An animal model for pulmonary hypersensitivity to airborne industrial chemicals is being developed. Repeated inhalation exposure of guinea pigs to toluene diisocyanate (TDI) has resulted in production of pulmonary hypersensitivity. The response has been detected by bronchial provocation challenge (BPC) with aerosols of TDI-protein conjugates and measurement of respiratory response during challenge. To improve simulation of industrial conditions, further development of the animal model will be directed toward BPC with the reactive chemical followed by continuous 24 hr measurement of respiratory reactivity. Concentration-response studies will permit assessment of pulmonary sensitizing potency. To allow prediction of safe industrial exposure levels, the animal model will be calibrated to man. Sensitization of animals will be attempted using chemical for which exposures causing human sensitivity have been documented (i.e., plicatic acid, diphenylmethane diisocyanate, subtilisin). Long-term effects of repeated episodes of respiratory hypersensitivity reactions on pulmonary function will be assessed. Resistance of sensitized guinea pigs will be evaluated using the CO2 challenge method. In order to propose a diagnostic method for early detection of developing hypersensitivity, the immunologic nature of the respiratory hypersensitivity induced by inhalation exposure will be characterized. Sera and lung lavage will be evaluated for antibodies and antigen-specific lymphocytes. In addition, animals will be tested for development of dermal sensitivity resulting from inhalation sensitization. In this way, factors associated with developing hypersensitivity reactions will be identified.
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