Effect of drug metabolism inducer and inhibitor on O,O,S-trimethyl phosphorothioate-induced delayed toxicity in rats.

Abstract:

:Oral administration of O,O,S-trimethyl phosphorothioate (OOS), an impurity present in widely used organophosphorus insecticides, causes delayed toxicity in rats, i.e., death occurring as late as 28 days after the treatment. The signs of toxicity include body weight loss (maximum on day 3), red staining around the nose, mouth and eyes, and an increased level of lactate dehydrogenase (LDH) in bronchopulmonary lavage fluid accompanied by morphological alteration of non-ciliated bronchiolar epithelial Clara cells. Pretreatment with phenobarbital, piperonyl butoxide (2 h), SKF 525-A, or small multiple doses of OOS protected against the OOS-induced elevated level of bronchopulmonary lavage LDH, and the other signs of delayed toxicity including morphological alteration of Clara cells. These studies support the view that OOS-induced delayed toxicity is mediated by the cytochrome P-450 dependent metabolism of OOS, and the lung may be the major target organ of delayed toxicity produced by OOS.

journal_name

Chem Biol Interact

authors

Imamura T,Hasegawa L,Gandy J,Fukuto TR

doi

10.1016/0009-2797(83)90042-x

subject

Has Abstract

pub_date

1983-07-01 00:00:00

pages

53-64

issue

1

eissn

0009-2797

issn

1872-7786

pii

0009-2797(83)90042-X

journal_volume

45

pub_type

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