Phenobarbital pretreatment protects against morphologic changes in rat bronchiolar epithelium caused by an impurity...

Oral administration (20 mg/kg) of O,O,S-trimethyl phosphorothioate (OOS) causes delayed toxicity in rats; ie, death occurs as late as 28 days after treatment. OOS-treated rats show morphologic changes in the bronchiolar epithelium of the lung; nonciliated (Clara) cells are fewer but larger 3 days after treatment. We have now found that pretreatment with the P-450-dependent mixed-function oxidase inducer, phenobarbital, protects against the morphologic changes caused by OOS. These results support the view that the lung is a target organ of the delayed toxicity caused by OOS and that OOS detoxification is mediated by P-450-dependent metabolism.