TOTAL IGE ANTIBODY-PRODUCTION IN BALB C MICE AFTER DERMAL EXPOSURE TOCHEMICALS/

Chemicals that bind to protein may cause immunological responses that include respiratory hypersensitivity mediated by IgE antibodies. The B ALB/c mouse model has been used to characterize chemicals that induce an IgE antibody response. This model may be a useful predictive tool f or the evaluation and classification of chemicals that induce IgE anti body production in humans. Total serum IgE content was determined afte r dermal exposure to various concentrations of isophorone diisocyanate (IPDI), diphenylmethane-4,4'-diisocyanate (MDI), toluene diisocyanate (TDI), 2,4-dinitrochlorobenzene (DNCB), trimellitic anhydride (TMA), formaldehyde (FA), and glutaric dialdehyde (GA). Chemicals were genera lly administered in acetone:olive oil on Days 1 and 7. Mouse serum was collected 14 days after the initial administration and subsequently t otal IgE antibody content was evaluated by an enzyme-linked immunosorb ent assay. Mice treated with TMA, IPDI, MDI, and TDI had statistically (p < 0.01) higher concentrations of serum IgE antibodies than control animals. Total serum IgE content was examined at various times after TMA or TDI administration. Mice treated with a total of 37.5 mg TMA or 3 mg TDI had elevated IgE antibodies for 8-41 days after initial admi nistration. In other studies where various concentrations of TDI were administered 15 times over a 3-week period or 30 times over a 6-week p eriod, the apparent TDI threshold for IgE antibody production signific antly increased with an increase in the number of TDI applications. Th e threshold concentrations for TDI-mediated induction of IgE antibodie s were increased nearly four times with 15 doses and 6 times with 30 d oses when compared to the total amount of TDI that induced IgE antibod y production when applied in two doses. While FA did not induce an IgE antibody response, mice treated with DNCB and GA had slightly higher concentrations of serum IgE antibodies than controls. DNCB (3 mg) and GA (9.38 mg) produced a small but significant elevation in IgE. Lower concentrations of either compound showed no significant IgE response. These studies suggest that the BALB/c mouse model may be useful in ass essing whether chemicals are capable of inducing an IgE antibody respo nse. (C) Society of Toxicology.