Agency Response Letter GRAS Notice No. GRN 000187
CFSAN/Office of Food Additive Safety
March 20, 2006
787 Seventh Avenue
New York, New York 10019
Re: GRAS Notice No. GRN 000187
Dear Ms. McEnroe:
The Food and Drug Administration (FDA) is responding to the notice, dated December 9, 2005, that you submitted on behalf of S & G Resources and Changmao Biochemical Engineering (the notifiers) 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 this notice on December 14, 2005, filed it on December 15, 2005, and designated it as GRN No. 000187.
The subject of the notice is L (+) tartaric acid prepared using an enzyme from immobilized Rhodococcus ruber cells, a method different from that described in 21 CFR 184.1099. For the purpose of this letter, we will refer to the subject of the notice as L (+) tartaric acid (alternative method) and to tartaric acid in general as tartaric acid. The notice informs FDA of the view of the notifiers that L (+) tartaric acid (alternative method) is GRAS, through scientific procedures, for use as an alternative source of tartaric acid in food at levels not to exceed current good manufacturing practices, for use as a firming agent, a flavor enhancer, a flavoring agent, a humectant and a pH control agent, as described in 21 CFR 184.1099.
The notifiers describe generally available information about the manufacture of L (+) tartaric acid. L (+) tartaric acid (alternative method) is produced by the conversion of maleic anhydride to tartaric acid through the enzymatic action of the enzyme cis-epoxisuccinate hydrolase, contained in immobilized R. ruber cells. In comparison, 21 CFR 184.1099 specifies that tartaric acid is obtained as a by-product of wine manufacture. Because the notifiers' L (+) tartaric acid will substitute for the uses of tartaric acid prepared as described in 21 CFR 184.1099, total daily intake of tartaric acid is not expected to change from the current level.
L (+) tartaric acid (alternative method) is chemically identical to tartaric acid affirmed as GRAS in 21 CFR 184.1099, and meets the specifications for tartaric acid in the Food Chemical Codex (FCC), 5th ed., 2003. In addition to FCC specifications, the notifiers specify limits on arsenic (≤3 milligrams/kilogram), D (-)-tartaric acid (≤0.3%), maleic acid (≤0.05%), and fumaric acid (≤1%).
As part of its notice, the notifiers discuss the published results of an Ames assay, a host mediated assay, an in vitro cytogenic assay, an in vivo cytogenic assay, and an in vivo dominant lethal assay. Based on their evaluation of these studies, the notifiers conclude that tartaric acid lacks genotoxic potential.
In their notice, the notifiers reference published comprehensive reviews and studies that have been conducted in support of the safety of tartaric acid and related compounds. Additionally, the notice contains a list summarizing several published repeated dose oral toxicity studies that have been conducted with tartaric acid or monosodium tartrate in rats, rabbits, and dogs. In its evaluation of the safety of tartaric acid, the notifiers note that tartaric acid has been evaluated by the Joint FAO/WHO Expert Committee on Food Additives.
In their evaluation of the safety of R. ruber, the notifiers state that they have reviewed publicly available information and conclude that R. ruber does not pose a toxigenic nor pathogenic concern and thus the use of the enzyme isolated from this organism is appropriate for the production of L (+) tartaric acid (alternative method).
Based on the information provided by the notifiers, as well as other information available to FDA, the agency has no questions at this time regarding the notifiers' conclusion that L (+) tartaric acid (alternative method) is GRAS under the intended conditions of use. The agency has not, however, made its own determination regarding this method for manufacturing L (+) tartaric. As always, it is the continuing responsibility of S & G Resources and Changmao Biochemical Engineering 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 homepage of the Office of Food Additive Safety (on the Internet at http://www.cfsan.fda.gov/~lrd/foodadd.html).
Laura M. Tarantino, Ph.D.
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition