Identification of Chemical Respiratory Allergens: Dose-Response Relationships in the Mouse IgE Test

Abstract

A mouse IgE test for the prospective identification of chemical respiratory allergens has been proposed previously. In this method, respiratory sensitizing potential is measured as a function of induced changes in the serum concentration of IgE following topical exposure of mice to the test material. In previous studies, changes in serum IgE were measured after treatment of mice with only a single concentration of chemical. The purpose of the investigations reported here was to examine dose-response relationships in the mouse IgE test with both chemical respiratory allergens and chemicals considered not to cause pulmonary hypersensitivity. The respiratory sensitizers examined were toluene diisocyanate (TDI), di-phenylmethane-4,4′-diisocyanate (MDI), hexamethylene diisocyanate (HDI), and trimellitic anhydride (TMA), all of which are known to cause occupational respiratory allergy in a proportion of exposed individuals. Results were compared with those obtained with 2,4-dinitrochlorobenzene (DNCB) and oxazolone, two contact allergens known or suspected not to cause sensitization of the respiratory tract. In each case, induced changes in serum IgE were measured under conditions of exposure, with respect to application concentrations, where all chemicals elicited positive responses in the local lymph node assay provoking lymphocyte hyperplasia in lymph nodes draining the site of treatment. In the mouse IgE test, exposure to TDI, MDI, HDI, and TMA in each instance caused a substantial dose-related increase in the serum concentration of IgE measured 14 days following the initiation of treatment. In contrast, exposure of mice to the contact allergens DNCB and oxazolone resulted in either no change in serum IgE levels (DNCB) or only a comparatively modest increase (oxazolone). These data confirm that chemical contact and respiratory allergens differ markedly with respect to the quality of immune response induced in mice and their ability to stimulate changes in the serum concentration of IgE. It is proposed that the mouse IgE test may provide a useful alternative approach to the prospective identification of chemicals that have the ability to cause sensitization of the respiratory tract.