[Toluene diisocyanate-induced bronchial hyperreactivity in an animal model of occupationally-induced lung diseases]

Abstract

Diisocyanates, widely used in industry for the production of polyurethanes, paints and adhesives represent a growing problem in occupational medicine. Beside toxic responses, isocyanates induce sensitization of exposed workers and may cause asthmatic reactions. To study the pathomechanisms of acute isocyanate induced lung injury, we developed an animal model using anaesthetised rabbits. Inhalation of toluene diisocyanate (TDI) in the range of threshold limit value (TLV) of 10 ppb (as well as 5 and 30 ppb) four times for a period of one hour, performed in 3 groups of 8 rabbits, did not significantly alter airway resistance (R), dynamic elastance (Edyn), slope of inspiratory pressure generation (dPoes/TI), arterial pressure (Pa) or arterial blood-gas tensions (PaO2, Pa-CO2) within time of exposure. In these experiments, before and after each TDI inhalation, unspecific airway responsiveness to 2% Acetylcholine (ACH) aerosol, inhaled for 1 minute, was measured. After 4 hours of TDI-inhalation, the amplitude of the bronchoconstrictory responses to ACH rose significantly (p < 0.005) to 3.6 times of the control value. Similar changes in the amplitude of airway resistance were measured. After inhalation of 5 ppb TDI no significant changes in airway reactivity were noticed, whereas the responses were further enhanced with 30 ppb TDI. In a control group of 8 animals, not undergoing TDI inhalation, the responses of Edyn, R and delta Pöes/TI to ACH aerosol inhalation did not significantly alter from one challenge to another.

Conclusion: Diisocyanate atmospheres of threshold limit value of 10 ppb cause bronchial hyperreactivity within 4 hours of exposure in our rabbit model of occupational lung disease.