Sequential and dose-dependent alterations in rat bronchiolar epithelium during O,O,S-trimethyl phosphorothioate induced delayed toxicity.

The sequential and dose-dependent effects of O,O,S-trimethyl phosphorothioate (OOS-Me) on rat lung bronchiolar epithelium were investigated using scanning electron microscopy. At 12 h after oral treatment (20 mg/kg), there was a small increase in debris in the bronchioles and, by 24 h, there was much debris as well as phagocytic cells in the bronchioles. After 3 days, there was a decrease in the number of bronchiolar Clara cells as determined by the loss of their characteristic apical bulges. Concomitantly, there was a significant increase in lactate dehydrogenase activity in bronchopulmonary lavage fluid. By day 7, the Clara cells appeared to be reforming and, by day 14, the morphology of bronchiolar epithelium had returned to normal. Dose-dependent studies revealed a threshold dose level of OOS-Me between 10 and 20 mg/kg which produced the observed effects in Clara cells. Both sequential and dose-dependent effects of OOS-Me on Clara cells were correlated with changes in bronchopulmonary lavage lactate dehydrogenase activity.