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U.S. Department of Health and Human Services

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Agency Response Letter GRAS Notice No. GRN 000237

CFSAN/Office of Food Additive Safety
October 14, 2008

Edward A. Steele
EAS Consulting Group, LLC
1940 Duke Street, Suite 200
Alexandria, VA 22314

Re: GRAS Notice No. GRN 000237

Dear Mr. Steele:

The Food and Drug Administration (FDA) is responding to the notice, dated November 28, 2007, that you submitted on behalf of Cognis Corporation (Cognis) 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 12, 2007, filed it on December 19, 2007, and designated it as GRAS Notice No. GRN 000237.

The subject of the notice is alkyl polyglycosides. The notice informs FDA of the view of Cognis that alkyl polyglycosides are GRAS, through scientific procedures, for use in the cleaning of foods, including fruits, vegetables, meat, and poultry products.

Cognis provides information about the identity, composition and method of manufacture of alkyl polyglycosides. Alkyl polyglycosides are prepared by reacting glucose with fatty alcohols ranging from C8 – C16 in the presence of an acidic catalyst. The resulting mixture, which contains 50-80% fatty alcohol, is neutralized, and the excess fatty alcohol is removed by vacuum distillation. The alkyl glucosides are then dissolved in water producing a viscous 50-70% alkyl polyglycoside finished product. The product may then be refined in a bleaching step. This mixture of monomer (fatty alcohol with one glucose unit) and oligomers (fatty alcohols plus various numbers of glucose units) has a distribution that can be described by the degree of polymerization. The average degree of polymerization ranges from 1.3 to 1.8 glucose units. The empirical formula for alkyl polyglycosides can be written as H-(C6H10O5)n-O-CxH2x+1, where n equals the average number of glucose units present in the saccharide moiety and x equals the number of carbon atoms of the alkyl chain. Cognis states that the final product meets all specifications, including limits for peroxides and heavy metals.

Cognis provides estimates of the final residual concentration of alkyl polyglycosides for the intended food categories. Cognis anticipates that alkyl polyglycosides would be present in cleaning product formulations at a final use level of less than 2%. However, the notifier calculates estimates of daily intake (EDI) using conservative intake levels and the assumption that 100% of the alkyl polyglycosides will be distributed on the food. The calculated EDIs are 32.1 milligrams alkyl polyglycosides per person per day (mg/p/day) for beef and up to 50 mg/p/day for poultry. Cognis notes that for use on beef carcasses there would be little residue as usage is always followed by a potable water rinse. For fruits and vegetables, Cognis calculates 1.4 to 80.6 mg/p/day when using a C8-C10 alkyl polyglycoside, 1.2 to 69.3 mg/p/day when using a C10-C16 alkyl polyglycoside, and 1.4 to 76.6 mg/p/day when using a C9-C11 alkyl polyglycoside.

Cognis discusses a scenario whereby a solution containing alkyl polyglycosides is used during the lye peeling of sugar beets. This process would incorporate a potable water rinse resulting in an EDI of residual alkyl polyglycosides of 0.13 mg/p/day.

In its discussion, Cognis provides generally available information on the metabolism of alkyl polyglycosides. Cognis reports that alkyl polyglycosides with different fatty alcohols (C-chains C8, C12 and C16) are readily degraded after oral intake due to the rapid hydrolysis of the ß-glycosidic bond. Cognis notes that based on the similarity in hydrolysis, alkyl polyglycosides containing different C-chain length of fatty alcohols behave identically after oral intake and the metabolites (sugar and fatty alcohol) are toxicologically of no concern. Cognis states that alkyl polyglycosides with branched fatty alcohols (C9, C11) also rapidly degrade after oral intake due to the hydrolysis of the ß-glycosidic bond.

Hydrolysis of alkyl polyglycosides results in differing fatty alcohols, including C8 linear, C9 branched, C10 linear, C11 branched, C12 linear, C14 linear and C16 linear. Cognis describes mammalian metabolism of fatty alcohols to conclude that long chained alcohols are efficiently metabolized. Cognis concludes that there is limited potential for retention or bioaccumulation for the parent alcohols and their biotransformation products.

Cognis discusses the safety of alkyl polyglycosides. Cognis describes the results and conclusions of published toxicity studies, including an acute oral toxicity study, a mutagenicity study, a subchronic toxicity study, a reproductive and developmental toxicity study, metabolism information, as well as other supportive information. Cognis notes that alkyl polyglycosides are not mutagenic, estrogenic, embryotoxic or teratogenic.

Cognis concludes that fatty alcohols can be considered as a category having comparable toxicological properties with regard to systemic toxicity. Cognis expects that alkyl polyglycosides as a group would show similar toxicological properties on repeated-dose toxicity. Therefore, Cognis considers the results from studies obtained with C12 and C16 alkyl polyglycosides as representative for the whole group of C8 - C16 alkyl polyglycosides.

Cognis concludes that the toxicological endpoints evaluated provide a scientific basis to determine the low order of toxicity for alkyl polyglycosides.

Use in Meat and Poultry Products

During its evaluation of GRN 000237, FDA consulted with the Labeling and Program Delivery Division of the Food Safety and Inspection Service (FSIS) of the United States Department of Agriculture (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 no objection to the use of the alkyl polyglycosides in hog scalding and poultry defeathering solutions, at a level sufficient for the purpose of increasing the wetting ability of the caustic solution, and to the use of alkyl polyglycosides to wash meat (i.e., beef carcasses, after the hide has been removed, to remove any extraneous hair, dirt, etc.) during butchering at a level of 2% active solution, followed by a potable water rinse. Any further questions regarding use in meat and poultry products should be directed to Dr. John Hicks, Jr., Director, Risk Management Division, Office of Policy and Program Development,(1) 1400 Independence Avenue., SW, Room 3549, South Agriculture Building, Washington, DC 20250-3700. The telephone number for that office is (202) 205-0210 and the telefax is (202) 720-7027.

Use in Products Regulated by FDA's Center for Veterinary Medicine

As FDA discussed in the GRAS proposal, notice to the Center for Food Safety and Applied Nutrition that a substance is GRAS for use in human food does not encompass use of that substance in animal feed. Given that byproducts of sugar processing are often used in animal feed, we have sent the Center for Veterinary Medicine (CVM) a copy of this letter. If Cognis wishes to inform CVM that alkyl polyglycosides may reasonably be expected to become a component of animal feed, the contact is Dr. Michaela Alewynse, Center for Veterinary Medicine (HFV-220), Food and Drug Administration, 7519 Standish Pl., Rockville, MD 20855. You can also reach Dr. Alewynse by telephone at (240) 453-6866 or by telefax at (240) 453-6882.

Section 301(ll) of the Federal Food, Drug, and Cosmetic Act (FFDCA)

The Food and Drug Administration Amendments Act of 2007, which was signed into law on September 27, 2007, amends the FFDCA to, among other things, add section 301(ll). Section 301(ll) prohibits the introduction or delivery for introduction into interstate commerce of any food that contains a drug approved under section 505 of the FFDCA, 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. Cognis provided FDA with a legal opinion regarding the impact of section 301(ll) on the GRAS status of alkyl polyglycosides intended for use in the cleaning of foods, including fruits, vegetables, meat, and poultry products. In its review of Cognis' notice that alkyl polyglycosides are GRAS for such use, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing alkyl polyglycosides. Accordingly, this response should not be construed as a statement that foods that contain alkyl polyglycosides, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll). FDA will address Cognis' legal opinion in separate correspondence.

Conclusions

Based on the information provided by Cognis, as well as other information available to FDA, the agency has no questions at this time regarding Cognis' conclusion that alkyl polyglycosides are 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 alkyl polyglycosides. As always, it is the continuing responsibility of Cognis 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 000237, as well as a copy of the information in this notice that conforms to the information in the proposed GRAS exemption claim (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).

Sincerely,
Laura M. Tarantino, Ph.D.
Director
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition



cc: John Hicks, DVM, MPH.
Risk Management Division
Office of Policy and Program Development
Food Safety and Inspection Service
1400 Independence Ave., S.W., Room 3549, South Building
Washington, DC 20250-3700

Michaela Alewynse, Ph.D.
Center for Veterinary Medicine
Office of Surveillance and Compliance
HFV-220
Food and Drug Administration
7519 Standish Pl.
Rockville, MD 20855


(1)Effective June 1, 2008, the Office of Policy and Program Development of FSIS has transferred the review process of ingredient submissions from the Labeling and Program Delivery Division to the Risk Management Division.