The effect of pretreatment of Sprague-Dawley-rats with ethanol (64175) on the metabolism of bis(2-methoxyethyl)ether (111966) (diglyme) was examined in-vivo and in isolated hepatocytes. The principal metabolite from hepatocytes and in the urine was (2- methoxyethoxy)acetic-acid (16024569) (MEAA). Other prominent metabolites included 2-(2-methoxyethoxy)ethanol (111773), methoxyacetic-acid (625456) (MAA), 2-methoxyethanol (109864) and diglycolic-acid (110996). The results of an in-vivo/in-vitro comparative metabolism study indicated that isolated rat hepatocytes in monolayer culture can be used to predict the urinary metabolites of diglyme. The urinary metabolite MEAA would best serve as a short term indicator of exposure to diglyme. The in-vitro metabolism of diglyme in hepatocytes isolated from rats pretreated with ethanol was increased over that in hepatocytes from untreated rats. Of particular significance was the induction of hepatic enzymes by ethanol which resulted in the conversion of increased amounts of diglyme to MAA, the metabolite associated with the reproductive and developmental toxicity of diglyme.
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