June 19, 2001

Peter N. Gray, Ph.D.
Bernard Technologies, Inc.
919 North Michigan Avenue, Suite 1710
Chicago, IL 60611

Re: GRAS Notice No. GRN 000062

Dear Dr. Gray:

The Food and Drug Administration (FDA) is responding to the notice, dated November 30, 2000, that you submitted in accordance with the agency's proposed regulation, proposed 21 CFR 170.36 (62 FR 18938; April 17, 1997; Substances Generally Recognized as Safe (GRAS)). FDA received your notice on December 4, 2000, and designated it as GRAS Notice No. GRN 000062.

The subject of the notice is chlorine dioxide generated from particles (less than 30 micrometers) composed of sodium polyphosphate, magnesium sulfate, sodium silicate and sodium chlorite that are incorporated into low density polyethylene (LDPE) food-packaging films, at levels not exceeding 17.5 micrograms chlorite/in² of finished package film. The chlorine dioxide generated in this manner will hereafter be referred to as the ingredient. The particles (less than 30 micrometers) composed of sodium polyphosphate, magnesium sulfate, sodium silicate and sodium chlorite will hereafter be referred to as the particles. This notice informs FDA of the view of BTI that the ingredient is GRAS through scientific procedures for the following uses:

1. for packaging meats, poultry and seafood that will be cooked prior to being consumed, and
2. for packaging fresh fruits and vegetables and foods in transit or storage from producers to processors, or institutional users, that will be washed with a potable water rinse and further processed before being consumed.

BTI originally submitted this GRAS Notice for the use of this ingredient without regard to the types of food packaged. In a letter dated March 8, 2001, BTI amended the notice to clearly restrict the uses of the ingredient to those listed under 1 and 2.

The particles are blended with the LDPE film for the purpose of delivering a controlled, time-released dose of chlorine dioxide to food in order to extend its shelf life. The notice states that the mechanism by which this "functional packaging" operates is as follows: water from inside the package migrates to the particles in the film and initiates the solid state conversion of chlorite ions to chlorine dioxide. The chlorine dioxide then migrates out of the package and extends the shelf life of the food by exerting an antimicrobial effect on spoilage bacteria in or on the packaged food.

As part of its notice, BTI includes a statement of individuals (BTI's GRAS panel) who evaluated the data and information that are the basis for BTI's GRAS determination. BTI considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. BTI states that its GRAS panel has carefully reviewed and evaluated the publicly available information summarized in BTI's notice, especially regarding the potential human exposure and toxicity of chlorine dioxide. BTI's GRAS panel concludes that no evidence exists in the available information on chlorine dioxide that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public health when chlorine dioxide is used at levels that might reasonably be expected from use of the ingredient as defined in BTI's GRAS notice.

BTI describes the method of manufacture of the particles that will generate the chlorine dioxide. Sodium polyphosphate, magnesium sulfate, sodium silicate and sodium chlorite are combined by a physical mixing process that does not include any additional chemical reagents, or solvents, other than water. The mixing, blending and drying procedures do not involve any chemical reactions between the individual components. The particles are incorporated into LDPE pellets by melt blending them with LDPE in a twin screw extruder and cutting the blend into pellets as it exits the extruder. These pellets are then shipped to packaging manufacturers where they are further blended with more LDPE to the appropriate final loading of the particles, extruded through dies, then rolled, or blown, into films. BTI provided some specifications for the particles. These specifications include moisture (2-10 percent), particle size (less than 30 micrometers), chlorite (less than 30 mg/kg), lead (less than 5 mg/kg), and other heavy metals (less than 10 mg/kg).

BTI originally estimated human exposure to chlorine dioxide and chlorite by assuming that all of the chlorite in the package film would be converted to chlorine dioxide that would migrate to food. BTI further assumed that the chlorine dioxide would subsequently be converted back to chlorite in the food. Although this exposure estimate is very conservative, it provided a simple model for estimating the highest possible exposure to chlorite from all possible uses.

On March 8, 2001, BTI amended its notice with a revised estimate of human exposure to chlorine dioxide and chlorite. BTI based its revised exposure estimate on generally available information about the decomposition of chlorite to chloride in solution and during cooking, the removal of residues of sodium chlorite by washing, and its concomitant amendment to limit the proposed uses of the ingredient as follows: 1) for packaging meats, poultry and seafood that will be cooked prior to being consumed, and, 2) for packaging fresh fruits and vegetables and foods in transit or storage from producers to processors, or institutional users, that will be washed with a potable water rinse and further processed before being consumed. In its revised estimate of human exposure, BTI concluded that there would be no exposure to chlorite or chlorine dioxide from their proposed use of the ingredient.

The intended technical effect of a package film containing the particles is to generate time-released chlorine dioxide inside of the package to extend the shelf life of the food by exerting an antimicrobial effect against a broad range of spoilage organisms in or on the food. BTI provides a graph depicting the release of chlorine dioxide from LDPE film containing the particles over a period of 115 hours. BTI also packaged several types of food in films containing the various loadings of the particles, and in films containing none of the particles as controls. BTI includes photographs of these foods to illustrate its view that the ingredient maintains food quality.

BTI provides a reference to published data on antimicrobial activity of ClO₂, and describes experiments that it conducted to demonstrate the nonspecific activity of this antimicrobial. BTI described an experiment designed to test whether the antimicrobial activity of the released chlorine dioxide could result in a scenario where microorganisms normally present in packaged foods would be selectively killed and replaced by opportunistic pathogens. Cherry tomatoes were co-inoculated with two bacterial cocktails - one containing two common spoilage organisms, and one containing Listeria monocytogenes - then packaged in LDPE bags containing the particles. BTI states that there was no difference in the resulting response from that observed for cherry tomatoes inoculated separately. In a second experiment, cherry tomatoes were co-inoculated with two species of Listeria (monocytogenes and innocua) and exposed to chlorine dioxide generated from the particles. The presence of the second bacterial strain did not affect the antimicrobial response observed for Listeria monocytogenes, indicating that the antimicrobial activity of chlorine dioxide is nonspecific and unlikely to lead to the opportunistic growth of pathogens.

To establish that the ingredient does not result in any negative effects on the packaged food, BTI examined the effects of three levels of particle loading in LDPE films on various food quality parameters in several model food systems, including fresh produce, poultry meat, and beef muscle meat.

FDA consulted with the Labeling and Consumer Protection Staff of the Food Safety and Inspection Service of the United States Department of Agriculture (FSIS). In a memorandum dated April 18, 2001, USDA requested FDA to advise BTI that FSIS would need additional information to complete its own review, under the statutes it implements, relating to the suitability of the use of the ingredient in contact with meat and poultry products that are not ready-to-eat. This information includes data to establish that the ingredient is used at the minimum level required to accomplish the intended technical effect, and data to address the possibility that the appearance of treated meat and poultry products may be altered, thereby misleading consumers into believing that the product is more fresh than is actually the case. This information also includes data from efficacy testing on ground meat and poultry as well as data on poultry with and without skin. USDA also requested FDA to advise BTI that FSIS would need information regarding an actual exposure estimate of the packaged meat and poultry to chlorine dioxide. Finally, USDA requested that FDA advise BTI that the use of this ingredient may involve issues relating to labeling, and possibly standards of identity. BTI should direct any inquiry about the use of the ingredient in products regulated by FSIS to Dr. Robert Post, Director, Labeling and Consumer Protection Staff, Office of Policy, Program Development and Evaluation, Food Safety and Inspection Service, 300 12th Street, SW, Room 602, Washington, DC 20250-3700. The telephone number of his office is (202) 205-0279 and the FAX number is (202)205-3625.

Based on the information provided by BTI, as well as other information available to FDA, the agency has no questions at this time regarding BTI's conclusion that chlorine dioxide generated from particles (less than 30 micrometers) composed of sodium polyphosphate, magnesium sulfate, sodium silicate and sodium chlorite that are incorporated into low density polyethylene (LDPE) food-packaging films, at levels not exceeding 17.5 micrograms chlorite/in² of finished package film is GRAS under the intended conditions of use. The agency has not, however, made its own determination regarding the GRAS status of the subject use of the ingredient. As always, it is the continuing responsibility of BTI to ensure that food ingredients that the firm markets are safe, and are otherwise in compliance with all applicable legal and regulatory requirements.

For foods regulated by FDA, section 403(a) of the Federal Food, Drug, and Cosmetic Act (FFDCA) provides that a food shall be deemed to be misbranded if its labeling is false or misleading in any particular. Section 403(i)(2) of the FFDCA provides that a food shall be deemed to be misbranded unless its label bears the common or usual name of each ingredient. In addition, section 403(k) of the FFDCA provides that a food shall be deemed to be misbranded if it bears or contains any chemical preservative, unless it bears labeling stating that fact. BTI's use of the subject ingredient constitutes use as a preservative. Therefore, the ingredient statement on labels of foods treated with this ingredient must comply with 21 CFR 101.22(j) which requires a food to which a chemical preservative is added to bear a label declaration stating both the common or usual name of the ingredient and a separate description of its function. Further, food that is subjected to any form of preservation, except as provided in 21 CFR 101.95(c), may not be labeled as "fresh."

If BTI has any questions about the appropriate declaration of this ingredient, or labeling of foods that contain this ingredient and that are regulated by FDA, you should contact the Division of Standards and Labeling Regulations, Office of Nutritional Products, Labeling, and Dietary Supplements (HFS-820), Center for Food Safety and Applied Nutrition, FDA, 200 C Street, S.W., Washington, DC 20204. You can reach this division by telephone at (202) 205-4168. For questions about the appropriate labeling of meats, poultry, or other food products that contain this ingredient and that are regulated by FSIS, you should contact Dr. Robert Post at FSIS.

In accordance with proposed 21 CFR 170.36(f), a copy of the text of this letter, as well as a copy of the information in your notice that conforms to the information in proposed 21 CFR 170.36(c)(1), is available for public review and copying on the homepage of the Office of Food Additive Safety (on the Internet at http://www.cfsan.fda.gov/~lrd/foodadd.html).

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