Absorption, bioavailability, and metabolism of para-nonylphenol in the rat
Absorption, bioavailability, and metabolism of para-nonylphenol in the rat
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DOI：
10.1016/s0273-2300(03)00048-5
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发表时间：
2003-08-01
影响因子：
3.4
通讯作者：
Joiner, RL
中科院分区：
文献类型：
--
作者：
Green, T;Swain, C;Joiner, RL
为了更好地解释对-去甲苯基苯酚的反应，（NP; CASRN 84852 -15-3）在体内毒性研究（包括雌激素样活性）中，在雄性和雌性CD大鼠中测定了10和100 mg/kg单次经口给药、10 mg/kg单次静脉内给药、或每日重复经口给药10 mg/kg，持续14 d。高达80%的NP口服剂量被迅速吸收，其余以原型经粪便排泄。给药后24小时内排泄基本完成。吸收后，NP在肝脏中代谢，大部分代谢产物在胆汁中排泄，主要为葡糖苷酸结合物。仅在给予100 mg/kg剂量的雌性大鼠的胆汁和尿液中发现了原型NP，表明发生了代谢饱和。重复给药后，在7天内达到稳态。没有证据表明尿液中的组织隔室中存在显著蓄积，也没有证据表明尿液中的清除率或代谢产物谱存在显著变化。这些数据表明，在雌性大鼠口服约50 mg/kg/d或更高剂量NP的毒性研究中观察到的雌激素样作用是代谢饱和后NP生物利用度增加的结果。(C)2003 Elsevier Science（美国）。All rights reserved.
To better interpret the responses to para-nortylphenol (NP; CASRN84852-15-3) in in vivo toxicity studies, including estrogen-like activity, the bioavailability of C-14-radiolabelled NP has been determined in male and female CD rats following either single oral doses of 10 and 100 mg/kg, single i.v. doses of 10 mg/kg, or repeated daily oral doses of 10 mg/kg for up to 14 d. Up to 80% of an oral dose of NP was rapidly absorbed, the remainder being excreted unchanged in faeces. Excretion was largely complete within 24 h of dosing. Following absorption, NP was metabolised in the liver, with the majority of the metabolites excreted in bile, mainly as glucuronide conjugates. Unchanged NP was found only in bile and urine from female rats given a 100 mg/kg dose, indicating that metabolic saturation occurred. Following repeated dosing, steady state was reached within 7 d. There was no evidence of significant accumulation into tissue compartments nor of a significant change in clearance or the metabolite profiles in urine. These data suggest that the estrogen-like effects observed in toxicity studies with female rats at oral NP doses of approximately 50 mg/kg/d and greater are a result of the increased bioavailability of NP which occurs following metabolic saturation. (C) 2003 Elsevier Science (USA). All rights reserved.