Agency Response Letter GRAS Notice No. GRN 000412
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CFSAN/Office of Food Additive Safety
June 18, 2012
Véronique Maquet, Ph.D.
Rue Haute Claire, 4
Parc Industriel des Hauts-Sarts, Zone 2
Re: GRAS Notice No. GRN 000412
Dear Dr. Maquet:
The Food and Drug Administration (FDA) is responding to the notice, dated November 17, 2011, 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); the GRAS proposal). FDA received the notice on December 15, 2011, filed it on January 5, 2012, and designated it as GRAS Notice No. GRN 000412.
The subject of the notice is chitin-glucan from Aspergillus niger (chitin-glucan). The notice informs FDA of the view of KitoZyme S.A. (KitoZyme) that chitin-glucan from A. niger is GRAS, through scientific procedures, for use in microbial stabilization, removal of contaminants, and/or clarification in alcoholic beverage production at levels between 10 and 500 grams per hectoliter (100 liters).
As part of its notice, KitoZyme includes the report of a panel of individuals (KitoZyme’s GRAS Panel) who evaluated the data and information that are the basis for KitoZyme’s GRAS determination. KitoZyme considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. KitoZyme’s GRAS panel discusses identity, specifications, method of manufacture, dietary exposure, and safety of chitin-glucan, including the history and current regulatory status of A. niger and chitin-glucan in food, and concludes that chitin-glucan is GRAS under the intended conditions of use.
KitoZyme describes chitin-glucan, a mixture of chitin (poly-N-acetyl-D-glucosamine) and β-(1,3)-D-glucan, as an insoluble, non-digestible fiber derived from the post-fermentation biomass of non-viable A. niger used to manufacture food-grade citric acid. KitoZyme states that strains of A. niger used in the production of citric acid are nonpathogenic and nontoxigenic, and have a long history of safe use worldwide.
Hydrolysis of the A. niger material produces chitin and β-1(1,3)-glucan polysaccharides, which are dried, milled, and sieved to result in greater than 95 percent of the granulation particles sized less than 500 μm. All materials and processing aids used in the manufacture of chitin-glucan are food-grade. The notifier provides product specifications for chitin-glucan, including microbiological limits, heavy metals, and chemical characterization.
KitoZyme reported on a published 13-week subchronic toxicity study in Wistar rats. Twenty rats per sex were fed chitin and β-glucan from A. niger in a 30:70 ratio. KitoZyme reported the No Observable Adverse Effect Level to be the highest dose tested, equivalent to 6,589 and 7,002 milligrams/kilogram body weight/day for the male and female rats, respectively.
When chitin-glucan is used in the production of alcoholic beverages, it is removed from the wine, must, beer, cider, or spirits at the end of the treatment using physical separation processes, such as racking, centrifugation, or filtering.
KitoZyme notes that chitin-glucan preparations are insoluble in both water and ethanol, and because the material is removed from solution, intake modeling is not considered necessary. In addition, high performance liquid chromatography of wine processed with chitin-glucan indicated that the final product was free from detectable chitin-glucan. In addition, KitoZyme notes that chitin-glucan is not digested by the human gastrointestinal tract, therefore, absorption and systemic exposure to chitin-glucan would not occur.
Section 301(ll) of the Federal Food, Drug, and Cosmetic Act (FD&C Act)
The Food and Drug Administration Amendments Act of 2007, which was signed into law on September 27, 2007, amends the FD&C Act to, among other things, add section 301(ll). Section 301(ll) of the FD&C Act prohibits the introduction or delivery for introduction into interstate commerce of any food that contains a drug approved under section 505 of the FD&C Act, a biological product licensed under section 351 of the Public Health Service Act, or a drug or a biological product for which substantial clinical investigations have been instituted and their existence made public, unless one of the exemptions in section 301(ll)(1)-(4) applies. In its review of KitoZyme’s notice that chitin-glucan is GRAS for the intended uses, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing chitin-glucan. Accordingly, this response should not be construed to be a statement that foods that contain chitin-glucan if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by KitoZyme, as well as other information available to FDA, the agency has no questions at this time regarding KitoZyme’s conclusion that chitin-glucan from A. niger 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 chitin-glucan. As always, it is the continuing responsibility of KitoZyme 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 responding to GRN 000412, as well as a copy of the information in this notice that conforms to the information in the GRAS exemption claim (proposed 21 CFR 170.36(c)(1)), is available for public review and copying at http://www.fda.gov/grasnoticeinventory.
Dennis M. Keefe, Ph.D.
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition