Konno N, Fukuto T R, Imamura T
Toxicol Appl Pharmacol. 1984 Sep 15;75(2):219-28. doi: 10.1016/0041-008x(84)90204-7.
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.
O,S,S-三甲基二硫代磷酸酯（OSS-Me）是有机磷杀虫剂中的一种杂质，可引起大鼠和小鼠终末无纤毛细支气管上皮（克拉拉）细胞的形态改变。在给大鼠口服OSS-Me后，研究了其对肺和肝微粒体酶的影响。OSS-Me对大鼠的口服28天半数致死量为67毫克/千克。给动物分别以40、100和160毫克/千克的剂量服用OSS-Me，24小时后处死。此时相对肺重量未受影响。肺微粒体苯并[a]芘羟化酶显著降低；最低剂量时活性低于对照组的36%。相比之下，OSS-Me处理对肝单加氧酶活性的影响适中。任何剂量的OSS-Me处理均未影响苯并[a]芘羟化酶、对硝基苯甲醚脱甲基酶或7-乙氧基香豆素脱乙基酶的活性。OSS-Me处理后肺和肝马拉硫磷羧酸酯酶活性降低。肝脏中的降低更为明显。通过以40毫克/千克的剂量处理大鼠来研究OSS-Me处理对这些参数的时间进程影响，并在处理后6、12、24和72小时处死动物。72小时时肺相对湿重显著增加。处理后24和72小时肺微粒体的苯并[a]芘羟化酶活性降低，72小时时降幅最大。此时，肺中的谷胱甘肽显著耗竭。肝单加氧酶活性未观察到显著降低。72小时时肝脏谷胱甘肽含量未降低。整个时间进程中肺和肝马拉硫磷羧酸酯酶活性均降低。OSS-Me选择性抑制苯并[a]芘羟化酶活性，耗竭谷胱甘肽，并导致大鼠肺中克拉拉细胞的形态改变。尽管OSS-Me产生的毒性机制尚不清楚，但这些结果支持肺是OSS-Me诱导的迟发性毒性的靶器官这一观点。
