Agency Response Letter GRAS Notice No. GRN 000363
CFSAN/Office of Food Additive Safety
June 6, 2011
Hyman, Phelps & McNamara, P.C.
700 Thirteenth Street, NW
Washington, DC 20005-5929
Re: GRAS Notice No. GRN 000363
Dear Mr. Carvajal:
The Food and Drug Administration (FDA) is responding to the notice, dated November 11, 2010, that you submitted on behalf of Del Monte Foods (Del Monte) 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 November 29, 2010, filed it on December 21, 2010, and designated it as GRAS Notice No. GRN 000363.
The subjects of the notice are calcium disodium ethylenediaminetetraacetic acid (EDTA) and disodium EDTA. The notifier states that calcium disodium EDTA and disodium EDTA are manufactured in accordance with current good manufacturing practices and meet appropriate food grade specifications as for calcium disodium EDTA (21 CFR 172.120) and disodium EDTA (21 CFR 172.135). The notice informs FDA of the view of Del Monte that calcium disodium EDTA and disodium EDTA are GRAS, through scientific procedures, for use alone or together as color, flavor, and/or texture retention agents in packaged cooked sweet corn products with or without sauce, including mixed vegetable and similar products that contain 8 to 50% corn by weight, at levels up to 200 milligrams per kilogram (mg/kg) calcium disodium EDTA and 165 mg/kg disodium EDTA.
As part of its notice, Del Monte includes the report of a panel of individuals (Del Monte’s GRAS panel) who evaluated the data and information that are the basis for Del Monte’s GRAS determination. Del Monte considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Del Monte’s GRAS panel discusses identity, specifications, method of manufacture, exposure, genotoxicity studies, sub-chronic and chronic animal studies, as well as absorption, distribution, metabolism and excretion (ADME) information. Based on the review, and the totality of scientific evidence, Del Monte’s GRAS panel concluded that calcium disodium EDTA and disodium EDTA are GRAS under the intended conditions of use.
Del Monte estimates that the dietary exposure to EDTA from the intended use at 200 mg/kg would be 0.34 mg/kg body weight/day (mg/kg bw/d) at the 90th percentile for the 2 years and older age group. The notifier states that the dietary exposure at the 90th percentile from the current uses is 1.4 mg/kg bw/d. This estimate was based on data from GRN 000178, which includes other prior food uses of EDTA. Finally, the notifier assumes the 90th percentile intakes from the current and intended uses to arrive at 1.74 mg/kg bw/d for all uses. Del Monte considers this intake is an overestimation, because it assumes that all intended food categories will contain EDTA at a level of 200 mg/kg and that the consumer at the 90th percentile will also consume 1.4 mg/kg bw/d EDTA from other foods. Del Monte also indicates that this conservative estimate is lower than the WHO/FAO Joint Expert Committee on Food Additives acceptable daily intake for calcium disodium EDTA and disodium EDTA of 2.5 mg/kg bw/d.
For its safety determination on calcium disodium EDTA and disodium EDTA, Del Monte notes that EDTA is poorly absorbed and largely excreted. Del Monte discusses published acute, subacute, and chronic oral toxicity studies in rats, mice, rabbits, and dogs. Del Monte states that subchronic and chronic toxicity studies conducted in animals reveal that EDTA compounds exhibit general adverse effects only at a very high exposure levels (approximately 1000 mg/kg bw/d and greater). The notifier further notes that EDTA salts were found to be non-mutagenic and non-genotoxic in published studies under conditions that do not deplete essential trace elements required for normal cell function.
Standards of Identity
In the notice, Del Monte states its intention to use calcium disodium EDTA and disodium EDTA 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.
Potential Labeling Issues
Section 403(k) of the Federal Food, Drug, and Cosmetic Act (FFDCA) provides that a food shall be deemed to be misbranded if it bears or contains any chemical preservative, unless it bears labeling stating that fact. Section 403(i)(2) of the FFDCA provides that a food shall be deemed to be misbranded unless its label bears the common or usual name of each ingredient. Section 403(a) of the FFDCA provides that a food shall be deemed to be misbranded if its labeling is false or misleading in any particular. Del Monte’s use of calcium disodium EDTA and disodium EDTA constitutes use as a chemical preservative. Therefore, the ingredient statement on labels of food products that contain calcium disodium EDTA and disodium EDTA must comply with the labeling regulations that implement sections 403(k) and 403(i)(2) of the FFDCA. For example, 21 CFR 101.22(j) requires that the food to which a chemical preservative is added bear a label declaration stating both the common or usual name of the ingredient and a separate description of its function. If Del Monte has any questions about the appropriate labeling of this food ingredient, Del Monte should contact the staff in the Office of Nutrition, Labeling, and Dietary Supplements.
The Food and Drug Administration Amendments Act of 2007, which was signed into law on September 27, 2007, amends the 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 Del Monte’s notice that calcium disodium EDTA and disodium EDTA are GRAS for the intended uses, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing calcium disodium EDTA and disodium EDTA. Accordingly, this response should not be construed to be a statement that foods that contain calcium disodium EDTA and disodium EDTA introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by Del Monte, as well as other information available to FDA, the agency has no questions at this time regarding Del Monte’s conclusion that calcium disodium EDTA and disodium EDTA are 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 calcium disodium EDTA and disodium EDTA. As always, it is the continuing responsibility of Del Monte 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 000363, 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/grasnoticeinventory.
Mitchell A. Cheeseman, Ph.D.
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition