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CFSAN/Office of Premarket Approval
October 5, 2000
Alan B. Richards, Ph.D.
Hayashibara International Inc.
2201 Civic Circle
Amarillo, TX 79109
Re: GRAS Notice No. GRN 000045
Dear Dr. Richards:
The Food and Drug Administration (FDA) is responding to the notice, dated May 8, 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 May 17, 2000 and designated it as GRAS Notice No. GRN 000045.
The subject of your notice is trehalose. The notice informs FDA of the view of Hayashibara International Inc. (Hayashibara) that trehalose is GRAS, through scientific procedures, as a multipurpose ingredient for use in food in general (including meat products) in accordance with current good manufacturing practice. Hayashibara identifies expected applications for trehalose as a coloring adjuvant, flavor enhancer, humectant, nutritive sweetener, stabilizer, thickener, synergist, and texturizer in a broad range of food categories.
Your notice provides a report of a specially convened panel of individuals (Hayashibara's GRAS panel) who evaluated the data and information that are the basis for Hayashibara's GRAS determination. Hayashibara considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food.
Your notice describes published information pertaining to trehalose's chemical identity and its natural occurrence. Trehalose (CAS Reg. No. 99-20-7 for anhydrous and CAS Reg. No. 6138-23-4 for dihydrate) is a non-reducing disaccharide composed of two glucose molecules linked in an alpha, alpha, 1 to 1 configuration. Trehalose exists naturally in plants, animals and microorganisms, and has long been consumed by humans as a component of mushrooms, baker's and brewer's yeasts, seaweeds, and lobsters. Metabolically, trehalose is hydrolyzed to glucose in a manner similar to the digestion of other disaccharides. The hydrolysis of trehalose is catalyzed by the enzyme trehalase.
Your notice describes the manufacturing process for trehalose, including published information pertaining to trehalose-producing enzymes and the source soil organism from which these trehalose-producing enzymes are derived. Your notice provides information on specifications for trehalose, including a lead specification of less than 0.1 parts per million. Your notice states that trehalose manufactured by Hayashibara is identical to naturally occurring trehalose.
Your notice presents what Hayashibara considers to be realistic use levels of trehalose in a broad range of food categories. Your notice estimates that the mean intake of trehalose would be approximately 34 grams per person per day, and that the 90th percentile intake would be approximately 68 grams per person per day.
Your notice provides information on unpublished toxicity studies, including a micronucleus assay in mice, acute toxicity studies in mice, rats, and dogs, 14-day toxicity studies in mice and dogs, 13-week toxicity studies in mice, embryotoxicity/teratogenicity studies in rats and rabbits, and a two-generation reproductive study in rats, and published information regarding studies on human trehalase activity, human trehalose tolerance, and the potential relationship between mushroom intolerance and trehalose intolerance. You consider that these studies, along with increased consumption of trehalose in Japan since 1995, corroborate the safety of trehalose for human consumption.
Based on the information provided by Hayashibara as well as other information available to FDA, the agency has no questions at this time regarding Hayashibara's conclusion that trehalose 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 trehalose. As always, it is the continuing responsibility of Hayashibara to ensure that food ingredients that the firm markets are safe, and are otherwise in compliance with all applicable legal and regulatory requirements.
During its evaluation of GRN 000045, OPA consulted with the Labeling and Additives Policy Division (LAPD) of the Food Safety and Inspection Service of the United States Department of Agriculture (FSIS) regarding the use of trehalose in meat products. FSIS advises that the Federal meat and poultry inspection regulations list specific binding additives generally for use below 3.5% of product formulation. Based on the information submitted by Hayashibara, FSIS concludes that trehalose, when used at up to 2% of the product, would be acceptable for binding and purge control in various non-standardized meat and poultry products. Currently, there are no allowances for the use of trehalose in standardized meat and poultry products. Therefore, FSIS would have to consider rulemaking to amend the Federal meat and poultry inspections regulations to permit such use. LAPD requested that FDA advise Hayashibara to seek regulatory guidance from LAPD about the use of trehalose in meat and poultry products. You should direct your inquiry to Dr. Robert Post, Director, LAPD, 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 for LAPD is (202) 205-0279 and the FAX number is (202)205-3625.
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
cc: Dr. Robert Post, Director, LAPD
Office of Policy, Program Development and Evaluation
Food Safety and Inspection Service
300 12th Street, SW, Room 602
Washington, DC 20250-3700