Agency Response Letter GRAS Notice No. GRN 000421
CFSAN/Office of Food Additive Safety
August 10, 2012
10559 Citation Drive
Brighton, MI 48116
Re: GRAS Notice No. GRN 000421
Dear Mr. Jackson:
The Food and Drug Administration (FDA) is responding to the notice, dated January 31, 2012, that you submitted on behalf of Libaeration, Ltd., (Libaeration) 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 February 14, 2012, filed it on February 23, 2012, and designated it as GRAS Notice No. GRN 000421.
The subject of the notice is sucrose fatty acid esters (SFAE). The notice informs FDA of the view of Libaeration that SFAE are GRAS, through scientific procedures, for use as surface-active agents (i.e., foaming agents) at a maximum level of 0.2 percent in foams produced using alcoholic beverages. Libaeration explains that the use of SFAE allows for the base liqueur to foam when under pressure through a pump system. The resulting foam is intended for use as a topping on alcohol-based mixed drinks, cocktails, and dessert drinks (hereafter referred to as alcohol-based mixed drinks).
Libaeration provides information on the identity, composition, and method of manufacture of SFAE. SFAE are described as stiff gels, soft solids or white to grayish white powders. They are manufactured by the inter-esterification of a mixture of mono-, di-, and tri-esters of sucrose with methyl esters of fatty acids. The fatty acids are derived from edible vegetable oils and fats. The crude SFAE are purified by dissolution with an organic solvent followed by water extraction. Libaeration states that the SFAE described in the notice are manufactured using food-grade materials and good manufacturing practices; finished food-grade SFAE meet the specifications established in Title 21 of the Code of Federal Regulations (CFR) Section 172.859 and in the Food Chemicals Codex, Eighth Edition (2012).
Libaeration determines the estimated daily intake (EDI) of SFAE from foams applied to alcohol-based mixed drinks, using spirit consumption data from the National Institute on Alcohol Abuse and Alcoholism and from the Alcohol Research Group. Assuming that 100 percent of alcohol-based mixed drinks will be topped with foam made with SFAE at the intended use level, Libaeration calculates the EDI to be 0.04 milligrams SFAE per kilogram bodyweight per day (mg/kg bw/d). Libaeration also calculates a cumulative EDI of SFAE, taking into consideration the use of SFAE in foams and in foods as described in 21 CFR 172.859 and in GRNs 000129, 000176, and 000248. Based on an additive approach (that is, not substitutional), the cumulative EDI calculated by Libaeration is approximately 26 mg/kg bw/d.
Libaeration discusses the safety of SFAE, incorporating by reference the safety information previously summarized in GRN 000129 and in reports of the Joint FAO/WHO Expert Committee on Food Additives (JECFA) on SFAE. The published animal studies discussed by Libaeration include a 13-week toxicity study and a combined carcinogenicity/chronic toxicity study, both conducted in rats administered SFAE. In the two year carcinogenicity/chronic toxicity study, the maximum SFAE dose administered to Fischer F344/DuCrj male rats was 1970 mg/kg bw/d and female rats was 2440 mg/kg bw/d. No toxicologically significant effects were reported in this or any of the other cited studies. Libaeration explains that it conducted a comprehensive literature search in November 2011, which did not identify any relevant toxicological data beyond the data previously described in GRN 000129 and the JECFA reports.
Libaeration discusses and agrees with an Acceptable Daily Intake (ADI) determined by JECFA. JECFA reviewed the rat toxicity study data, along with additional human tolerance data, and concluded that the use of an ADI of 0-30 mg/kg bw/d would be appropriate. The JECFA ADI1 is based on the No Observed Effect Level of 2000 mg/kg bw/d utilizing a safety factor of 50.2 Although this procedure would yield an ADI of 40 mg/kg bw/d, the ADI was limited to 30 mg/kg bw/d on the basis of human tolerance study data, which showed potential laxative effects at doses exceeding 30 mg/kg bw/d. In its safety assessment, the notifier considers that (1) the cumulative EDI for SFAE is less than the ADI determined by JECFA and that (2) the EDI for the use of SFAE in foam toppings on alcohol-based mixed drinks is less than 1 percent of the cumulative EDI for all notified uses of SFAE. Libaeration concludes that the available data support the intended use of SFAE as GRAS.
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 Federal Food Drug and Cosmetic Act (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 Libaeration’s notice that SFAE are GRAS for their intended use, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing SFAE. Accordingly, this response should not be construed to be a statement that foods that contain SFAE, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by Libaeration, as well as other information available to FDA, the agency has no questions at this time regarding Libaeration’s conclusion that SFAE 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. As always, it is the continuing responsibility of Libaeration 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 000421, 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 www.fda.gov/grasnoticeinventory.
Dennis M. Keefe, Ph.D.
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition
1The ADI determined by JECFA is a group ADI, which includes SFAE and sucroglycerides.
2A safety factor of 50 was used instead of the typical 100-fold safety factor, because SFAE are known to be hydrolyzed to normal dietary constituents in the gastrointestinal tract prior to absorption.