Evaluation of a mouse model of food allergy for determination of threshold oral elicitation doses (P6224)

Abstract

Abstract Food allergies are a significant public health problem because they trigger life-threatening systemic allergic reactions. We have previously reported a novel mouse model that uses transdermal exposure (TDE) to nut protein for sensitization followed by oral challenge (OC) to elicit systemic reactions. Here we evaluated the utility of this model to determine the oral threshold doses for hazelnut (HN). Groups of mice (n=8-10/group) were sensitized with 2, 3, 4 or 5 TDE to HN or saline, followed by OC with HN to induce systemic anaphylaxis. The data demonstrated that a minimum of 4 TDE to HN and a definition of >/=1 o C drop in rectal temperature (RT) at 30 minutes post OC, ensures 100% positive responses and <10% false positive responses. We then evaluated threshold oral elicitation doses in three scenarios: (1) homogeneous 4 TDE to allergen, followed by repeated OC with different doses of HN at weekly intervals; 2) homogeneous 4 TDE to allergen, followed by single OC per dose per group; and 3) heterogeneous (i.e., 4, 5 or 6) TDE with HN followed by single/repeated OC to simulate the human exposure conditions that are generally heterogeneous. The percent responder curves were established for each case and the NOAEL and LOAEL (25 and 50% responses) were estimated. The NOAELs were </=125 mg/Kg; the 25% response LOAELs ranged from 270-312 mg/Kg; and the 50% response LOAELs ranged from 362-412 mg/Kg.