Methanol inhalation: Site and other factors influencing absorption, and an inhalation toxicokinetic model for the rat

Purpose. This investigation was conducted to identify the site and characteristics of methanol absorption and to develop an inhalation model relating methanol absorption, blood concentration, and elimination. Methods. Rats were exposed to methanol in chambers that allowed measurement of methanol uptake, ventilation, and blood concentrations; anesthetized rats with a tracheal cannula were examined to determine tracheal concentrations. In separate experiments, methanol-exposed rats received an iv methanol bolus to examine the effect of blood methanol on ventilation and absorption; ventilation also was manipulated by CO₂ or pentobarbital to assess the effect of ventilation rate on methanol absorption. These data were combined to construct a semi-physiologic model of methanol uptake. Results. Only 1-3% of inhaled methanol reached the trachea, primarily from systemic methanol partitioning into the trachea; blood methanol did not alter methanol absorption. Manipulation of ventilation and application of the pharmacokinetic model indicated that ventilation was less significant than environmental methanol concentration in determining the fraction of inhaled methanol absorbed, although both parameters were important determinants of the total mass adsorbed. Conclusions. These data indicate that methanol uptake is a complex process that depends upon several parameters. Despite these complexities, a relatively simple semi-physiologic model was capable of describing methanol uptake over a wide range of exposure concentrations in the rat.