COMPARATIVE TOXICITY OF METHYL ISOCYANATE AND ITS HYDROLYTIC DERIVATIVES IN RATS .2. PULMONARY HISTOPATHOLOGY IN THE SUBACUTE AND CHRONIC PHASES

This paper describes the long-term (subacute and chronic) histopatholo gical effects in the lungs of rats subjected to a single exposure to m ethyl isocyanate (MIC) by both the inhalation and subcutaneous (s.c.) routes as well as the role of methylamine (MA) and N,N'-dimethylurea ( DMU), the hydrolytic derivatives of MIC in eliciting the observed chan ges. At the subacute phase, the intraalveolar and interstitial edema w ere prominent only in the inhalation group as against the more pronoun ced inflammatory response in the s. c. route. With the progress of tim e the evolution of lesions appeared to be similar, culminating in the development of significant interstitial pneumonitis and fibrosis. MA, one of the hydrolytic derivatives of MIC, also caused interstitial pne umonitis progressing to fibrosis, albeit to a lesser extent than MIC, indicating its contribution to the long-term pulmonary damage. The dif fuse interstitial pulmonary fibrosis observed at 10 weeks after a sing le exposure to MIC by either route is of greater significance in the c ontext of the occurrence of pulmonary fibrosis in the late autopsies o f Bhopal gas victims and also clinical sequelae in some of the survivo rs.