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 cha racteristics of methanol absorption and to develop an inhalation model relating methanol absorption, blood concentration, and elimination. M ethods. Rats were exposed to methanol in chambers that allowed measure ment of methanol uptake, ventilation, and blood concentrations; anesth etized rats with a tracheal cannula were examined to determine trachea l concentrations. In separate experiments, methanol-exposed rats recei ved an iv methanol bolus to examine the effect of blood methanol on ve ntilation and absorption; ventilation also was manipulated by CO2 or p entobarbital to assess the effect of ventilation rate on methanol abso rption. These data were combined to construct a semi-physiologic model of methanol uptake. Results. Only 1-3% of inhaled methanol reached th e trachea, primarily from systemic methanol partitioning into the trac hea; blood methanol did not alter methanol absorption. Manipulation of ventilation and application of the pharmacokinetic model indicated th at ventilation was less significant than environmental methanol concen tration in determining the fraction of inhaled methanol absorbed, alth ough both parameters were important determinants of the total mass abs orbed. Conclusions. These data indicate that methanol uptake is a comp lex process that depends upon several parameters. Despite these comple xities, a relatively simple semi-physiologic model was capable of desc ribing methanol uptake over a wide range of exposure concentrations in the rat.