Keadtisuke S, Dheranetra W, Nakatsugawa T, Fukuto T R
Department of Entomology, University of California, Riverside.
Toxicol Lett. 1990 Jun;52(1):35-46. doi: 10.1016/0378-4274(90)90163-g.
Administration of a single oral dose of the malathion impurity, O,O,S-trimethyl phosphorothioate (OOS-Me) or O,S,S-trimethyl phosphorodithioate (OSS-Me), to the rat resulted in hemostatic disorders, e.g. prolongation of blood clotting, prothrombin and thrombin time. Deficiency of coagulation Factors II, V and VII was also observed. OOS-Me and OSS-Me also caused dose-dependent increases of beta-glucuronidase in the blood with a maximum of 15- and 31-fold observed following treatment with 60 mg/kg OOS-Me and 40 mg/kg OSS-Me, respectively. Analysis of serum beta-glucuronidase by isoelectrofocusing electrophoresis showed that the liver endoplasmic reticulum was the source of this enzyme released into the blood. Co-treatment of OOS-Me with 5% O,O,O-trimethyl phosphorothioate (OOO-Me), a potent antagonist of OOS-Me-induced delayed toxicity, prevented hemostatic disorders but had no effect in reducing beta-glucuronidase levels. However, pretreatment of rats with piperonyl butoxide reduced the amount of beta-glucuronidase released into the blood. Of other O,O,S-trialkyl phosphorothioates examined, the O,O-diethyl S-alkyl phosphorothioates showed the highest activity in increasing beta-glucuronidase levels.
给大鼠单次口服马拉硫磷杂质O,O,S-三甲基硫代磷酸酯（OOS-Me）或O,S,S-三甲基二硫代磷酸酯（OSS-Me）会导致止血障碍，例如凝血时间、凝血酶原时间和凝血酶时间延长。还观察到凝血因子II、V和VII缺乏。OOS-Me和OSS-Me还导致血液中β-葡萄糖醛酸酶剂量依赖性增加，分别用60 mg/kg OOS-Me和40 mg/kg OSS-Me处理后，最高分别观察到增加15倍和31倍。通过等电聚焦电泳分析血清β-葡萄糖醛酸酶表明，肝脏内质网是释放到血液中的这种酶的来源。OOS-Me与5%的O,O,O-三甲基硫代磷酸酯（OOO-Me）共同处理，OOO-Me是OOS-Me诱导的延迟毒性的有效拮抗剂，可预防止血障碍，但对降低β-葡萄糖醛酸酶水平没有作用。然而，用胡椒基丁醚预处理大鼠可减少释放到血液中的β-葡萄糖醛酸酶量。在所检测的其他O,O,S-三烷基硫代磷酸酯中，O,O-二乙基S-烷基硫代磷酸酯在增加β-葡萄糖醛酸酶水平方面表现出最高活性。
