Agency Response Letter GRAS Notice No. GRN 000586
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See also Generally Recognized as Safe (GRAS).
CFSAN/Office of Food Additive Safety
December 9, 2015
Ashley Roberts, Ph.D.
Intertek Scientific & Regulatory Consultancy
2233 Argentia Road, Suite 201
Mississauga, Ontario L5N 2X7
Re: GRAS Notice No. GRN 000586
Dear Dr. Roberts:
The Food and Drug Administration (FDA) is responding to the notice, dated May 13, 2015, that you submitted 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 June 16, 2015, filed it on July 21, 2015, and designated it as GRAS Notice No. GRN 000586.
The subject of the notice is taurine. Taurine is chemically identified as 2-aminoethanesulfonic acid. The notice informs FDA of the view of Intertek Scientific & Regulatory Consultancy (Intertek) that taurine is GRAS, through scientific procedures, for use as an ingredient in noncarbonated, flavored, water-based beverages at a level of 0.0045%.
As part of its notice, Intertek includes the report of a panel of individuals (Intertek’s GRAS panel) that evaluated the data and information that are the basis for Intertek’s GRAS determination. Intertek considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Intertek’s GRAS panel evaluated the method of manufacture, product specifications, estimates of dietary exposure, as well as published and unpublished studies supporting the safety of taurine. Based on this review, Intertek’s GRAS panel concluded that taurine meeting its established food grade specifications is GRAS under the conditions of its intended use.
Intertek describes the method of manufacture of taurine. Taurine is synthesized from sodium bisulfite, ethylene oxide, ammonia, and sulfuric acid. The resulting taurine is purified, filtered, and crystallized. Intertek states that taurine meets the specifications in the Food Chemicals Codex (9th edition), including those for taurine purity (98.5 to 101.5%), lead (≤5 milligrams per kilogram (mg/kg)), and arsenic (≤2 mg/kg). Intertek provides analyses of three lots of taurine that indicate that their product complies with these specifications. Intertek provides results of tests showing that taurine was stable for up to 36 months under various storage conditions, as judged by appearance and measured taurine concentration.
Intertek estimates dietary exposure to taurine. Intertek first estimates dietary exposure based on the notified use using the USDA’s What We Eat in America National Health and Nutrition Examination Survey (NHANES, 2007–2012). The estimated dietary exposures to taurine are 15.9 mg/person/day (0.24 mg/kg body weight (bw)/day for a 70 kg person) at the mean and 29.3 mg/person/day (0.45 mg/kg bw/day) at the 90th percentile level. Taurine is currently also sold as an ingredient in some dietary supplements. Taking dietary supplement use into account, the mean dietary exposure in the total population increases to 24.8 mg/person/day (0.37 mg/kg bw/day) and the 90th percentile level of exposure increases to 42.6 mg/person/day (0.61 mg/kg bw/day). Next, Intertek discusses other sources of exposure to taurine. Taurine is naturally present in meats and dairy products, and is therefore a component of a typical U.S. diet. Intertek estimates that omnivorous diets provide 9 to 400 mg taurine/person/day.
Intertek discusses information used to conclude that taurine is GRAS for its intended use. This information includes commonly known and accepted information about taurine, such as its production in cells from the metabolism of methionine and cysteine, and utilization for various cellular functions. Humans are also exposed to taurine through the consumption of meat and dairy products. Citing published information, Intertek states that orally ingested taurine is absorbed in the small intestine in both rodents and humans, and excess taurine is eliminated primarily by renal excretion. Intertek discusses four toxicological studies in rats: 18-month and 8-week published studies, and two unpublished 13-week studies. The 18-month study showed that dietary administration of taurine up to 2500 mg/kg bw/day produced no treatment-related adverse effects in male or female rats. The unpublished studies were reviewed by the European Food Safety Agency (EFSA) and the Scientific Committee of Food (SCF) of the European Commission. The scientific opinions of EFSA and SCF are publicly available. The notifier reiterates the scientific opinions of EFSA and SCF, which conclude that up to 1000 mg taurine/kg bw/day administered through gavage and up to 1656 mg taurine/kg bw/day administered through drinking water produced no treatment-related adverse effects in male and female rats. Additionally, based on the published reports as well as the opinions of EFSA and SCF, the notifier states that taurine does not have any potential for reproductive or developmental toxicity, mutagenicity, genotoxicity, or carcinogenicity. The notifier also cites a published review that evaluated human studies to identify a potential safe upper level of taurine dietary exposure, and established 3,000 mg/day as the observed safe level for taurine dietary exposure in humans. Based on the totality of evidence, the notifier concludes that the intended use of taurine is GRAS.
Potential Labeling Issues
In describing the intended use of taurine and in describing the information that Intertek relies on to conclude that taurine is GRAS under the conditions of its intended use, Intertek raises a potential issue under the labeling provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act). This issue consists of scientific studies reporting effects on blood pressure, anti-oxidant activity, neuro-inhibitory activity, and as a proposed treatment for other medical conditions. 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 taurine bear any claims on the label or in labeling, such claims are the purview of the Office of Nutrition, Labeling, and Dietary Supplements (ONLDS) in the Center for Food Safety and Applied Nutrition. The Office of Food Additive Safety neither consulted with ONLDS on this labeling issue nor evaluated the information in your notice to determine whether it would support any claims made about taurine 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 Intertek’s notice that taurine is GRAS for the intended uses, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing taurine. Accordingly, this response should not be construed to be a statement that foods that contain taurine, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by Intertek and other information available to FDA, the agency has no questions at this time regarding Intertek’s conclusion that taurine 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 taurine. As always, it is the continuing responsibility of Intertek 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 00 0586, 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