Functional Evidence of Persistent Airway Obstruction in Rats Following a Two-Hour Inhalation Exposure to Methyl Isocyanate

摘要

Pulmonary function was assessed in male F-344 rats 1, 2, 4, 7 and 13 weeks after a single, 2 hour exposure to 0, 3, 10 or 30 ppm MIC. No significant changes were observed in the 3 ppm rats through 13 weeks. Diffusing capacity (DLco), quasi static lung compliance (Crs) and the homogeneity of ventilation as determined by multibreath nitrogen washout were depressed in the 10 and 30 ppm rats by one week postexposure. No 30 ppm rats survived beyond 1 week. By 13 weeks, the 10 ppm rats had dramatic increases in lung volumes while DLco and lung compliance were only mildly affected. Expiratory times during tidal breathing were increased, and the distribution of ventilated air was severely impaired in the group. Collectively, these results suggest the development and likely progression of a severe obstructive airway lesion with associated gas trapping, and the existence of a pronounced concentration-response relationship between 3 and 10 ppm MIC.