U. S. Food and Drug Administration
Center for Food Safety and Applied Nutrition
Office of Food Additive Safety
May 5, 2003

Claire L. Kruger, Ph.D.
Environ
4350 North Fairfax Drive
Suite 300
Arlington, Virginia, 22203

Re: GRAS Notice No. GRN 000118

Dear Dr. Kruger:

The Food and Drug Administration (FDA) is responding to the notice, dated November 4, 2002, that you submitted on behalf of Imperial Sensus, LLC (Imperial Sensus) 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); the GRAS proposal). FDA received the notice on November 7, 2002, filed it on November 14, 2002, and designated it as GRAS Notice No. GRN 000118.

The subject of the notice is inulin from the root of the chicory plant (Cichorium intybus). The notice informs FDA of the view of Imperial Sensus that inulin is GRAS, through scientific procedures, for use in food in general, including meat and poultry products, as a bulking agent. Imperial Sensus lists 43 proposed food categories that would contain inulin at varying use levels. Based on these proposed uses, Imperial Sensus estimates that dietary intake of inulin at the 90th percentile level would be approximately 6 grams per day for infants less than one year of age, approximately 15 grams per day for infants one year of age, and approximately 20 grams per day for the general population (i.e., two years of age and older).

Imperial Sensus' notice includes the findings of a panel of individuals who evaluated the data and information that serve as the basis for Imperial Sensus' GRAS determination. Imperial Sensus considers these individuals to be qualified by scientific training and experience to evaluate the safety of substances added to food.

Imperial Sensus describes published information about inulin, which is a polysaccharide that occurs naturally in plants such as chicory, Jerusalem artichokes, some cereal grains, and onions. It contains a chain of fructose units that are linked in a beta 2-1 configuration, usually with a single terminal glucose molecule. The degree of polymerization (DP) (i.e., the number of fructose units in the chain) ranges from two to greater than 60, depending on the plant source, the time of harvest and the duration and conditions of post-harvest storage.

Imperial Sensus describes published information about other "fructan" polysaccharides - i.e., polysaccharides that contain a chain of fructose units. These fructan polysaccharides include fructooligosaccharide (FOS; DP ranging from three to five) and oligofructoses (DP ranging from two to twenty). Because the fructose units in inulin, FOS, and oligofructoses all contain the characteristic beta 2-1 linkage, Imperial Sensus assesses the safety of inulin using data and information regarding all three of these fructan polysaccharides.

Imperial Sensus describes the manufacture of inulin, which is extracted from the root of the chicory plant. The harvested roots are washed via a process similar to that used in the sugar beet industry. The washed roots are sliced and fed into a scalding apparatus that renders the plant cell walls semi-permeable. After scalding, the chicory root slices are fed into a diffusion tower, where inulin is extracted in a continuous countercurrent process. The raw inulin juice emerging from this process is cooled and further purified and concentrated. Spray drying of this concentrated juice results in a final concentration of greater than 95 percent dry matter. Imperial Sensus provides specifications for this spray dried product.

Imperial Sensus describes published information about the presence of inulin as the energy reserve in a number of plants consumed as food world-wide, including chicory, dahlia, Jerusalem artichoke, murnong, and yacon. Imperial Sensus notes that these sources of inulin have been consumed either as dietary staples or as sustenance crops in times of hardship. Imperial Sensus describes published information about approximately two dozen inulin-containing food sources, including the percent of inulin contained in the edible part of the plant. Imperial Sensus notes that the inulin content of edible plants ranges from less than one percent (e.g., in many cereal grains) to more than 20 percent (e.g., in Jerusalem artichokes and other tubers). Imperial Sensus also cites a publication regarding the consumption of Jerusalem artichokes by some populations as a substitute for white potatoes and estimates that consumption of inulin by these populations may have reached 25 to 32 grams per day. In the U.S., the most commonly consumed inulin-containing foods are cereal grains, bananas, garlic, onions, and tomatoes. Based on published reports, Imperial Sensus estimates that the average intake of inulin and oligofructose in the U.S. is 2.6 grams per day, primarily from consumption of wheat and onions. In Europe, Imperial Sensus estimates that the intake of inulin and oligofructose may be as high as 10 grams per day.

Imperial Sensus cites published information to support its view that the beta 2-1 linkage between fructose units of inulin is largely resistant to digestion by mammalian digestive enzymes of the small intestine and that ingested inulin will pass largely intact to the colon, where it is subject to fermentation by the resident microbial flora. This fermentation results in the production of gases such as hydrogen, carbon dioxide, and methane, as well as short-chain fatty acids. The short-chain fatty acids are either utilized locally as an energy source by the resident flora, taken up systemically via the colonocytes and transported to the liver for caloric utilization by the host, or excreted in the feces.

Imperial Sensus describes results from published in vitro genetic toxicity studies with a commercially available fructooligosaccharide and concludes that these studies demonstrate that this fructooligosaccharide lacks any significant genotoxic potential. Imperial Sensus also discusses published human studies and reviews related to human tolerance of inulin and related fructans and concludes that regular consumption of 40 to 70 grams per day of inulin by healthy adults appears to result in no significant adverse effects, especially when the consumption is divided over the course of the day.

Based on the information provided by Imperial Sensus, as well as other information available to FDA, the agency has no questions at this time regarding Imperial Sensus' conclusion that inulin 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 inulin. As always, it is the continuing responsibility of Imperial Sensus to ensure that food ingredients that the firm markets are safe, and are otherwise in compliance with all applicable legal and regulatory requirements.

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 the 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).

Potential Labeling Issues

Under section 403(a) of the Federal Food, Drug, and Cosmetic Act (FFDCA), a food is misbranded if its labeling is false or misleading in any particular. Section 403(r) of the FFDCA lays out the statutory framework for a health claim. In describing the intended use of inulin and in describing the information that Imperial Sensus relies on to conclude that inulin is GRAS under the conditions of its intended use, Imperial Sensus raises potential labeling issues under these provisions of the FFDCA. These labeling issues consist of Imperial Sensus' assertion that inulin has a variety of physiological effects that Imperial Sensus views as beneficial. If products that contain inulin bear any claims about such benefits on the label or in labeling, such claims are the purview of the Office of Nutritional Products, Labeling, and Dietary Supplements (ONPLDS) in the Center for Food Safety and Applied Nutrition (CFSAN). The Office of Food Additive Safety (OFAS) neither consulted with ONPLDS on these labeling issues nor evaluated the information in Imperial Sensus' notice to determine whether it would support any claims made about inulin on the label or in labeling.

Use in Meat and Poultry Products

During its evaluation of GRN 000118, FDA consulted with the Labeling and Consumer Protection Staff of the Food Safety and Inspection Service (FSIS) of the USDA. Under the Federal Meat Inspection Act and the Poultry Products Inspection Act, FSIS is responsible for determining the efficacy and suitability of food ingredients in meat and poultry products as well as prescribing safe conditions of use. Suitability relates to the effectiveness of the ingredient in performing the intended purpose of use and the assurance that the conditions of use will not result in an adulterated product, or one that misleads consumers.

FSIS has previously evaluated the use of inulin as a water binder, emulsifier, stabilizer and texturizer at a level between two and five percent in processed meat food products.⁽¹⁾ FSIS advised that, based on the current use of inulin in the production of meat products, FSIS would not object to the proposed use of inulin in non-standardized meat or poultry products at four percent of the total product formula. In regard to the use of inulin in standardized meat and poultry products, FSIS is currently in the process of completing rulemaking that would permit the use of any safe and suitable binder in the production of meat and poultry products where standards of identity and other Federal regulations already permit the addition of binders, e.g., hot dogs. Until this rulemaking is complete, inulin cannot be used to formulate meat and poultry products with a standard of identity in Title 9 of the Code of Federal Regulations, parts 319 and 381.

cc: Dr. Robert Post, Director
Labeling and Consumer Protection Staff
Office of Policy, Program Development and Evaluation
Food Safety and Inspection Service
1400 Independence Ave., SW, Suite 602, Annex
Washington, DC 20250-3700

⁽¹⁾In a letter dated May 9, 1997, from FSIS to FDA, FSIS requested consultation with FDA regarding a request, from Imperial-Suiker Unie, that FSIS advise Imperial-Suiker Unie of the acceptability of the use of inulin as a water binder, emulsifier, stabilizer and texturizer at a level between 2 and 5 per cent in processed meat food products. In a letter dated May 14, 1999, FDA informed FSIS that FDA had completed its evaluation of the information submitted by Imperial-Suiker Unie as well as other information available to the agency. Based on its evaluation, FDA determined that, at that time, the agency would not challenge Imperial-Suiker Unie's conclusion that inulin is GRAS under the proposed conditions of use.