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An Animal Oral Exposure Model – Sensitization vs. Tolerance
Citation:
SELGRADE, M. K. AND C. BOWMAN. An Animal Oral Exposure Model – Sensitization vs. Tolerance. Presented at 2009 Annual Society of Toxicology Meeting, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
The abstract describes two complementary mouse models designed to assess potential allergenicity of genetically modified food crops.
Description:
Animal models are needed to assess novel proteins produced through biotechnology for potential dietary allergenicity. The exact characteristics that give certain foods allergenic potential are unclear, but must include both the potential to sensitize (induce IgE) as well as the capacity to avoid induction of oral tolerance (specific inhibition of IgE production). EPA has developed two complementary mouse models; one which distinguishes allergenic from non-allergenic food extracts using oral sensitization with adjuvant (cholera toxin) and another which further distinguishes highly potent allergens following oral administration without adjuvant based on the development (or not) of tolerance. For the foods tested thus far (roasted or raw peanut, Brazil nut, egg white, turkey, and spinach), the ability to sensitize and/or tolerize in these models are consistent with observed allergenicity as well as persistence and severity among allergens. In vitro studies of digestibility in simulated gastric fluid (pepsin) and simulated intestinal fluid (trypsin) have supported the notion that pepsin stability is associated with allergenicity and sensitization in the mouse model. However, both pepsin stability and trypsin stability appear required for oral tolerance induction. Of the foods tested only egg white exhibited this unique pattern of digestibility and was able to induce oral tolerance, consistent with the frequent resolution of egg white allergy in childhood. Varying the pH of the oral dosing solution altered both sensitization and tolerance induction for different foods, indicating that the material preparation or matrix in which the food is presented is an important consideration for test methods. This abstract does not reflect EPA policy.