Agency Response Letter GRAS Notice No. GRN 000401
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CFSAN/Office of Food Additive Safety
March 22, 2012
Robert S. McQuate, Ph.D.
GRAS Associates, LLC
20482 Jacklight Lane
Bend, OR 97702-3074
Re: GRAS Notice No. GRN 000401
Dear Dr. McQuate:
The Food and Drug Administration (FDA) is responding to the notice, dated September 9, 2011, that you submitted on behalf of O'Laughlin (Tianjin) Biotechnology Company (O'Laughlin) 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 September 13, 2011, filed it on September 28, 2011, and designated it as GRAS Notice No. GRN 000401.
The subject of the notice is erythritol produced through fermentation of glucose by Moniliella pollinis. The notice informs FDA of the view of O'Laughlin that erythritol is GRAS, through scientific procedures, for use as a flavor enhancer, formulation aid, humectant, nutritive sweetener, stabilizer and thickener, sequestrant, and texturizer in a variety of foods as described in previous submissions for food uses of erythritol (GRN 000076, GRN 000208, and GRN 000382).
As part of its notice, O'Laughlin includes the report of a panel of individuals (O'Laughlin's GRAS Panel) who evaluated the data and information that are the basis for O'Laughlin's GRAS determination. O'Laughlin considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. O'Laughlin's GRAS panel discusses identity, specifications, method of manufacture, dietary exposure, and safety of erythritol, including the history and current regulatory status of M. pollinis and erythritol in food, and concludes that erythritol is GRAS under the intended conditions of use.
O'Laughlin provides information about the chemical identity and specifications for erythritol. Erythritol is identified by CAS Registry No. 149-32-6 and the empirical formula is C4H10O4. O'Laughlin provides specifications for erythritol, including purity (> 99.5%), reducing sugars (< 0.3%), ribitol and glycerol (< 0.1%), microbial limits, and limits on lead (< 0.5 milligram per kilogram (mg/kg)).
O'Laughlin states that erythritol is manufactured through fermentation of a simple sugar solution using a pure culture of M. pollinis; this organism was also utilized in the production of erythritol for GRN 000076. Following fermentation, the culture is filtered to remove microbial cells and the resulting filtrate is decolorized with activated charcoal. The solution is then subjected to an ion exchange resin to remove inorganic salts, pigments, and organic impurities. The solution is then concentrated by vacuum evaporation, cooled, and erythritol crystals are removed by filtration. The resulting crystals are dissolved in hot water, decolorized with charcoal, and then subjected to a second crystallization step. The crystals are separated by centrifugation, dried, sifted, and then packaged.
O'Laughlin states that erythritol is GRAS under the same conditions of use as described in GRN 000076 and GRN 000208. Consequently, O'Laughlin notes that the uses of erythritol in GRN 000401 will not result in any exposure to erythritol beyond what was estimated previously.
O'Laughlin provides an updated review of the data supporting the safety of erythritol as a food ingredient, noting that erythritol has been extensively reviewed and evaluated previously, citing previous reviews that were conducted as part of GRN 000208 and GRN 000076, as well as a review conducted by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 2000. A more recent review conducted by the European Food Safety Authority was released in 2010. O'Laughlin notes that JECFA assigned an acceptable daily intake of "not specified" for erythritol.  O'Laughlin states that these reviews included reviews of published and unpublished in vivo, in vitro, and clinical data that provided no evidence of adverse toxicological effects associated with erythritol.
Standards of Identity
In the notice, O'Laughlin states its intention to use erythritol 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.
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 O'Laughlin's notice that erythritol is GRAS for the intended uses, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing erythritol. Accordingly, this response should not be construed to be a statement that foods that contain erythritol, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by O'Laughlin, as well as other information available to FDA, the agency has no questions at this time regarding O'Laughlin's conclusion that erythritol produced by M. pollinis 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 erythritol. As always, it is the continuing responsibility of O'Laughlin 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 000401, 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 at http://www.fda.gov/grasnoticeinventory.
Dennis M. Keefe, Ph.D.
Office of Food Additive Safety
Center for Food Safety
and Applied Nutrition
 Cough drops are omitted from the list of intended uses for GRN 000401.
 FDA notes that the present GRN 000401 differs from GRN 000076 by variations in the erythritol purification process and some differences in specifications.
 JECFA describes an acceptable daily intake of "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.