COMPARATIVE TOXICOKINETICS OF METHANOL IN THE FEMALE MOUSE AND RAT

The toxicokinetics of methanol in female CD-1 mice and Sprague-Dawley rats were examined to explore the possibility of species differences i n the disposition of the compound, Mice received a single dose of 2.5 g/kg methanol either po (by gavage) or iv (as a 1-min infusion), Rats received a single oral dose of 2.5 gl kg methanol, As expected, the di sposition of methanol was nonlinear in both species. Data obtained aft er iv administration of methanol to mice were well described by a one- compartment model with Michaelis-Menten elimination, Blood methanol co ncentration-time data after oral administration could be described by a one-compartment (mice) or two-compartment (rats) model with Michaeli s-Menten elimination from the central compartment and biphasic absorpt ion from the gastrointestinal tract, Kinetic parameters (V-max for eli mination, apparent volume of the central compartment [V-c], first-orde r rate constants for intercompartmental transfer [k(12) and k(21)], an d first-order absorption rate constants for fast [k(AF)] and slow [k(A S)] absorption processes) were compared between species. When normaliz ed for body weight, mice evidenced a higher maximal elimination rate t han rats (V-max = 117 +/- 3 mg/hr/kg vs 60.7 +/- 1.4 mg/hr/kg for rats ). The contribution of the fast absorption process to overall methanol absorption also was larger in the mouse than in the rat. (C) 1995 Soc iety of Toxicology.