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CFSAN/Office of Food Additive Safety
June 15, 2009
William A. Olson, Ph.D.
Center for Regulatory Services, Inc.
5200 Wolf Run Shoals Road
Woodbridge, VA 22192-5755
Re: GRAS Notice No. GRN 000270
Dear Dr. Olson:
The Food and Drug Administration (FDA) is responding to the notice, dated November 21, 2008, that you submitted on behalf of Stepan Company 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 December 1, 2008, filed it on December 3, 2008, and designated it as GRAS Notice No. GRN 000270.
The subject of the notice is polyglycerol polyricinoleic acid (PGPR). The notice informs FDA of the view of Stepan Company that PGPR is GRAS, through scientific procedures, for use as an emulsifier in the formulation of color additives, intended for use in processed foods for which colors are permitted, with limitation based on good manufacturing practices.
Stepan Company describes the identity of and manufacturing methods for PGPR as well as for its constituent components – polyglycerol and polyricinoleic acid. PGPR is a clear, light brown, viscous liquid prepared by the esterification of polyglycerol and polyricinoleic acid. Polyglycerol is produced by polymerization of epichlorohydrin, followed by steam distillation (also known as deodorization) and hydrolyzation of the resulting epichlorohydrin polymers under basic conditions, using either sodium or potassium hydroxide, to produce polyglycerol. The polyglycerol is dried and filtered to remove sodium chloride by-product. Polyricinoleic acid is produced by heating castor oil fatty acids (80 – 90 percent ricinoleic acid), with or without a catalyst, to promote self-condensation of the fatty acids. The notifier states that acceptable catalysts for use in the condensation reaction include acids such as phosphoric acid, bases such as sodium hydroxide, and lipase enzymes, all of which are currently used to interesterify food-grade fats and oils. The final PGPR product is obtained through heat treatment of the polyglycerol and the polyricinoleic acid components resulting in their transesterification. Stepan Company states that food-grade PGPR is consistent with the specifications established in the Food Chemicals Codex (6th edition).
The notifier addresses the issue of the potential for residual epichlorohydrin monomer in PGPR obtained from this method of manufacture. Epichlorohydrin monomer is sequentially reduced during three different stages in the manufacturing process: (1) the steam distillation step where levels are typically reduced to below 1 milligram per kilogram (mg/kg), (2) the hydrolysis step where residual monomer is hydrolyzed to glycerin, and (3) the transesterification step, where residual monomer is hydrolyzed to glycerol. Stepan Company further notes that residual epichlorohydrin would also be reduced by factors of “dilution” as the polyglycerol is used at a level of 9 percent in the production of PGPR and as PGPR is used at a maximum level of 5 percent (by weight of the formulation) in the color additives. Stepan Company concludes that residual epichlorohydrin monomer is below detectable limits in the food-grade PGPR and, subsequently, in the color additives.
Stepan Company describes the intended use of PGPR as an emulsifier in color additives intended for use in processed foods for which colors are permitted, with limitation based only on good manufacturing practices. The concentration is based on the amount needed for the emulsification of the specific color additive. Typical ranges for the intended uses are between 0.1 and 5 percent by weight of the formulation. The notifier describes the use of color additives in processed foods, stating that this would include use in foods such as processed fruits and vegetables, milk, eggs, and meat but not in foods such as beverages and infant formula. Assuming that the color additives would be added to all processed foods and noting that the use of food colors is self-limiting, Stepan Company calculates an estimated daily intake of PGPR from the intended use as 0.25 mg/kg of bodyweight per day (bw/day). Taking into consideration previous GRAS notices for the use of PGPR,(1) Stepan Company estimates that the total dietary intake of PGPR would be 5.35 mg/kg bw/day and 7.5 mg/kg bw/day, for the average and 90th percentile consumers respectively.
In its safety evaluation of PGPR, Stepan Company cites a review, conducted in 1973 by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). The JECFA review considered published animal safety studies, human clinical studies, and metabolic fate studies of PGPR, and concluded that the acceptable daily intake (ADI) is 0 – 7.5 mg/kg bw/day. The notifier states that its estimated average and 90th percentile total dietary intakes are consistent with the ADI as established by JECFA. Stepan Company incorporates – by reference – the data and information used to support the safety assessments of PGPR in two previous GRAS notices (i.e., GRN 000009 and GRN 000179) submitted to the FDA. Stepan Company concludes, based on its critical review and analysis of the available information on PGPR, that the body of data supports the safety of PGPR for use as an emulsifier in the formulation of color additives intended to be added to food.
Standards of Identity
In the notice, Stepan Company states its intention to use PGPR in several food categories, including foods for which standards of identity exist, located in Title 21 of the Code of Federal Regulations. We note that an ingredient that is lawfully added to food products may be used in a standardized food only if it is permitted by the applicable standard of identity.
Use in Meat, Poultry, and Egg Products
During its evaluation of GRN 000270, FDA consulted with the Risk and Innovations Management Division (RIMD), Office of Policy and Program Development (OPPD), of the Food Safety and Inspection Service (FSIS) of the United States Department of Agriculture (USDA). Under the Federal Meat Inspection Act, Poultry Products Inspection Act, and the Egg Products Inspection Act, FSIS is responsible for determining the efficacy and suitability of food ingredients in meat, poultry, and egg products as well as prescribing safe conditions of use. Suitability relates to the effectiveness of the ingredient in performing the intended purpose of use and the assurance that the conditions of use will not result in an adulterated product, or one that misleads consumers.
FSIS does not have any objection to the use of PGPR as an emulsifier in the formulation of color additives which are subsequently used in meat, poultry, or egg products so long as the functionality of PGPR is confined to the color additive. FSIS requested that FDA advise Stepan Company to seek regulatory guidance from RIMD/OPPD/FSIS about other uses of PGPR, some of which may not be suitable in meat, poultry, or egg products. Stepan Company should direct such an inquiry to Dr. John M. Hicks, Jr., via email at firstname.lastname@example.org or to Dr. David C. Zeitz at email@example.com.
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 Federal Food Drug and Cosmetic Act (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 Stepan Company’s notice that PGPR is GRAS for its intended use, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing PGPR. Accordingly, this response should not be construed to be a statement that foods that contain PGPR, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by Stepan Company, as well as other information available to FDA, the agency has no questions at this time regarding Stepan Company’s conclusion that PGPR 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 PGPR. As always, it is the continuing responsibility of Stepan Company 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 000270, 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 via the FDA home page at http://www.fda.gov. To view or obtain an electronic copy of the text of the letter, follow the hyperlinks from the “Food” topic to the “Food Ingredients and Packaging” section to the “Generally Recognized as Safe (GRAS)” page where the GRAS Inventory is listed.
Laura M. Tarantino, Ph.D.
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition
cc: John M. Hicks, Jr. DVM, MPH
Risk and Innovations Management Division
Office of Policy and Program Development
Food Safety and Inspection Service
U.S. Department of Agriculture
1400 Independence Avenue., S.W., Room 3549, South Agriculture Building
Washington, DC 20250-3700
(1)Stepan Company’s estimation of the total dietary intakes includes the estimated dietary intake levels of PGPR reported in GRAS Notifications GRN 000009 (the intended use of PGPR as an emulsifier in chocolate) and GRN 000179 (the intended use of PGPR as an emulsifier in margarines, low fat margarines, spreads, creamers, and dairy analogs).