Ghanayem B I, Burka L T, Sanders J M, Matthews H B
National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, NC 27709.
Drug Metab Dispos. 1987 Jul-Aug;15(4):478-84.
Ethylene glycol monobutyl ether (2-butoxyethanol, BE) is a major industrial chemical with multiple and diverse uses that may result in significant risk of human exposure and environmental contamination. The current studies were undertaken to investigate the metabolism and disposition of this chemical in male F344 rats. Data presented in this report showed that BE is rapidly absorbed after gavage administration, metabolized, and eliminated. Tissue distribution of BE revealed that BE is distributed to all tissues with the highest levels (determined 48 hr after dosing) detected in the forestomach followed by the liver, kidney, spleen, and the glandular stomach. However, the increase in the tissue concentration in rats treated with 500 mg/kg (as compared to that in rats treated with 125 mg/kg BE) was not proportional to the increase in BE dose. The major route of BE elimination was in the urine, followed by 14CO2 exhalation. The portion of the BE dose eliminated in urine or as 14CO2 was significantly higher in rats treated with 125 mg/kg than in the rats treated with 500 mg/kg. This may indicate that saturation of BE-metabolizing enzymes occurs at the high dose. A small portion (8%) of the administered dose (500 mg/kg) was excreted in the bile in 8 hr after dosing. Qualitative and quantitative HPLC analysis of the urinary and biliary metabolites of BE revealed that the major urinary metabolite, butoxyacetic acid (BAA), accounted for more than 75% of the radioactivity excreted in the urine. The second major metabolite in urine was the glucuronide conjugate of BE (BEG).(ABSTRACT TRUNCATED AT 250 WORDS)
乙二醇单丁醚(2-丁氧基乙醇,BE)是一种主要的工业化学品,用途广泛多样,这可能导致人类接触和环境污染的重大风险。当前的研究旨在调查这种化学品在雄性F344大鼠体内的代谢和处置情况。本报告中的数据表明,灌胃给药后BE迅速被吸收、代谢并消除。BE的组织分布显示,BE分布于所有组织,给药后48小时检测到前胃中含量最高,其次是肝脏、肾脏、脾脏和腺胃。然而,用500mg/kg处理的大鼠组织浓度增加(与用125mg/kg BE处理的大鼠相比)与BE剂量的增加不成比例。BE消除的主要途径是通过尿液,其次是呼出14CO2。用125mg/kg处理的大鼠尿液或作为14CO2消除的BE剂量部分明显高于用500mg/kg处理的大鼠。这可能表明高剂量时BE代谢酶发生了饱和。给药剂量(500mg/kg)的一小部分(8%)在给药后8小时经胆汁排出。对BE的尿液和胆汁代谢物进行的定性和定量HPLC分析表明,主要的尿液代谢物丁氧基乙酸(BAA)占尿液中排出放射性的75%以上。尿液中的第二大主要代谢物是BE的葡萄糖醛酸共轭物(BEG)。(摘要截短至250字)