Ra. Perkins et al., COMPARATIVE TOXICOKINETICS OF INHALED METHANOL IN THE FEMALE CD-1 MOUSE AND SPRAGUE-DAWLEY RAT, Fundamental and applied toxicology, 28(2), 1995, pp. 245-254
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