Lung injury and delayed toxicity produced by O,S,S-trimethyl phosphorodithioate, an impurity of malathion.
O,S,S,-Trimethyl phosphorodithioate (OSS-Me), an impurity present in organophosphorus insecticides, produced morphological alteration of rat and mouse terminal nonciliated bronchiolar epithelial (Clara) cells. The effects of OSS-Me on pulmonary and hepatic microsomal enzymes were studied following its po administration to rats. Oral 28-day LD50 of OSS-Me for rats was 67 mg/kg. The animals were treated with OSS-Me at 40, 100, and 160 mg/kg and killed 24 hr later. The relative lung weights were not affected at this time. Pulmonary microsomal benzo[a]pyrene hydroxylase decreased significantly; activities were less than 36% of control at the lowest dose. In contrast, the effect of OSS-Me treatment on hepatic monooxygenase activity was moderate. Benzo[a]pyrene hydroxylase, p-nitroanisole demethylase, or 7-ethoxycoumarin deethylase were not affected by OSS-Me treatment at any dose. Pulmonary and hepatic malathion carboxylesterase activities decreased following OSS-Me treatment. The decrease was more marked in liver. Time course effects of OSS-Me treatment on these parameters were examined by treating rats at 40 mg/kg, and the animals were killed at 6, 12, 24, and 72 hr after treatment. The lung relative wet weight was increased markedly at 72 hr. The benzo[a]pyrene hydroxylase activity of pulmonary microsomes was decreased at 24 and 72 hr after treatment, the maximum decrease being observed at 72 hr. At this time, glutathione of the lungs was depleted markedly. Significant decreases were not observed in hepatic monooxygenase activities. Liver glutathione content was not reduced at 72 hr. Pulmonary and hepatic malathion carboxylesterase activities decreased throughout the time course. OSS-Me selectively inhibited benzo[a]pyrene hydroxylase activity, depleted glutathione, and caused morphological alteration of Clara cells in lungs of rats. Although the toxic mechanism(s) produced by OSS-Me remains unknown, these results support the view that the lung is a target organ of OSS-Me-induced delayed toxicity.
D000284:Administration, Oral; D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008861:Microsomes / Q000187:drug effects; D008995:Monoamine Oxidase / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D063086:Organothiophosphates / Q000633:toxicity*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013482:Superoxide Dismutase / Q000378:metabolism
D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; C033125:O,S,S-trimethyl phosphorodithioate; D001579:Benzopyrene Hydroxylase; D013482:Superoxide Dismutase; D008995:Monoamine Oxidase