Agency Response Letter GRAS Notice No. GRN 000272
CFSAN/Office of Food Additive Safety
June 24, 2009
Carrie Rabe, Ph.D.
The Weinberg Group Inc.
1220 Nineteenth St. NW, Suite 300
Washington, DC 20036
Re: GRAS Notice No. GRN 000272
Dear Dr. Rabe:
The Food and Drug Administration (FDA) is responding to the notice, dated December 5, 2008, that you submitted on behalf of Smart Salt, Inc. 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 December 17, 2008, filed it on December 18, 2008, and designated it as GRAS Notice No. GRN 000272.
The subject of the notice is triple salt of magnesium, ammonium, and potassium chloride, hexahydrate (triple salt). The notice informs FDA of the view of Smart Salt, Inc. that triple salt is GRAS, through scientific procedures, for use as a substitute for a portion of the sodium chloride used in food in general, including meat, poultry, and egg products, but excluding infant formula.
21 CFR 101.4 states that all ingredients must be declared by their common or usual name. In addition, 21 CFR 102.5 outlines general principles to use when establishing common or usual names for nonstandardized foods. Our use of the term “triple salt” in this letter should not be considered to be 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. 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.
Smart Salt, Inc. provides information about the identity, composition and method of manufacture of triple salt. Triple salt is the product resulting from the co-crystallization of one part potassium chloride, three parts ammonium chloride, and four parts magnesium chloride hexahydrate; it is identified by the Chemical Abstracts Service (CAS) Registry Number 1044829-32-4. The manufacturing process begins by mixing the dry, food grade component salts followed by the addition of water. The slurry is boiled to dissolve the component salts; subsequently, the water content is reduced under vacuum and the final product is cooled, filtered, and dried at temperatures between 50° and 80° Celsius. An anticaking agent such as silicon dioxide or calcium silicate is generally added to the final product.
Smart Salt, Inc. describes triple salt as a water-soluble white crystalline solid with a salty taste. Smart Salt, Inc. notes that the manufacturing process results in a product with a uniform crystalline structure that differs from that of any of the component salts, as demonstrated by x-ray powder diffraction spectroscopy. As further evidence that triple salt is not a simple mixture of the individual component salts, Smart Salt, Inc. states that residual potassium chloride and magnesium chloride crystals are present at a level of less than one percent and no residual ammonium chloride crystals are present, as evidenced by a comparison of the x-ray diffraction patterns of reference standards for the individual salts to the pattern of triple salt. As part of its notice, Smart Salt, Inc. provides a table of specifications for triple salt that includes limits for magnesium, ammonium, potassium, pH, lead, arsenic, and moisture content.
Smart Salt, Inc. provides an estimated daily intake (EDI) of triple salt from its intended use as a replacement for a portion of sodium chloride used in foods in general. In calculating the EDI, the notifier assumes that triple salt will be used by both food manufacturers and individual consumers. The notifier further states that triple salt will not be a 100 percent replacement for sodium chloride because of palatability issues when used alone or as a high proportion of the regular sodium chloride content of foods. Based on the assumption that triple salt will replace a maximum of 50 percent of sodium chloride added to food, due to the palatability issues associated with the use of higher proportions, the notifier estimates the intake of triple salt would be a maximum of 7.3 grams per day (g/day) at the 90th percentile for males in all age groups. Using the most conservative intake estimate of 7.3 g/day, the notifier calculates the intake estimates for each cation present in triple salt as: 681 milligrams per day (mg/day) magnesium, 382 mg/day ammonium, and 274 mg/day potassium.
Smart Salt, Inc. discusses the safety of triple salt and notes that triple salt readily dissolves into its component chloride salts in aqueous media. Therefore the safety determination may reasonably include a consideration of the safety of each of the component chloride salts. Smart Salt, Inc. notes that FDA has affirmed each of the component salts as GRAS for use as direct human food ingredients (magnesium chloride, for use as a flavoring agent and adjuvant, and a nutrient supplement in 21 CFR 184.1426; potassium chloride, for use as a flavor enhancer, a flavoring agent, a nutrient supplement, a pH control agent, and as a stabilizer or thickener in 21 CFR 184.1622; ammonium chloride, for use as a dough strengthener, a flavor enhancer, a leavening agent, and a processing aid in 21 CFR 184.1138). Smart Salt, Inc. also notes that other expert bodies have issued opinions on the safety of triple salt’s component salts. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) has established an acceptable daily intake (ADI) of “not specified”1 for magnesium, potassium, and ammonium chloride salts. The U.S. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes of the Food and Nutrition Board of the Institute of Medicine (IOM) and the European Union Scientific Committee on Foods have evaluated the upper tolerable limits of exposure for magnesium and potassium ions present in foods. No tolerable upper limit was defined for either magnesium or potassium ions present in foods.
Smart Salt, Inc. discusses the safety of each of the constituent cations in triple salt with respect to exposure at the 90th percentile intake level and finds that the increase in the intake level of potassium and ammonium does not exceed any established limits. Regarding the safety of magnesium, Smart Salt, Inc. notes that the IOM has established an upper tolerable limit of 350 mg for supplementary magnesium administered as a single dose (i.e., via the use of magnesium-containing laxatives as tablets, capsules, or liquids). This limit set by the IOM is based on available information that mild gastrointestinal effects such as nausea and mild diarrhea have been observed at higher doses. The total daily exposure of magnesium from triple salt consumed in food is estimated to be 500–680 mg/day. Although this is higher than the tolerable limit set by the IOM, Smart Salt, Inc. emphasizes that the IOM limit applies only to supplementary magnesium and not to magnesium consumed with foods. Smart Salt, Inc. also notes that the 500–680 mg/day of magnesium present in triple salt would be consumed over the course of a day with food, and not all at once; thus it is expected to be delivered slowly to the intestines, and not likely to result in an exposure of more than 350 mg at any one time. The notifier concludes that at the 90th percentile intake level of the constituent cations, the use of triple salt would not produce adverse effects.
Standards of Identity
In the notice, Smart Salt, Inc. states its intention to use triple salt 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 Meat, Poultry, and Egg Products
During its evaluation of GRN 000272, FDA consulted with the Risk and Innovations Management Division (RIMD), Office of Policy and Program Development (OPPD), of 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 and poultry 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 triple salt as a replacement for a portion of the sodium chloride normally used in meat and poultry products. FSIS advises that triple salt will need to be listed by its common or usual name in the ingredients statement on the label for any meat and/or poultry product in which it is used. Any further questions regarding use in meat and poultry products should be directed to Dr. John M. Hicks, Jr., RIMD/OPPD/FSIS via email at email@example.com or to Mr. David Culak, RIMD/OPPD/FSIS, via email at firstname.lastname@example.org.
Section 301(ll) of the Federal Food, Drug, and Cosmetic Act (FFDCA)
The Food and Drug Administration Amendments Act of 2007, which was signed into law on September 27, 2007, amends the Federal Food Drug and Cosmetic Act (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 Smart Salt Inc.’s notice that triple salt is GRAS for use in food in general, including meat, poultry, and egg products, but excluding infant formula, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing triple salt. Accordingly, this response should not be construed to be a statement that foods that contain triple salt, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by Smart Salt, Inc., as well as other information available to FDA, the agency has no questions at this time regarding Smart Salt, Inc.’s conclusion that triple salt 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 triple salt. As always, it is the continuing responsibility of Smart Salt, Inc. 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 000272, 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. To view or obtain an electronic copy of the text of the letter, follow the hyperlinks from the “Food” topic to the “Food Ingredients and Packaging” section to the “Generally Recognized as Safe (GRAS)” page where the GRAS Inventory is listed.
Laura M. Tarantino, Ph.D.
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition
cc: John M. Hicks, Jr. DVM, MPH
Risk and Innovations Management Division
Office of Policy and Program Development
Food Safety and Inspection Service
U. S. Department of Agriculture
1400 Independence Avenue, S.W., Room 3549, South Agriculture Building
Washington, DC 20250-3700
1As determined by JECFA, an ADI of “not specified” means that consumption of these salts to achieve the desired effect and from its acceptable background in food does not represent a hazard to health and the establishment of a numerical ADI value is not necessary.