Allergic hypersensitivity to the insecticide malathion in BALB/c mice

The widely used insecticide malathion (diethylmercaptosuccinate, S ester with O,O-dimethylphosphorodithioate) has been reported to cause allergic responses in some exposed people and in guinea pigs. In this study, IgE antibody-mediated and cell-mediated hypersensitivity to malathion was evaluated in female BALB/c mice. To elicit malathion-specific antibodies of the IgE class, a conjugate of the anhydride of the diacid metabolite of malathion (MMA) with keyhole limpet hemocyanin was administered ip with aluminum hydroxide as adjuvant. Sera collected following three sequential sensitizations were tested for specific IgE with the passive cutaneous anaphylaxis (PCA) test in Sprague-Dawley rats. MMA coupled to bovine serum albumin was used as the challenge antigen. Specific IgE was produced following the second and third sensitization in the mice receiving 10 and 100 micrograms of conjugate and following the third sensitization in the mice receiving 1 microgram of conjugate. A paper radioallergosorbent test (PRAST) was as sensitive as and showed a good correlation with the PCA assay for samples analyzed by both procedures. Malathion applied epicutaneously on 2 days or over 4 weeks failed to elicit delayed-type hypersensitivity as determined by change in ear thickness, 5-[125I]iodo-2'-deoxyuridine incorporation in the ear, and histology of the ear following ear challenge, with or without pretreatment of the mice with cyclophosphamide. MMA-specific IgE antibodies were not detected by the PCA test in the serum of mice treated epicutaneously for 4 weeks.