Comparative toxicity of methyl isocyanate and its hydrolytic derivatives in rats. II. Pulmonary histopathology in the subacute and chronic phases.
This paper describes the long-term (subacute and chronic) histopathological effects in the lungs of rats subjected to a single exposure to methyl isocyanate (MIC) by both the inhalation and subcutaneous (s.c.) routes as well as the role of methylamine (MA) and N,N'-dimethyl-urea (DMU), the hydrolytic derivatives of MIC in eliciting the observed changes. At the subacute phase, the intraalveolar and interstitial edema were prominent only in the inhalation group as against the more pronounced inflammatory response in the s.c. route. With the progress of time 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 pneumonitis progressing to fibrosis, albeit to a lesser extent than MIC, indicating its contribution to the long-term pulmonary damage. The diffuse interstitial pulmonary fibrosis observed at 10 weeks after a single exposure to MIC by either route is of greater significance in the context of the occurrence of pulmonary fibrosis in the late autopsies of Bhopal gas victims and also clinical sequelae in some of the survivors.
Sriramachari
S
S
Institute of Pathology, New Delhi, India.
Jeevaratnam
K
K
D000280:Administration, Inhalation; D000818:Animals; D000986:Antisickling Agents / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006868:Hydrolysis; D007279:Injections, Subcutaneous; D017953:Isocyanates / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D017563:Lung Diseases, Interstitial / Q000139:chemically induced / Q000473:pathology; D055370:Lung Injury; D008297:Male; D008744:Methylamines / Q000378:metabolism / Q000633:toxicity; D008782:Methylurea Compounds / Q000378:metabolism / Q000633:toxicity; D011654:Pulmonary Edema / Q000139:chemically induced / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000986:Antisickling Agents; D017953:Isocyanates; D008744:Methylamines; D008782:Methylurea Compounds; C027451:methylamine; C008461:methyl isocyanate; C018275:1,1-dimethylurea