COMPARATIVE TOXICOKINETICS OF INHALED METHANOL IN THE FEMALE CD-1 MOUSE AND SPRAGUE-DAWLEY RAT

Female CD-1 mice were exposed for 8 hr, both individually and in group s of eight to nine, to 2500, 5000, and 10,000 ppm methanol vapor in a flowthrough exposure chamber. The ventilation of individually exposed mice and the absorption of methanol from the chamber airstream were me asured, The extraction of methanol from the airstream and the blood me thanol concentration at various time points during and following expos ure were determined for the group-exposed mice. The similarity of syst emic kinetic parameters (volume of distribution; Michaelis-Menten elim ination parameters, V-max and K-M) between inhalation exposure and iv and po routes of administration was verified. Total 8-hr ventilation d ecreased slightly with increasing exposure concentration. The fraction of inhaled methanol absorbed (0.85 +/- 0.14) did not vary statistical ly with exposure concentration. Measured ventilation, fractional absor ption, and systemic kinetic parameters were combined in a semiphysiolo gic pharmacokinetic model that yielded accurate predictions of blood m ethanol concentrations during and after an 8-hr exposure. Model predic tions for the mouse were compared to a previously developed inhalation toxicokinetic model for the rat. The comparison demonstrated that at similar methanol vapor concentrations, mice evidenced a two- to threef old higher blood methanol concentration than rats, despite the fact th at the apparent V-max for methanol elimination in the mouse is twofold larger than that in the rat. These data may have significant implicat ions in understanding species differences in methanol-induced teratoge nic effects. (C) 1995 Society of Toxicology