Agency Response Letter GRAS Notice No. GRN 000403
CFSAN/Office of Food Additive Safety
May 15, 2012
Robert S. McQuate, Ph.D.
GRAS Associates, LLC
20482 Jacklight Lane
Bend, OR 97702-3074
Re: GRAS Notice No. GRN 000403
Dear Dr. McQuate:
The Food and Drug Administration (FDA) is responding to the notice, dated September 26, 2011, that you submitted on behalf of ICL Performance Products LP (ICL Performance) 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 September28, 2011, filed it on October 4, 2011, and designated it as GRAS Notice No. GRN 000403.
The subject of the notice is carnallite sea salt (magnesium chloride, potassium chloride, salt [referred to in this letter as carnallite]). The notice informs FDA of the view of ICL Performance that carnallite is GRAS, through scientific procedures, for use as a substitute for a portion of the sodium chloride used in food in general, including meat and poultry, but excluding infant formula. The amount of carnallite added to foods would not exceed that reasonably required to accomplish the intended technical effect.
Our use of “carnallite” in this letter should not be considered an endorsement or recommendation of that term as an appropriate common or usual name for the purpose of declaring the substance in the ingredient statement of foods that contain that ingredient. Title 21 CFR 101.4 states that each ingredient must be declared by its common or usual name. In addition, 21 CFR 102.5 outlines general principles to use when establishing common or usual names for nonstandardized foods. Issues associated with labeling and the appropriate common or usual name of a food are the responsibility of the Office of Nutrition, Labeling, and Dietary Supplements in the Center for Food Safety and Applied Nutrition.
ICL Performance provides information about the identity and composition of carnallite. Carnallite (CAS Number 107762-48-1) is a white to off-white crystalline solid with high water solubility; it is composed of magnesium chloride and potassium chloride. Impurities include low levels of sodium chloride and bromide.
ICL Performance describes the manufacturing process for carnallite, which starts in solar evaporation ponds using sea water from the Dead Sea. The sea water is pumped to a series of basins where evaporation of water results in precipitation of minerals. In the initial ponds, there is a 50 percent reduction in water volume, causing precipitation of sodium salts. The remaining low sodium brine is pumped into the final product ponds where it is further concentrated until the carnallite crystallizes and precipitates. The crystals are harvested, washed, dried, sized, and packaged. ICL Performance notes that carnallite is produced under current good manufacturing practices (cGMPs). As part of its notice, ICL Performance provides specifications for carnallite that include limits for sodium, bromide, lead, and sizing.
ICL Performance calculates the estimated daily intake (EDI) of carnallite from its intended use as a replacement for a portion of sodium chloride used in foods in general, and using data from the United States Department of Agriculture (USDA) Dietary Guidelines for Americans (2010-2011). ICL Performance assumes a 25 percent replacement of sodium chloride in the diet with carnallite, and estimates the 90th percentile consumption level is 4,150 milligrams per person per day (mg/p/d).
ICL Performance discusses the safety of carnallite and notes that its mineral constituents are essential for human nutrition and are commonly ingested. As a result, the mineral constituents have all been reviewed for their safety by numerous national and international regulatory agencies and organizations. Using the intake estimate of 4,150 mg/p/d, the notifier states that the EDIs of potassium (457-565 mg/p/d), magnesium (319-360 mg/p/d), and sodium (116 mg/p/d) through the consumption of carnallite are within the respective limits of the Dietary Reference Intakes (a nutrient reference value) established by the Food and Nutrition Board of the Institute of Medicine (IOM) for each element. Furthermore, the IOM and the European Union Scientific Committee on Foods have evaluated the tolerable upper intake levels (UL) of exposure for magnesium and potassium ions present in foods. No UL was defined for magnesium from food because it has not been demonstrated to exert adverse effects when ingested as a naturally occurring substance in foods; no UL was defined for potassium because the dietary intake for most Americans is lower than the adequate intake, and in a generally healthy population, potassium ions from foods are readily excreted in the urine.
ICL Performance also discusses the safety of the bromide impurity. The calculated EDI of bromide (17 mg/p/d) through consumption of carnallite exceeds the published typical daily intake in the United States (2-8 mg/p/d). Hence, ICL Performance provides additional safety data about the consumption of bromide. ICL Performance discusses published animal studies such as ADME (absorption, distribution, metabolism, and excretion), acute toxicity, short term toxicity, subchronic toxicity, reproductive toxicity and mutagenicity studies, as well as human safety studies in support of the safety of bromide. The authors of a published review, which is cited in the notice, propose an acceptable daily intake (ADI) for bromide of 0.4 milligram per kilogram body weight (mg/kg bw/d), equivalent to 24 mg/p/d for a 60 kg person. This ADI is based on a review of toxicology literature for the bromide ion. Members of the Joint FAO/WHO Meeting on Pesticide Residues recommend that the ADI for bromide is 0-1 mg/kg bw/d, equivalent to 0-60 mg/p/d. The calculated maximum EDI for bromide from carnallite is 17 mg/p/d, which is lower than the estimated maximum ADI values. Therefore, ICL Performance states that the calculated EDI of bromide does not raise safety concerns.
Standards of Identity
In the notice, ICL Performance states its intention to use carnallite 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.
Use in Products under USDA Jurisdiction
During its evaluation of GRN 000403, FDA consulted with the Risk, Innovations, and Management Division of the Food Safety and Inspection Service (FSIS) of the USDA. Under the Federal Meat Inspection Act, 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 the use of carnallite as a replacement for a portion of the sodium chloride normally used in meat and poultry products at per serving levels that reflect cGMPs in that the quantities added do not exceed the respective amounts necessary to accomplish the intended technical effect. When used in meat or poultry food product it should be listed on the ingredients statement as “Carnallite Sea Salt (magnesium chloride, potassium chloride, salt).” Since FSIS does not permit fortification of meat or poultry products, ICL Performance cannot use the ingredient as a “nutrient” in FSIS regulated products.
FDA advises ICL Performance to seek regulatory guidance from FSIS, Risk, Innovations, and Management Division, regarding the use of carnallite in meat and poultry products. ICL Performance should direct such an inquiry to Dr. William K. Shaw, Jr., Director, Risk, Innovations, and Management Division, Office of Policy and Program Development, Food Safety and Inspection Service, Stop Code 3782, Patriots Plaza III, 1400 Independence Avenue SW, Washington, DC 20250-3700.
Section 301(ll) of the Federal Food, Drug, and Cosmetic Act (FD&C Act)
The Food and Drug Administration Amendments Act of 2007, which was signed into law on September 27, 2007, amends the FD&C Act to, among other things, add section 301(ll). 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 ICL Performance’s notice that carnallite is GRAS for the intended uses, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing carnallite. Accordingly, this response should not be construed to be a statement that foods that contain carnallite, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by ICL Performance, as well as other information available to FDA, the agency has no questions at this time regarding ICL Performance’s conclusion that carnallite 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 carnallite. As always, it is the continuing responsibility of ICL Performance 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 000403, as well as the information in this notice that conforms to the information described in the proposed 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
cc: William K. Shaw, Jr., Ph.D.
Stop Code 3782, Patriots Plaza III
1400 Independence Ave. SW
Washington, DC 20250-3700