Agency Response Letter GRAS Notice No. GRN 000321
CFSAN/Office of Food Additive Safety
August 18, 2010
Lewis & Harrison, LLC
122 C Street NW, Suite 740
Washington, DC 20001
Re: GRAS Notice No. GRN 000321
Dear Mr. Harrison:
The Food and Drug Administration (FDA) is responding to the notice, dated January 28, 2010, that you submitted on behalf of Cabot Corporation (Cabot) 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 January 29, 2010, filed it on February 18, 2010, and designated it as GRAS Notice No. GRN 000321. In letters dated May 14, 2010 and July 15, 2010, Cabot limited the intended direct use of the ingredient to those categories described in the following paragraph and table.
The subject of the notice is synthetic amorphous silica (SAS). The notice informs FDA of the view of Cabot that SAS is GRAS, through scientific procedures, for use as an anticaking agent, defoaming agent, stabilizer, adsorbent, carrier, conditioning agent, chill proofing agent, filter aid, emulsifying agent, viscosity control agent, and anti-settling agent in food categories listed in Table 1 (based on the Codex Alimentarius General Standard for Food Additives food category system) at levels up to 2.0 percent weight/weight (w/w), and as an indirect additive in the manufacturing of adhesives, coatings, defoaming agents, greases and lubricants, paper and paperboard, and polymers that are then used as components of food-packaging material.
|Codex Alimentarius Food Category or Subcategory|
|01.1.2||Dairy-based drinks, flavoured and/or fermented|
|01.3||Condensed milk and analogues (plain)|
|01.4.3||Clotted cream (plain) and cream analogues|
|01.5||Milk powder and cream powder and powder analogues (plain)|
|01.6||Cheese analogues (excluding Whey cheese (01.6.3) and Whey protein cheese (01.6.6)|
|01.8.1||Liquid whey and whey products (excluding whey cheeses)|
|02.2.2||Fat spreads, dairy fat spreads and blended spreads|
|02.3||Fat emulsions mainly of type oil-in-water, including mixed and/or flavoured products based on fat emulsions|
|02.4||Fat-based desserts excluding dairy-based dessert products of food category 01.7|
|03.0||Edible ices, including sherbet and sorbet|
|04.2.2||Processed vegetables (excluding frozen vegetables and fermented vegetables)|
|06.3||Breakfast cereals, including rolled oats|
|06.4.3||Pre-cooked pastas and noodles and like products|
|06.5||Cereal and starch based desserts|
|06.7||Pre-cooked or processed rice products, including rice cakes|
|06.8||Soybean products, excluding soybean-based seasonings and condiments of food category 12.9|
|11.6||Table-top sweeteners, including those containing high-intensity sweeteners|
|12.0||Salts, spices, soups, sauces, salads, protein products (excluding salts and salt substitutes and herbs and spices)|
|13.3||Dietetic foods intended for special medical purposes, excluding products of food category 13.1|
|13.4||Dietetic formulae for slimming purposes and weight reduction|
|13.5||Dietetic foods, excluding products of food categories 13.1 - 13.4 and 13.6|
|14.1.4||Water-based flavoured drinks, including "sport," "energy," or "electrolyte" drinks and particulated drinks|
|14.2||Alcoholic beverages, including alcohol-free and low-alcoholic counterparts (excluding Grape wines (14.2.3))|
|16.0||Composite foods - foods that could not be placed in categories 01 - 15|
Cabot provides information about the identity of and specifications for SAS. Cabot states that silica denotes the compound silicon dioxide, SiO2, and includes both naturally occurring and synthetic silicas. Cabot states that the physical forms of silica can be as crystalline, amorphous, and synthetic amorphous. Cabot notes that SAS is a synthetic non-crystalline form of silicon dioxide. Cabot describes SAS as a white, non-crystalline powder with a purity of greater than 95 percent by weight. Cabot notes that SAS is chemically identical to naturally occurring silicon dioxide and has the same CAS Registry No. 7631-86-9. Cabot notes that most solid SAS particles range from 0.1 to 1 micrometer and do not exist as easily dispersible nanoparticles. Cabot states that the specifications for SAS include lead (less than or equal to 5 milligrams/kilogram, (mg/kg)), and overall heavy metal content (less than 0.1 percent). Cabot’s specifications are consistent with those established by the Food Chemicals Codex 5th Edition.
Cabot describes the manufacturing processes of SAS using either a wet route for producing silica gel or precipitated silica, a thermal route for producing pyrogenic silica, or by a dispersal of SAS in a liquid to produce silica sols (colloidal silica). The wet route involves the controlled polymerization and precipitation of a sodium silicate solution to produce an amorphous SAS powder with high water content. The thermal route involves the hydrolysis of chlorosilanes in a high temperature oxygen/hydrogen flame to yield an amorphous SAS powder with low water content. The direct production of silica sols involves either the polymerization of a sodium silicate solution or the hydrolysis of silicon tetrachloride. The silica sols may be indirectly produced by the re-dispersion of SAS particles into a liquid, typically water.
Cabot intends to use SAS for its intended technical effect in the food categories listed in Table 1 at levels up to 2.0 percent (w/w), and as an indirect additive under the aforementioned intended conditions of use. Cabot states that the intended uses of SAS will not increase the dietary intake of silicon dioxide, and will not contribute to higher levels of silicon dioxide in human tissues and bones.
Cabot states that a number of organizations have evaluated the safety of both naturally occurring and synthetic forms of silicon dioxide, including SAS. Cabot cites the 1979 report of the Select Committee on GRAS Substances (SCOGS), the 2004 report of the Organization of Economic Cooperation and Development (OECD) Screening Information Data Sets program, and the 2006 report of the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC). Cabot notes SCOGS concluded that the available data demonstrated that no significant tissue accumulation, pathology, or toxicity has been reported from the ingestion of silicon compounds. Cabot states that the OECD and ECETOC documents also provide a comprehensive evaluation of the safety of multiple forms of silicon dioxide. Cabot notes that no deaths or significant toxicity were reported at doses up to 5000 mg silica/kg body weight in multiple published and unpublished acute oral toxicity studies conducted in rats. Cabot also provides detail about published repeat dose oral toxicity studies in rats and mice using hydrophilic silicas, subchronic studies where silica was administered to rats, and chronic toxicity studies where silica gel was orally administered in rats. Cabot states that the authors of these studies concluded that there were no treatment-related adverse effects and no signs of reproductive or developmental toxicity, or of carcinogenicity. Cabot concludes that the OECD and ECETOC documents confirm the overall safety assessment of the SCOGS report. Based on the conclusion of the SCOGS report, as well as the OECD and ECETOC documents, Cabot concludes there are no safety concerns.
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 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 Cabot’s notice that SAS is GRAS, through scientific procedures, for the intended uses, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing SAS. Accordingly, this response should not be construed to be a statement that foods containing SAS, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by Cabot, as well as other information available to FDA, the agency has no questions at this time regarding Cabot’s conclusion that SAS 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 SAS. As always, it is the continuing responsibility of Cabot 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 000321, 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.
Mitchell A. Cheeseman, Ph.D.
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition
1Foods from the Codex Alimentarius "Food Supplement" category would be considered dietary supplements under the Federal Food, Drug, and Cosmetic Act. The uses described in this notice involve the non-dietary ingredient component of a dietary supplement.