Agency Response Letter GRAS Notice No. GRN 000121
CFSAN/Office of Food Additive Safety
July 18, 2003
Lee B. Dexter and Assoc.
15704 Webberville Road
Austin, TX 78724
Re: GRAS Notice No. GRN 000121
Dear Ms. Dexter:
The Food and Drug Administration (FDA) is responding to the notice, dated October 1, 2002, that you submitted on behalf of Ingredients Solutions, Inc. and Zibo Zhongxuan Biological Product Co, Ltd. (Ingredients Solutions) 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 this notice on January 17, 2003, filed it on January 21, 2003, and designated it as GRN No. 000121.
The subject of the notice is xanthan gum, purified by recovery with ethyl alcohol (ethanol). The notice informs FDA of the view of Ingredients Solutions that xanthan gum purified by recovery with ethanol is GRAS, through scientific procedures, for use as an emulsifier, flavor enhancer, formulation aid, humectant, stabilizer and thickener, synergist, and texturizer in food in general at a level determined by good manufacturing practice. For the purpose of this letter, FDA refers to the xanthan gum that is the subject of GRN 000121 as "xanthan gum (ethanol precipitate)."
As part of its notice, Ingredients Solutions includes the report of a panel of individuals (Ingredients Solutions' GRAS panel) who evaluated the data and information that are the basis for Ingredients Solutions' GRAS determination. Ingredients Solutions considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Ingredients Solutions' GRAS panel discusses published reports of human consumption of xanthan gum, published reports on the purification and processing of other food ingredients with ethanol, and published reports concerning the safety and technical effects of xanthan gum and ethanol in food. Ingredients Solutions' GRAS panel concludes that xanthan gum (ethanol precipitate), meeting the specifications described in the notice and produced and used in accordance with current good manufacturing practices (cGMP), is GRAS for use as a food ingredient.
Ingredients Solutions describes xanthan gum (ethanol precipitate) as an anionic, soluble exopolysaccharide produced by fermentation of the nontoxigenic and nonpathogenic bacterium Xanthomonas campestris. It has a molecular weight of approximately 2-4 million daltons and is composed of a beta-(1-4)-D-glucose backbone with a trisaccharide side chain linked to the third carbon of every other glucose residue. The trisaccharide side chain consists of a beta-D-mannose-(1-4)-beta-D-glucuronic acid-(1-2)-alpha-D-mannose-(1-3) with approximately 50 percent of the terminal D-mannose units containing a pyruvic acid moiety as a 4,6-cyclic acetal. The non-terminal D-mannose unit is stoichiometrically substituted at O-6 with an acetyl group. Ingredients Solutions considers that these chemical properties of xanthan gum (ethanol precipitate) are consistent with the xanthan gum that is identified by the Chemical Abstract Service (CAS) Registry Number 11138-66-2.
Ingredients Solutions describes its methods for the production of xanthan gum (ethanol precipitate). Fermentation occurs in a suitable culture medium and requires agitation and temperatures of approximately 30 degrees C for several days. The production of gum in the mature culture diminishes the effects of agitation and decreases mass transfer within the fermentation vat. Patented mixing equipment is used to maintain aeration, which promotes continued production of xanthan gum. Following fermentation, the medium is thermally treated to inactivate the organism. The gum is then isolated from the bulk medium by precipitation with ethanol. The precipitate is centrifuged and the xanthan gum is dried, milled, sieved, and packaged. Ingredients Solutions discusses critical control points that are incorporated into the manufacturing process and address receipt of raw materials, mixing, sterilization, fermentation, precipitation, milling, sieving and packaging.
Ingredients Solutions describes the properties of four xanthan gum products prepared by precipitation with ethanol: ZB2, ZB3, ZBG and ZBT. These products are cream colored powders and differ in particle size, ease of dispersion and transparency. Ingredients Solutions considers that the products ZB2 and ZB3 are suitable for use in food. Ingredients Solutions provides specifications for these products, including limits on appearance, viscosity, pH, moisture, ash, particle size, pyruvic acid, lead, arsenic, other heavy metals, residual ethanol, and microbiologicals. Using its proposed use levels and data from the United States Department of Agriculture 1994-96 Continuing Survey of Food Intakes by Individuals, Ingredients Solutions estimates that the intake of xanthan gum from consumption in conventional foods would be approximately 0.7 grams per person per day (g/p/d) at the mean and approximately 1.3 g/p/d at the 90th percentile.(1)
Ingredients Solutions discusses published animal and human studies conducted with xanthan gum purified by recovery with a different solvent - i.e., isopropanol. These studies include a two year feeding study in rats and dogs, a three generation reproduction study in rats, and feeding studies of up to 23 days in humans. Ingredients Solutions states that no untoward effects were noted. Ingredients Solutions reports that chemical analyses demonstrated the equivalence of xanthan gum purified by recovery with either ethanol or isopropanol. Ingredients Solutions concludes that the physiological effects of the xanthan gum purified by recovery with ethanol would be the same as those of xanthan gum purified by recovery with isopropanol.
Ingredients Solutions notes that xanthan gum (purified by recovery with either isopropanol or ethanol) has been evaluated by the Joint Food and Agriculture Organization/World Health Organization's (FAO/WHO) Expert Committee on Food Additives (JECFA) and that JECFA has established an Acceptable Daily Intake (ADI) of "not specified."(2)
Use in Meat and Poultry Products
During its evaluation of GRN 000121, FDA consulted with the Labeling and Consumer Protection Staff of the Food Safety and Inspection Service (FSIS) of the United States Department of Agriculture (USDA). Under the Federal Meat Inspection Act and the Poultry 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 advised that it has no objection to the use of xanthan gum (ethanol precipitate) in non-standardized meat and poultry products as well as products with a standard of identity (in 9 CFR Part 319 and 381 Subpart P) that currently permit the use of xanthan gum as an ingredient in accordance with 9 CFR 424.21 (c). If, however, Ingredients Solutions has any questions about the use of xanthan gum (ethanol precipitate) in the production of meat and poultry products, they should direct such an inquiry to Dr. Robert Post, Director, Labeling and Consumer Protection Staff, Office of Policy, Program Development and Evaluation, Food Safety and Inspection Service, 1400 Independence Ave., S.W., Suite 602, Annex, Washington, DC 20250-3700. The telephone number for his office is (202) 205-0279 and the telefax number is (202) 205-3625.
Based on the information provided by Ingredients Solutions, as well as other information available to FDA, the agency has no questions at this time regarding Ingredients Solutions' conclusion that xanthan gum (ethanol precipitate) 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 xanthan gum (ethanol precipitate). As always, it is the continuing responsibility of Ingredients Solutions to ensure that food ingredients that the firm markets are safe, and are otherwise in compliance with all applicable legal and regulatory requirements.
Ingredients Solutions notes that xanthan gum is approved as a food additive for use as a stabilizer, emulsifier, thickener, suspending agent, bodying agent, and foam enhancer in foods (21 CFR 172.695). Under 21 CFR 172.695, xanthan gum is purified by recovery with isopropyl alcohol. FDA notes that xanthan gum (ethanol precipitate) does not comply with 21 CFR 172.695, because that food additive regulation describes xanthan gum as being purified by recovery with isopropyl alcohol. In order for xanthan gum (ethanol precipitate) to comply with 21 CFR 172.695, that food additive regulation would have to be amended to include purification of xanthan gum by recovery with ethyl alcohol. If Ingredient Solutions wishes to submit a food additive petition to amend 21 CFR 172.695, the firm should contact the Division of Petition Review (HFS-265), Office of Food Additive Safety, Center for Food Safety and Applied Nutrition, Food and Drug Administration, 5100 Paint Branch Parkway, College Park, MD 20740. This division can be reached by telephone at (202) 418-3035.
In accordance with proposed 21 CFR 170.36(f), a copy of the text of this letter, as well as a copy of the information in your notice that conforms to the information in proposed 21 CFR 170.36(c)(1), is available for public review and copying on the homepage of the Office of Food Additive Safety (on the Internet at http://www.cfsan.fda.gov/~lrd/foodadd.html).
Laura M. Tarantino, Ph.D.
Office of Food Additive Safety
Center for Food Safety
and Applied Nutrition
cc: Dr. Robert Post, Director
Labeling and Consumer Protection Staff
Office of Policy, Program Development and Evaluation
Food Safety and Inspection Service
1400 Independence Ave., SW, Suite 602, Annex
Washington, DC 20250-3700
(1)Ingredients Solutions also estimates that the intake of xanthan gum from additional uses in dietary supplement products could be in the range of 1.5 to 4.5 g/p/d.
(2)JECFA describes "ADI not specified" as a term applicable to a food component of very low toxicity for which the total dietary intake of the substance does not, in the opinion of the Committee, represent a hazard to health.