Agency Response Letter GRAS Notice No. GRN 000640
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See also Generally Recognized as Safe (GRAS).
CFSAN/Office of Food Additive Safety
September 21, 2016
David Becthel, Ph.D.
Intertek Scientific & Regulatory Consultancy
100 Davidson Avenue, Suite 102
Somerset, NJ 08873
Re: GRAS Notice No. GRN 000640
Dear Dr. Becthel:
The Food and Drug Administration (FDA) has received the notice, dated March 8, 2016, that you submitted on behalf of Choco Finesse, LLC (Choco Finesse) 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 this notice on March 14, 2016, filed it on April 8, 2016, and designated it as GRAS Notice No. GRN 000640. In an amendment dated June 8, 2016, Choco Finesse provided cumulative exposure estimates for esterified propoxylated glycerol (EPG) and α-tocopherol. In an amendment dated July 21, 2016, Choco Finesse provided background information on the use of a tocopherol concentrate to stabilize EPG and included a discussion on tocopherol safety.
The subject of the notice is EPG. The notice informs FDA of the view of Choco Finesse that EPG is GRAS, through scientific procedures, for use as a fat replacement in baked goods and baking mixes, frozen dairy desserts and mixes, grain products and pastas, gravies and sauces, nuts and nut products, and soft candy at a maximum level of 21% EPG in finished foods.
As part of its notice, Choco Finesse includes the report of a panel of individuals (Choco Finesse’s GRAS panel) that evaluated the data and information that are the basis for Choco Finesse’s GRAS determination. Choco Finesse considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Choco Finesse’s GRAS panel evaluated information describing the identity and composition, manufacturing process and specifications, and estimated dietary exposure to EPG, as well as published studies supporting the safety of EPG. Based on this review, Choco Finesse’s GRAS panel concludes that EPG produced in accordance with good manufacturing practices is GRAS under the conditions of its intended use.
Choco Finesse describes EPG as an off-white powder that does not melt at temperatures below about 38°C. The primary fatty acids in EPG are stearic acid (4-10%), oleic acid (20-30%), linoleic acid (1-3%), arachidic (38-48%), and behenic acids (20-30%). Choco Finesse states that the version of EPG that is the subject of the current GRAS notice differs from EPG that was the subject of GRN 000583 in that one-fourth to one-third of the saturated fatty acids have been replaced with unsaturated fatty acids.
Choco Finesse describes the chemical synthesis of EPG as a two-step process. In the first step, food grade glycerol is reacted with propylene oxide under base catalysis to form propoxylated glycerol. In the second step, propoxylated glycerol is esterified using an excess of fatty acids which are derived from edible fats and oils. After the esterification step, the unreacted fatty acids are removed from crude EPG by steam stripping under vacuum.
Choco Finesse provides specifications for EPG. These include specifications for purity (> 99.5%) and total for α-, β-, γ-, and δ-tocopherols (0.09-0.13%). Specifications also include limits on arsenic and lead (< 0.05 mg/kg) and limits for microbial contaminants. Choco Finesse provides analytical results from three non-consecutive lots to demonstrate compliance with these specifications.
Choco Finesse calculates the dietary exposure to EPG from the intended food use based on National Health and Nutrition Examination Survey 2011-2012 data. The estimated mean and 90th percentile exposures to EPG for all-users are 3.6 grams/person/day (g/p/d; or 63 mg/kg body weight (bw)/d) for a 57 kg individual), and 8.0 g/p/d (146 mg/kg bw/d), respectively, for the total U.S. population. The estimated mean and 90th percentile cumulative exposures from the current intended and previously notified uses are 11.06 g/p/d (203 mg/kg bw/d) and 24.11 g/p/d (469 mg/kg bw/d), respectively, for the total U.S. population. Using the above cumulative exposure estimates, Choco Finesse calculates that if α-tocopherol is present in a final food product at the maximum specified level of 230 mg/kg EPG, the estimated mean and 90th percentile exposures to α-tocopherol for all-users would be 2.5 mg/p/d and 5.5 mg/p/d, respectively, for the total U.S. population.
Choco Finesse discusses unpublished and published animal studies and published human studies previously submitted in GRN 000583 to support the safety of EPG. Choco Finesse discusses unpublished absorption, distribution, metabolism, and elimination data in rats that show that ingested EPG is not significantly absorbed or metabolized, with the majority of EPG excreted in the feces. Choco Finesse discusses unpublished studies on EPG that showed no subchronic toxicity in mice and beagle dogs, and published studies that showed no subchronic toxicity in rats and minipigs. Choco Finesse also discusses unpublished studies on EPG that showed no chronic toxicity in mice, rats, micro pigs, and beagle dogs. In addition, Choco Finesse discusses an unpublished study in rats and published studies in rats and rabbits that showed no adverse effects due to dietary administration of EPG on reproduction and offspring development. Choco Finesse discusses that although EPG animal studies have shown some decreases in measured levels of some fat-soluble vitamins, none of the animals exhibited clinical signs or microscopic evidence of vitamin deficiency, nor required vitamin supplementation. Choco Finesse also discusses four published genotoxicity studies (including a bacterial reverse mutation assay, mouse lymphoma assay in L5178Y tk +/- cells, a chromosomal aberration test using human lymphocytes, and unscheduled DNA synthesis tests in rats) that showed that EPG is non-mutagenic. Finally, Choco Finesse discusses a published clinical study in which no adverse effects (including decreased fat-soluble vitamin status) were observed over 8 weeks with consumption of up to 40 g EPG/d.
Based on the totality of the data and information described above, Choco Finesse concludes that EPG is GRAS for its intended use in food.
Standards of Identity
In the notice, Choco Finesse states its intention to use EPG in several food categories, including foods for which standards of identity exist, located in Title 21 of the Code of Federal Regulations. FDA notes 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.
Potential Labeling Issues
In describing the intended uses of EPG and in describing the information that Choco Finesse relies on to conclude that EPG is GRAS under the conditions of its intended use, Choco Finesse raises a potential issue under the labeling provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act). Under section 403(a) of the FD&C Act, a food is misbranded if its labeling is false or misleading in any particular. Section 403(r) of the FD&C Act lays out the statutory framework for the use of labeling claims that characterize the level of a nutrient in a food or that characterize the relationship of a nutrient to a disease or health-related condition. If products that contain EPG bear any claims on the label or in labeling, such claims are the purview of the Office of Nutrition and Food Labeling (ONFL) in the Center for Food Safety and Applied Nutrition. The Office of Food Additive Safety neither consulted with ONFL on this labeling issue nor evaluated the information in your notice to determine whether it would support any claims made about EPG on the label or in labeling.
Section 301(ll) of the FD&C Act
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 Choco Finesse’s notice that EPG is GRAS for the intended uses, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing EPG. Accordingly, this response should not be construed to be a statement that foods that contain EPG, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by Choco Finesse, as well as other information available to FDA, the agency has no questions at this time regarding Choco Finesse’s conclusion that EPG 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 EPG. As always, it is the continuing responsibility of Choco Finesse 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 000640, 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
 GRN 000583 described the intended use of EPG in coatings for confectionary applications. FDA evaluated GRN 000583 and issued a no-questions response letter for this use of EPG. In GRN 000640 the substitution of saturated fatty acids with unsaturated fatty acids does not alter the digestibility of cocoa butter substitute, but it imparts different functional properties.