Morphological alterations of rat lung bronchiolar epithelium produced by various trialkyl phosphorothioates.

A single oral administration of O, O, S-trimethyl phosphorothioate (OOS-Me), an impurity in widely used organophosphorus insecticides, causes delayed toxicity (delayed death) which is accompanied by morphological changes in the bronchiolar epithelium of rat lungs. A series of simple O,O-dimethyl and O,O-diethyl S-alkyl phosphorothioate esters, which induce delayed toxicity, were examined for their effect on rat bronchiolar epithelium. The structural analogues synthesized and tested include O, O-dimethyl S-ethyl phosphorothioate, O,O-dimethyl S-isopropyl phosphorothioate, O,O,S-triethyl phosphorothioate, and O,O-diethyl S-methyl phosphorothioate. The present investigation demonstrated that these analogues of OOS-Me which cause delayed toxicity produce body weight loss, accompanied by morphological alterations of terminal bronchiolar epithelium, i.e. loss of the apical bulge of non-ciliated Clara cells. Another impurity which produces delayed toxicity, O,S,S-trimethyl phosphorodithioate, was also capable of producing similar effects at near the LD50 level.