Hasegawa J, Wada Y, Sageshima M, Suzuki M, Kamiyama S, Abe N, Koizumi A
Department of Anesthesiology, Akita University School of Medicine, Japan.
Pharmacol Toxicol. 1990 May;66(5):367-72. doi: 10.1111/j.1600-0773.1990.tb00764.x.
The structure-pulmonary toxicity relationship was investigated using three different O,O,S-trimethylphosphorothioate (OOS-TMP) analogues, which is known to induce a typical mortality pattern (delayed death) and pulmonary injury; O,O-dimethyl S-ethyl (OOS-DMEP), O,O-dimethyl S-propyl (OOS-DMPP), and O,O-dimethyl S-butyl (OOS-DMBP) phosphorothioates. The mortality pattern in rats dosed with OOS-DMEP was similar to the "delayed death" pattern: the LD50s in rats for OOS-DMEP decreased dramatically from more than 200 mg/kg within 24 hr to 41.1 (males) or 13.8 (females) mg/kg 7 days after treatment while the LD50s in rats for OOS-DMPP and OOS-DMBP did not. Histopathological examinations revealed that OOS-DMEP induced pulmonary oedema and bleeding at a dose of 1/2 LD50 by 72 hr after dosing while the other two compounds did not. Thus, it was concluded that OOS-DMEP induces pulmonary injury, thereby eliciting the "delayed death" mortality pattern.
使用三种不同的O,O,S-三甲基硫代磷酸酯（OOS-TMP）类似物研究了结构与肺毒性之间的关系，已知该类似物会引发典型的死亡模式（延迟死亡）和肺损伤；O,O-二甲基S-乙基（OOS-DMEP）、O,O-二甲基S-丙基（OOS-DMPP）和O,O-二甲基S-丁基（OOS-DMBP）硫代磷酸酯。用OOS-DMEP给药的大鼠的死亡模式与“延迟死亡”模式相似：OOS-DMEP在大鼠中的半数致死剂量（LD50）在24小时内从超过200毫克/千克急剧下降到治疗7天后的41.1（雄性）或13.8（雌性）毫克/千克，而OOS-DMPP和OOS-DMBP在大鼠中的LD50则没有。组织病理学检查显示，OOS-DMEP在给药72小时后以1/2 LD50的剂量诱导肺水肿和出血，而其他两种化合物则没有。因此，得出结论，OOS-DMEP会诱导肺损伤，从而引发“延迟死亡”的死亡模式。
