Immunotoxicologic Evaluation of the Respiratory System: Animal Models for Immediate- and Delayed-Onset Pulmonary Hypersensitivity

Immunotoxicologic Evaluation of the Respiratory System: AnimalModels for Immediate-and Delayed-Onset Pulmonary Hypersensitivity.KAROL, M. H., STADLER, J. C, AND MAGRENI, C. M. (1985). Fundam.Appl. Toxicol. 5, 459–472. A wide variety of industrialmaterials is known to cause allergic pulmonary reactions. Respiratorysymptoms may occur either immediately upon exposure to the agent(immediate-onset response), or several hours later (delayed-onsetreaction). In order to determine both the mechanism of response,and a safe exposure level which would prevent development ofpulmonary sensitization, animal models are currently being developedfor both types of sensitivity responses. In the models, emphasisis placed on simulating conditions present in the industrialenvironment. For example, (1) exposure to agents is via theinhalation route, (2) animals are unrestrained and unanesthetizedboth 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 betweenthe concentration of agent inhaled and the percentage of animalsbecoming sensitized. Agents employed were bacterial subtilisinand toluene diisocyanate. Identification of "no observable effect"threshold concentrations implies that exposure levels can beproposed for industrial chemicals which will not result in sensitizationof workers. Further development of the animal models, followedby calibration of the models to humans, should allow immunotoxicologicevaluation of chemicals for their respiratory sensitizing abilityand recommendation of threshold-limit values (TLVs) which wouldprevent Sensitization