Comparative toxicokinetics of methanol in pregnant and nonpregnant rodents

Methanol toxicokinetics were examined in pregnant Sprague-Dawley rats and CD-1 mice to explore the possibility of gestational-associated alterations in metabolism and disposition. In vitro biotransformation of methanol in rat and mouse fetal livers also was examined to assess the capability of the near-term rodent fetus to metabolize methanol. In the in vivo studies, rats received a single dose (100 or 2,500 mg/kg) of methanol either orally (by gavage) or intravenously; mice received a single oral or intravenous 2500-mg/kg dose. The maximal rate of methanol elimination (V(max)) in vivo decreased at term in both rodent species; V(max) in near- term rats and mice was only 65-80% of that in nonpregnant animals. Gestation also affected intercompartmental transfer rate constants, although there was no obvious relationship between these changes and gestational stage. In vitro metabolism studies supported the in vivo data; adult near-term rodent livers metabolized methanol with a V(max) of 85% that in livers from nonpregnant rodents (p < 0.05). Fetal rodent liver was capable of metabolizing methanol in vitro, but only at a rate <5% of respective adult livers. Data generated in these experiments demonstrate that alterations in methanol disposition associated with gestational stage must be accounted for in the development of a toxicokinetic model for methanol in pregnant mammals.