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2',2''-二硫代双苯甲酰胺经静脉注射、口服及皮肤给药后在啮齿动物体内的处置与代谢

Disposition and metabolism of 2',2'"-Dithiobisbenzanilide in rodents following intravenous and oral administration and dermal application.

作者信息

Garner C Edwin, Wegerski Christopher J, Doyle-Eisele Melanie, McDonald Jacob D, Sanders J Michael, Moeller Benjamin C, Waidyanatha Suramya

机构信息

Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.

Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.

出版信息

Toxicol Rep. 2020 Jul 23;7:883-892. doi: 10.1016/j.toxrep.2020.07.006. eCollection 2020.

Abstract

2',2'''-Dithiobisbenzanilide (DTBBA) is a high-production-volume chemical used as a peptizing agent for rubber. The disposition and metabolism of [C]DTBBA were determined in male and female rats and mice following oral (4, 40, or 400 mg/kg) and intravenous (IV) (4 mg/kg) administration and dermal application (0.4 or 4 mg/kg). [C]DTBBA was well absorbed following oral administration (> 60%) and dermal application (∼40-50%) in rats and mice. Following oral administration, the majority of radioactivity was excreted in urine (29 - 70%) and feces (16 - 45%). Unlike rats, mice excreted ∼1-5% of the dose as exhaled CO. The residual radioactivity in tissues was <1% in both species and sexes. The pattern of disposition following IV administration in male rats was similar to that following oral. When [C]DTBBA was administered via IV to rats, a significant portion of the dose was recovered in bile (∼13%) suggesting that at least a portion of the dose recovered in feces following oral administration was likely the absorbed dose. The profiles of urine from rats and mice were similar and consisted of four major metabolites and three minor metabolites. The predominant metabolite in urine was the -glucuronide of the thiol/sulfide cleavage product -(2-mercaptophenyl)benzamide, which accounted for more than 50% of radioactivity in the radiochromatogram.

摘要

2',2'''-二硫代双苯甲酰胺(DTBBA)是一种高产量化学品,用作橡胶的胶溶剂。在雄性和雌性大鼠及小鼠经口(4、40或400mg/kg)、静脉注射(IV)(4mg/kg)给药以及皮肤涂抹(0.4或4mg/kg)后,测定了[C]DTBBA的处置和代谢情况。在大鼠和小鼠中,经口给药(>60%)和皮肤涂抹(约40 - 50%)后,[C]DTBBA吸收良好。经口给药后,大部分放射性物质通过尿液(29 - 70%)和粪便(16 - 45%)排出。与大鼠不同,小鼠呼出的CO排出约1 - 5%的剂量。两种物种和性别的组织中残留放射性均<1%。雄性大鼠静脉注射后的处置模式与经口给药后的相似。当[C]DTBBA经静脉注射给大鼠时,很大一部分剂量在胆汁中回收(约13%),这表明经口给药后在粪便中回收的至少一部分剂量可能是吸收的剂量。大鼠和小鼠的尿液图谱相似,由四种主要代谢物和三种次要代谢物组成。尿液中的主要代谢物是硫醇/硫化物裂解产物-(2-巯基苯基)苯甲酰胺的葡萄糖醛酸苷,其在放射色谱图中占放射性的50%以上。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eeff/7390853/9c169d965fc8/gr1.jpg

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