Kao L R, Birnbaum L S
J Toxicol Environ Health. 1986;18(3):441-58. doi: 10.1080/15287398609530884.
The disposition and metabolism of o-benzyl-p-chlorophenol (BCP) were studied in male Fischer-344 rats. Three days after oral administration of [14C]BCP at 10, 100, or 1000 mg/kg, more than 90% of each dose was excreted in urine and feces. Comparison of disposition after intravenous, dermal, or oral administration indicated that BCP was not completely absorbed from the gastrointestinal tract or skin. Biliary excretion of BCP was dose-dependent, with proportionally less BCP-derived radioactivity being excreted in the bile as the dose was raised. The results also indicated that enterohepatic circulation was involved in BCP disposition. The major in vivo metabolites were glucuronyl conjugates of BCP and hydroxy-BCP. Glutathione conjugates were also present in urine. In vitro metabolism studies support the observation that microsomal oxidation and glutathione and glucuronyl conjugation play major roles in BCP metabolism. Spleen, kidney, and liver contained the highest tissue concentrations of BCP-derived radioactivity. The presence of more nonextractable BCP-derived radioactivity in kidney than in liver is compatible with the hypothesis that covalent binding of BCP to renal tissue may be associated with BCP-induced nephrotoxicity.
在雄性Fischer-344大鼠中研究了邻苄基对氯苯酚（BCP）的处置和代谢情况。以10、100或1000mg/kg的剂量口服给予[14C]BCP三天后，各剂量的90%以上通过尿液和粪便排出。静脉注射、经皮给药或口服给药后处置情况的比较表明，BCP不能从胃肠道或皮肤完全吸收。BCP的胆汁排泄呈剂量依赖性，随着剂量增加，胆汁中BCP衍生的放射性比例相应减少。结果还表明，肝肠循环参与了BCP的处置。主要的体内代谢产物是BCP和羟基BCP的葡糖醛酸共轭物。尿液中也存在谷胱甘肽共轭物。体外代谢研究支持了微粒体氧化以及谷胱甘肽和葡糖醛酸共轭作用在BCP代谢中起主要作用的观察结果。脾脏、肾脏和肝脏中BCP衍生的放射性组织浓度最高。肾脏中比肝脏中存在更多不可提取的BCP衍生放射性，这与BCP与肾组织的共价结合可能与BCP诱导的肾毒性有关的假设相符。
