Nonciliated bronchiolar epithelial (Clara) cell necrosis induced by organometallic carbonyl compounds

The administration of transition metal organometallic compounds such as manganese, chromium, and iron carbonyls by the i.p. route, and nickel by inhalation (mice) or intravenously (rats), resulted in selective necrosis of the nonciliated bronchiolar epithelial (Clara) cells and variable pulmonary parenchymal damage in BALB/c mice and Fischer-derived rats within 24 h of administration. The pulmonary toxicity of methylcyclopentadienyl manganese tricarbonyl (MMT), a representative of this group of compounds, was enhanced by pretreatment with piperonyl butoxide (PB), an inhibitor of the mixed-function oxidase system. This finding suggests that Clara cell necrosis can result from direct toxicity and that the specificity of toxic agents for Clara cells may not be related solely to the presence of the mixed-function oxidase system.