Agency Response Letter GRAS Notice No. GRN 000070
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CFSAN/Office of Premarket Approval*
April 23, 2001
Dr. W. Gary Flamm
622 Beachland Blvd.
Vero Beach, FL 32964
Re: GRAS Notice No. GRN 000070
Dear Dr. Flamm:
The Food and Drug Administration (FDA) is responding to the notice, dated February 16, 2001, that you submitted on behalf of Thixo Limited (Thixo) 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 February 21, 2001 and designated it as GRAS Notice No. GRN 000070.
The subject of the notice is stearyl alcohol. The notice informs FDA of the view of Thixo that stearyl alcohol is GRAS, through scientific procedures, for use as an oil structuring and solidifying agent (a texturizer) in margarine, shortening, and foods containing semi-solid and solid fats, at levels of up to 10 percent of the oil content of the food.
Thixo provides a report of a specially convened panel of individuals (Thixo's GRAS panel) who conducted a comprehensive search of the scientific literature and evaluated the data and information that are the basis for Thixo's GRAS determination. Thixo considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Thixo's GRAS panel evaluated data and information about the chemical identity, manufacture and processing, conditions of proposed use, and estimated daily intakes. Thixo's GRAS panel also evaluated a number of published studies, including metabolic studies, acute and medium-term toxicity studies in experimental animals, mutagenicity studies, and clinical studies on the nutritional effects of stearyl alcohol. These studies were conducted with stearyl alcohol, stearic acid (a known metabolic product of stearyl alcohol), or stearyl citrate (which is metabolized to stearyl alcohol). Based on the data and information reviewed, Thixo's GRAS panel concludes that stearyl alcohol, when produced in accordance with current good manufacturing practice and meeting appropriate food grade specifications, is GRAS, through scientific procedures under the conditions of intended use.
Thixo describes published information pertaining to the chemical identity of stearyl alcohol. The notice describes stearyl alcohol as a colorless saturated fatty alcohol with a very mild odor. Its structural formula is CH3(CH2)16CH2OH and its Chemical Abstract Service (CAS) registry number is 112-92-5. It is soluble in alcohol, ether, benzene and acetone, and insoluble in water.
Thixo describes the method of manufacture of stearyl alcohol. Stearyl alcohol is produced by transesterification and distillation of unrefined coconut oil and palm kernel oil in the presence of methanol and zinc (as a catalyst) followed by hydrogenation of the resulting methyl esters in the presence of copper (as a catalyst). Both catalysts are removed during the fractional distillation process, as confirmed by the lack of heavy metals in the final product (less than 10 milligrams per kilogram (mg/kg), equivalent to less than 10 parts per million (ppm)). Thixo provides specifications for food grade stearyl alcohol, including a lead specification of less than 1 mg/kg (equivalent to less than 1 ppm).
Thixo considers the use of stearyl alcohol to be self-limiting at levels greater than 10 percent, because such use levels may cause foods that contain stearyl alcohol to become too hard, or cause other characteristics of the food (such as texture, mouth feel, and melting point) to be altered. Thixo estimates the intake of stearyl alcohol by the total population from the proposed food uses in the United States to be approximately 0.90 grams per person per day (g/p/d) at the mean level and approximately 1.7 g/p/d at the 90th percentile level.
In its report, Thixo's GRAS panel discusses the results of published metabolism studies, which show that approximately 90 percent of absorbed stearyl alcohol is converted enzymatically, in the intestinal mucosal cells, to stearic acid. The stearic acid is then taken up from the blood and oxidized as a source of energy or converted in the liver to triacylglycerols, phospholipids, lipid esters or waxes. Thixo's GRAS panel also discusses (a) published studies conducted in rats with stearyl alcohol, including a 13-day study and a 3-4 week study; (b) a published 3-week study conducted in mice with stearic acid; and (c) published studies conducted in multiple species with stearyl citrate, including a 6-week study in rats, a 6-week study in rabbits, a 12-week study in dogs, a 2-year study in rats, and a 10-week multi-generation study in rats. Thixo's GRAS panel found that no treatment-related abnormalities or adverse effects were observed in those studies. Based on the studies conducted with stearyl citrate, Thixo's GRAS panel concludes that a no-observed-effect-level (NOEL) for stearyl citrate is 5 grams/kg body weight/day (equivalent to 300 g/p/d), which corresponds to 240 g/p/d for stearyl alcohol. This NOEL for stearyl alcohol is 140 times greater than the estimated 90th percentile intake of stearyl alcohol from the proposed use.
In its report, Thixo's GRAS panel also discusses published Ames tests conducted with strains of Salmonella typhimurium and Escherichia coli to evaluate the mutagenic potential of stearyl alcohol. No evidence of mutagenic activity was reported. Stearyl alcohol was also tested in a mouse bone marrow micronucleus assay, with negative results.
Thixo's GRAS panel discusses several human nutritional studies on saturated fatty acids, which have been associated with increased serum cholesterol levels. The panel concludes that stearic acid is not strongly or positively associated with higher total cholesterol or LDL cholesterol levels.
Based on the information provided by Thixo as well as other information available to FDA, the agency has no questions at this time regarding Thixo's conclusion that stearyl alcohol 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 stearyl alcohol. As always, it is the continuing responsibility of Thixo 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://www.cfsan.fda.gov/~lrd/foodadd.html).
Alan M. Rulis, Ph.D.
Office of Premarket Approval
Center for Food Safety and Applied Nutrition
* The Office of Premarket Approval became the Office of Food Additive Safety on June 18, 2001.