METABOLISM AND DISPOSITION OF ETHYLENE-GLYCOL MONOBUTYL ETHER (2-BUTOXYETHANOL) IN RATS

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  • 1 July 1987
    • journal article
    • research article
    • Vol. 15  (4) , 478-484
Abstract
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 gravage 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 adminsitered 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). The opposite was true in the bile, where the major biliary metabolite was BEG followed by BAA. A small quantity of the radioactivity excreted in the urine of rats treated with the low dose of Be was the sulfate conjugate of BE (BES); however, no BES was detected in the urine of rats treated with the high dose of BE. In summary, the following metabolic pathways of BE are identified: (a) oxidation of BE to BAA, (b) conjugation of BE with UDP-glucuronic acid, and (c) conjugation of BE with the sulfate.