Immunotoxicologic evaluation of the respiratory system: animal models for immediate- and delayed-onset pulmonary...

A wide variety of industrial materials is known to cause allergic pulmonary reactions. Respiratory symptoms may occur either immediately upon exposure to the agent (immediate-onset response), or several hours later (delayed-onset reaction). In order to determine both the mechanism of response, and a safe exposure level which would prevent development of pulmonary sensitization, animal models are currently being developed for both types of sensitivity responses. In the models, emphasis is placed on simulating conditions present in the industrial environment. For example, (1) exposure to agents is via the inhalation route, (2) animals are unrestrained and unanesthetized both during exposure and during elicitation of response, and (3) reactive chemicals, as opposed to hapten-protein conjugates, are used for exposure. In the model for immediate-onset sensitivity, concentration-response relationships have been observed between the concentration of agent inhaled and the percentage of animals becoming sensitized. Agents employed were bacterial subtilisin and toluene diisocyanate. Identification of "no observable effect" threshold concentrations implies that exposure levels can be proposed for industrial chemicals which will not result in sensitization of workers. Further development of the animal models, followed by calibration of the models to humans, should allow immunotoxicologic evaluation of chemicals for their respiratory sensitizing ability and recommendation of threshold-limit values (TLVs) which would prevent sensitization.