weight per day. Silicon compounds that are GRAS for use as direct food ingredient, except potassium and sodium silicates, are insoluble or very slightly soluble in water and appear to be biologically inert. The water-soluble silicates are also of low acute toxicity. The acute oral LD50 in rats of sodium aluminosilicate is >1g per kg. No significant tissue accumulation, pathology, or
toxicity has been reported from the ingestion of those insoluble or very slightly soluble GRAS silicon compounds for which data are available. Of the five substances that were reported as added to foods in the NRC survey, biologic effects and safety data are available for all except sodium calcium aluminosilicate, and there is no reason to suspect that the toxicity of the latter would differ from those for which there are data. The results of two studies (1967-1970) in which various silicon compounds were fed to laboratory animals for 1 mo at a level of 0.8g per kg body weight (as silicon dioxide) and for 3 mo at levels of 6 to 30 mg per kg body weight suggests there may be a species-related susceptibility to renal damage from ingestion of sodium silicate, magnesium trisilicate, and finely ground quartz. No substantiating reports of these effects have appeared. Magnesium trisilicate was recognized as safe for prolonged use in human ingestion in large amount as a component of antacid
preparations by the Advisory Review Panel on Over-the-Counter Drugs, and the available evidence on the acute toxicity of sodium silicate indicates that it is low. Consumption data are lacking for aluminium calcium silicate and tricalcium silicate, two compounds that are listed as GRAS for use as anticaking agents. However, their use in keeping with good manufacturing practice and in currently regulated amounts would be of the same order of magnitude as the other GRAS silicates. In addition, the Select Committee has limited information on the amounts of talc that are currently used in foods. However a major food use of talc is in the coating of rice. Assuming package label statements are ignored and coated rice is not washed prior to cooking and no other losses occur, maximun per capita intake of talc from this source appears to be 0.5g per day. With respect to paper and cotton food- packaging products, the possibility is remote that biologically significant amounts of talc,
diatomaceous earth, or sodium silicate migrate to food from packaging, materials containing these substances. Perlite, a naturally occuring polysilicate substance, has an oral LD50 in the rat of >10g per kg body weight. Estimates of the maximun quantities of minerals that might be extracted from perlite and diatomaceous earth used as filteraids in food processing indicates no hazard to public health. There are no food grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc. Such specifications for the substances used in foods are desirable. Specification for food grade talc should limit the content of asbestos fibers even though the potential hazard of ingested asbestos fibers even though the potential hazard of ingested asbestos is not clearly established. The Food and Drug Administration is sponsoring the development of an assay method for asbestos fibers. An upper limit for cadmium should be added to the specifications for food-grade perlite, and
consideration should be given to the need for limitation of cadmium content of other silicates. In the light of all of the foregoing, the Select Committee concludes that: It is essential to establish food-grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc, with provision for an upper limit of asbestos fibers in talc. There is no evidence in the available information on aluminum calcium silicate, calcium silicate, magnesium silicate, potassium silicate, sodium silicate, sodium aluminosilicate, sodium calcium aluminosilicate, tricalcium silicate, silica aerogel, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on diatomaceous earth, silicon dioxides, sodium silicate, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the
public when they are used as ingredients of paper and paperboard products used in food packaging in accordance with current practice. There is no evidence in the available information on sodium silicate and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of cotton and cotton fabrics used in dry food packaging in accordance with current practice. There is no evidence in the available information on diatomaceous earth and perlite that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used as filteraids in food processing at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Silicon dioxides | 14808-60-7 | 61 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
Silicon dioxide and various silicates occur abundantly in the earth's crust, are present in practically all natural waters,animals, and plants, and are part of the normal human diet. The question of whether or not silicon is an essential human nutrient remains unresolved. Silicon compounds consumed as added food ingredients contribute only a minor proportion of the total dietary silicon intake. The estimated possible human intake of sodium aluminosilicate, the predominant silicate added to foods in this country, is approximately 0.3mg per kg body weight per day. Silicon compounds that are GRAS for use as direct food ingredient, except potassium and sodium silicates, are insoluble or very slightly soluble in water and appear to be biologically inert. The water-soluble silicates are also of low acute toxicity. The acute oral LD50 in rats of sodium aluminosilicate is >1g per kg. No significant tissue accumulation, pathology, or
toxicity has been reported from the ingestion of those insoluble or very slightly soluble GRAS silicon compounds for which data are available. Of the five substances that were reported as added to foods in the NRC survey, biologic effects and safety data are available for all except sodium calcium aluminosilicate, and there is no reason to suspect that the toxicity of the latter would differ from those for which there are data. The results of two studies (1967-1970) in which various silicon compounds were fed to laboratory animals for 1 mo at a level of 0.8g per kg body weight (as silicon dioxide) and for 3 mo at levels of 6 to 30 mg per kg body weight suggests there may be a species-related susceptibility to renal damage from ingestion of sodium silicate, magnesium trisilicate, and finely ground quartz. No substantiating reports of these effects have appeared. Magnesium trisilicate was recognized as safe for prolonged use in human ingestion in large amount as a component of antacid
preparations by the Advisory Review Panel on Over-the-Counter Drugs, and the available evidence on the acute toxicity of sodium silicate indicates that it is low. Consumption data are lacking for aluminium calcium silicate and tricalcium silicate, two compounds that are listed as GRAS for use as anticaking agents. However, their use in keeping with good manufacturing practice and in currently regulated amounts would be of the same order of magnitude as the other GRAS silicates. In addition, the Select Committee has limited information on the amounts of talc that are currently used in foods. However a major food use of talc is in the coating of rice. Assuming package label statements are ignored and coated rice is not washed prior to cooking and no other losses occur, maximun per capita intake of talc from this source appears to be 0.5g per day. With respect to paper and cotton food- packaging products, the possibility is remote that biologically significant amounts of talc,
diatomaceous earth, or sodium silicate migrate to food from packaging, materials containing these substances. Perlite, a naturally occuring polysilicate substance, has an oral LD50 in the rat of >10g per kg body weight. Estimates of the maximun quantities of minerals that might be extracted from perlite and diatomaceous earth used as filteraids in food processing indicates no hazard to public health. There are no food grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc. Such specifications for the substances used in foods are desirable. Specification for food grade talc should limit the content of asbestos fibers even though the potential hazard of ingested asbestos fibers even though the potential hazard of ingested asbestos is not clearly established. The Food and Drug Administration is sponsoring the development of an assay method for asbestos fibers. An upper limit for cadmium should be added to the specifications for food-grade perlite, and
consideration should be given to the need for limitation of cadmium content of other silicates. In the light of all of the foregoing, the Select Committee concludes that: It is essential to establish food-grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc, with provision for an upper limit of asbestos fibers in talc. There is no evidence in the available information on aluminum calcium silicate, calcium silicate, magnesium silicate, potassium silicate, sodium silicate, sodium aluminosilicate, sodium calcium aluminosilicate, tricalcium silicate, silica aerogel, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on diatomaceous earth, silicon dioxides, sodium silicate, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the
public when they are used as ingredients of paper and paperboard products used in food packaging in accordance with current practice. There is no evidence in the available information on sodium silicate and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of cotton and cotton fabrics used in dry food packaging in accordance with current practice. There is no evidence in the available information on diatomaceous earth and perlite that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used as filteraids in food processing at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium acetate | 977127-84-6 | 82 | 1977 | 1 | 184.1721 |
SCOGS Opinion:
Acetates are common constituents of plant and animal tissues. They are normal metabolic intermediates produced in relatively large quantities during the digestion and metabolism of foods.
Although the Select Committee is not aware of any long-term feeding studies of acetic acid or the acetates, short term studies have revealed no untoward effects at concentrations far exceeding those consumed in the normal diet and do not suggests that adverse effects might be revealed by longer term studies.
No data on carcinogenic evaluation of acetic acid and the acetate salts have come to the attention of the Select Committee. Limited data indicate that acetic acid is not teratogenic in vivo; sodium acetate is not mutagenic and acetic acid is probably not mutagenic in vitro.
No reports of biological studies on sodium diacetate have been found, but since this substance dissociates in the body to sodium acetate and acetic acid, neither of which elicits adverse effects under current conditions of use, the Select Committee beleives that use of sodium diacetate can be considered to be without adverse effects.
In light of these considerations, the Select Committee concludes that: There is no evidence in the available information on acetic acid, sodium acetate, and sodium diacetate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium alginate | 9005-38-3 | 24 | 1973 | 2 | 184.1724 |
SCOGS Opinion:
The available information on the alginates reveals no significant adverse toxicological effects from oral administration in non-pregnant animals or humans in daily amounts greatly exceeding those currently consumed in the diet. However, in pregnant mice, very large doses of propylene glycol alginate, while not teratogenic, cause a significant increase in maternal mortality. Such increased maternal toxicity does not occur at a dose of propylene glycol alginate which is 26-fold or more greater than that estimated to be the average daily adult dietary intake. No respect but studies of propylene glycol, made by the same investigators and is without maternal toxicity even at very large doses. This indicates that the adverse effects reported for propylene glycol alginate may be due to the alginate moiety. It is noteworthy that similar toxic effects have been observed in identical tests on a large number of other polysaccarides (gum
arabic, sterculia gum, carob bean gum, guar gum, gum ghatti, gum tragacanth, carrageenan, methyl cellulose, and agar-agar) fed at very high levels. The relative sensitivity of the several animal species to these effects, varies depending on the particular polysaccaride tested, but in all cases very large doses are required. Until these effects have been adequately explained, it appears to be inappropriate to conclude that unrestricted use of such substances in food would be withou hazard. The Select Committee has weighed all of the foregoing and concludes that: There is no evidence in the available information on ammonium, calcium, potassium, sodium, and propylene glycol alginates that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption of these substances would
constitute a dietary hazard.
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
SCOGS Opinion:
Silicon dioxide and various silicates occur abundantly in the earth's crust, are present in practically all natural waters,animals, and plants, and are part of the normal human diet. The question of whether or not silicon is an essential human nutrient remains unresolved. Silicon compounds consumed as added food ingredients contribute only a minor proportion of the total dietary silicon intake. The estimated possible human intake of sodium aluminosilicate, the predominant silicate added to foods in this country, is approximately 0.3mg per kg body weight per day. Silicon compounds that are GRAS for use as direct food ingredient, except potassium and sodium silicates, are insoluble or very slightly soluble in water and appear to be biologically inert. The water-soluble silicates are also of low acute toxicity. The acute oral LD50 in rats of sodium aluminosilicate is >1g per kg. No significant tissue accumulation, pathology, or
toxicity has been reported from the ingestion of those insoluble or very slightly soluble GRAS silicon compounds for which data are available. Of the five substances that were reported as added to foods in the NRC survey, biologic effects and safety data are available for all except sodium calcium aluminosilicate, and there is no reason to suspect that the toxicity of the latter would differ from those for which there are data. The results of two studies (1967-1970) in which various silicon compounds were fed to laboratory animals for 1 mo at a level of 0.8g per kg body weight (as silicon dioxide) and for 3 mo at levels of 6 to 30 mg per kg body weight suggests there may be a species-related susceptibility to renal damage from ingestion of sodium silicate, magnesium trisilicate, and finely ground quartz. No substantiating reports of these effects have appeared. Magnesium trisilicate was recognized as safe for prolonged use in human ingestion in large amount as a component of antacid
preparations by the Advisory Review Panel on Over-the-Counter Drugs, and the available evidence on the acute toxicity of sodium silicate indicates that it is low. Consumption data are lacking for aluminium calcium silicate and tricalcium silicate, two compounds that are listed as GRAS for use as anticaking agents. However, their use in keeping with good manufacturing practice and in currently regulated amounts would be of the same order of magnitude as the other GRAS silicates. In addition, the Select Committee has limited information on the amounts of talc that are currently used in foods. However a major food use of talc is in the coating of rice. Assuming package label statements are ignored and coated rice is not washed prior to cooking and no other losses occur, maximun per capita intake of talc from this source appears to be 0.5g per day. With respect to paper and cotton food- packaging products, the possibility is remote that biologically significant amounts of talc,
diatomaceous earth, or sodium silicate migrate to food from packaging, materials containing these substances. Perlite, a naturally occuring polysilicate substance, has an oral LD50 in the rat of >10g per kg body weight. Estimates of the maximun quantities of minerals that might be extracted from perlite and diatomaceous earth used as filteraids in food processing indicates no hazard to public health. There are no food grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc. Such specifications for the substances used in foods are desirable. Specification for food grade talc should limit the content of asbestos fibers even though the potential hazard of ingested asbestos fibers even though the potential hazard of ingested asbestos is not clearly established. The Food and Drug Administration is sponsoring the development of an assay method for asbestos fibers. An upper limit for cadmium should be added to the specifications for food-grade perlite, and
consideration should be given to the need for limitation of cadmium content of other silicates. In the light of all of the foregoing, the Select Committee concludes that: It is essential to establish food-grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc, with provision for an upper limit of asbestos fibers in talc. There is no evidence in the available information on aluminum calcium silicate, calcium silicate, magnesium silicate, potassium silicate, sodium silicate, sodium aluminosilicate, sodium calcium aluminosilicate, tricalcium silicate, silica aerogel, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on diatomaceous earth, silicon dioxides, sodium silicate, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the
public when they are used as ingredients of paper and paperboard products used in food packaging in accordance with current practice. There is no evidence in the available information on sodium silicate and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of cotton and cotton fabrics used in dry food packaging in accordance with current practice. There is no evidence in the available information on diatomaceous earth and perlite that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used as filteraids in food processing at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium Benzoate | 532-32-1 | 7 | 1973 | 1 | 184.1733 |
SCOGS Opinion:
There are extensive metabolic data on benzoic acid and sodium benzoate in experimental animals and man. It appears that the rat and human have similar metabolic pathways. Short- and long-term feeding studies, as well as teratological investigations, have also been reported in the rat. Interpolation of the rat data and consumer exposure data indicates that the highest no effect level reported in the long-term laboratory feeding study of sodim benzoate is approximately 180 fold the amount usually present in man's daily diet. The highest no effect level reported in laboratoy animal feeding is approximately 90 fold the amount that would be consumed if an individual's diet were to consist only of those foods containng the greatest amoutns of sodium benzoate in current usage. In the light of the foregoing the Select Committee concludes that: There is no evidence in the available information to show that benzoic acid and sodium benzoate
as food ingredients constitute a hazard to the general public when used at levels that are now current or that might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium bicarbonate | 144-55-8 | 26 | 1975 | 1 | 184.1736 |
SCOGS Opinion:
The Select committee is not aware of any long-term experimental studies on chronic administration of any of the carbonate salts. The results of acute toxicity and short-term feeding experiments are not readily extrapolated in determining toxic levels for carbonate salts consumed by humans. Treatment of gastric or peptic ulcers in patients with large amounts of carbonate salts in various forms has been utilized for many years and only rarely have deleterious results of changes of acid-base balance been reported. When the human respiratory and renal functions are normal, the mechanisms for disposing of bicarbonate intake in large amounts through excretion appear to be highly efficient. Studies of mice suggest that large intakes of calcium carbonate may interfere with reproductive performance. Such effects could be indirectly attributable to certain trace nutrient deficiences. Comparable intake levels of calcium may occur when
calcium carbonate is used for therapeutic purposes but the amounts added to foods in normal manufacturing processes are not high enough to be harmful. While the Select Committee is not aware of any studies on sodium sequicarbonate per se, reasoned judgment suggests its biochemical conversion and metabolism would be similar to that of sodium carbonate and bicarbonate. On the consideration of the foregoing, the Select Committee concludes that: There is no evidence in the available information on calcium carbonate, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, or sodium sesquicarbonate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium bisulfite | 7631-90-5 | 15 | 1976 | 2 | 182.3739 |
SCOGS Opinion:
Based upon chronic toxicity tests in animals, primarily in rats, the no observed adverse effect level of SO2 is estimated to be in the range of 30 to 100 mg of SO2 per kg of body weight per day. These values are considerably higher than the estimated average per capita consumption of about 0.2 mg of SO2 equivalent per kg body weight per day, and well above the estimates of up to 2 mg per kg body weight per day that some individuals may consume if they select foods and beverages relatively high in SO2 content. The margin of only about fifteenfold between the SO2 that may be ingested by high-intake consumers and the lowest estimated no observed adverse effect level is relatively narrow. However, consideration of the significance of this difference should recognize the difficulties in estimating with confidence the components which are the basis of the calculated margin. While the biological effects of sulfiting agents are still
incompletely understood, certain conclusions are warranted. There is no reason to believe the direct, local, irritating effects of sulfite, seen in high-dose acute toxicity tests, constitute a hazard from ingestion of sulfiting agents as they are presently used in foods. Orally administered sulfite is very rapidly oxidized to sulfate in all species studied. The metabolic removal of sulfite appears to be the critical defense mechanism, and this points to the important role of the enzyme, sulfite oxidase. Congenital deficiency of hepatic sulfite oxidase has been described as a rare metabolic disorder in man. There is also paucity of data on the normal development of this enzyme with age in various species, and on the possible effects of dietary factors and disease on sulfite oxidase activity. Moreover, sulfite is capable of deaminating cytosine in vitro and inhibiting several enzymes requiring NAD or pyridoxal as cofactors which suggests that sulfite might be toxic in vivo if sulfite
oxidase activity were sufficiently impaired or this metabolic mechanism were sufficiently overloaded, to prevent rapid oxidation of ingested sulfite to sulfate. Information in these respects would be helpful in assessing any special risk factors that may apply for select subpopulations. Destruction of thiamine can occur as a result of the sulfiting of foods but suffiecient thiamine is present in usual mixed diets, particularly because use of sulfiting agents is prohibited by regulation in foods known to be major sources of the vitamin. While there is no evidence that the sulfiting agents are teratogenic, there is evidence that directly added sulfite produces mutations in bacteria by alteration of nucleic acids. None of the available mammalian in vivo studies confirms these observations. Because the same organisms are not affected in the host-mediated assay, it seems reasonable to infer that rapid destruction of sulfite by the host's sulfite oxidase provides protection. In view of the
foregoing, the Select Committee concludes that: There is no evidence in the available information on potassium bisulfite, potassium metabisulfite, sodium bisulfite, sodium metabisulfite, sodium sulfite, and sulfur dioxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
Silicon dioxide and various silicates occur abundantly in the earth's crust, are present in practically all natural waters,animals, and plants, and are part of the normal human diet. The question of whether or not silicon is an essential human nutrient remains unresolved. Silicon compounds consumed as added food ingredients contribute only a minor proportion of the total dietary silicon intake. The estimated possible human intake of sodium aluminosilicate, the predominant silicate added to foods in this country, is approximately 0.3mg per kg body weight per day. Silicon compounds that are GRAS for use as direct food ingredient, except potassium and sodium silicates, are insoluble or very slightly soluble in water and appear to be biologically inert. The water-soluble silicates are also of low acute toxicity. The acute oral LD50 in rats of sodium aluminosilicate is >1g per kg. No significant tissue accumulation, pathology, or
toxicity has been reported from the ingestion of those insoluble or very slightly soluble GRAS silicon compounds for which data are available. Of the five substances that were reported as added to foods in the NRC survey, biologic effects and safety data are available for all except sodium calcium aluminosilicate, and there is no reason to suspect that the toxicity of the latter would differ from those for which there are data. The results of two studies (1967-1970) in which various silicon compounds were fed to laboratory animals for 1 mo at a level of 0.8g per kg body weight (as silicon dioxide) and for 3 mo at levels of 6 to 30 mg per kg body weight suggests there may be a species-related susceptibility to renal damage from ingestion of sodium silicate, magnesium trisilicate, and finely ground quartz. No substantiating reports of these effects have appeared. Magnesium trisilicate was recognized as safe for prolonged use in human ingestion in large amount as a component of antacid
preparations by the Advisory Review Panel on Over-the-Counter Drugs, and the available evidence on the acute toxicity of sodium silicate indicates that it is low. Consumption data are lacking for aluminium calcium silicate and tricalcium silicate, two compounds that are listed as GRAS for use as anticaking agents. However, their use in keeping with good manufacturing practice and in currently regulated amounts would be of the same order of magnitude as the other GRAS silicates. In addition, the Select Committee has limited information on the amounts of talc that are currently used in foods. However a major food use of talc is in the coating of rice. Assuming package label statements are ignored and coated rice is not washed prior to cooking and no other losses occur, maximun per capita intake of talc from this source appears to be 0.5g per day. With respect to paper and cotton food- packaging products, the possibility is remote that biologically significant amounts of talc,
diatomaceous earth, or sodium silicate migrate to food from packaging, materials containing these substances. Perlite, a naturally occuring polysilicate substance, has an oral LD50 in the rat of >10g per kg body weight. Estimates of the maximun quantities of minerals that might be extracted from perlite and diatomaceous earth used as filteraids in food processing indicates no hazard to public health. There are no food grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc. Such specifications for the substances used in foods are desirable. Specification for food grade talc should limit the content of asbestos fibers even though the potential hazard of ingested asbestos fibers even though the potential hazard of ingested asbestos is not clearly established. The Food and Drug Administration is sponsoring the development of an assay method for asbestos fibers. An upper limit for cadmium should be added to the specifications for food-grade perlite, and
consideration should be given to the need for limitation of cadmium content of other silicates. In the light of all of the foregoing, the Select Committee concludes that: It is essential to establish food-grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc, with provision for an upper limit of asbestos fibers in talc. There is no evidence in the available information on aluminum calcium silicate, calcium silicate, magnesium silicate, potassium silicate, sodium silicate, sodium aluminosilicate, sodium calcium aluminosilicate, tricalcium silicate, silica aerogel, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on diatomaceous earth, silicon dioxides, sodium silicate, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the
public when they are used as ingredients of paper and paperboard products used in food packaging in accordance with current practice. There is no evidence in the available information on sodium silicate and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of cotton and cotton fabrics used in dry food packaging in accordance with current practice. There is no evidence in the available information on diatomaceous earth and perlite that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used as filteraids in food processing at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium carbonate | 497-19-8 | 26 | 1975 | 1 | 184.1742 |
SCOGS Opinion:
The Select committee is not aware of any long-term experimental studies on chronic administration of any of the carbonate salts. The results of acute toxicity and short-term feeding experiments are not readily extrapolated in determining toxic levels for carbonate salts consumed by humans. Treatment of gastric or peptic ulcers in patients with large amounts of carbonate salts in various forms has been utilized for many years and only rarely have deleterious results of changes of acid-base balance been reported. When the human respiratory and renal functions are normal, the mechanisms for disposing of bicarbonate intake in large amounts through excretion appear to be highly efficient. Studies of mice suggest that large intakes of calcium carbonate may interfere with reproductive performance. Such effects could be indirectly attributable to certain trace nutrient deficiences. Comparable intake levels of calcium may occur when
calcium carbonate is used for therapeutic purposes but the amounts added to foods in normal manufacturing processes are not high enough to be harmful. While the Select Committee is not aware of any studies on sodium sequicarbonate per se, reasoned judgment suggests its biochemical conversion and metabolism would be similar to that of sodium carbonate and bicarbonate. On the consideration of the foregoing, the Select Committee concludes that: There is no evidence in the available information on calcium carbonate, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, or sodium sesquicarbonate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Cellulose is a major constituent of many foods of plant origin. As such it is a significant portion of the diet, but is neither degraded nor absorbed. Cellulose derivatives considered in this report are virtually unabsorbed and little or no degradation of absorbed and little or no degradation of absorbable products occurs in the human digestive tract. In man, consumption of large amounts appears to have no effect other than providing dietary bulk, reducing the nutritive value of such foodstuffs and possibly exerting a laxative effect. However, the existence of certain data and the different categorization of cellulose and the several cellulose derivatives on the GRAS list suggest that the Select Committee should render a separate opinion on each substance considered in this report.
A. CELLULOSE, MICROCRYSTALLINE CELLULOSE
Although pure cellulose and regenerated cellulose, including microcrystalline cellulose are not on the GRAS list, there is nothing in the available information to suggest that such forms of cellulose have significantly different biological properties that distinguish these forms of cellulose from those currently considered as GRAS or from naturally occurring cellulose. In view of the foregoing, the Select Committee concludes that: There is no evidence in the available information on pure and regenerated cellulose, including microcrystalline cellulose, that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current, or that might reasonably be expected in future.
B. METHYL CELLULOSE
In humans, virtually 100 percent of orally ingested methyl cellulose can be recovered in the feces withihn four days, indicating that absorption does not occur. However, in pregnant mice, very high doses of methyl cellulose, while not teratogenic, cause a significant increase in maternal mortality and retardation of fetal maturation. Such increased maternal and fetal toxicity does not occur at a dose of methyl cellulose which is 26-fold (or more) greater than that estimated to be the average daily adult dietary intake. It is noteworthy in this regard that similar toxic effects have been observed in identical tests performed by the same investigators on a large number of other polysaccharides fed at very high doses. The relative sensitivity of the several animal species to these effects varies, depending on the particular polysaccharide tested, but in all cases very large doses are required. Until these effects have been adequately explained, it appears to be inappropriate to conclude
that unrestricted use of such substances in food would be without hazard. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on methyl cellulose that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
C. CARBOXYMETHYL CELLULOSE
Carboxymethyl cellulose is converted spontaneously to a salt in alkaline solution, and it is probable that the distinction between carboxymethyl cellulose and its salts is artificial. However, carboxymethyl cellulose is liested as GRAS as a substance migrating to food from cotton or cotton fabrice used in dry foods packaging, while its sodium salt is listed as GRAS as a miscellaneous or general purpose food additive. In view of the separate listing of carboxymethyl cellulose, the Select Committee concludes that: There is no evidence in the available information on carboxymethyl cellulose that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used in dry food packaing materials originating from cotton or cotton fabrics as now practed or as it might reasonably be expected to be used for such purposes in future.
D. SODIUM CARBOXYMETHYL CELLULOSE
Despite the probable lack of distinction between sodium carboxy methyl cellulose and its parent compound, carboxymethyl cellulose, only the sodium carboxymethyl cellulose is GRAS as a miscellaneous and general purpose food additive. As such, there are no data that suggest it reacts differently than pure and regenerated cellulose or carboxymethyl cellulose. In view of the foregoing the Select Committee concludes that: There is no evidence in the available information on sodium carboxymethyl cellulose that demonstrtes, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in future.
E. HYDROXYPROPYLMETHYL CELLULOSE
Hydroxypropylmethyl cellulose is not listed as GRAS. It is a food additive used as a thickening agent, stabilizer and emulsifier. Hydroxypropylmethyl cellulose is sinthesized from methyl cellulose by the action of alkali and propylene oxide. There are no data available to suggest that hydroxypropylmethyl cellulose possesses adverse health effects; however, teratology studies dimilar to those conducted with mehtyl cellulose are not available for its hydroxypropyl derivative. Therefore, it is suggested that, in due course, appropriate studies should be conducted with hydroxypropylmethyl cellulose. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on hydroxypropylmethyl cellulose that demonstrates, or suggested reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current and in the manner now practiced (21 CFR 121.1021)
F. ETHYL CELLULOSE AND CELLULOSE ACETATE
There is a paucity of data concerning possible adverse health effects of ethyl cellulose and cellulose acetate. both are included in the GRAS list as substances migrating to food from paper or paperboard products used in food packaging. According to the NRC survey (6), very small amounts of ethyl cellulose also appear to be used in hard candy and chewing gum. In the GRAS context, the quantity of ethyl cellulose or cellulose acetate migrating to foods from packaging would be orders of magnitude below the levels of cellulose and cellulose derivaties now known to occur in foods. In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on ethyl cellulose and cellulose acetate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used in food packaging materials as now practiced or as they might be expeccted to be used for such purposes in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium caseinate | 9005-46-3 | 96 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
Casein in milk and milk products has been a major component of the diet of man for centuries. Long term animal feeding studies have shown that extremely high dietary levels of casein, in common with other food proteins, may be injurious to the kidneys. However, per capita daily consumption of casein and caseinates added to foods is less than 0.2g and represents a minor contribution to the total average daily intake of protein, about 99g, by the U.S. population.
Heating casein under strongly alkaline conditions at 90°C or autoclaving at higher temperature under near neutral conditions has been shown to result in the formation of lysinoalanine as a component of the protein molecule. Lysinoalanine has been reported in commercial samples of casein, calcium caseinate, and sodium caseinate. Lysinoalanine also has been detected at relatively low concentration in a number of commercial food products and in home-cooked frankfurters, chicken, and egg white.
Sensitivity to lysinoalanine differs among animals species and is dependent on the protein nature of the diet; feeding free lysinoalanine at dietary levels of 1000 ppm to five mammalian species other than the rat, including subhuman primates, failed to produce renal cytomegalic changes. Renal cytomegalic changes have been demonstrated in rats fed free lysinoalanine, or alkalitreated soy protein isolate, lactalbumin or casein containing bound lysinoalanine. The alkali-treated proteins were fed as the sole source of protein at dietary levels of 20 to 30 percent; cytomegaly did not occur or was markedly reduced in rats fed diets in which alkali-treated protein was supplemented with an untreated protein, suggesting that the renal syndrome was caused by protein bound lysinoalanine in diets deficient or imbalanced with respect to one or more amino acids. Although the available information indicates that the present consumption levels of casein and caseinates, less than 0.2g per capita as
currently used, pose no hazard to the consumer,a limitation with respect to lysinoalanine content in specifications for food grade products would avoid possible future problems in this regard.
A small proportion of infants and lesser numbers of children and adults experience untoward reactions to casein and other milk proteins. Casein is only mildly antigenic but the presence of whey proteins in commercial casein may increase the frequency of hypersensitivity reactions. However, the relatively low consumption of casein, sodium and calcium caseinates added to processed foods, as compared to consumption of casein in milk, cheese, other dairy products, and foods containing dairy products as an ingredient, does not appear to significantly exposure to this antigen.
Although few nitrite analyses of caseinates dried in direct fired spray driers were available to the Select Committee, the available data and the finding of nitrite in samples of other products dried in similar equipment indicates that nitrite can occur at low levels in spray-dried products. According to available information, casein and some caseinates are dried in indirectly heated driers and would not be exposed to nitrite from the drying gases. Nitrite content is of concern because of its toxicity, per se, and because it can react with other nitrogen containing compounds to produce nitrosamines, many of which have been shown to be carcinogenic in experimental animals. It is important to ensure that preformed nitrosamines are not present in caseinates and are not formed in processed foods containing caseinates.
Consideration must be given to the potential for nitrosamine formation in vivo from ingestion of foods containing nitrite, and the latter reacting with other nitrogen containing compounds in foods, drugs, and endogenous amines, must be considered. Many natural and processed foods, including spraydried products, contribute to the total human intake of nitrite even though bacterial reduction of nitrate to nitrate in saliva is the mejor source of nitrite entering the stomach.
It has been reported from recent unpublished work with rats fed nitrite that the frequency of lymphoreticular tumor was increased. The possibility that nitrite has a direct adverse effect of this type raises questions about the total body burden of nitrite and the relative contributions from food, saliva, and the estimated larger amount produced by bacteria in the intestinal tract. A study of these sources and their relative importance is required for individuals of different age groups and dietary habits to obtain reliable figures. Specifications should be developed for food grade caseinates which limit the content of nitrite and nitrosamines.
Caseinates appear to contribute a minor quantity of nitrite to total human exposure. Preliminary estimates of per capita exposure indicate they account for less than 0.2 percent of that taken in as an ingredient of food and present in saliva, and less than 0.005 percent of the total taken in as food ingredient, present in the saliva, and generated in the intestinal tract. From the standpoint of relative contributions to the controllable nitrite load and/or total body burden, caseinates do not appear to be cause for concern at this time. Nevertheless, the possible adverse effects of nitrite call for more explicit knowledge and actions for maintaining a low level of the compound in the commercial product and for continued monitoring of its relative contributions, with adjustments as necessary, as the major sources of commercially added nitrites are progressively decreased through regulatory procedures underway.
The Select Committee has weighed the foregoing information and concludes that: It is essential that food grade specifications for casein, sodium caseinate, and calcium caseinate be established including provisions for acceptable levels of lysinoalanine, nitrite, and nitrosamines.
Assuming that acceptable levels of lysinoalanine, nitrite, and nitrosamine are established, there is no evidence in the available information on casein, sodium caseinate, or clacium caseinate that demonstrates or suggest reasonable grounds to suspect a hazard when they are used at levels that are now current or that may reasonably be expected in the future.
There is no evidence in the available information on casein that demonstrates or suggests reasonable grounds to suspect a hazard when it is used in paper and paperboard products for food packaging at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium Chloride | 7647-14-5 | 102 | 1979 | 1 (dry food packaging), 4 (direct additive) | 182.70 |
SCOGS Opinion:
Sodium chloride, an essential constituent of the body and present in many foods, exhibits acute and chronic toxic effects when ingested in excessive amounts. Excess sodium chloride may induce hypertension in rats. There is a strong genetic component in the hypertensive response, and by selective breeding, strains of "spontaneusly" hypertensive rats have been developed. Hypertension has been evoked by excess sodium chloride in the food or drinking water of dogs but the effects were reversible and related to osmotic factors. Salt appetite is an important expression of personal preference in relation to diet, and salt contributes to palatabiity of foods. For some, salt-containing foods have important cultural values. Foods in which salt is important for preparation or preservation are a prominent component of many diets. The causes of hypertension in man are related to genetic and environmental factors: race, family
history, variations in endocrine and kidney function, degree of obesity, and life-style. Although the findings of epidemiological studies suggest a relationship between salt intake and onset of hypertension, the evidence that salt consumption is a major factor in causing hypertension is not conclusive. However, available data suggest that 10 to 30 percent of the U.S. population is genetically predisposed to hypertension and is exposed to a higher risk by ingestion of sodium at current levels. The Select Committee believes that a reduction of sodium chloride consumption by the population will reduce the requency of hypertension. For man, the daily requirement of sodium chloride is less than 1 g (17 mg per kg), an amount exceeded by that present as a naturally-occurring ingredient of most diets. The daily requirement is subject to considerable fluctuation from such conditions as excessive sweating and diarrhea. It is not possible, on the basis of currently available data, to
recommend a level of intake of sodium chloride that could be considered optimal for health. Other dietary sources of sodium, the level of potassium, and the sodium to potassium ration in the diet need to be considered. Because of increasing use of processed foods in the diet, individuals who prefer to restrict salt intake find it difficult. The amount of sodium chloride consumed as a result of commercial food processing is about 70 to 100 mg per kg per day. The average daily intake of sodium expressed as sodium chloride from all sources is about 180 mg per kg for an adult (10 to 12 g per day). Such an intake exceeds estimates of the amount (range 2 to 10 g per day) that may elicit hypertension in susceptible individuals. A lower daily consumption of sodium chloride promises health benefits for the proportion of the population susceptible to hypertension. It is the prevalent judgment of the scientific community that the consumption of sodium chloride in the aggregate should be
lowered in the United States. The Select Committee agrees and favors development of guidelines for restricting the amount of salt in processed foods, a major contributor of dietary sodium. Adequate labeling of the sodium content of foods would help meet these objectives. Based on these considerations, the Select Committee concludes that: The evidence on sodium chloride is insufficient to determine that the adverse effects reported are not deleterious to the health of a significant proportion of the public when it is used at levels that are now current and in a manner now practiced. There is no evidence in the available information on sodium chloride that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used as an ingredient of cotton and cotton fabrics used in dry food packaging and as an ingredient of paper and paper board products used in food packaging in the manner now practiced or that might reasonably
be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium citrate | 68-04-2 | 84 | 1977 | 1 | 184.1751 |
SCOGS Opinion:
The citrate ion is widely distributed in plants and animals and is a naturally occurring component of the diet. It is a common metabolite in oxidative metabolism and an important component of bone. Exogenous citrate administered to infants and adults as a component of commonly consumed diets is considered completely metabolizable. The addition of citric acid to foods is considered equivalent to adding citrate salts except in foods of very high acidity. The amount of citrate added to foods by foods processors is about 500mg per person per day. This amount occurs naturally in 2 ounces of orange juice and does not constitute a significant addition to the total body load. Although data on acute and chronic effects of orally administered sodium citrate, calcium citrate and potassium citrate are limited, no biological effects of the citrate-containing substances evaluated in this report cause concern about the safety of these GRAS
substances used in reasonable amounts and in accordance with prescribed tolerances and limitations.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on citric acid, sodium citrate, potassium citrate, calcium citrate, ammonium citrate, isopropyl citrate, stearyl citrate, and triethyl citrate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium diacetate | 126-96-5 | 82 | 1977 | 1 | 184.1754 |
SCOGS Opinion:
Acetates are common constituents of plant and animal tissues. They are normal metabolic intermediates produced in relatively large quantities during the digestion and metabolism of foods.
Although the Select Committee is not aware of any long-term feeding studies of acetic acid or the acetates, short term studies have revealed no untoward effects at concentrations far exceeding those consumed in the normal diet and do not suggests that adverse effects might be revealed by longer term studies.
No data on carcinogenic evaluation of acetic acid and the acetate salts have come to the attention of the Select Committee. Limited data indicate that acetic acid is not teratogenic in vivo; sodium acetate is not mutagenic and acetic acid is probably not mutagenic in vitro.
No reports of biological studies on sodium diacetate have been found, but since this substance dissociates in the body to sodium acetate and acetic acid, neither of which elicits adverse effects under current conditions of use, the Select Committee beleives that use of sodium diacetate can be considered to be without adverse effects.
In light of these considerations, the Select Committee concludes that: There is no evidence in the available information on acetic acid, sodium acetate, and sodium diacetate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
L-ascorbic acid, vitamin C, occurs in nutritionally significant amounts as a natural constituent of many fruits, vegetables, berries, and melons. As a vitamin it is needed in the diet of all age groups. L-ascorbic acid and its sodium salt are antioxidants and they are extensively used as preservatives, color stabilizers and for related functions in various foods and beverages. Calcium ascorbate and ascorbyl palmitate, a derivative of ascorbic acid having greater fat solubility, also are anti-oxidants, but appear not to have significant use in processed foods. In addition to their use in foods as antioxidants, L-ascorbic acid and its salts are added to some foods as a source of vitamin C. These sources constitute a significant proportion of the total ascorbate intake of the general population. Erythorbic acid (D-isoascorbic acid), a stereoisomer of L-ascorbic acid, and its sodium salt, also are effective antioxidants and are used
for this purpose in a number of food products. The quantities used in 1970 were substantially less than for the ascorbates. The vitamin activity of erythorbates is only one -twentieth that of ascorbic acid, and their anti-oxidant effectiveness is not greater than for the ascorbates. For this reason, it would seem desirable, where possible, to use L-ascorbic acid rather than erythorbic acid as an antioxidant. From studies in guinea pigs and man it can be concluded that although erythorbic acid shares the same absorption and tissue uptake system as ascorbic acid it has little antiscorbutic activity. Although competition between ascorbic acid and erythorbic acid has been demosntrated at a biochemical level, there is no firm evidence that such competition will produce a scorbutic state. Whether this biochemical interaction could result in a clinically significant depletion of ascorbic acid remains to be established. Both short- and long-term toxicity studies have demonstrated tolerance
without adverse effects for large amounts of orally administered L-ascorbic acid, sodium L-ascorbate, and erythorbic acid in several species including mice, rats, guinea pigs, rabbits, and dogs. A substantial number of short-term experiments with human subjects ingesting 1 to 4 g of ascorbate daily have generally not revealed any harmful effects. Some subjects have received higher amounts, up to at least 8 to 10 g per day. In most instances no untoward results have been noted. But there is marked paucity of such studies that were well controlled and in which inquiring attention was given to possible harmful effects. In due course, such studies would be desirable. In the various studies on the effect of ingesting excessive amounts of ascorbates, attention has been focused on questions including oxalate excretion and renal tract stones, effets on the utilization of copper, iron, and other metals, need for vitamin B12, blood coagulation,and reproductive performance. The findings indicate
that the tolerance to excessive amounts of ascorbic acid and its sodium salt is high. Several investigators have reported the development of dependency in animals and human after ingestion of large amounts of ascorbates for extended time periods; however, the levels of ascorbates added to foods by 1 to 3 orders of magnitude. It is notable that no data have been found concerning the possible effects of ascorbyl palmitate and calcium ascorbate in humans, and there is practically no information regarding the latter in animals. Information concerning ascorbyl palmitate in animals is almost as limited. The few meaningful experiments suggest that ascorbyl palmitate is tolerated about the same as ascorbic acid and sodium ascorbate. This should be expected. It is reasonable to assume that the tolerance to calcium ascorbate is approximately the same as for sodium ascorbate and this is a high level. In view of the foregoing, The Select Committee concludes that: There is no evidence in the
available information on L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, ascorbyl palmitate (palmitoyl L-ascorbic), erythorbic acid (D-isoascorbic acid), and sodium erythorbate (sodium D-isoascorbate) that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used as food ingredients at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium ferric EDTA | 15708-41-5 | 35 | 1980 | 5 | There is no CFR citation. |
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
Serious deficiences exist in the experimental data or clinical experience with a number of iron compounds employed or suggested as iron fortifying agents for foods. The Select Committee concludes that: In view of the deficiency of relevant biological studies, it has insufficient data upon which to base an evaluation of ferric oxide, iron peptonate, iron polyvinyl pyrrolidone, sodium ferric EDTA, sodium ferricitropyrophosphate, or ferric sodium pyrophosphate when it is used as a food ingredient.
SCOGS Opinion:
The body content of iron in the normal individual is regulated primarily by absorptive processes. Relatively small amounts of iron are absorbed when body stores of iron are high, and relatively large amounts when body stores are low. This regulation of iron absorption is faulty in individuals with the metabolic disorder, hemochromatosis. Although hemochromatosis is generally considered a rare, genetically transmitted disorder, several investigators believe that a latent form of hemochromatosis may be much more common. In Sweden, where food fortification with iron is at a higher level than in the United States, and where medicinal iroin supplements are widely consumed, investigators reported several cases of hemochromatosis and iron overload in a sparsely populated district. The significance of these findings suggest that it is possible that a significant number of apparently normal and unidentified individuals might be at risk
of developing liver damage from intakes of iron which are innocuous and, in fact, probably beneficial for the population at large. It should be noted that in the United States (and probably inother industrialized countries), individuals ingesting large amounts of iron may achieve these intakes through regular consumption or iron supplements. For these individuals, food fortification contributes a relatively small fraction of total intake. The question of total intake of iron by the U.S. population and its relation to chronic iron toxicity merit further study. Monitoring of the population with respect to iron nutritional status is essential. The estimated per capita intake of 5 mg per day obtained from food fortification comprises more than one-third the toal iron intake for much of the population. Iron deficiency is a leading nutritional problem in the United States. Intakes of iron are below recommended levels for a large fraction of the population. hence, it is evident that an
increase in iron fortification of selected foods could be an important public health measure. The form of iron utilized to fortify foods should be of adequate bioavailability. Iron forms evaluated in this report which appear to be adequately bioavailable are elemental iron (reduced, electrolytic, carbonyl), ferrous ascorbate, ferrous citrate, ferrous fumarate, ferrous gluconate, ferrous lactate, ferrous sulfate, ferric ammonium citrate, ferric chloride, and ferric citrate. In contrast, the bioavailability of ferrous carbonate, ferrous oxide, ferric oxide, ferric phosphate, ferric pyrophosphate, or ferric sodium pyrophosphate is relatively low compared with ferrous sulfate. Insufficient data are available to judge the relative bioavailability of the other jiron preparations considered in this report.
Experimental data are sparse for most of the forms of iron considered in this report. Animal studies have been largely confined to the determination of acute toxicities and bioavailability of specific iron compounds. Such studies have limited relevance in evaluating the possible hazards of the addition of iron to foods. Few reports are available on the effects of long-term feeding experiments. An extensive literature exists on the use of certain forms given as hematinics, but the reports are largely anecdotal and their interpretation is of questionable value. Certain compounds have been employed extensively for many years both as additions to food and in the treatment of iron deficiency with no reported adverse effects. In view of the need for, and wide use of, iron compounds, it would appear prudent to place this historical and anecodotal experience on a scientifically rigorous basis in the reasonably near future. The Select Committee emphasizes the need for well-controlled clinical
and chronic feeding studies with most of the individual compounds before confident appraisal can be made of their relative merits or hazards.
Serious deficiences exist in the experimental data or clinical experience with a number of iron compounds employed or suggested as iron fortifying agents for foods. The Select Committee concludes that: In view of the deficiency of relevant biological studies, it has insufficient data upon which to base an evaluation of ferric oxide, iron peptonate, iron polyvinyl pyrrolidone, sodium ferric EDTA, sodium ferricitropyrophosphate, or ferric sodium pyrophosphate when it is used as a food ingredient.
SCOGS Opinion:
Formic acid is a natural constituent of many foods. It is a metabolite in normal intermediary metabolism, and is a precursor in the biosynthesis of several body constituents. The tolerance of the body to large amounts is relatively high. For example, 160mg of formic acid per kg of body weight orally was tolerated by rats; men reportedly 8 mg of formic acid per kg per day orally for a period of four weeks; and no adverse effects were reported in rats that received 730mg of sodium formate per kg in their diet for one and a half years. Average daily intake of ethyl formate and formic acid is about 1 mg per kg or less as formic acid. Although formic acid appears to be moderately mutagenic in E.coli and Drosophila, ethyl formate is not mutagenic toward strain D4 of Saccharomyces cerevisiae or to three strains of Salmonella typhimuriu. No adverse effects attibutable to formate were found in five successive generations of rats given up
to 200 mg of calcium formate per kg of body weight daily. Based on these considerations, the Select Committee concludes that: There is no evidence in the available information on formic acid and sodium formate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of paper and paperboard food packaging materials, or as they might reasonably be expected to be used for such purposes in the future. There is no evidence in the available information on ethyl formate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when it is used at levels that are now current and in the manner now practiced or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium gluconate | 527-07-1 | 78 | 1978 | 1 | 182.6757 |
SCOGS Opinion:
Gluconates are useful as nutritional supplements since their high solubility allows relatively rapid absorption of the cations. Evidence suggests that any possible toxicity is a function of the cation rather than of the gluconate portion of these substances. Thus, the acute toxic responses to the various gluconate salts are comparable with other salts of the same metals and long-term toxicities seem related to the tissue deposition of these metals. These observations could have been anticipated because gluconic acid is a normal metabolic product of glucose. The amount of gluconic acid produced endogenously is many times greater than the largest amounts likely to be consumed from food. Because the toxicological activities of these gluconates appear to be a function of their cationic components, safe and acceptable levels in foods are limited only by the nature of the specific cations. There is no evidence in the available
information on sodium gluconate, potassium gluconate, magnesium gluconate, and zinc gluconate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
SCOGS Opinion:
Information on the toxicity of sodium hydrosulfite is extremely limited. Nevertheless, the available data indicate that the oral administration of up to 1g of the sodium salt per kg body weight does not cause significant harm in dogs, and the intravenous injection of 25 to 50mg per kg has resulted in no apparent ill effects in rats. These doses are many orders of magnitude greater than those that could result from the consumption of foods packaged in sodium hydrosulfite-containing paper and paperboard packaging materials. Because zinc compounds, such as the carbonate and sulfate do not elicit adverse effects when administered orally to experimental animals at levels of 50mg per kg., and sodium hydrosulfite is without apparent adverse effects at equivalent levels it is reasonable to conclude that zinc hydrosulfite would react similarly. In the light of these considerations, the Select Committee concludes that: There is no
evidence in the available information on sodium hydrosulfite and zinc hydrosulfite that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used in food packaging materials as now practiced or as they might reasonably be expected to be used for such purposes in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium hydroxide | 1310-73-2 | 85 | 1976 | 1 | 184.1763 |
SCOGS Opinion:
The Select Committee has found no data suggesting that the use of sodium or potassium hydroxides, as currently practiced in food processing, is hazardous to consumers. The corrosive effect of ingestion of large amounts of strong alkalis such as sodium and potassium hydroxides has been amply demonstrated. However, these alkalis are not present as such in foods as consumed. The small amounts added for pH adjustment during food processing react rapidly with food acids to form neutral salts. Moreover, any free alkali that might be present in food, either from direct addition or from migration from packaging materials, is rapidly converted to neutral salts in the stomach.
The amounts of sodium and potassium hydroxide used in food processing contribute only 2 to 5 percent of the total sodium and potassium intake from all dietary sources. Accordingly, these alkais, as now used in food processing, do not add significantly to the usual dietary load of sodium and potassium.
In light of the foregoing, and the information elsewhere in this report, the Select Committee concludes that: There is no evidence in the available information on potassium hydroxide or sodium hydroxide that demonstrates, or suggests reasonable grounds to suspect a hazard to the public, when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on sodium hydroxide that demonstrates, or suggests, reasonable grounds to suspect a hazard to the public when it is used as an ingredient of food packaging materials in the manner now practiced or that might reasonably be expected in the future.
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
SCOGS Opinion:
The hypophosphites do not appear to be currently used as ingredients in foods as indicated by a survey of the food industry conducted by a National Research Council subcommittee in 1970 and more recent information obtained from industry by the Select Committee. They had limited medical use many years ago in tonics and as therapeutic agents but appear to be no longer used for these purposes.
The acute toxicity of hypophosphites is relatively low; injected intraperitoneally in mice, the LD50 (30days) for the sodium salt was 1.6g per kg body weight. Calcium and sodium hypophosphites given orally or parenterally to experimental animals and man are rapidly excreted as hypophosphite in the urine. It is the opinion on the Select Committee that potassium hypophosphite is comparable to the sodium salt in excretion and toxicity.
Although animal feeding experiments indicate that the phosphorus in hypophosphites is not biologically available, no adverse effects were reported in young rats fed diets containing calcium hypophosphite (up to 4.3g per kg). Growth and calcium assimilation were as good as observed on diets containing salts recognized as good sources of calcium.
Although no reports were available on the biological effects of manganese hypophosphite, an evaluation of the health aspects of other manganous salts by the Select Committee has found no evidence that would indicate a hazard from manganous hypophosphite if used as a nutrient or dietary supplement.
In view of the foregoing the Select Committee concludes that: There is no evidence in the available information on manganous, calcium, potassium or sodium hypophosphite that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used in the manner now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium L-ascorbate | 134-03-2 | 59 | 1979 | 1 | 182.3731 |
SCOGS Opinion:
L-ascorbic acid, vitamin C, occurs in nutritionally significant amounts as a natural constituent of many fruits, vegetables, berries, and melons. As a vitamin it is needed in the diet of all age groups. L-ascorbic acid and its sodium salt are antioxidants and they are extensively used as preservatives, color stabilizers and for related functions in various foods and beverages. Calcium ascorbate and ascorbyl palmitate, a derivative of ascorbic acid having greater fat solubility, also are anti-oxidants, but appear not to have significant use in processed foods. In addition to their use in foods as antioxidants, L-ascorbic acid and its salts are added to some foods as a source of vitamin C. These sources constitute a significant proportion of the total ascorbate intake of the general population. Erythorbic acid (D-isoascorbic acid), a stereoisomer of L-ascorbic acid, and its sodium salt, also are effective antioxidants and are used
for this purpose in a number of food products. The quantities used in 1970 were substantially less than for the ascorbates. The vitamin activity of erythorbates is only one -twentieth that of ascorbic acid, and their anti-oxidant effectiveness is not greater than for the ascorbates. For this reason, it would seem desirable, where possible, to use L-ascorbic acid rather than erythorbic acid as an antioxidant. From studies in guinea pigs and man it can be concluded that although erythorbic acid shares the same absorption and tissue uptake system as ascorbic acid it has little antiscorbutic activity. Although competition between ascorbic acid and erythorbic acid has been demosntrated at a biochemical level, there is no firm evidence that such competition will produce a scorbutic state. Whether this biochemical interaction could result in a clinically significant depletion of ascorbic acid remains to be established. Both short- and long-term toxicity studies have demonstrated tolerance
without adverse effects for large amounts of orally administered L-ascorbic acid, sodium L-ascorbate, and erythorbic acid in several species including mice, rats, guinea pigs, rabbits, and dogs. A substantial number of short-term experiments with human subjects ingesting 1 to 4 g of ascorbate daily have generally not revealed any harmful effects. Some subjects have received higher amounts, up to at least 8 to 10 g per day. In most instances no untoward results have been noted. But there is marked paucity of such studies that were well controlled and in which inquiring attention was given to possible harmful effects. In due course, such studies would be desirable. In the various studies on the effect of ingesting excessive amounts of ascorbates, attention has been focused on questions including oxalate excretion and renal tract stones, effets on the utilization of copper, iron, and other metals, need for vitamin B12, blood coagulation,and reproductive performance. The findings indicate
that the tolerance to excessive amounts of ascorbic acid and its sodium salt is high. Several investigators have reported the development of dependency in animals and human after ingestion of large amounts of ascorbates for extended time periods; however, the levels of ascorbates added to foods by 1 to 3 orders of magnitude. It is notable that no data have been found concerning the possible effects of ascorbyl palmitate and calcium ascorbate in humans, and there is practically no information regarding the latter in animals. Information concerning ascorbyl palmitate in animals is almost as limited. The few meaningful experiments suggest that ascorbyl palmitate is tolerated about the same as ascorbic acid and sodium ascorbate. This should be expected. It is reasonable to assume that the tolerance to calcium ascorbate is approximately the same as for sodium ascorbate and this is a high level. In view of the foregoing, The Select Committee concludes that: There is no evidence in the
available information on L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, ascorbyl palmitate (palmitoyl L-ascorbic), erythorbic acid (D-isoascorbic acid), and sodium erythorbate (sodium D-isoascorbate) that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used as food ingredients at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Based upon chronic toxicity tests in animals, primarily in rats, the no observed adverse effect level of SO2 is estimated to be in the range of 30 to 100 mg of SO2 per kg of body weight per day. These values are considerably higher than the estimated average per capita consumption of about 0.2 mg of SO2 equivalent per kg body weight per day, and well above the estimates of up to 2 mg per kg body weight per day that some individuals may consume if they select foods and beverages relatively high in SO2 content. The margin of only about fifteenfold between the SO2 that may be ingested by high-intake consumers and the lowest estimated no observed adverse effect level is relatively narrow. However, consideration of the significance of this difference should recognize the difficulties in estimating with confidence the components which are the basis of the calculated margin. While the biological effects of sulfiting agents are still
incompletely understood, certain conclusions are warranted. There is no reason to believe the direct, local, irritating effects of sulfite, seen in high-dose acute toxicity tests, constitute a hazard from ingestion of sulfiting agents as they are presently used in foods. Orally administered sulfite is very rapidly oxidized to sulfate in all species studied. The metabolic removal of sulfite appears to be the critical defense mechanism, and this points to the important role of the enzyme, sulfite oxidase. Congenital deficiency of hepatic sulfite oxidase has been described as a rare metabolic disorder in man. There is also paucity of data on the normal development of this enzyme with age in various species, and on the possible effects of dietary factors and disease on sulfite oxidase activity. Moreover, sulfite is capable of deaminating cytosine in vitro and inhibiting several enzymes requiring NAD or pyridoxal as cofactors which suggests that sulfite might be toxic in vivo if sulfite
oxidase activity were sufficiently impaired or this metabolic mechanism were sufficiently overloaded, to prevent rapid oxidation of ingested sulfite to sulfate. Information in these respects would be helpful in assessing any special risk factors that may apply for select subpopulations. Destruction of thiamine can occur as a result of the sulfiting of foods but suffiecient thiamine is present in usual mixed diets, particularly because use of sulfiting agents is prohibited by regulation in foods known to be major sources of the vitamin. While there is no evidence that the sulfiting agents are teratogenic, there is evidence that directly added sulfite produces mutations in bacteria by alteration of nucleic acids. None of the available mammalian in vivo studies confirms these observations. Because the same organisms are not affected in the host-mediated assay, it seems reasonable to infer that rapid destruction of sulfite by the host's sulfite oxidase provides protection. In view of the
foregoing, the Select Committee concludes that: There is no evidence in the available information on potassium bisulfite, potassium metabisulfite, sodium bisulfite, sodium metabisulfite, sodium sulfite, and sulfur dioxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
SCOGS Opinion:
Although there are no data available to the Select Committee on the amounts of sodium oleate and sodium palmitate used in fabricating food containers or the amount that might migrate to food therefrom, it is evident that the amount of these compounds that could transfer to foodstuffs in the package would be many orders of magnitude below the quantities of the respective fatty acids normally present as triglycerides in many foods. The sodium salts of the fatty acids are toxicologically indistinguishable from the latter when consumed in small amounts. the Select Committee recognizes that large amounts of the free fatty acids can distort the physiological processes in a system that is organized to absorb and utilize the triglycerides, but such excesses would not be expected from the use of sodium oleate and sodium palmitate as food packaging material ingredients.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on sodium oleate and sodium palmitate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of paper and paperboard food packaging materials in the manner now practiced or as they might be expected to be used for such purposes in the future.
SCOGS Opinion:
Although there are no data available to the Select Committee on the amounts of sodium oleate and sodium palmitate used in fabricating food containers or the amount that might migrate to food therefrom, it is evident that the amount of these compounds that could transfer to foodstuffs in the package would be many orders of magnitude below the quantities of the respective fatty acids normally present as triglycerides in many foods. The sodium salts of the fatty acids are toxicologically indistinguishable from the latter when consumed in small amounts. the Select Committee recognizes that large amounts of the free fatty acids can distort the physiological processes in a system that is organized to absorb and utilize the triglycerides, but such excesses would not be expected from the use of sodium oleate and sodium palmitate as food packaging material ingredients.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on sodium oleate and sodium palmitate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of paper and paperboard food packaging materials in the manner now practiced or as they might be expected to be used for such purposes in the future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
SCOGS Opinion:
Aluminum and its salts are found in varying amounts in nearly all foods. In addition to the aluminum occurring naturally in foods, man can be exposed to the aluminum added to foods, to that in aluminum antacids he may take, and to that from aluminum cooking vessels. It has been estimated that the daily aluminum intake for man from all dietary sources can range from 10 to 100 mg per day and that of this amount, the intake from aluminum compounds added to food may average about 20 mg per day, about 75 percent of which is in the form of sodium aluminum phosphate. In relation to body weight, these amounts are less than those needed to produce toxic responses in experimental animals. It should be noted, however, that this amount may be considerably increased by the consumption of aluminum-containing antacids. When aluminum salts are ingested in excessive amounts, their toxicity appears to be associated with interference in phosphorus
metabolism resulting in rachitic or osteomalacic effects, kidney damage, and interference with glucose metabolism, apparently due to interference with phosphorylating enzymes. These effects are reduced and controlled by maintaining sufficient phosphorus in the diet and are exacerbated by kidney dysfunction. Clearly, dietary phosphorus level is a controlling factor, and care should be taken by patients with kidney disease when consuming food containg high levels of aluminum salts. The high intake of phosphorus in the American diet may provide a protective effects, especially in persons who consume large amounts of aluminum antacid preparations that do not contains phosphorus. However, since high phosphate intakes cannot be assured for specific individuals at all times, and since there is some evidence that persons with kidney disease may be at risk, appropriate labeling or other means to indicate the possibility of such hazards may warrant consideration. The Select Committee has found
no relevant toxicologic studies on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate (substances that may migrate to food from paper packaging materials). But the nature of the inorganic compounds at least does not suggest that, ingested in such small amounts, they would have a different effect than the other aluminum compounds considered in this report, all of which exhibit low orders of toxicity. Even in the absence of direct evidence, it cannot be concluded that the use of any of these compounds in packaging materials would have any likelihood of being hazardous. In the light of the foregoing, the Select Committee concludes that: 1.) There is no evidence in the available information on aluminum ammonium sulfate, aluminum potassium sulfate, aluminum sodium sulfate, aluminum sulfate, acidic sodium aluminum phosphate, basic sodium aluminum phosphate, and aluminum hydroxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the
public when they are used at levels that are now current or that might reasonably be expected in the future. 2). No consumption or biological information is available on aluminum oleate, aluminum palmitate, sodium aluminate, and sodium phosphoaluminate. However, there are no reasonable grounds to suspect a hazard to the public when they are consumed at the levels that are likely if these substances should migrate from paper and paperboard used as food packaging materials; or that might reasonably occur when they are used for this purpose in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium propionate | 137-40-6 | 79 | 1979 | 1 | 184.1784 |
SCOGS Opinion:
Propionic acid occurs naturally in various foods including butter and cheese. Its absorption and metabolism are demonstrated in experimental animals and humans where it is a normal intermediary metabolite. As incorporated in foods as its sodium or calcium salt or as the free acid, propionic acid does not occur at the concentrations or under the conditions that are necessary to produce signs of mucosal damage in experimental animals. Propionic acid, sodium propionate, and calcium propinate have demonstrated low acute toxicity after oral administration to mice or rats. The adverse effects observed in chicken embryos occurred only after injection of large amounts of calcium propionate or sodium propionate into the yolk sac, and the reversions observed in a host-mediated assay of calcium propionate were unrelated to dose. These results in chickenembryos and the host-mediated assay must be viewed in the light of other microbial
assays and animal studies that demonstrate no adverse effects and the fact that propionate is a normal intermediary metabolite. Microbial assays for mutagenicity of propionic acid and calcium and sodium propionate were negative. Investigations of the teratogenicity of calcium propionate in four mammalian systems also were negative. Short-term feeding tests show the most sensitive animals tested, young and vitamin B12-deficient animals, experience adverse effects on weight gain only when propionate intakes are many orders of magnitude greater than the estimate of human dietary intake of propionate used as a food ingredient, about 1 mg per kg per day. Long-term feeding studies of propionic acid and calcium propionate have not been reported. However, a long-term feeding study of sodium propionate showed no adverse effects in rats. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on propionic acid, calcium propionate, and
sodium propionate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
SCOGS Opinion:
The Select committee is not aware of any long-term experimental studies on chronic administration of any of the carbonate salts. The results of acute toxicity and short-term feeding experiments are not readily extrapolated in determining toxic levels for carbonate salts consumed by humans. Treatment of gastric or peptic ulcers in patients with large amounts of carbonate salts in various forms has been utilized for many years and only rarely have deleterious results of changes of acid-base balance been reported. When the human respiratory and renal functions are normal, the mechanisms for disposing of bicarbonate intake in large amounts through excretion appear to be highly efficient. Studies of mice suggest that large intakes of calcium carbonate may interfere with reproductive performance. Such effects could be indirectly attributable to certain trace nutrient deficiences. Comparable intake levels of calcium may occur when
calcium carbonate is used for therapeutic purposes but the amounts added to foods in normal manufacturing processes are not high enough to be harmful. While the Select Committee is not aware of any studies on sodium sequicarbonate per se, reasoned judgment suggests its biochemical conversion and metabolism would be similar to that of sodium carbonate and bicarbonate. On the consideration of the foregoing, the Select Committee concludes that: There is no evidence in the available information on calcium carbonate, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, or sodium sesquicarbonate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium silicate | 1344-09-8 | 61 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
Silicon dioxide and various silicates occur abundantly in the earth's crust, are present in practically all natural waters,animals, and plants, and are part of the normal human diet. The question of whether or not silicon is an essential human nutrient remains unresolved. Silicon compounds consumed as added food ingredients contribute only a minor proportion of the total dietary silicon intake. The estimated possible human intake of sodium aluminosilicate, the predominant silicate added to foods in this country, is approximately 0.3mg per kg body weight per day. Silicon compounds that are GRAS for use as direct food ingredient, except potassium and sodium silicates, are insoluble or very slightly soluble in water and appear to be biologically inert. The water-soluble silicates are also of low acute toxicity. The acute oral LD50 in rats of sodium aluminosilicate is >1g per kg. No significant tissue accumulation, pathology, or
toxicity has been reported from the ingestion of those insoluble or very slightly soluble GRAS silicon compounds for which data are available. Of the five substances that were reported as added to foods in the NRC survey, biologic effects and safety data are available for all except sodium calcium aluminosilicate, and there is no reason to suspect that the toxicity of the latter would differ from those for which there are data. The results of two studies (1967-1970) in which various silicon compounds were fed to laboratory animals for 1 mo at a level of 0.8g per kg body weight (as silicon dioxide) and for 3 mo at levels of 6 to 30 mg per kg body weight suggests there may be a species-related susceptibility to renal damage from ingestion of sodium silicate, magnesium trisilicate, and finely ground quartz. No substantiating reports of these effects have appeared. Magnesium trisilicate was recognized as safe for prolonged use in human ingestion in large amount as a component of antacid
preparations by the Advisory Review Panel on Over-the-Counter Drugs, and the available evidence on the acute toxicity of sodium silicate indicates that it is low. Consumption data are lacking for aluminium calcium silicate and tricalcium silicate, two compounds that are listed as GRAS for use as anticaking agents. However, their use in keeping with good manufacturing practice and in currently regulated amounts would be of the same order of magnitude as the other GRAS silicates. In addition, the Select Committee has limited information on the amounts of talc that are currently used in foods. However a major food use of talc is in the coating of rice. Assuming package label statements are ignored and coated rice is not washed prior to cooking and no other losses occur, maximun per capita intake of talc from this source appears to be 0.5g per day. With respect to paper and cotton food- packaging products, the possibility is remote that biologically significant amounts of talc,
diatomaceous earth, or sodium silicate migrate to food from packaging, materials containing these substances. Perlite, a naturally occuring polysilicate substance, has an oral LD50 in the rat of >10g per kg body weight. Estimates of the maximun quantities of minerals that might be extracted from perlite and diatomaceous earth used as filteraids in food processing indicates no hazard to public health. There are no food grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc. Such specifications for the substances used in foods are desirable. Specification for food grade talc should limit the content of asbestos fibers even though the potential hazard of ingested asbestos fibers even though the potential hazard of ingested asbestos is not clearly established. The Food and Drug Administration is sponsoring the development of an assay method for asbestos fibers. An upper limit for cadmium should be added to the specifications for food-grade perlite, and
consideration should be given to the need for limitation of cadmium content of other silicates. In the light of all of the foregoing, the Select Committee concludes that: It is essential to establish food-grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc, with provision for an upper limit of asbestos fibers in talc. There is no evidence in the available information on aluminum calcium silicate, calcium silicate, magnesium silicate, potassium silicate, sodium silicate, sodium aluminosilicate, sodium calcium aluminosilicate, tricalcium silicate, silica aerogel, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on diatomaceous earth, silicon dioxides, sodium silicate, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the
public when they are used as ingredients of paper and paperboard products used in food packaging in accordance with current practice. There is no evidence in the available information on sodium silicate and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of cotton and cotton fabrics used in dry food packaging in accordance with current practice. There is no evidence in the available information on diatomaceous earth and perlite that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used as filteraids in food processing at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium sorbate | 7757-81-5 | 57 | 1975 | 1 | 182.3795 |
SCOGS Opinion:
Sorbic acid and its salts demonstrate very low acute or chronic toxicity for experimental animals. In animals sorbate is metabolized by the normal fatty acid pathway. Although no metabolic or toxicological studies have been conducted in man, the similarity on the pathway of fatty acid metabolism in man and animals suggests that no deleterious effects are to be expected from sorbic acid in the diet even in amounts many times greater than those at which it appears to be used. Based on these considerations the Select Committee concludes that: There is no evidence in the available information on sorbic acid and its sodium, potassium and calcium salts that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium sulfite | 7757-83-7 | 15 | 1976 | 2 | 182.3798 |
SCOGS Opinion:
Based upon chronic toxicity tests in animals, primarily in rats, the no observed adverse effect level of SO2 is estimated to be in the range of 30 to 100 mg of SO2 per kg of body weight per day. These values are considerably higher than the estimated average per capita consumption of about 0.2 mg of SO2 equivalent per kg body weight per day, and well above the estimates of up to 2 mg per kg body weight per day that some individuals may consume if they select foods and beverages relatively high in SO2 content. The margin of only about fifteenfold between the SO2 that may be ingested by high-intake consumers and the lowest estimated no observed adverse effect level is relatively narrow. However, consideration of the significance of this difference should recognize the difficulties in estimating with confidence the components which are the basis of the calculated margin. While the biological effects of sulfiting agents are still
incompletely understood, certain conclusions are warranted. There is no reason to believe the direct, local, irritating effects of sulfite, seen in high-dose acute toxicity tests, constitute a hazard from ingestion of sulfiting agents as they are presently used in foods. Orally administered sulfite is very rapidly oxidized to sulfate in all species studied. The metabolic removal of sulfite appears to be the critical defense mechanism, and this points to the important role of the enzyme, sulfite oxidase. Congenital deficiency of hepatic sulfite oxidase has been described as a rare metabolic disorder in man. There is also paucity of data on the normal development of this enzyme with age in various species, and on the possible effects of dietary factors and disease on sulfite oxidase activity. Moreover, sulfite is capable of deaminating cytosine in vitro and inhibiting several enzymes requiring NAD or pyridoxal as cofactors which suggests that sulfite might be toxic in vivo if sulfite
oxidase activity were sufficiently impaired or this metabolic mechanism were sufficiently overloaded, to prevent rapid oxidation of ingested sulfite to sulfate. Information in these respects would be helpful in assessing any special risk factors that may apply for select subpopulations. Destruction of thiamine can occur as a result of the sulfiting of foods but suffiecient thiamine is present in usual mixed diets, particularly because use of sulfiting agents is prohibited by regulation in foods known to be major sources of the vitamin. While there is no evidence that the sulfiting agents are teratogenic, there is evidence that directly added sulfite produces mutations in bacteria by alteration of nucleic acids. None of the available mammalian in vivo studies confirms these observations. Because the same organisms are not affected in the host-mediated assay, it seems reasonable to infer that rapid destruction of sulfite by the host's sulfite oxidase provides protection. In view of the
foregoing, the Select Committee concludes that: There is no evidence in the available information on potassium bisulfite, potassium metabisulfite, sodium bisulfite, sodium metabisulfite, sodium sulfite, and sulfur dioxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium tetraphosphate | 14986-84-6 | 32 | 1975 | 1 | There is no CFR citation. |
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sodium thiosulfate | 10102-17-7 | 52 | 1975 | 1 | 184.1807 |
SCOGS Opinion:
Thiosulfate is a normal constituent fo human body fluids, and is a metabolite of dietary constituents. Experimental animal studies show that sodium thiosulfate is well tolerated. All investigations in which it has been administered to normal and diseased persons, clearly show that very large therapeutic doses cause no adverse effects. The reported use of sodium thiosulfate as a stabilizer of potassium iodide salt, as a sequestrant in alcoholic beverages, and as a substance that may migrate to foods from packaging materials, results in human exposure far below that needed to produce untoward biological effects. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on sodium thiosulfate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in the
future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
SCOGS Opinion:
The Select Committee recognizes many variables to be considered regarding the safety to the public of the current uses of phosphates in foods. These include: (a) the variety and different characteristics of phosphates and their scope of use; (b) the close metabolic interrelationships between vitamin D, calcium, and phosphorus; and (c) the possible variations between different segments of the population in the level of phosphate consumed both in foods and in beverages. Better data are needed on the calcium and phosphorus intake and the Ca:P ration of the U.S. diet. It is probably that many adults in the U.S. ingest less than 800 mg of calcium and more than 800 mg of phosporus per day, which are the Recommended Dietary Allowances. Although there is a difference of scientific opinion, it is the opinion of the Select Committee that the Ca:P ratio of the diet is important, especially if it varies substantially from 1:1 owing to the
relatively high intake of phosphorus. Most of the evidence shows that in general a desirable Ca:P ration is between 2:1 and 1:1. Thus if the calcium intake is 800 mg per person per day the total phophorus intake should not greatly exceed that amount. The fragmentary data available suggest that the typical Ca:P ratio in this country is lower than 1:1. Some estimates suggest it may be substantially lower. In laboratory animals and presumably in man, nutritional secondary hyperparathyroidism and bone resoption may be induced when the diet furnishes an otherwise adequate amount of calcium but excessive levels of phosphorus. None of the GRAS phosphates is intrinsically harmful and thie use in foods does not present a hazard when the total amount of phosphorus ingested and the intakes of calcium, magnesium, vitamin D, and other nutrients are satisfactory. The current use of calcium phosphates in food processing is without harmful effects on the health of consumers and, in some instances, may
be advantageous. The phosporus supplied by GRAS phosphates, other than calcium phosphates, added to foods is low in relation to the total amount of phosporus naturally present in the diet. However, the possibility that unreasonable increases in the usage of these phosphates in commonfoods would significantly lower the Ca:P ration and increase the total phosporus intake for some segments of the population, must be considered in assessing the probability of a health hazard existing because of the ingestion of excessive levels of phosphorus. The Select Committee has no evidence that the use of any of these non-calcium phosphates as food ingredients at current levels is creating such a problem. However, if distortion of the Ca:P ratio should become of concern, this question should be accorded separate study. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on ammonium phosphate, dibasic; ammonium phophate, monobasic;
calcium hexametaphophate; calcium phosphate, dibasic; calcium phosphate, mono basic; calcium phosphate, tribasic; calcium pyrophosphate; phosphoric acid; potassium phophate, dibasic; potassium phosphate, monobasic; potassium phosphate, tribasic; potassium polymetaphosphate; potassium pyrophosphate; potassium tripolyphosphate; sodium acid pyrophosphate; sodium phosphate, dibasic; sodium phosphate, monobasic; sodium phosphate, tribasic; tetrasodium pyrophosphate; sodium tripolyphosphate; and straight-chain sodium polyphophates (including sodium hexametaphosphate, sodium metaphosphate, and sodium tetraphosphate) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sorbic acid | 110-44-1 | 57 | 1975 | 1 | 182.3089 |
SCOGS Opinion:
Sorbic acid and its salts demonstrate very low acute or chronic toxicity for experimental animals. In animals sorbate is metabolized by the normal fatty acid pathway. Although no metabolic or toxicological studies have been conducted in man, the similarity on the pathway of fatty acid metabolism in man and animals suggests that no deleterious effects are to be expected from sorbic acid in the diet even in amounts many times greater than those at which it appears to be used. Based on these considerations the Select Committee concludes that: There is no evidence in the available information on sorbic acid and its sodium, potassium and calcium salts that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sorbitol | 50-70-4 | 9 | 1972 | 1 | 184.1835 |
SCOGS Opinion:
The available information reveals that there are no short-term toxicological consequences in rats, mice, monkeys, or man, and no long-term toxicological consequences in rats, of consuming sorbitol in amounts exceeding those currently consumed in the normal diet of the U.S. population. There is no evidence that consumption of sorbitol as a food ingredient has had adverse effects on man in the many years it has been so used. It is to be noted that sorbitol begins to exert a laxative effect at levels that are about twice the estimated average adult intake level and about equal to the estimated maximum adult intake level. It should be noted also that the average consumption levels of children in the age groups 6-11 months and 12-23 months are not estimated to be close to, or in excess of, those capable of exerting a laxative effect. However, because the reported average and maximum intake levels are known to be generous
overestimates, it is the opinion of the Select Committee that the use of sorbitol in food in the present or reasonably foreseeable amounts poses no problem in this regard. The Select Committee is concerned that the actual consumption of sorbitol may be considerably higher than average consumption in certain segments of the population. These individuals, for dietary reasons, may select foods containing particularly high levels of sorbitol. Currently available food consumption data do not permit the Select Committee to determine the extent and significance of this problem in regard to sorbitol. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information to show that sorbitol as a food ingredient constitues a hazard to the general public when used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The results of sorbose-feeding test with fasted rats showed no acute toxic effects for sorbose given excess of potential human dietary exposure. The metabolic products of sorbose metabolism in animals do not appear to include toxic substances and the chemical structure of sorbose does not suggest potential hazards. The results of the only study of the carcinogenicity of sorbose, involving parenteral administration in rats, have been judged by the investigator and reviewers to be negative. Based on these considerations, and the fact that sorbose is permitted only as an ingredient of cotton fabrics used in dry food packaging, the Select Committee concludes that: There is no evidence in the available information on sorbose that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Soy protein isolate | 977076-84-8 | 101 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
Many studies of soy protein isolates prepared for food use have been carried out with experimental animals and with human subjects. In most studies of experimental animals, fortification of soy protein isolate with methionine increased nutritional quality. Under certain experimental conditions, feeding of soy protein isolates as the sole or major source of protein to animals has impaired the utilization of fat-soluble vitamins or of minerals, especially calcium, phosphorus, magnesium, zinc, and copper. In a number of studies of experimental animals and in a few studies of human infants, growth was reported to be more rapid when proteins of animal origin were fed than when equal amounts of soy protein isolate were fed. However, in other studies of human infants, rates of gain in weight in infants fed formulas with protein from cow milk were similar to those fed formulas with protein from soy protein isolate. In most studies of
human subjects, nitrogen balance has been similar with isonitrogenous diets supplying protein of animal origin or methionine fortified soy protein isolate.
A 24 week study of six men in a metabolic ward failed to demonstrate adverse effects from consumption of a diet in which all of the protein was provided from soy protein isolate. It is estimated that 10 percent of infants in the United States receive formulas with protein from soy protein isolates during the early months of life, some consuming more than 4g of soy protein per kg per day, without evidence of adverse effects. Several multigeneration studies of rats fed soy protein isolates have failed to indicate evidence of long term toxicity. Thus, it seems likely that well- processed soy protein isolate adequately supplement with methionine, vitamins and minerals, either by addition to the soy isolate product or as provided by other components of the diet, is without hazard.
Soy protein isolates subjected to relatively severe alkali treatments that modify their viscosity and adhesive properties are used as sizing and coating adhesives in the production of certain paper and paperboard products used in food packaging. These alkali treatments also result in marked loss of certain nutritionally essential amino acids and formation of lysinoalanine as a component of the protein molecule. Renal cytomegalic changes have been demonstrated in rats fed diets containing high levels (20 to 30 percent) of alkali modified soy protein isolate as the sole source of protein. Alkali-treated casein and lactoalbumin at high levels in the diets of rats, and free lysinoalanine above certain levels, also produce cytomegalic changes. Removal of alkali-treated protein from the diet appears to reverse the changes. Cytomegaly was reduced or did not occur in rats in which alkali-treated protein was supplemented with an untreated protein suggesting that the renal syndrome was caused by
protein bound lysinoalanine in diets deficient or imbalanced with respect to one or more amino acids. Feeding free lysinoalanine at 1000ppm in the diet to five mammalian species other than the rat, including subhuman primates has failed to produce renal cytomegalic changes.
Data available to the Select Committee suggests that alkali-treated soy protein isolates account for less than 1 percent by weight of paper and paper board products in which they are used. Because of this relatively small concentration of soy protein and because only a small fraction of the coating from a food package would be expected to be transferred into the food by attrition or migration, the intake of alkali- treated soy protein entering the diet from food packaging materials is assumed to be exceedingly small, and, accordingly, the lysinoalanine intake from this sources is of no moment.
Lysinoalanine has been reported at relatively low levels in some samples of food grade soy protein isolate including spun fibers of soy protein isolate used in fabricating meat analogs. Lysinoalanine also has been found in a number of milk, meat, egg and vegetable protein products that had been heated at neutral or alkaline pH in processing. While the available information indicates that the levels of lysinoalanine in food grade soy protein isolates as currently used pose no hazard to the consumer, a limitation with respect to lysinoalanine in the specifications for food grade isolates and products derived from them would avoid possible future problems in this regard.
It is important to ensure that preformed nitrosamines are not present in soy protein isolates and are not formed in processed foods containing soy protein isolates. Many nitrosamines have been shown to be carcinogenic in experimental animals. Specifications should be developed for food grade soy protein isolates which exclude nitrosamines.
The presence of up to 50 ppm nitrite in soy protein isolates raises other possibilities of concern. The potential for nitrisamine formation in vivo from the ingestion of foods containing nitrite, and the latter reacting with other nitrogen- containing compounds in foods, drugs and endogenous amines, must be considered. Many natural and processed foods, including spray dried products, contribute to the total human intake of nitrite even though bacterial reduction of nitrate to nitrite in saliva is the major source of nitrite reaching the gastrointestinal tract. It was reported from recent unpublished work with rats fed nitrites that the frequency of lymphoreticular neoplasms was increased. The possibility that nitrite has an adverse effect of this type raises questions about the total body burden of nitrite and the relative contribution from food, saliva and the estimated larger amount produced by bacteria in the intestinal tract. A study of these sources and their relative importance
is required for individuals of different age groups and dietary habits to obtain reliable figures.
It is recognized that soy protein isolates constitute a currently minor source of nitrite as far as human exposure is concerned. Preliminary estimates of per capita exposure indicate that they account for less than 0.5 percent of the amount ingested as food ingredients, less than 0.05 percent of that taken in as food ingredients and present in the saliva; and less than 0.0075 percent of the total taken in as food ingredients, present in the saliva, and generated in the intestinal tract. From the standpoint of relative contributions to the controllable nitrite load and/or total body burden, soy protein isolates do not appear to be cause for concern at this time. Nevertheless, the possible adverse effects of nitrite call for more explicit knowledge and actions for maintaining a low level of the compound in the commercial products and for continued monitoring of its relative contributions, with adjustments as necessary, as the major sources of commercially added nitrites are progressively
decreased through regulatory procedures underway.
The Select Committee has weighed the available information and concludes:
1. It is essential that specifications for food grade soy protein isolates be established including provisions for acceptable levels of lysinoalanine, nitrite and nitrosamines.
2.Assuming that acceptable levels of lysinoalanine, nitrite and nitrosamines are established, there is no evidence in the available information on soy protein isolates that demonstrates or suggests reasonable grounds to suspect a hazard when they are used at levels that are now current or that might reasonably be expected in the future.
3. There is no evidence in the available information on soy protein isolates that demonstrates or suggests reasonable grounds to suspect a hazard when used in paper and paperboard products for food packaging at levels that are now current or that may reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Soy sauces | There is no ID Code | 37b | 1980 | 1 | There is no CFR citation. |
SCOGS Opinion:
The average level of consumption of protein hydrolyzates for flavoring purposes is less than 3 mg per kg per day. Protein hydrolyzates are not used for flavoring purposes in commercially processed baby foods wich formerly may have contained about 2 percent by weight. The Select Committee was unable to locate reports of experimentally demostrable adverse effects of high concentrations of glutamate in dietary mixtures.
In light of the above, and assuming that appropriate product specifications are adopted, the Select Commitee concludes that:
There is no evidence in the available information on acid hydrolyzed proteins, enzymatically hydrolyzed protein, yeast autolysates, and soy sauces, that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used as flavoring agents at levels that are now current or that might reasonably be expected in the future.
The situation is different regarding the use of enzymatic casein hydrolyzates as nutrients. These hydrolyzates are consumed or administered in much higher doses, frequently as the sole source of dietary protein in products that are used as special dietary foods.
Decades of clinical experience have revealed no reports of untoward effects when casein hydrolyzates are administered orally in combination with other nutrients such as glucose. Adverse effects of the dicarboxylic amino acid components have been reported only in rodents under unusual conditions of administration (e.g., gavage or subcutaneous injection) and are not considered relevant to the use of casein hydrolyzates by humans.
The Select Commitee therefore concludes that: There is no evidence in the available information on enzymatically hydrolyzed casein that demostrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used as a nutrient in special dietary foods at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Stannous Chloride | 7772-99-8 | 31 | 1974 | 1 | 184.1845 |
SCOGS Opinion:
Feeding tests of stannous chloride on several species of animals, including observations on carcinogen icty and teratogenicity, at dosage levels significantly above those present in the daily diet, did not reveal evidence that this compound is harmful. Human experience gained after the accidental ingestion of large amounts of tin containing materials or experimental intravenous injection of such materials reinforces this conclusion. In the light of the foregoing, the Select committee concludes that: There is no evidence in the available information on stannous chloride that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Starch Acetate | 9045-28-7 | 115 | 1979 | 2 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Starch Sodium Succinate | 37231-92-8 | 115 | 1979 | 3 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Starch, Sodium Octenyl | 66829-29-6 | 115 | 1979 | 3 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Starter distillate | 977019-27-4 | 94 | 1980 | 1 | 184.1848 |
SCOGS Opinion:
Diacetyl is added to some foods for flavoring purposes. It is metabolized in mammals, is of low acute toxicity, and the no-adverse-effect level, based on a 90-day study in rats, is approximately 90mg per kg body weight. The per capita daily intake of diacetyl added to food, both as a component of starter distillate and as diacetyl itself , is estimated to be less than 0.3mg.
Available studies of the biological effects of commercial starter distillate consist of two report; the one showed that starter distillate exhibited no mutagenic activity in in vitro test systems; the other showed that it was without teratogenic activity when administered orally in doses as high as 1600mg per kg body weight to pregnant mice, rats, hamsters, and rabbits.
The per capita daily intake of starter distillate is about 5mg or about 0.1mg on an anhydrous basis. Diacetyl and acetic acid are major components of starter distillate; total daily per capita intake of all organic components of starter distillate, other than diacetyl and acetic acid, is estimated to be less than 0.08mg per body weight. Based on the nature of the starting material and the process used to produce starter distillate, the Select Committee has no grounds to suspect that the small amount of unidentified ingredients poses a hazard. It would appear that the possibility of hazard from the addition of starter distillate is minimal. However, no food grade standars exist for starter distillate. It is a mixture of many substances, not all of which have been identified, whose qualitiative and quantitative composition may vary depending on the combinations of microorganism used in the starter culture, and on the conditions of steam distillation. Hence, there is need for establishing
practical food grade standards for starter distillate specifying acceptable limits of variability.
In light of these considerations the Select Committee concludes that: There is no evidence in the available information on diacetyl or starter distillate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Tallow and stearic acid, one of its chemical components, are consumed as part of normal human diets primarily in meats and in smaller quantities as ingredients of shortening and oleomargarine. Calcium stearate appears to be a normal product of digestion of diets containing calcium and stearic acid. Hydrogenated tallow, including tallow flakes, is used to some extent in the manufacture of shortening. Feeding tests with animals show a high utilization of tallow as an energy source, but a relatively low digestibility of hydrogenated tallow, stearic acid, and calcium stearate. None of the feeding tests involving amounts of these substances comparable to those estimated to be consumed as food additives showed any toxic effects. Furthermore, the toxicity of stearic acid at very high concentrations is markedly reduced by the presence in the diet of glycerides of substantially lower melting point, such as those containing unsaturated fatty acids. Carcinogenicity test of stearic acid have shown
negative results. This report is directed toward the GRAS status of tallow, hydrogenated tallow, and stearic acid as given in the Code of Federal Regulations 121.101(i) as substances migrating to food from cotton and cotton fabrics used in dry food packaging and calcium stearate as a GRAS substance (unpublished). Even at the levels estimated as being consumed by man from all added sources of these substances there is no evidence to demonstrate a hazard to the public. In light of these observations, the Select Committee concludes that: As a substances that may migrate to foods from cotton or cotton fabrics, there is no evidence in the available information on tallow, hydrogenated tallow, or stearic acid that demonstrates, or suggests reasonably grounds to suspect, a hazard to the public, when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on calcium stearate that demonstrates, or suggests
reasonable grounds to suspect a hazard to the public, when it is used as a direct food additive at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Stearyl citrate | 1337-33-3 | 84 | 1977 | 1 | 184.1851 |
SCOGS Opinion:
The citrate ion is widely distributed in plants and animals and is a naturally occurring component of the diet. It is a common metabolite in oxidative metabolism and an important component of bone. Exogenous citrate administered to infants and adults as a component of commonly consumed diets is considered completely metabolizable. The addition of citric acid to foods is considered equivalent to adding citrate salts except in foods of very high acidity. The amount of citrate added to foods by foods processors is about 500mg per person per day. This amount occurs naturally in 2 ounces of orange juice and does not constitute a significant addition to the total body load. Although data on acute and chronic effects of orally administered sodium citrate, calcium citrate and potassium citrate are limited, no biological effects of the citrate-containing substances evaluated in this report cause concern about the safety of these GRAS
substances used in reasonable amounts and in accordance with prescribed tolerances and limitations.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on citric acid, sodium citrate, potassium citrate, calcium citrate, ammonium citrate, isopropyl citrate, stearyl citrate, and triethyl citrate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
While the literature on biological effects of sterculia gum is not extensive, it does permit of several observtions on the health aspects of the substance as a food ingredient. Sterculia gum can cause allergic reaction in sensitive individuals. What proportion of the population is so affected is not known. A statistically-significant survey, conducted by practicing allergists, would help to determine whether significant numbers of persons are being placed in a state of receptiveness to cross-reactive allergies based upon lifelong daily exposures to sterculia gum and the other two gums alleged to be allergenic: gum arabic and gum tragacanth. Growth-depressing properties have been attributed to sterculia gum when it is fed in large amounts to laboratory animals. However, it is to be expected that the unpalatability of the gum in any diet to which it is added at a high level would ultimately affect consumption and hence the growth
curve. While no fetotoxic effects were reported in teratologic tests, the data indicated that sterculia gum fed at a level of 800 mg per kg of body weight for 10 days resulted in maternal deaths of one-third of the pregnant mice. The Select Committee has noted the same type of result in other reports by this institution, using high doses of a variety of vegetable gums, tested on a variety of laboratory animals. The doses of gum were generally much higher than those to which humans are likely to be exposed. Nevertheless, these tests should be repeated, in due course, to determine the cause of the material toxicity. With due consideration for the foregoing observations, the Select Committee concludes that: There is no evidence in the available iniformation on sterculia gum that demonstrates or suggests reasonable grounds to suspect a hazard to the public when it is used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without
additional data, whether a significant increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Succinic acid | 110-15-6 | 53 | 1975 | 1 | 184.1091 |
SCOGS Opinion:
Succinic acid occurs widely as a natural constituent of the plants and animals which are commonly used for human food. As one of the intermediary metabolites in the citric acid cycle, it may participate in the net synthesis of glucose and other sugars and fatty acids normally present in plant and animal tissue. At the level succinic acid occurs naturally in foods, there is no evidence that it is hazardous to man or animals. Moreover, experimental animals tolarate succinic acid in amounts equivalent to several g per kg of body weight. By contrast, a reasonable average daily intake of succinic acid added to foods is estimated to be less than 0.01 mg per day, a dosage that is orders of magnitude less than that required to elicit toxic signs in experimental animals. There have been few scientific studies designed to explore possible untoward effects of succinic acid. However, the normal role of succinic acid as an intermediary
metabolite in living organisms including man, is persuasive in favor of its safety. Based on these considerations, the Select Committee concludes that: There is no evidence in the available information on succinic acid that demonstrates, or suggests reasonable ground to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sucrose | 57-50-1 | 69 | 1976 | 2 | 184.1854 |
SCOGS Opinion:
Sucrose is the standard of naturally occurring sweetness, joining other nutrients usually carbohydrate in nature, that comprise a group of palatable foodstuffs known to be relatively efficient sources of energy, simple in composition and rapidly metabolizable for utilization and storage. Sucrose has been used routinely since antiquity to improve the palatability of food preparations.
By all conventional tests, sucrose is a substance of extremely low acute toxicity. Consumption of sucrose in large amounts or at frequent intervals contributes to the development of dental caries. Over consumption of sucrose probably contributes to obesity and possibly results in dietary imbalances and in modification of lipid metabolism which potentiates coronary heart disease. Tenuous relationships beteween sucrose ingestion and diabetes mellitus and other disieases also have been suggested. The possibility that sucrose may be involved in such deleterious effects continues to stir controversy, as is evident by the size of the scientific and popular literature on sugar in the human diet and the appearance of new research findings and concepts. Consequently, broad generalizations based upon the inconclusive evidence now available must be made and viewed with caution.
One of the important facts is that sucrose is both a significant natural constituent of food and a major additive to foods and beverages. It is commonly used as such by the consumer and added by food processors as a component of various foods. While per capita consumption of sucrose has changed little in the United States over the past 50 years, it is also true that about 70 percent of the per capita intake is now contributed by processed foods. This situation makes it difficult to exercise individual choice in the selection of a low sucrose diet.
Unlike most other foods, sucrose furnishes virtually only energy. While sucrose makes a substantial contribution to dietary caloric needs, in excessive amounts its effect on the intake of other nutrients may result in nutritional imbalances and, at least marginal, dietary deficiencies. Since over 15 percent of the per capita caloric intake of the population in the United States is from sucrose, it is likely that some individuals may eat enough to exclude adequate amounts of other foods that furnish required nutrients.
Findings linking ingestion of sucrose with diabetes are essentially circumstantial. There is no plausible evidence that sucrose, except as it is a non-specific source of excessive calories, is related to the disease. In those experiments in which impaired glucose tolerance was measured, highly distorted dietary patterns and excessive sucrose intakes were required.
The experimental evidence associating sucrose with cardiovascular disease is also less than clear. It seems likely that the observed hyperlipidemic effects of hight levels of sucrose in the diet of animals and man are due primarily to its relatively rapid rate of hydrolysis and absorption and that any differences between the metabolism of its hydrolytic products, glucose and fructose, are of questionable significance. There is no evidence that ingestion of sucrose in the concentrations that occur in the average diet causes significant elevations in blood cholesterol or other lipids. Furthermore, it would appear that the primary dietary factors involved in cardiovascular disease are the nature and amount of fat in the diet. Thus, the role of sucrose in cardiovascular disease appears to be secondary although it may represent a potentiating factor in its etiology.
Of all the carbohydrates tested, sucrose is among the most cariogenic. Individuals who assiduously avoid consumption of sucrose because of an inborn error of metabolism- fructose intolerance- generally have little or no dental caries. However, dental caries can and do occur in people who have never used sugar or processed foods. Various factors affect the cariogenicity of sucrose and other foods. These include frequently and duration of exposure, age of the subject, and stickiness of the sugar or materials with which it is consumed. Honey and figs, for example, are highly cariogenic and pregelatinized starches also are conductive to the development of dental caries. The significant effects of between-meal eating in the frequency and severity of dental caries has been demonstrated. Protection against dental caries is facilitated by limitation of the frequency of consumption of sucrose and other cariogenic foods. Informing the consumer of the sugar content of foods by appropriate
labeling could lead to judicious selection of sweetened foods. Choices could be made easier with a greater selection of less sugared foods in the market place.
In light of all of the foregoing, the Select Commitee concludes that:
1. Reasonable evidence exists that sucrose is a contributor to the formation of dental caries when used at levels that are now current and in the manner now practiced.
2. Other than the contribution made to dental caries, there is no clear evidence in the available information on sucrose that demonstrates a hazard to the public when used at the levels that are now current and in the manner now practiced. However, it is no possible to determine without additional data, wether an increase in sugar consumption that would result if there were a significant increase in the total of sucrose, corn sugar, *corn syrup, *and invert sugar, *added to foods would constitute a dietary hazard.
*Health aspects of corn sugar (dextrose), corn syrup, and invert sugar are evaluated in a report of the Select Committee.
SCOGS Opinion:
It seems most unlikely that more than minute amounts of sulfamic acid might occasionally enter foods by migration or abrasion from packaging materials. The acute toxicity of sulfamic acid is relatively low; it does not appear to be metabolized but is excreted unchanged in the urine. The Select Committee has weighed the foregoing and concludes that: There is no evidence in the available information on sulfamic acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used in food packaging materials as now practiced or as it might be expected to be used for such purposes in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sulfur dioxide | 7446-09-5 | 15 | 1976 | 2 | 182.3862 |
SCOGS Opinion:
Based upon chronic toxicity tests in animals, primarily in rats, the no observed adverse effect level of SO2 is estimated to be in the range of 30 to 100 mg of SO2 per kg of body weight per day. These values are considerably higher than the estimated average per capita consumption of about 0.2 mg of SO2 equivalent per kg body weight per day, and well above the estimates of up to 2 mg per kg body weight per day that some individuals may consume if they select foods and beverages relatively high in SO2 content. The margin of only about fifteenfold between the SO2 that may be ingested by high-intake consumers and the lowest estimated no observed adverse effect level is relatively narrow. However, consideration of the significance of this difference should recognize the difficulties in estimating with confidence the components which are the basis of the calculated margin. While the biological effects of sulfiting agents are still
incompletely understood, certain conclusions are warranted. There is no reason to believe the direct, local, irritating effects of sulfite, seen in high-dose acute toxicity tests, constitute a hazard from ingestion of sulfiting agents as they are presently used in foods. Orally administered sulfite is very rapidly oxidized to sulfate in all species studied. The metabolic removal of sulfite appears to be the critical defense mechanism, and this points to the important role of the enzyme, sulfite oxidase. Congenital deficiency of hepatic sulfite oxidase has been described as a rare metabolic disorder in man. There is also paucity of data on the normal development of this enzyme with age in various species, and on the possible effects of dietary factors and disease on sulfite oxidase activity. Moreover, sulfite is capable of deaminating cytosine in vitro and inhibiting several enzymes requiring NAD or pyridoxal as cofactors which suggests that sulfite might be toxic in vivo if sulfite
oxidase activity were sufficiently impaired or this metabolic mechanism were sufficiently overloaded, to prevent rapid oxidation of ingested sulfite to sulfate. Information in these respects would be helpful in assessing any special risk factors that may apply for select subpopulations. Destruction of thiamine can occur as a result of the sulfiting of foods but suffiecient thiamine is present in usual mixed diets, particularly because use of sulfiting agents is prohibited by regulation in foods known to be major sources of the vitamin. While there is no evidence that the sulfiting agents are teratogenic, there is evidence that directly added sulfite produces mutations in bacteria by alteration of nucleic acids. None of the available mammalian in vivo studies confirms these observations. Because the same organisms are not affected in the host-mediated assay, it seems reasonable to infer that rapid destruction of sulfite by the host's sulfite oxidase provides protection. In view of the
foregoing, the Select Committee concludes that: There is no evidence in the available information on potassium bisulfite, potassium metabisulfite, sodium bisulfite, sodium metabisulfite, sodium sulfite, and sulfur dioxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Sulfuric Acid | 7664-93-9 | 33 | 1975 | 1 | 184.1095 |
SCOGS Opinion:
Sulfates are natural constituents of foods and normal products of sulfur metabolism in animals. In much of the publishedliterature, toxicity evaluation of the sulfates has not been the primary objective of the work conducted, but it is evident that the toxic manifestations following oral administration of the sulfates considered in this report appear only at levels that are many times greater than those to which man is exposed in his daily diet. In light of the information contained in this report the Select Committee concludes that: There is no evidence in the available information on sulfuric acid, and on ammonium, calcium, potassium, and sodium sulfates that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in future.
SCOGS Opinion:
Silicon dioxide and various silicates occur abundantly in the earth's crust, are present in practically all natural waters,animals, and plants, and are part of the normal human diet. The question of whether or not silicon is an essential human nutrient remains unresolved. Silicon compounds consumed as added food ingredients contribute only a minor proportion of the total dietary silicon intake. The estimated possible human intake of sodium aluminosilicate, the predominant silicate added to foods in this country, is approximately 0.3mg per kg body weight per day. Silicon compounds that are GRAS for use as direct food ingredient, except potassium and sodium silicates, are insoluble or very slightly soluble in water and appear to be biologically inert. The water-soluble silicates are also of low acute toxicity. The acute oral LD50 in rats of sodium aluminosilicate is >1g per kg. No significant tissue accumulation, pathology, or
toxicity has been reported from the ingestion of those insoluble or very slightly soluble GRAS silicon compounds for which data are available. Of the five substances that were reported as added to foods in the NRC survey, biologic effects and safety data are available for all except sodium calcium aluminosilicate, and there is no reason to suspect that the toxicity of the latter would differ from those for which there are data. The results of two studies (1967-1970) in which various silicon compounds were fed to laboratory animals for 1 mo at a level of 0.8g per kg body weight (as silicon dioxide) and for 3 mo at levels of 6 to 30 mg per kg body weight suggests there may be a species-related susceptibility to renal damage from ingestion of sodium silicate, magnesium trisilicate, and finely ground quartz. No substantiating reports of these effects have appeared. Magnesium trisilicate was recognized as safe for prolonged use in human ingestion in large amount as a component of antacid
preparations by the Advisory Review Panel on Over-the-Counter Drugs, and the available evidence on the acute toxicity of sodium silicate indicates that it is low. Consumption data are lacking for aluminium calcium silicate and tricalcium silicate, two compounds that are listed as GRAS for use as anticaking agents. However, their use in keeping with good manufacturing practice and in currently regulated amounts would be of the same order of magnitude as the other GRAS silicates. In addition, the Select Committee has limited information on the amounts of talc that are currently used in foods. However a major food use of talc is in the coating of rice. Assuming package label statements are ignored and coated rice is not washed prior to cooking and no other losses occur, maximun per capita intake of talc from this source appears to be 0.5g per day. With respect to paper and cotton food- packaging products, the possibility is remote that biologically significant amounts of talc,
diatomaceous earth, or sodium silicate migrate to food from packaging, materials containing these substances. Perlite, a naturally occuring polysilicate substance, has an oral LD50 in the rat of >10g per kg body weight. Estimates of the maximun quantities of minerals that might be extracted from perlite and diatomaceous earth used as filteraids in food processing indicates no hazard to public health. There are no food grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc. Such specifications for the substances used in foods are desirable. Specification for food grade talc should limit the content of asbestos fibers even though the potential hazard of ingested asbestos fibers even though the potential hazard of ingested asbestos is not clearly established. The Food and Drug Administration is sponsoring the development of an assay method for asbestos fibers. An upper limit for cadmium should be added to the specifications for food-grade perlite, and
consideration should be given to the need for limitation of cadmium content of other silicates. In the light of all of the foregoing, the Select Committee concludes that: It is essential to establish food-grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc, with provision for an upper limit of asbestos fibers in talc. There is no evidence in the available information on aluminum calcium silicate, calcium silicate, magnesium silicate, potassium silicate, sodium silicate, sodium aluminosilicate, sodium calcium aluminosilicate, tricalcium silicate, silica aerogel, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on diatomaceous earth, silicon dioxides, sodium silicate, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the
public when they are used as ingredients of paper and paperboard products used in food packaging in accordance with current practice. There is no evidence in the available information on sodium silicate and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of cotton and cotton fabrics used in dry food packaging in accordance with current practice. There is no evidence in the available information on diatomaceous earth and perlite that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used as filteraids in food processing at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Because tall oil as a GRAS or prior sanctioned substance is currently restricted to use in dry food packaging materials or in their preparation, it can be assumed that the amount of tall oil consumed in food through migration from or abrasion of these materials is minute.
There have been no reports of significant harmful biological effects of tall oil when fed to animals even at levels that are considerably greater than could conceivably be consumed by man as tall oil is now used in packaging materials.
In the light of these considerations, the Select Commitee concludes that: There is no evidence in the available information on tall oil that demosntrates, or suggests reasonable grounds to suspects, a hazard to the public when it is used in food packaging materials as now practiced, or as it might be expected to be used for such purposes in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Tallow (packaging) | 61789-97-7 | 54 | 1975 | 1 | 186.1555 |
SCOGS Opinion:
Tallow and stearic acid, one of its chemical components, are consumed as part of normal human diets primarily in meats and in smaller quantities as ingredients of shortening and oleomargarine. Calcium stearate appears to be a normal product of digestion of diets containing calcium and stearic acid. Hydrogenated tallow, including tallow flakes, is used to some extent in the manufacture of shortening. Feeding tests with animals show a high utilization of tallow as an energy source, but a relatively low digestibility of hydrogenated tallow, stearic acid, and calcium stearate. None of the feeding tests involving amounts of these substances comparable to those estimated to be consumed as food additives showed any toxic effects. Furthermore, the toxicity of stearic acid at very high concentrations is markedly reduced by the presence in the diet of glycerides of substantially lower melting point, such as those containing unsaturated fatty acids. Carcinogenicity test of stearic acid have shown
negative results. This report is directed toward the GRAS status of tallow, hydrogenated tallow, and stearic acid as given in the Code of Federal Regulations 121.101(i) as substances migrating to food from cotton and cotton fabrics used in dry food packaging and calcium stearate as a GRAS substance (unpublished). Even at the levels estimated as being consumed by man from all added sources of these substances there is no evidence to demonstrate a hazard to the public. In light of these observations, the Select Committee concludes that: As a substances that may migrate to foods from cotton or cotton fabrics, there is no evidence in the available information on tallow, hydrogenated tallow, or stearic acid that demonstrates, or suggests reasonably grounds to suspect, a hazard to the public, when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on calcium stearate that demonstrates, or suggests
reasonable grounds to suspect a hazard to the public, when it is used as a direct food additive at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
The Select Committee considers only hydrolyzable gallotannins to be within the definition of tannic acid. Tannic acid yields gallic acid and either glucose or quinic acid as hydrolysis products. These hydrolysis products. These hydrolysis products are consumed as naturally occurring constituents of many foods. The total dietary intake of added tannic acid resulting from its use as a flavoring agent or processing aid can be inferred to be very small. The level of addition of tannic acid to various foods is about 100ppm or less. Thus, the potential level of consumer exposure is orders of magnitude below the lowest levels for which adverse biological effects are reported to occur after oral administration of tannic acid to experimental animals. While the evidence seems clear that food grade tannic acid at concentrations reportedly added to foods is hydrolyzed prior to absortion from the small intestine, the extent and nature of its absorption have not been established for man. In
experimental animals, intact tannic acid is apparently absorbed only after mucosal damage caused by large doses of concentrated aqueous tannic acid solutions intubates into empty stomachs or by artificially prolonged exposure of the mucosa to these solutions. Data available to the Select Comittee contain no evidence that tannic acid as currently used in foods can induce mucosal damage. However, toxic effects following parenteral administration to animals suggest that additional studies should be made related to the absorption of tannic acid at dietary levels by individuals with gastrointestinal disorders. Some investigators have reported that daily oral administration of tannic acid to experimental animals by stomach tube for periods of months may cause damage to their liver and other organs similar to that seen after parenteral administration of hydrolyzable tannins to experimentals animals, and to that reported historically in man following topical treatment of burns with tannic
acid. None of these effects is reported, however, in experimental animals receiving tannic acid as a component of their ration, even at levels of several percent of the diet. Nevertheless, the reported hepatocarcinogenic effect of parenterally injected hydrolyzable gallotannins is of concern to the Select Committee owing, in part, to the lack of uniformity of composition and sources of the preparations used in the tests available in the literature for evaluation. While the evidence available to the Select Committe does not demonstrate hazard of carcinogenicity inherent in food grade tannic acid, research is needed to answer the question of why there are such extreme differences between the results of parenterally and orally administered hydrolyzable tannins in rodents. There is no evidence of a clear and present danger to the public health occasioned by the current use of dietary tannic acid as a food ingredient. The Select Commitee, therefore, in the light of the foregoing concludes
that: There is no evidence in the available information on tannic acid (hydrolyzable gallotannins) that demonstrates or suggests reasonable grounds to suspect a hazard to the public when it is used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Tapioca Starch | 977002-81-5 | 115 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Taurocholic acid | 81-24-3 | 44 | 1975 | 1 | There is no CFR citation. |
SCOGS Opinion:
The amounts of the bile acids ingested as constituents of ox bile extract used as a food additive are relatively insignificant, compared to the amounts normally present in the bile of man. The available information indicates that orally administered cholic acid, desoxycholic acid, glycocholic acid, and taurocholic acid are readily absorbed and excreted without accumulation. They exhibit a relatively low toxicity for several animal species tested. The Select Commitee has no information to indicate that the individual bile acids or their salts are used in foods. However, the intake estimates available for ox bile extract, of which bile acids and their salts are major constituents, indicate that average daily consumption of ox bile extract added to foods is small, amounting to 0.1 mg or less. The intake of individuals bile acids or their salts would be, commensurately, very small. Such biological effects as have been reported in
animal studies, have been elicited at levels of administration that are several orders of magnitude greater that the levels to which man is now exposed in his daily diet. In the light of the information contained in this report, the Select Commitee concludes that: There is no evidence in the available information on ox bile extraxt, or its constituents cholic acid, desoxycholic acid. glycocholic acid, and taurocholic acid- that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in future.
SCOGS Opinion:
Thiamin (thiamine) salts have been administered to man for months in daily doses up to 1 g or more without reported adverse effects, except hundred times the estimated intake of thiamin hydrochloride and thiamin monotrinate added to foods. Most cases of sensitiviity were induced by previous topical or parenteral exposure to thiamin.
Similarly, mice and rats fed daily for three generations with several hundred times their normal requirements of thiamin showed no adverse effects.
Absorption of orally administered thiamin is regulated by a transport mechanism which offers an effective protection against overdosage. Excess thiamin in the tissues is rapidly excreted in the urine.
In view of the above considerations, the Select Committee concludes that:
There is no evidence in the available information on thiamin hydrochloride or thiamin mononitrate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Thiamin (thiamine) salts have been administered to man for months in daily doses up to 1 g or more without reported adverse effects, except hundred times the estimated intake of thiamin hydrochloride and thiamin monotrinate added to foods. Most cases of sensitiviity were induced by previous topical or parenteral exposure to thiamin.
Similarly, mice and rats fed daily for three generations with several hundred times their normal requirements of thiamin showed no adverse effects.
Absorption of orally administered thiamin is regulated by a transport mechanism which offers an effective protection against overdosage. Excess thiamin in the tissues is rapidly excreted in the urine.
In view of the above considerations, the Select Committee concludes that:
There is no evidence in the available information on thiamin hydrochloride or thiamin mononitrate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
A survey of industry indicated thiodipropionic acid and dilauryl thiodipropionate were not added to processed foods in 1970. There might be some quantity of these compounds in antioxidant formulations in use today that the Select Committee has not been able to identify. If so, it is most likely to be small. In any case, it may be advisable that this value be ascertained. These substances are of limited value as antioxidants in food systems but may be of greater importance in food packaging films. If thiodipropionic acid and dilauryl thiodipropionate are added to food, present limitations require that the total content of antioxidants may not exceed 0.02 percent of fat or oil content, including essential (volatile) oil content of the food. When used in food packaging, the resulting level of addition to the packaged food must be less than 0.005 percent.
Thiodipropionic acid and dilauryl thiodipropionate are of low acute toxicity when orally administered to experimental animals. Doses of 100 mg per kg administered to rats were absorbed and largely excreted in the urine within a few days as thiodipropionic acid or an acid labile-conjugate. Apparently less than 10 percent is otherwise metabolized, and in the case of the ester, evidence of some incorporation into fat depots was detected. No studies of the disposition of these compounds in humans or subhuman primates are available for review. Test of the teratogenic and mutagenic effects of both compounds did not suggest cause for concern. The only reports of feeding studies are unpublished and of limited thoroughness. The unpublished feeding studies on thiodipropionic acid in rats and guinea pigs presented no adverse effects as measured by growth rate or mortality. However, in unpublished long term studies, the investigators noted increased mortality in groups of rats fed dilauryl
thiodipropionate as 0.5 and 3 percent of the diet and as a mixture with thiodipropionic acid as 1.1 percent of the diet. It would seem advisable to conduct adequate long term feeding studies on thiodipropionic acid and dilauryl thiodipropionate should it be ascertained that significant amounts are currently being used.
In light of these considerations, the Select Commitee concludes that: There is no evidence in the available information on thiodipropionic acid and dilauryl thiodipropionate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard. There is no evidence in the available information on thiodipropionic acid and dilauryl thiodipropionate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients in food packaging materials at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Magnesium is a dietary essential. It is involved in myriad metabolic reactions and is necessary for the activity of many intracellular enzymes. Also, with certain other cations, it is important in electrolyte balance. Magnesium is present in fruits, vegetables, grains, milk, meat and fish and the natural content of these foods is the major source of the current dietary intake. The Food and Nutrition Board, NRC, has recommended that cereal grain products be fortified with magnesium in view of potential risk of deficiency among significant segments of the population. The usual adult intake is about 300mg or less per day from all sources and the contribution of food additives to total magnesium intake is very small. The administration of magnesium sulfate in very high doses to humans occasionally has resulted in severe and even fatal episodes, especially in the presence of pre-existing disease. These occurrences should not be prejudicial to the use of magnesium salts as foods ingredients
since the dosages given were orders of magnitude greater than the daily intake of magnesium added to food. While chronic toxicity data are lacking, the status of magnesium as a ubiquitous and essential dietary ingredient for the maintenance of homeostatic and bioenergetic mechanisms leads to the opinion that none of the available evidence suggests any probable hazard when any of the GRAS compounds of magnesium is used as a food ingredient. In view of the foregoing, The Select Committee concludes that: There is no evidence in the available information on magnesium carbonate, magnesium chloride, magnesium sulfate, magnesium hydroxide, magnesium oxide, magnesium stearate, dibasic magnesium phosphate and tribasic magnesium phosphate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced, or which might reasonably be expected in the future.
SCOGS Opinion:
Silicon dioxide and various silicates occur abundantly in the earth's crust, are present in practically all natural waters,animals, and plants, and are part of the normal human diet. The question of whether or not silicon is an essential human nutrient remains unresolved. Silicon compounds consumed as added food ingredients contribute only a minor proportion of the total dietary silicon intake. The estimated possible human intake of sodium aluminosilicate, the predominant silicate added to foods in this country, is approximately 0.3mg per kg body weight per day. Silicon compounds that are GRAS for use as direct food ingredient, except potassium and sodium silicates, are insoluble or very slightly soluble in water and appear to be biologically inert. The water-soluble silicates are also of low acute toxicity. The acute oral LD50 in rats of sodium aluminosilicate is >1g per kg. No significant tissue accumulation, pathology, or
toxicity has been reported from the ingestion of those insoluble or very slightly soluble GRAS silicon compounds for which data are available. Of the five substances that were reported as added to foods in the NRC survey, biologic effects and safety data are available for all except sodium calcium aluminosilicate, and there is no reason to suspect that the toxicity of the latter would differ from those for which there are data. The results of two studies (1967-1970) in which various silicon compounds were fed to laboratory animals for 1 mo at a level of 0.8g per kg body weight (as silicon dioxide) and for 3 mo at levels of 6 to 30 mg per kg body weight suggests there may be a species-related susceptibility to renal damage from ingestion of sodium silicate, magnesium trisilicate, and finely ground quartz. No substantiating reports of these effects have appeared. Magnesium trisilicate was recognized as safe for prolonged use in human ingestion in large amount as a component of antacid
preparations by the Advisory Review Panel on Over-the-Counter Drugs, and the available evidence on the acute toxicity of sodium silicate indicates that it is low. Consumption data are lacking for aluminium calcium silicate and tricalcium silicate, two compounds that are listed as GRAS for use as anticaking agents. However, their use in keeping with good manufacturing practice and in currently regulated amounts would be of the same order of magnitude as the other GRAS silicates. In addition, the Select Committee has limited information on the amounts of talc that are currently used in foods. However a major food use of talc is in the coating of rice. Assuming package label statements are ignored and coated rice is not washed prior to cooking and no other losses occur, maximun per capita intake of talc from this source appears to be 0.5g per day. With respect to paper and cotton food- packaging products, the possibility is remote that biologically significant amounts of talc,
diatomaceous earth, or sodium silicate migrate to food from packaging, materials containing these substances. Perlite, a naturally occuring polysilicate substance, has an oral LD50 in the rat of >10g per kg body weight. Estimates of the maximun quantities of minerals that might be extracted from perlite and diatomaceous earth used as filteraids in food processing indicates no hazard to public health. There are no food grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc. Such specifications for the substances used in foods are desirable. Specification for food grade talc should limit the content of asbestos fibers even though the potential hazard of ingested asbestos fibers even though the potential hazard of ingested asbestos is not clearly established. The Food and Drug Administration is sponsoring the development of an assay method for asbestos fibers. An upper limit for cadmium should be added to the specifications for food-grade perlite, and
consideration should be given to the need for limitation of cadmium content of other silicates. In the light of all of the foregoing, the Select Committee concludes that: It is essential to establish food-grade specifications for aluminum calcium silicate, sodium calcium aluminosilicate, and talc, with provision for an upper limit of asbestos fibers in talc. There is no evidence in the available information on aluminum calcium silicate, calcium silicate, magnesium silicate, potassium silicate, sodium silicate, sodium aluminosilicate, sodium calcium aluminosilicate, tricalcium silicate, silica aerogel, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future. There is no evidence in the available information on diatomaceous earth, silicon dioxides, sodium silicate, and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the
public when they are used as ingredients of paper and paperboard products used in food packaging in accordance with current practice. There is no evidence in the available information on sodium silicate and talc that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used as ingredients of cotton and cotton fabrics used in dry food packaging in accordance with current practice. There is no evidence in the available information on diatomaceous earth and perlite that demonstrates or suggests reasonable ground to suspect a hazard to the public when they are used as filteraids in food processing at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Triethyl citrate | 77-93-0 | 84 | 1977 | 1 | 184.1911 |
SCOGS Opinion:
The citrate ion is widely distributed in plants and animals and is a naturally occurring component of the diet. It is a common metabolite in oxidative metabolism and an important component of bone. Exogenous citrate administered to infants and adults as a component of commonly consumed diets is considered completely metabolizable. The addition of citric acid to foods is considered equivalent to adding citrate salts except in foods of very high acidity. The amount of citrate added to foods by foods processors is about 500mg per person per day. This amount occurs naturally in 2 ounces of orange juice and does not constitute a significant addition to the total body load. Although data on acute and chronic effects of orally administered sodium citrate, calcium citrate and potassium citrate are limited, no biological effects of the citrate-containing substances evaluated in this report cause concern about the safety of these GRAS
substances used in reasonable amounts and in accordance with prescribed tolerances and limitations.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on citric acid, sodium citrate, potassium citrate, calcium citrate, ammonium citrate, isopropyl citrate, stearyl citrate, and triethyl citrate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Urea | 57-13-6 | 103 | 1978 | 1 | 184.1923 |
SCOGS Opinion:
Urea is normally a normal body constituent and is constantly being produced during amino acid and protein metabolism. It is a natural constituent in commonly consumed foods. Several grams per kilogram of body weight can be ingested by nonruminants, including man, without untoward effects. Most of the nitrogen consumed in food is excreted in the form of urea. A 70 kg individual consuming a normal diet will excrete an average of 25g urea daily. While urea appears to be teratogenic in chick and frog embryos, no teratogenic effects were observed after ingestion of large doses of urea by pregnant rats and cows.
If all urea not used in animal feed and fertilizer were utilized in human food, it would amount to about 5g per capita daily. However, it is known that the majority of this urea is used for the production of urea formaldehyde resins and other non food ingredients is much less than 5g daily.
In the light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on urea that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Vitamin A | 68-26-8 | 118 | 1980 | 2 | 184.1930 |
SCOGS Opinion:
Vitamin A is an essential nutrient for man and other animals. Deficiency of vitamin A causes at least four physiologically distinct and clinically recognized states: loss of night vision; defects in bone growth; defects in reproduction; and defects in the growth and differentiation of epithelial tissues. The recommended dietary allowance of vitamin A for adults is about 3,300 international Units (IU) daily. A daily intake of 3,300 IU would amount to about 50 IU per kg for an adult.
Dietary vitamin A activity is supplied by animal products (preformed vitamin A), plant products (provitamin A, such as carotene), and by the addition of vitamin A (retinol) and/or its esters (retinyl acetate and retinyl palmitate) to fortify certain foods. Mean daily intake of vitamin A from all food sources (excluding vitamin preparations) was approximately 5,000 IU in 1971 to 1974. However, some 47 percent of young adults were found to consume no more than 3,500 IU daily. Nevertheless, there is no clear evidence that Vitamin A nutriture is a problem of public health significance in the United States. Per capita daily intake of vitamin A used for the fortification of foods is assumed to be about 800 IU (about 13 IU per kg body weight in adults). However, accurate data on the amounts actually added are not available. The Select Committee believes such data should be obtained.
Signs of hypervitaminosis A in laboratory animals include abnormal bone development and fractures, exophtalmos, intramuscular hemorrhages, alopecia, reduced rate of growth or weight loss, adrenal hypertrophy, and at highly toxic dose levels, death. The lowest reported adverse effect level in experimental animals appears to be in the range 25,000 to 60,000 IU per kg per day for periods of 3 to 5 weeks. In man, where expressed feelings of pain or illness on the part of the patient provide an early indication of adverse effects, the symptoms and signs of hypervitaminosis A vary in severity with the dose level, and include skin dryness, anorexia, headache, weakness, hair loss, joint pain, vomiting, irritability, enlarged liver and spleen, and bulging fontanel and increased intracranial pressure in babies. The lowest reported adverse effect level in man appears to lie in the range 700 to 1,000 IU per kg per day, if continued for periods of several months.
With excessive maternal doses of vitamin A, abortions, resorptions, and a large variety of teratogenic effects can be consistently produced in experimental animals, the effectiveness of vitamin A in this regard being greater when administered in the early stages of pregnancy. Administration of a range of doses of vitamin A at the stage of pregnancy when teratogenic effects are most likely to occur, indicate that the highest no effect level in mice, rats, and hamsters lies in the range 2,500 to 100,00 IU per kg per day. Species differ in sensitivity; the small amount of information available with respect to the relative sensitivity of man indicates that maternal doses of the order of 700 to 800 IU vitamin A per kg daily for most of gestation may lead to abnormalities of the urinary tract in offspring may lead to abnormalities of the urinary tract in offspring. It is to be noted that congenital malformations also occur in offspring of vitamin A deficient mothers.
Vitamin A has been found to exhibit no mutagenic activity in in vitro tests. There is no evidence that it is carcinogenic.
The lowest doses of vitamin A that produce toxic manifestations in animals and humans are manyfold greater than the daily doses human adults receive from food consumed, only a small portion of which represents from food consumed, only a small portion of which represents vitamin A or its esters that are added to food. Nevertheless, this margin of safety may be compromised by the total intake of vitamin A from all sources.
Based on the foregoing considerations, the Select Committee concludes that:
There is no evidence in the available information on vitamin A, vitamin A acetate, and vitamin A palmitate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Vitamin A acetate | 127-47-9 | 118 | 1980 | 2 | 184.1930 |
SCOGS Opinion:
Vitamin A is an essential nutrient for man and other animals. Deficiency of vitamin A causes at least four physiologically distinct and clinically recognized states: loss of night vision; defects in bone growth; defects in reproduction; and defects in the growth and differentiation of epithelial tissues. The recommended dietary allowance of vitamin A for adults is about 3,300 international Units (IU) daily. A daily intake of 3,300 IU would amount to about 50 IU per kg for an adult.
Dietary vitamin A activity is supplied by animal products (preformed vitamin A), plant products (provitamin A, such as carotene), and by the addition of vitamin A (retinol) and/or its esters (retinyl acetate and retinyl palmitate) to fortify certain foods. Mean daily intake of vitamin A from all food sources (excluding vitamin preparations) was approximately 5,000 IU in 1971 to 1974. However, some 47 percent of young adults were found to consume no more than 3,500 IU daily. Nevertheless, there is no clear evidence that Vitamin A nutriture is a problem of public health significance in the United States. Per capita daily intake of vitamin A used for the fortification of foods is assumed to be about 800 IU (about 13 IU per kg body weight in adults). However, accurate data on the amounts actually added are not available. The Select Committee believes such data should be obtained.
Signs of hypervitaminosis A in laboratory animals include abnormal bone development and fractures, exophtalmos, intramuscular hemorrhages, alopecia, reduced rate of growth or weight loss, adrenal hypertrophy, and at highly toxic dose levels, death. The lowest reported adverse effect level in experimental animals appears to be in the range 25,000 to 60,000 IU per kg per day for periods of 3 to 5 weeks. In man, where expressed feelings of pain or illness on the part of the patient provide an early indication of adverse effects, the symptoms and signs of hypervitaminosis A vary in severity with the dose level, and include skin dryness, anorexia, headache, weakness, hair loss, joint pain, vomiting, irritability, enlarged liver and spleen, and bulging fontanel and increased intracranial pressure in babies. The lowest reported adverse effect level in man appears to lie in the range 700 to 1,000 IU per kg per day, if continued for periods of several months.
With excessive maternal doses of vitamin A, abortions, resorptions, and a large variety of teratogenic effects can be consistently produced in experimental animals, the effectiveness of vitamin A in this regard being greater when administered in the early stages of pregnancy. Administration of a range of doses of vitamin A at the stage of pregnancy when teratogenic effects are most likely to occur, indicate that the highest no effect level in mice, rats, and hamsters lies in the range 2,500 to 100,00 IU per kg per day. Species differ in sensitivity; the small amount of information available with respect to the relative sensitivity of man indicates that maternal doses of the order of 700 to 800 IU vitamin A per kg daily for most of gestation may lead to abnormalities of the urinary tract in offspring may lead to abnormalities of the urinary tract in offspring. It is to be noted that congenital malformations also occur in offspring of vitamin A deficient mothers.
Vitamin A has been found to exhibit no mutagenic activity in in vitro tests. There is no evidence that it is carcinogenic.
The lowest doses of vitamin A that produce toxic manifestations in animals and humans are manyfold greater than the daily doses human adults receive from food consumed, only a small portion of which represents from food consumed, only a small portion of which represents vitamin A or its esters that are added to food. Nevertheless, this margin of safety may be compromised by the total intake of vitamin A from all sources.
Based on the foregoing considerations, the Select Committee concludes that:
There is no evidence in the available information on vitamin A, vitamin A acetate, and vitamin A palmitate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
Vitamin A is an essential nutrient for man and other animals. Deficiency of vitamin A causes at least four physiologically distinct and clinically recognized states: loss of night vision; defects in bone growth; defects in reproduction; and defects in the growth and differentiation of epithelial tissues. The recommended dietary allowance of vitamin A for adults is about 3,300 international Units (IU) daily. A daily intake of 3,300 IU would amount to about 50 IU per kg for an adult.
Dietary vitamin A activity is supplied by animal products (preformed vitamin A), plant products (provitamin A, such as carotene), and by the addition of vitamin A (retinol) and/or its esters (retinyl acetate and retinyl palmitate) to fortify certain foods. Mean daily intake of vitamin A from all food sources (excluding vitamin preparations) was approximately 5,000 IU in 1971 to 1974. However, some 47 percent of young adults were found to consume no more than 3,500 IU daily. Nevertheless, there is no clear evidence that Vitamin A nutriture is a problem of public health significance in the United States. Per capita daily intake of vitamin A used for the fortification of foods is assumed to be about 800 IU (about 13 IU per kg body weight in adults). However, accurate data on the amounts actually added are not available. The Select Committee believes such data should be obtained.
Signs of hypervitaminosis A in laboratory animals include abnormal bone development and fractures, exophtalmos, intramuscular hemorrhages, alopecia, reduced rate of growth or weight loss, adrenal hypertrophy, and at highly toxic dose levels, death. The lowest reported adverse effect level in experimental animals appears to be in the range 25,000 to 60,000 IU per kg per day for periods of 3 to 5 weeks. In man, where expressed feelings of pain or illness on the part of the patient provide an early indication of adverse effects, the symptoms and signs of hypervitaminosis A vary in severity with the dose level, and include skin dryness, anorexia, headache, weakness, hair loss, joint pain, vomiting, irritability, enlarged liver and spleen, and bulging fontanel and increased intracranial pressure in babies. The lowest reported adverse effect level in man appears to lie in the range 700 to 1,000 IU per kg per day, if continued for periods of several months.
With excessive maternal doses of vitamin A, abortions, resorptions, and a large variety of teratogenic effects can be consistently produced in experimental animals, the effectiveness of vitamin A in this regard being greater when administered in the early stages of pregnancy. Administration of a range of doses of vitamin A at the stage of pregnancy when teratogenic effects are most likely to occur, indicate that the highest no effect level in mice, rats, and hamsters lies in the range 2,500 to 100,00 IU per kg per day. Species differ in sensitivity; the small amount of information available with respect to the relative sensitivity of man indicates that maternal doses of the order of 700 to 800 IU vitamin A per kg daily for most of gestation may lead to abnormalities of the urinary tract in offspring may lead to abnormalities of the urinary tract in offspring. It is to be noted that congenital malformations also occur in offspring of vitamin A deficient mothers.
Vitamin A has been found to exhibit no mutagenic activity in in vitro tests. There is no evidence that it is carcinogenic.
The lowest doses of vitamin A that produce toxic manifestations in animals and humans are manyfold greater than the daily doses human adults receive from food consumed, only a small portion of which represents from food consumed, only a small portion of which represents vitamin A or its esters that are added to food. Nevertheless, this margin of safety may be compromised by the total intake of vitamin A from all sources.
Based on the foregoing considerations, the Select Committee concludes that:
There is no evidence in the available information on vitamin A, vitamin A acetate, and vitamin A palmitate that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
Vitamin B12 has shown no toxicity to animals at several thousand times their nutritional requirements. In man, pernicious anemia patients have received daily doses for years 10 to 20 times that of the highest estimate of average daily consumption. The only reaction to vitamin B12 so far demonstrated in man is the development of sensitivity that can become manifest as allergy or anaphylaxis after parenteral administration of relatively high doses.
Vitamin B12 absortion is pecific and limited, so that only a very small proportion of vitamin B12 given orally becomes physiologically available and active. The body stores are depleted very slowly because of enterohepatic recirculation.
The addition of vitamin B12 to food, in amounts far in excess of need or of absorbability appears to be without hazard. On the basis of available evidence, the Select Committee concludes that: There is no evidence in the available information on vitamin B12 that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used at levels that are now current and in the manner now practiced, or that might reasonably be expected in the future.
SCOGS Opinion:
In the absence of adequate exposure to sunlight or equivalent light, dietary intake of vitamin D is required for maintenance of health. Vitamin D occurs naturally in fish and fish oils, eggs, liver and dairy products. The amounts naturally present in dairy products are generally inadequate to meet the requirements and vitamin D3 is added to evaporated milk, infant formulas, and to most fresh fluid cow milk solid by dairies. In addition, vitamin D2 or vitamin D3 is commonly added to margarines, to certain breakfast cereals and to a few other foods. Fortification of milk with vitamin D3 since the 1920s has been credited with the marked reduction in incidence of rickets.
The estimated requirement for vitamin D in the absence of exposure to ultraviolet light is believed to be 100 to 200 IU per day and the Recommended Dietary Allowance of the Food and Nutrition Board, National Research Council, is 400 IU per day. From food sources of vitamin D (naturally occurring or added) it is unlikely that an infant would receive more than 1000 IU per day (perhaps 200 IU per kg per day), a preschool child more than 2000 IU per day (less than 200 IU per kg per day) or an adult more than 5000 IU per day (less than 100 IU per kg per day). However, better estimates of current intakes of vitamin D from dietary sources should, in due course, be developed.
Unequivocal manifestations of vitamin D toxicity including vascular effects have not been reported from consumption of foods including foods fortified with the vitamin. Observations on patients undergoing vitamin D therapy have shown that intakes of vitamin D 1000 IU per kg per day or more (at least 60,000 IU per day for a 60kg adult) have in some instances been associated with evidence of toxicity. Studies of individuals with disorders qualifying them for disability pensions suggest that long-term ingestion of vitamin D in excess of 1000 IU per day may be a factor in the occurrence of myocardial infarction. However, for the adult there is relatively little likelihood of consumption of such amounts of vitamin D from that currently added to food.
The only suggestions that toxic effects may be produced by intakes of vitamin D less than 1000 IU per kg per day concern two special problems of infants: (1) such intakes may interfere with linear growth, and (2) the rare disorder, idiopathic hypercalcemia, may be caused by or aggravated by such intakes. For reasons detailed in the body of this report, the Select Committee finds unconvincing the few reports which attribute interference in linear growth to intakes of vitamin D less than 1000 IU per kg per day. The incidence of idiopathic hypercalcemia is estimated to be 1 in 20,000 births for all forms of the disorder and 1 in 275,000 births for the severe form. This incidence is low must be considered in relation to the demonstrated desirability of fortifying foods with vitamin D. The Committee recognizes also that vitamin D intake may aggravate the manifestations of idiopathic hypercalcemia but considers it unlikely that there is a casual relationship.
At the same time, it is evident that the margin of safety between intakes currently achieved by some infants from all sources (perhaps 200 IU per kg per day) and the amounts (1000 to 3000 IU per kg per day) that may produce toxic manifestations in otherwise normal infants is relatively low. There is strikingly little information on the effects of moderate overdoses of vitamin D, particularly in the range of about 200 to 3000 IU per kg per day for all age groups. Additional data are needed for evaluation of the safety of vitamin D in this dosage range. Moreover, evaluations should recognize that relatively long periods are required for adverse effects of vitamin D to become recognizable. Thus, there appears to be need to limit intakes of vitamin D from all sources, including food and vitamin preparations.
In light of these considerations the Select Committee concludes that: There is no evidence in the available information on vitamin D2 and vitamin D3 that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used in food at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.
SCOGS Opinion:
In the absence of adequate exposure to sunlight or equivalent light, dietary intake of vitamin D is required for maintenance of health. Vitamin D occurs naturally in fish and fish oils, eggs, liver and dairy products. The amounts naturally present in dairy products are generally inadequate to meet the requirements and vitamin D3 is added to evaporated milk, infant formulas, and to most fresh fluid cow milk solid by dairies. In addition, vitamin D2 or vitamin D3 is commonly added to margarines, to certain breakfast cereals and to a few other foods. Fortification of milk with vitamin D3 since the 1920s has been credited with the marked reduction in incidence of rickets.
The estimated requirement for vitamin D in the absence of exposure to ultraviolet light is believed to be 100 to 200 IU per day and the Recommended Dietary Allowance of the Food and Nutrition Board, National Research Council, is 400 IU per day. From food sources of vitamin D (naturally occurring or added) it is unlikely that an infant would receive more than 1000 IU per day (perhaps 200 IU per kg per day), a preschool child more than 2000 IU per day (less than 200 IU per kg per day) or an adult more than 5000 IU per day (less than 100 IU per kg per day). However, better estimates of current intakes of vitamin D from dietary sources should, in due course, be developed.
Unequivocal manifestations of vitamin D toxicity including vascular effects have not been reported from consumption of foods including foods fortified with the vitamin. Observations on patients undergoing vitamin D therapy have shown that intakes of vitamin D 1000 IU per kg per day or more (at least 60,000 IU per day for a 60kg adult) have in some instances been associated with evidence of toxicity. Studies of individuals with disorders qualifying them for disability pensions suggest that long-term ingestion of vitamin D in excess of 1000 IU per day may be a factor in the occurrence of myocardial infarction. However, for the adult there is relatively little likelihood of consumption of such amounts of vitamin D from that currently added to food.
The only suggestions that toxic effects may be produced by intakes of vitamin D less than 1000 IU per kg per day concern two special problems of infants: (1) such intakes may interfere with linear growth, and (2) the rare disorder, idiopathic hypercalcemia, may be caused by or aggravated by such intakes. For reasons detailed in the body of this report, the Select Committee finds unconvincing the few reports which attribute interference in linear growth to intakes of vitamin D less than 1000 IU per kg per day. The incidence of idiopathic hypercalcemia is estimated to be 1 in 20,000 births for all forms of the disorder and 1 in 275,000 births for the severe form. This incidence is low must be considered in relation to the demonstrated desirability of fortifying foods with vitamin D. The Committee recognizes also that vitamin D intake may aggravate the manifestations of idiopathic hypercalcemia but considers it unlikely that there is a casual relationship.
At the same time, it is evident that the margin of safety between intakes currently achieved by some infants from all sources (perhaps 200 IU per kg per day) and the amounts (1000 to 3000 IU per kg per day) that may produce toxic manifestations in otherwise normal infants is relatively low. There is strikingly little information on the effects of moderate overdoses of vitamin D, particularly in the range of about 200 to 3000 IU per kg per day for all age groups. Additional data are needed for evaluation of the safety of vitamin D in this dosage range. Moreover, evaluations should recognize that relatively long periods are required for adverse effects of vitamin D to become recognizable. Thus, there appears to be need to limit intakes of vitamin D from all sources, including food and vitamin preparations.
In light of these considerations the Select Committee concludes that: There is no evidence in the available information on vitamin D2 and vitamin D3 that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used in food at levels that are now current and in the manner now practiced. However, it is not possible to determine, without additional data, whether a significant increase in consumption would constitute a dietary hazard.:
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Waxy Maize Starch | 977050-52-4 | 115 | 1979 | 1 | There is no CFR citation. |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Wheat Starch | 977052-26-8 | 115 | 1979 | 1 | 182.70 |
SCOGS Opinion:
The digestibility of unmodified cereal and tapioca starches used commercially as food ingredients, both raw and after cooking, is almost complete. Potato and arrowroot starches are less completely digested when fed raw but their digestibility is similar to that of the cereal starches after cooking. Pregelatinized starches (dried, cooked starches) generally are highly digestible. Consumption of excessive quantities, pounds per day, of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. Most of the foods to which starch is added by the food industry are cooked in processing or are cooked before serving. Moreover, the total quantity of unmodified and pregelatinized starch added to processed foods is insignificant compared to the natural starch content of the American dietary, some of which is eaten in its native form in raw vegetables. No adverse effects have been attributed to these starches as added
food ingredients. It is suggested, however, that specifications for food grade unmodified starches be developed in order to distinguish them from the starches that are used in non-food applications.
In light of the foregoing, the Select Committee concludes that: There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo (also called grain sorghum starch), rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from paper and paperboard packaging.
There is no evidence in the available information on unmodified or pregelatinized corn, high amylose corn, waxy maize, wheat, milo, rice, potato, tapioca, or arrowroot starch that demonstrates or suggests reasonable grounds to suspect a hazard to the public when they are substances migrating to food from cotton and cotton fabrics used in dry food packaging.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Yeast autolyzates | 977046-75-5 | 37b | 1980 | 1 | There is no CFR citation. |
SCOGS Opinion:
The average level of consumption of protein hydrolyzates for flavoring purposes is less than 3 mg per kg per day. Protein hydrolyzates are not used for flavoring purposes in commercially processed baby foods wich formerly may have contained about 2 percent by weight. The Select Committee was unable to locate reports of experimentally demostrable adverse effects of high concentrations of glutamate in dietary mixtures.
In light of the above, and assuming that appropriate product specifications are adopted, the Select Commitee concludes that:
There is no evidence in the available information on acid hydrolyzed proteins, enzymatically hydrolyzed protein, yeast autolysates, and soy sauces, that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used as flavoring agents at levels that are now current or that might reasonably be expected in the future.
The situation is different regarding the use of enzymatic casein hydrolyzates as nutrients. These hydrolyzates are consumed or administered in much higher doses, frequently as the sole source of dietary protein in products that are used as special dietary foods.
Decades of clinical experience have revealed no reports of untoward effects when casein hydrolyzates are administered orally in combination with other nutrients such as glucose. Adverse effects of the dicarboxylic amino acid components have been reported only in rodents under unusual conditions of administration (e.g., gavage or subcutaneous injection) and are not considered relevant to the use of casein hydrolyzates by humans.
The Select Commitee therefore concludes that: There is no evidence in the available information on enzymatically hydrolyzed casein that demostrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used as a nutrient in special dietary foods at levels that are now current or that might reasonably be expected in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Zinc acetate | 557-34-6 | 21 | 1973 | 2 | There is no CFR citation. |
SCOGS Opinion:
The available information indicates that a wide margin exists between present intake levels of zinc salts and those that have been reported to produce noticeably harmful effects. Similarly, the suggestion that zinc chloride is carcinogenic has not been supported in carefully controlled animal studies. However, because of the central role of zinc as either an activator of certain enzymes or as a coenzyme in many metabolic reactions, it has been demonstrated that relatively large excesses of zinc salts in the diet can lead to metabolic dysfunctions. In particular, the interaction of zinc with several other mineral nutrients, notably iron, copper, and calcium, suggests that major modification of this nutritional balance might lead to significant metabolic disturbances. In consideration of this and the currently wide nutritional use of zinc sulfate and zinc oxide in infant formulas, it would be desirable, in due course, to expand our
knowledge of the interaction of zinc salts in association with dietary levels of other essential mineral nutrients. It would also be desirable to establish maximum limits for the levels of zinc salts in foods, particularly in formulas for infants, since this segment of the population may now consume the highest level of zinc salts when calculated on a daily or body weight basis. In view of the foregoing, the Select Committee concludes that: There is no evidence in the available information on zinc sulfate, zinc oxide, zinc acetate, zinc carbonate, and zinc chloride that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Zinc carbonate | 3486-35-9 | 21 | 1973 | 2 | There is no CFR citation. |
SCOGS Opinion:
The available information indicates that a wide margin exists between present intake levels of zinc salts and those that have been reported to produce noticeably harmful effects. Similarly, the suggestion that zinc chloride is carcinogenic has not been supported in carefully controlled animal studies. However, because of the central role of zinc as either an activator of certain enzymes or as a coenzyme in many metabolic reactions, it has been demonstrated that relatively large excesses of zinc salts in the diet can lead to metabolic dysfunctions. In particular, the interaction of zinc with several other mineral nutrients, notably iron, copper, and calcium, suggests that major modification of this nutritional balance might lead to significant metabolic disturbances. In consideration of this and the currently wide nutritional use of zinc sulfate and zinc oxide in infant formulas, it would be desirable, in due course, to expand our
knowledge of the interaction of zinc salts in association with dietary levels of other essential mineral nutrients. It would also be desirable to establish maximum limits for the levels of zinc salts in foods, particularly in formulas for infants, since this segment of the population may now consume the highest level of zinc salts when calculated on a daily or body weight basis. In view of the foregoing, the Select Committee concludes that: There is no evidence in the available information on zinc sulfate, zinc oxide, zinc acetate, zinc carbonate, and zinc chloride that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Zinc chloride | 7646-85-7 | 21 | 1973 | 2 | 182.8985 |
SCOGS Opinion:
The available information indicates that a wide margin exists between present intake levels of zinc salts and those that have been reported to produce noticeably harmful effects. Similarly, the suggestion that zinc chloride is carcinogenic has not been supported in carefully controlled animal studies. However, because of the central role of zinc as either an activator of certain enzymes or as a coenzyme in many metabolic reactions, it has been demonstrated that relatively large excesses of zinc salts in the diet can lead to metabolic dysfunctions. In particular, the interaction of zinc with several other mineral nutrients, notably iron, copper, and calcium, suggests that major modification of this nutritional balance might lead to significant metabolic disturbances. In consideration of this and the currently wide nutritional use of zinc sulfate and zinc oxide in infant formulas, it would be desirable, in due course, to expand our
knowledge of the interaction of zinc salts in association with dietary levels of other essential mineral nutrients. It would also be desirable to establish maximum limits for the levels of zinc salts in foods, particularly in formulas for infants, since this segment of the population may now consume the highest level of zinc salts when calculated on a daily or body weight basis. In view of the foregoing, the Select Committee concludes that: There is no evidence in the available information on zinc sulfate, zinc oxide, zinc acetate, zinc carbonate, and zinc chloride that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Zinc gluconate | 4468-02-4 | 78 | 1978 | 1 | 182.8988 |
SCOGS Opinion:
Gluconates are useful as nutritional supplements since their high solubility allows relatively rapid absorption of the cations. Evidence suggests that any possible toxicity is a function of the cation rather than of the gluconate portion of these substances. Thus, the acute toxic responses to the various gluconate salts are comparable with other salts of the same metals and long-term toxicities seem related to the tissue deposition of these metals. These observations could have been anticipated because gluconic acid is a normal metabolic product of glucose. The amount of gluconic acid produced endogenously is many times greater than the largest amounts likely to be consumed from food. Because the toxicological activities of these gluconates appear to be a function of their cationic components, safe and acceptable levels in foods are limited only by the nature of the specific cations. There is no evidence in the available
information on sodium gluconate, potassium gluconate, magnesium gluconate, and zinc gluconate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.
SCOGS Opinion:
Information on the toxicity of sodium hydrosulfite is extremely limited. Nevertheless, the available data indicate that the oral administration of up to 1g of the sodium salt per kg body weight does not cause significant harm in dogs, and the intravenous injection of 25 to 50mg per kg has resulted in no apparent ill effects in rats. These doses are many orders of magnitude greater than those that could result from the consumption of foods packaged in sodium hydrosulfite-containing paper and paperboard packaging materials. Because zinc compounds, such as the carbonate and sulfate do not elicit adverse effects when administered orally to experimental animals at levels of 50mg per kg., and sodium hydrosulfite is without apparent adverse effects at equivalent levels it is reasonable to conclude that zinc hydrosulfite would react similarly. In the light of these considerations, the Select Committee concludes that: There is no
evidence in the available information on sodium hydrosulfite and zinc hydrosulfite that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used in food packaging materials as now practiced or as they might reasonably be expected to be used for such purposes in the future.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Zinc oxide | 1314-13-2 | 21 | 1973 | 2 | 182.8991 |
SCOGS Opinion:
The available information indicates that a wide margin exists between present intake levels of zinc salts and those that have been reported to produce noticeably harmful effects. Similarly, the suggestion that zinc chloride is carcinogenic has not been supported in carefully controlled animal studies. However, because of the central role of zinc as either an activator of certain enzymes or as a coenzyme in many metabolic reactions, it has been demonstrated that relatively large excesses of zinc salts in the diet can lead to metabolic dysfunctions. In particular, the interaction of zinc with several other mineral nutrients, notably iron, copper, and calcium, suggests that major modification of this nutritional balance might lead to significant metabolic disturbances. In consideration of this and the currently wide nutritional use of zinc sulfate and zinc oxide in infant formulas, it would be desirable, in due course, to expand our
knowledge of the interaction of zinc salts in association with dietary levels of other essential mineral nutrients. It would also be desirable to establish maximum limits for the levels of zinc salts in foods, particularly in formulas for infants, since this segment of the population may now consume the highest level of zinc salts when calculated on a daily or body weight basis. In view of the foregoing, the Select Committee concludes that: There is no evidence in the available information on zinc sulfate, zinc oxide, zinc acetate, zinc carbonate, and zinc chloride that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public.
| Substance | ID Code | Rpt No. | Year | Conclusion* | CFR Section |
|---|
| Zinc sulfate | 7446-20-0 | 21 | 1973 | 2 | 182.8997 |
SCOGS Opinion:
The available information indicates that a wide margin exists between present intake levels of zinc salts and those that have been reported to produce noticeably harmful effects. Similarly, the suggestion that zinc chloride is carcinogenic has not been supported in carefully controlled animal studies. However, because of the central role of zinc as either an activator of certain enzymes or as a coenzyme in many metabolic reactions, it has been demonstrated that relatively large excesses of zinc salts in the diet can lead to metabolic dysfunctions. In particular, the interaction of zinc with several other mineral nutrients, notably iron, copper, and calcium, suggests that major modification of this nutritional balance might lead to significant metabolic disturbances. In consideration of this and the currently wide nutritional use of zinc sulfate and zinc oxide in infant formulas, it would be desirable, in due course, to expand our
knowledge of the interaction of zinc salts in association with dietary levels of other essential mineral nutrients. It would also be desirable to establish maximum limits for the levels of zinc salts in foods, particularly in formulas for infants, since this segment of the population may now consume the highest level of zinc salts when calculated on a daily or body weight basis. In view of the foregoing, the Select Committee concludes that: There is no evidence in the available information on zinc sulfate, zinc oxide, zinc acetate, zinc carbonate, and zinc chloride that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public.
* denotes Type of Conclusion 1, 2, 3, 4, or 5.
