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 groups 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 measured. The extraction of methanol from the airstream and the blood methanol concentration at various time points during and following exposure were determined for the group-exposed mice. The similarity of systemic kinetic parameters (volume of distribution; Michaelis-Menten elimination parameters, Vmax and KM) between inhalation exposure and iv and po routes of administration was verified. Total 8-hr ventilation decreased slightly with increasing exposure concentration. The fraction of inhaled methanol absorbed (0.85 +/- 0.14) did not vary statistically with exposure concentration. Measured ventilation, fractional absorption, and systemic kinetic parameters were combined in a semiphysiologic pharmacokinetic model that yielded accurate predictions of blood methanol concentrations during and after an 8-hr exposure. Model predictions 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 threefold higher blood methanol concentration than rats, despite the fact that the apparent Vmax for methanol elimination in the mouse is twofold larger than that in the rat. These data may have significant implications in understanding species differences in methanol-induced teratogenic effects.
Perkins
R A
RA
School of Medicine, University of North Carolina at Chapel Hill 27599-7360, USA.
Ward
K W
KW
Pollack
G M
GM
D000042:Absorption; D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D001259:Ataxia / Q000139:chemically induced; D001273:Atmosphere Exposure Chambers; D005260:Female; D007275:Injections, Intravenous; D007700:Kinetics; D000432:Methanol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D051379:Mice; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley
D000432:Methanol