Dw. Potter et Ks. Wederbrand, TOTAL IGE ANTIBODY-PRODUCTION IN BALB C MICE AFTER DERMAL EXPOSURE TOCHEMICALS/, Fundamental and applied toxicology, 26(1), 1995, pp. 127-135
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.