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ToxSci Advance Access published online on November 21, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm288
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Published by Oxford University Press 2007.

Differences in Allergenic Potential of Food Extracts Following Oral Exposure in Mice Reflect Differences in Digestibility: Potential Approaches to Safety Assessment

Christal C. Bowman and MaryJane K. Selgrade

Immunotoxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

Corresponding Author:Christal C. Bowman, US EPA/NHEERL, 109 T W Alexander Drive, MD B143-01, Research Triangle Park, NC 27711, e-mail: bowman.christal{at}epa.gov, phone: (919) 541-0152, fax: (919) 541-4284

Received September 25, 2007; revision received November 15, 2007; accepted November 18, 2007


  Abstract

An animal model for food allergy is needed to assess genetically modified food crops for potential allergenicity. The ideal model must produce allergic antibody (IgE) to proteins differentially according to known allergenicity before being used to accurately identify potential allergens among novel proteins. The oral route is the most relevant for exposure to food antigens, and a protein's stability to digestion is a current risk assessment tool based on this natural route. However, normal laboratory animals do not mount allergic responses to proteins administered orally due to oral tolerance, an immunologic mechanism which specifically suppresses IgE. To circumvent oral tolerance and evoke differential IgE responses to a panel of allergenic and non-allergenic food extracts, female C3H/HeJ mice were exposed subcutaneously or orally with cholera toxin as an adjuvant. All foods elicited IgE by the subcutaneous route. Oral exposure, however, resulted in IgE to allergens (peanut, Brazil nut, and egg white) but not to non-allergens (spinach and turkey), provided that the dose and exposures were limited. Additionally, in vitro digestibility assays demonstrated the presence of digestion-stable proteins in the allergenic food extracts but not in the non-allergenic foods. Our results suggest that the subcutaneous route is inadequate to distinguish allergens from non-allergens, but oral exposure under the appropriate experimental conditions will result in differential allergic responses in accordance with known allergenicity. Moreover, those foods containing digestion resistant proteins provoke allergic responses in this model, supporting the current use of pepsin resistance in the decision tree for potential allergenicity assessment.

Key Words: allergenicity; food allergy; biotechnology.


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