Concentration-dependent immunologic response to toluene diisocyanate (TDI) following inhalation exposure

Little is known concerning industrial exposure conditions which lead to development of allergic sensitivity in exposed workers. This study investigated the relationship between exposure concentration and the induction of antibodies and sensitivity in a guinea pig animal model for inhalation exposure to isocyanates (Karol et al., Toxicol. Appl. Pharmacol. 53, 260-270, 1980). Groups of guinea pigs were exposed, via inhalation, to TDI concentrations ranging from 0.12 to 10 ppm. Exposure was for 3 hr/day on 5 consecutive days. Beginning on Day 22, animals were evaluated for TDI-specific antibodies, skin sensitivity, and pulmonary sensitivity to TDI. No antibodies were detected in animals exposed to 0.12 ppm TDI, whereas 55% of animals exposed to 0.36 ppm TDI or greater displayed TDI-specific antibodies in their sera. Exposure to higher TDI concentrations resulted in both a greater percentage of animals producing antibodies and higher antibody titers. Pulmonary sensitivity, assessed by bronchial provocation challenge with TDI-protein antigen, was not detected in animals exposed to 0.12 ppm TDI but was present in guinea pigs exposed to TDI concentrations of 0.36 ppm or greater. However, exposure concentrations higher than 2 ppm were pneumotoxic and resulted in few pulmonary hypersensitivity reactions. Exposure of animals to 0.02 ppm TDI for 15 weeks did not result in either dermal sensitivity, pulmonary sensitivity, or production of TDI-specific antibody. The exposure protocol, as well as the exposure concentration, was important for establishment of sensitivity. Recognition of the concentration-response relationship governing immune reaction to inhaled TDI should permit establishment of safe airborne exposure levels for industrial workers to prevent sensitization.