Agency Response Letter GRAS Notice No. GRN 000046
CFSAN/Office of Premarket Approval
September 22, 2000
Gerhard Schmid, Ph.D.
Wacker Biochem Corporation
3301 Sutton Road
Adrian, MI 49221
Re: GRAS Notice No. GRN 000046
Dear Dr. Schmid:
The Food and Drug Administration (FDA) is responding to the notice, dated May 19, 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 the notice on May 22, 2000 and designated it as GRAS Notice No. GRN 000046.
The subject of your notice is gamma cyclodextrin. The notice informs FDA of the view of the Wacker Biochem Corporation (Wacker Biochem) that gamma cyclodextrin is GRAS, through scientific procedures, for use as a stabilizer, emulsifier, carrier and formulation aid as described in Table 1. Your notice includes the findings of a panel of individuals (Wacker Biochem's GRAS panel) who evaluated the data and information that are the basis for Wacker Biochem's GRAS determination. Wacker Biochem considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Wacker Biochem's GRAS panel reviewed the information described in the notice and concluded that this information demonstrates that gamma cyclodextrin is GRAS, through scientific procedures, under the conditions of its intended use in foods. According to your notice, this conclusion is consistent with the findings of the Joint Food and Agriculture Organization/World Health Organization's Expert Committee on Food Additives.
|Food||Maximum Level Of Use|
|Carrier for vitamins in dry food mixes and dietary supplement products||90 percent|
|Carrier for polyunsaturated fatty acids (including meal replacements and dietary supplement products)||80 percent|
|Flavor modifier - Soya milk||2 percent|
Your notice describes generally available information about the identity, characteristic properties, and functionality of gamma cyclodextrin. Gamma cyclodextrin is a cyclic, alpha-(1-4) -linked maltooligosaccharide consisting of eight glucose units. Due to the three-dimensional arrangement of the glucose units, the inner side of the torus-like cyclodextrin molecule is less polar than the outer side. This enables cyclodextrins to form inclusion complexes with various organic compounds. This property forms the basis for the applications of cyclodextrins in foods.
Your notice describes generally available information about the method of manufacture of gamma cyclodextrin and proposes specifications for food-grade gamma cyclodextrin, including a lead specification of not more than one part per million. In your notice, you estimate that dietary exposure to gamma cyclodextrin from its intended use in food products other than meal replacements would be approximately 9 grams per person per day at the 90th percentile consumption level. You also estimate that persons who consume gamma cyclodextrin in meal replacements that contain polyunsaturated fatty acids would consume approximately 4 grams of cyclodextrin per meal.
Your notice describes published absorption, distribution, metabolism, and excretion studies, which demonstrate that gamma cyclodextrin is readily hydrolyzed to smaller, metabolizable carbohydrates in the gastrointestinal tract. The main hydrolysis product is maltose, with smaller amounts of maltotriose and glucose. Your notice also describes other published studies conducted with gamma cyclodextrin, including acute and subchronic toxicity studies, embryotoxicity/teratogenicity studies, a human tolerance study, and other toxicity studies. In addition, your notice describes unpublished toxicity studies, including a chronic study and genotoxicity studies.
Based on the information provided by Wacker Biochem, as well as other information available to FDA, the agency has no questions at this time regarding Wacker Biochem's conclusion that gamma cyclodextrin 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 gamma cyclodextrin. As always, it is the continuing responsibility of Wacker Biochem 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 your notice that conforms to the information in proposed 21 CFR 170.36(c)(1), is available for public review and copying on the Office of Premarket Approval's homepage on the Internet (at http://vm.cfsan.fda.gov/~lrd/foodadd.html).
Alan M. Rulis, Ph.D.
Office of Premarket Approval
Center for Food Safety and Applied Nutrition