The Role of Enzyme Induction on Metabolite Formation of Bis(2-Methoxyethyl) Ether in the Rat

Abstract

The effect of enzyme induction on the metabolism of the reproductive toxicant bis (2-methoxyethyl) ether (diglyme) was studied in male Sprague-Dawley rats. Rats were given either daily doses of diglyme at 5.1 mmol/kg body wt. by gavage or 0.1% (w/v)phenobarbital (PB) in the drinking water for 22 consecutive days. In one study, a significant reduction in the hexobarbital sleeping time was determined for rats pretreated with diglyme or PB in comparison with that determined for naive rats. In a second study, naive and pretreated rats given single oral doses of¹⁴C-diglyme at 5.1 mmol/kg body wt. showed similar urinary ¹⁴C excretion patterns. Urinary metabolites were separated and quantified by hplc to evaluate the influence of pretreatment with either diglyme or PB on the ¹⁴C-diglyme urinary metabolite profile. The amount of (2-methoxyethoxy) acetic acid, the principal metabolite, was similar for rats given no pretreatment and for rats pretreated with either diglyme or PB. However, both pretreatments resulted in significant increases in the formation of methoxyacetic acid, a recognized reproductive toxicant.