Agency Response Letter GRAS Notice No. GRN 000248
CFSAN/Office of Food Additive Safety
October 24, 2008
Compass Foods Pte Ltd
12 Tuas Avenue 1
Re: GRAS Notice No. GRN 000248
Dear Mr. Comstock:
The Food and Drug Administration (FDA) is responding to the notice, dated March 17, 2008, 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 April 8, 2008, filed it on April 10, 2008, and designated it as GRAS Notice No. GRN 000248.
The subjects of the notice are sucrose fatty acid esters (i.e., sucrose monoesters of lauric acid, palmitic acid, and stearic acid) manufactured by reaction of sucrose with vinyl esters of lauric, palmitic, and stearic acids. Sucrose fatty acid esters, derived from sucrose and edible tallow or hydrogenated edible tallow or edible vegetable oils, are currently approved for use in a number of food categories under 21 CFR 172.859. For the purpose of this letter, we will refer to the subjects of the notice as SFAE (alternative method of manufacture) and to sucrose fatty acid esters in general as SFAE. The notice informs FDA of the view of Compass Foods Pte Ltd (Compass Foods) that SFAE (alternative method of manufacture) are GRAS, through scientific procedures, for use as emulsifiers in fruit-flavored beverages and beverage concentrates, at levels up to 50 milligrams per Liter (mg/L) as consumed.
As part of its notice, Compass Foods includes the report of a panel of individuals (Compass Foods' GRAS Panel) who evaluated the data and information that are the basis for Compass Foods' GRAS determination. Compass Foods considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. The panel reviewed information pertaining to the method of manufacture, product specifications, supporting analytical data, intended use levels in specified food products, consumption estimates for intended and current uses, and a comprehensive assessment of the available scientific literature pertaining to the safety of sucrose fatty acid esters and manufacture-related residues. Based on this review, Compass Foods' GRAS Panel concluded that SFAE (alternative method of manufacture), meeting food-grade specifications and manufactured in accordance with current Good Manufacturing Practices, are generally recognized as safe for use as emulsifiers for flavors added to fruit-flavored beverages.
Compass Foods describes SFAE (alternative method of manufacture) as white to grayish powders composed of sucrose monoesters (not less than 83 percent) of lauric acid, palmitic acid, or stearic acid and lesser amounts of di- and tri-esters. The three SFAE (alternative method of manufacture) products are manufactured by the inter-esterification of sucrose with vinyl esters of fatty acids. The method of manufacture of SFAE (alternative method of manufacture) is different from the traditional method of manufacture for SFAE in that the starting fatty acid esters are vinyl esters rather than the traditional methyl esters. This change in manufacturing methods results in trace levels of vinyl fatty acid esters, acetylaldehyde, and MEHQ (also known as p-methoxyphenol, p-hydroxyanisole),(1) residues not found in traditional SFAE.
Compass Foods provides specifications for its food-grade SFAE (alternative method of manufacture), including specifications for sucrose monoester content, combined sucrose mono- and di-ester content, acid value, free sucrose, residue on ignition, lead, dimethylsulfoxide, and isobutanol. Compass Foods' specifications for food-grade SFAE (alternative method of manufacture) are consistent with the specifications in the Food Chemicals Codex (2003 edition) monograph for SFAE.
Compass Foods estimates the daily intake of SFAE (alternative method of manufacture) from consumption of fruit-flavored beverages and beverage concentrates (intended uses), as well as from consumption of all foods for which SFAE is currently permitted (current uses). Compass Foods estimates daily intake for the intended uses and current uses would be 12.6 milligrams per kilogram body weight per day (mg/kg bw/day) and notes this level is below the current acceptable daily intake for SFAE of 30 mg/kg bw/day, as assigned by the FAO/WHO Joint Expert Committee on Food Additives.
Compass Foods discusses the metabolic fate of SFAE in general, citing published studies that include studies of general fat digestion and absorption and studies of SFAE absorption, digestion, metabolism, and excretion (ADME). These studies show that the majority of sucrose monoesters are hydrolyzed into sucrose and fatty acid components that are absorbed in the intestinal tract. Conversely, the majority of diesters and triesters are neither hydrolyzed nor absorbed. Compass Foods concludes that the results of the ADME studies demonstrate that the safety of SFAE (alternative method of manufacture) can be assessed on the basis of sucrose and the fatty acid component.
Compass Foods describes the results of published mutagenicity and toxicology studies of: (1) sucrose fatty acid esters of palmitic and stearic acids and (2) lauric acid. The studies cited for sucrose fatty acid esters of palmitic and stearic acid are an Ames assay, a chromosomal aberration assay, and subchronic and chronic toxicity studies in rodents. Compass Foods also describes a human tolerance study of a mixture of sucrose fatty acid esters of palmitic and stearic acids. The studies cited for lauric acid are a Salmonella mutagenicity assay and acute, subchronic, and chronic toxicity studies in rodents. Compass Foods concludes that the results of the toxicity studies demonstrate the safety of sucrose fatty acid esters of palmitic, stearic, and lauric acids and support its determination that SFAE (alternative method of manufacture) are GRAS for use as emulsifiers in fruit-flavored beverages and beverage concentrates at levels up to 50 mg/L as consumed.
Compass Foods discusses the safety of residual vinyl fatty acid esters, acetylaldehyde, and MEHQ present in the finished, food-grade product. Compass Foods concludes that the reported levels of residues from its manufacturing method do not pose health concerns under the intended conditions of use. Compass Foods provides summaries of published toxicology studies supporting its conclusion.
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) of the FFDCA 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. In its review of Compass Foods' notice that SFAE (alternative method of manufacture) are GRAS for use as emulsifiers in fruit-flavored beverages and beverage concentrates, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing SFAE (alternative method of manufacture). Accordingly, this response should not be construed to be a statement that foods that contain SFAE (alternative method of manufacture), if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by Compass Foods, as well as other information available to FDA, the agency has no questions at this time regarding Compass Foods' conclusion that SFAE (alternative method of manufacture) 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 SFAE (alternative method of manufacture). As always, it is the continuing responsibility of Compass Foods 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 000248, 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).
Laura M. Tarantino, Ph.D.
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition
(1)MEHQ is a stabilizer in the vinyl fatty acid esters.