Agency Response Letter GRAS Notice No. GRN 000069
CFSAN/Office of Premarket Approval*
May 14, 2001
Dr. W. Gary Flamm
622 Beachland Blvd.
Vero Beach, FL 32964
Re: GRAS Notice No. GRN 000069
Dear Dr. Flamm:
The Food and Drug Administration (FDA) is responding to the notice, dated February 8, 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 15, 2001 and designated it as GRAS Notice No. GRN 000069.
The subject of the notice is behenic acid. The notice informs FDA of the view of Thixo that behenic acid is GRAS, through scientific procedures, for use as an oil structuring and solidifying agent (i.e., as a texturizer as defined in 21 CFR 170.3(o)(32)) in margarine, shortening, and foods containing semi-solid and solid fats, at levels of up to 8 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, short-term and subchronic toxicity studies in experimental animals, and clinical studies on the nutritional effects of behenic acid. These studies were conducted with behenic acid-rich triglycerides. Based on the data and information reviewed, Thixo's GRAS panel concludes that behenic acid, 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 behenic acid, which is also called n-docosanoic acid. Its structural formula is CH3(CH2)20COOH and its Chemical Abstract Service (CAS) registry number is 112-85-6. The notice describes behenic acid as a clear solid saturated fatty acid that is soluble in ethyl alcohol and ether and has a light odor. It has a melting point of 80C to 82C, and a boiling point of 306C.
Thixo describes the method of manufacture of behenic acid. Behenic acid is produced by hydrolysis of high erucic acid rapeseed oil at a high temperature (at least 200C) under steam pressure, and subsequent hydrogenation of erucic acid to behenic acid in the presence of a nickel catalyst, which is used in accordance with 21 CFR 184.1537. Thixo provides specifications for food grade behenic acid, including a lead specification of not more than 1 milligram per kilogram (mg/kg) (i.e., not more than 1 part per million).
Given the physical properties of behenic acid, Thixo considers that a limited addition of behenic acid to oil enables the production of semi-solid and solid fats (such as margarine, shortening, and foods containing semi-solid and solid fats) without the need to hydrogenate the oil. Thixo considers the use of behenic acid to be self-limiting at levels greater than 8 percent, because such use levels may cause foods that contain behenic acid to become too hard, or cause other characteristics of the food (such as texture, mouth feel, and melting point) to be altered.
Thixo notes that behenic acid is currently consumed as a component of hydrogenated and partially hydrogenated menhaden oil (21 CFR 184.1472), hydrogenated and superglycerinated hydrogenated rapeseed oil (21 CFR 184.1555), glyceryl behenate (21 CFR 184.1328), and bohenin (which is the subject of GRAS Notice No. GRN 000050). Thixo notes that consumption of behenic acid from uses such as these has been estimated to be approximately 0.3 grams per person per day (g/p/d) based on per capita consumption data. Thixo estimates the intake of behenic acid by the total population in the United States from Thixo's proposed food uses to be approximately 0.68 g/p/d at the mean level and approximately 1.36 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 behenic acid is poorly absorbed. The behenic acid that does get absorbed can either undergo oxidation for use as an energy source or follow an anabolic path to be incorporated into wax esters, sphingolipids, glycolipids or acylglycerols. Thixo's GRAS panel also discusses (a) published studies conducted in rats with behenic acid-containing triglycerides, including a 23-day study , a 28-day study, and a 91-day study; and (b) a published 28-day study conducted in hamsters with behenic acid-containing triglycerides. Thixo's GRAS panel found that no treatment-related abnormalities or adverse effects were observed in those studies.
Thixo's GRAS panel notes that saturated fatty acids (such as palmitic, lauric, and myristic acid) have been associated with increased levels of serum cholesterol. The panel discusses several human nutritional studies conducted with behenic acid-containing triglycerides and concludes that behenic acid is not strongly or definitively 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 behenic acid 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 behenic acid. 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.