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1,2 - 二氯乙烷与双硫仑的相互作用。I. 毒理学效应。

Interaction between 1,2-dichloroethane and disulfiram. I. Toxicologic effects.

作者信息

Igwe O J, Que Hee S S, Wagner W D

出版信息

Fundam Appl Toxicol. 1986 May;6(4):733-46. doi: 10.1016/0272-0590(86)90186-7.

DOI:10.1016/0272-0590(86)90186-7
PMID:3710039
Abstract

Inhalation and intraperitoneal (ip) studies with 1,2-dichloroethane (1,2-DCE) using Sprague-Dawley rats fed 0.15% disulfiram (tetraethylthiuram disulfide; Antabuse; DSF) in AIN-76 diet [approx. (79 +/- 11) mg DSF/kg body wt/day] resulted in the observation of a toxic interaction relative to either agent alone. The combination treatment caused testicular atrophy and histopathology in the liver and testes at 1,2-DCE inhalation concentrations greater than 300 ppm (an estimated dose of 194 mg/kg body wt/day) administered 5 days/week for 30 days or at ip doses of 150 mg 1,2-DCE/kg body wt/day over 30 days, 7 days/week. DSF lowered the 1,2-DCE dose at which liver enlargement, decreased liver/body weight ratios, and decreased body weight gains appeared relative to exposure to the 1,2-DCE alone. For the ip study, a decrease in spleen weight also occurred. Testicular atrophy and liver pathology had previously been observed in rats exposed to 20 ppm of ethylene dibromide (EDB) and fed 0.05% DSF in rat chow diet; EDB or DSF alone did not elicit testicular atrophy. These toxic effects indicate that 1,2-DCE may interact with DSF as does EDB, but at a much higher dose.

摘要

使用Sprague-Dawley大鼠进行的1,2-二氯乙烷(1,2-DCE)吸入和腹腔注射(ip)研究中,给大鼠喂食AIN-76饮食中含0.15%双硫仑(四乙基秋兰姆二硫化物;戒酒硫;DSF)[约(79±11)mg DSF/千克体重/天],结果观察到相对于单独使用任一药物存在毒性相互作用。联合治疗在1,2-DCE吸入浓度大于300 ppm(估计剂量为194 mg/千克体重/天)、每周给药5天、持续30天,或腹腔注射剂量为150 mg 1,2-DCE/千克体重/天、每周7天、持续30天时,会导致睾丸萎缩以及肝脏和睾丸出现组织病理学变化。与单独接触1,2-DCE相比,DSF降低了出现肝脏肿大、肝脏/体重比降低和体重增加减少的1,2-DCE剂量。对于腹腔注射研究,脾脏重量也出现了下降。此前在暴露于20 ppm二溴乙烷(EDB)并在大鼠饲料中喂食0.05% DSF的大鼠中观察到睾丸萎缩和肝脏病变;单独使用EDB或DSF不会引发睾丸萎缩。这些毒性作用表明,1,2-DCE可能与DSF发生相互作用,就像EDB一样,但剂量要高得多。

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引用本文的文献

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Arch Toxicol. 1989;63(6):445-9. doi: 10.1007/BF00316446.
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Elemental alterations during the exposure of 1,2-dichloroethane (EDC), disulfiram (DSF), and EDC-DSF to male Sprague-Dawley rats.1,2 - 二氯乙烷(EDC)、双硫仑(DSF)以及EDC - DSF暴露于雄性斯普拉格 - 道利大鼠期间的元素变化。
Biol Trace Elem Res. 1988 Dec;18:9-28. doi: 10.1007/BF02917485.