Agency Response Letter GRAS Notice No. GRN 000194

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CFSAN/Office of Food Additive Safety

January 25, 2012

Mark Itzkoff
Olsson, Frank and Weeda, P.C.
Suite 400
1400 Sixteenth St., N.W.
Washington, DC 20036

Re: GRAS Notice No. GRN 000194

Dear Mr. Itzkoff:

The Food and Drug Administration (FDA) is responding to the notice, dated February 23, 2006, that you submitted on behalf of Freezing Machines, Inc. (FMI) 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 February 28, 2006, filed it on March 2, 2006, and designated it as GRAS Notice No. GRN 000194.

The subject of the notice is carbon monoxide (CO). The CO is dissolved in a brine/marinade solution that is injected into beef muscle parts that are vacuum-packed, and prepared for case-ready marketing. Carbon monoxide present in the brine/marinade system forms carboxymyoglobin that permits flexibility in distribution of retail meat. The packages will be labeled with a validated "use-or-freeze-by" date. The amount of the brine/marinade injected into the meat will be limited to 27.8 percent by weight. The maximum amount of CO dissolved in the brine/marinade solution is 21.4 milliliters per liter (ml/l) of water. The notice informs FDA of the view of FMI that this use of CO is GRAS, through scientific procedures.

Carbon monoxide was the subject of three previous GRAS notices (GRNs 000083, 000143, and 000167), which FMI incorporates by reference. These GRAS notices were for the use of CO in a modified atmosphere packaging (MAP) system. The MAP systems are used for packaging fresh cuts of muscle meat and ground meat to maintain wholesomeness, provide flexibility in distribution, and reduce shrinkage of the meat. The use of CO in the current GRN is not as part of a MAP system.

GRN 000194 describes publicly available information pertaining to the identity and characteristic properties of CO. FMI states that the CO will be "food-grade," with a composition of 98 percent CO; the remaining 2 percent is residual atmospheric gases, e.g., nitrogen, oxygen, carbon dioxide, argon, water, hydrogen and/or methane.

FMI provides an estimate of potential CO exposure from the use of its system. FMI notes that assuming complete absorption (100 percent) of the CO at 27.8 percent of the brine into the red meat, exposure would be limited to 1.3 milligrams (mg) of CO per 250 gram (g) serving of red meat. [1] FMI notes that this exposure is less than the amount of CO that a consumer would be exposed to from the uses in the previously submitted notices.

As part of GRN 000194, FMI incorporates GRN 000083, submitted by Pactiv Corporation; GRN 000143 submitted by Precept Foods, LLC; and, GRN 000167 submitted by Tyson Foods, Inc. by reference. FMI considers that the information in these related GRAS notices supports the safety of its use of CO.

FMI also addressed the question regarding the possibility that the use of CO in this application will "mask" normal spoilage of the processed red meat prior to use by consumers. FMI has sponsored two studies to address the impact of the process on the appearance of the processed beef. These studies showed that processed meat became discolored before the microbial load became sufficient to result in spoilage. On the basis of these studies, FMI concluded that consumers would reject meat that is not spoiled because of the change in color.

Use in Meat, Poultry, and Egg Products

During its evaluation of GRN 000194, FDA consulted with the Food Safety and Inspection Service (FSIS) of the United States Department of Agriculture. Under the Federal Meat Inspection Act, the Poultry Products Inspection Act, and the Egg Products Inspection Act, FSIS is responsible for determining the efficacy and suitability of food ingredients in meat, poultry, and egg products as well as prescribing safe conditions of use. Suitability relates to the effectiveness of the ingredient in performing the intended purpose of use and the assurance that the conditions of use will not result in an adulterated product, or one that misleads consumers.

FSIS does not object to this use of CO in a water or marinade solution provided that the meat is labeled with a "use-or–freeze-by" date or "in some other way that discloses the material fact that the shelf life of the product has been affected and thus to assure that the consumer is not misled." Any further questions regarding use in meat products should be directed to Dr. William K. Shaw, Jr., Risk, Innovations, and Management Division, Food Safety and Inspection Service, Stop Code 3782, Patriots Plaza III, Cubicle 8-163A, 1400 Independence Ave. SW, Washington, DC 20250-3700. The telephone number for that office is (301)504-0889.[2]

Section 301(ll) of the Federal Food Drug and Cosmetic Act (FFDCA)

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 FMI's notice that CO is GRAS when dissolved in a brine/marinade solution which is injected into beef muscle parts that are vacuum-packed and prepared for case-ready marketing, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing CO. Accordingly, this response should not be construed to be a statement that foods that contain CO, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).


Based on the information you provided on behalf of FMI, as well as other information available to FDA, the agency has no questions at this time regarding FMI's conclusion that CO is GRAS under the intended conditions of use, provided that the label has a "use-or–freeze-by" date or "in some other way that discloses the material fact that the shelf life of the product has been affected and thus to assure that the consumer is not misled." The agency has not, however, made its own determination regarding the GRAS status of the subject use of CO. As always, it is the continuing responsibility of FMI 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 000194, as well as a copy of the information in this notice that conforms to the information in the proposed GRAS exemption claim (proposed 21 CFR 170.36(c)(1)), is available for public review and copying at

Dennis M. Keefe, Ph.D.
Office of Food Additive Safety
Center for Food Safety
and Applied Nutrition

cc: William Shaw, Jr., Ph.D.
Risk, Innovations, and Management Division
Office of Policy and Program Development
Food Safety and Inspection Service
Stop Code 3782
Patriots Plaza III, Cubicle 8-163A
1400 Independence Ave. SW
Washington, DC 20250-3700

[1] Assuming that all of the CO dissolved into the brine will be consumed, the consumer will be exposed to 1.3 mg of CO through the consumption of 250 g of meat (21.4 ml/l x 27.8 percent brine/marinade injected x 1.145 g CO/l equals 1.3 mg/250 g consumed meat.)

[2] Effective June 1, 2008, the Office of Policy and Program Development (OPPD)/FSIS transferred the review process of ingredient submissions from the Labeling and Program Delivery Division to the Risk Management Division, which is now called the Risk, Innovations, and Management Division (RIMD).

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