Agency Response Letter GRAS Notice No. GRN 000014
CFSAN/Office of Premarket Approval
May 26, 1999
Clausen Ely, Jr.
Covington & Burling
1201 Pennsylvania Ave, N.W.
P.O. Box 7566
Washington, D.C. 20044-7566
Re: GRAS Notice No. GRN 000014
Dear Mr Ely:
The Food and Drug Administration (FDA) is responding to the notice dated February 12, 1999, that you submitted on behalf of Basic Vegetable Products, L.P. (BVP) 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 the notice on February 17, 1999, and designated it as GRAS Notice No. GRN 000014.
The subject of the notice is hydrogen peroxide. The notice informs FDA of the view of BVP that hydrogen peroxide is GRAS, through scientific procedures, for use in the processing of dehydrated onions to reduce the microbial load both in and on onions prior to dehydration at concentrations of 5 to 10 per cent. In telephone conversations with FDA on March 29, April 8, and April 9, 1999, you clarified that the intended use of hydrogen peroxide is as a processing aid in the manufacture of dehydrated onions to extend their shelf life.
The notice does not provide a sufficient basis for a determination that the subject use of hydrogen peroxide is GRAS because the notice fails to consider two matters. First, the notice fails to consider the regulatory status of hydrogen peroxide - i.e., under 21 CFR 184.1366(c), hydrogen peroxide is affirmed as GRAS, in accordance with 21 CFR 184.1(b)(2), only within specific limitations. Second, the notice fails to consider the associated regulatory framework for a substance that is affirmed as GRAS under the restriction imposed by § 184.1(b)(2).
Data and information regarding the safety of the use of hydrogen peroxide as a processing aid
The notice states that hydrogen peroxide is prepared by the autoxidation of an anthraquinone. The notice describes (1) BVP's process for dehydrating onions; (2) references to a publicly available report, from the Federation of American Societies for Experimental Biology, on the toxicity of hydrogen peroxide in humans; (3) published studies on acute, subchronic, chronic, reproductive/developmental, and carcinogenic effects of hydrogen peroxide on animals; (4) unpublished genotoxicity studies; and (5) unpublished studies on the potential secondary toxic effects of hydrogen peroxide added to foods, including the possible destruction of essential nutrients, and the production of potentially toxic reaction products. Due to the highly reactive nature of hydrogen peroxide, BVP estimates that dietary exposure to hydrogen peroxide will be negligible.
Under 21 CFR 184.1366 (c), current uses of hydrogen peroxide are affirmed as GRAS, in accordance with 21 CFR 184.1(b)(2), only within specific limitations. Further, § 184.1(b)(2) specifies that any use of hydrogen peroxide not in full compliance with each such established limitation requires a food additive regulation.
Under section 201(s) of the Federal Food, Drug, and Cosmetic Act, a determination that a use of a substance is GRAS through scientific procedures depends on the views of qualified experts who have evaluated the data and information that show that the substance is safe under the conditions of its intended use. Because new data and information about the safety of a use of a substance can become available at any time, a GRAS determination is time-dependent in nature. Therefore, the specific limitations that are described in § 184.1366(c), which were established in 1986, reflect the data and information that were available at that time and do not preclude a subsequent determination, through scientific procedures, that another use of hydrogen peroxide is GRAS, even though that use is outside the specific limitations that apply under § 184.1366(c).
During the rulemaking that established § 184.1(b)(2) (formerly § 121.104 (b)(2); 41 FR 53600; December 7, 1976), FDA addressed a comment that contended that, under proposed § 184.1(b)(2), a subsequently instituted use that may in fact be GRAS would have to covered by a food additive regulation. In response to this comment, FDA advised that § 184.1(b)(2) does not require that a subsequent use be covered by a food additive regulation even though it may be GRAS. FDA specifically pointed out that a regulation affirming a substance as GRAS with specific limitations on the conditions of use may be amended to cover additional uses that have become GRAS. Importantly, either mechanism requires rulemaking - i.e., rulemaking that results in a food additive regulation or rulemaking that amends the current GRAS affirmation regulation.
The rulemakings that established § 184.1(b)(2) and § 184.1366(c) bind FDA as well as the regulated industry. BVP's notice to FDA of its view that the use of hydrogen peroxide as a processing aid in the manufacture of dehydrated onions is GRAS is not a substitute for the rulemaking that is required under the current regulatory structure.
In light of BVP's view that the use of hydrogen peroxide in the manufacture of dehydrated onions is GRAS, the rulemaking that established § 184.1(b)(2) makes clear that the appropriate mechanism for BVP to lawfully use hydrogen peroxide outside the limitations established in § 184.1366(c) is to submit a petition to FDA. Options that are available to BVP include a food additive petition or a citizen petition, filed under 21 CFR 10.30, to amend § 184.1366(c) or § 184.1(b)(2).
In accordance with proposed 21 CFR 170.36(f), we have placed a copy of this letter, as well as a copy of the information in your notice that conforms to the information in proposed § 170.36(c)(1), in a file that is available for public review and copying in the public reading room of the agency's Freedom of Information Staff.
Alan M. Rulis, Ph.D.
Office of Premarket Approval
Center for Food Safety and Applied Nutrition