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 alt erations 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 t he in vivo studies, rats received a single dose (100 or 2,500 mg/kg) o f methanol either orally (by gavage) or intravenously; mice received a single oral or intravenous 2500-mg/kg dose. The maximal rate of metha nol elimination (V-max) in vivo decreased at term in both rodent speci es; V-max in near-term rats and mice was only 65-80% of that in nonpre gnant animals, Gestation also affected intercompartmental transfer rat e constants, although there was no obvious relationship between these changes and gestational stage. In vitro metabolism studies supported t he in vivo data; adult near-term rodent livers metabolized methanol wi th a V-max of similar to 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 generat ed in these experiments demonstrate that alterations in methanol dispo sition associated with gestational stage must be accounted for in the development of a toxicokinetic model for methanol in pregnant mammals.