A PHARMACOKINETIC MODEL OF INHALED METHANOL IN HUMANS AND COMPARISON TO METHANOL DISPOSITION IN MICE AND RATS

We estimated kinetic parameters associated with methanol disposition i n humans From data reported in the literature. Michaelis-Menten elimin ation parameters (V-max = 115 mg/L/hr; K-m = 460 mg/L) were selected f or input into a semi-physiologic pharmacokinetic model. We used report ed literature values for blood or urine methanol concentrations in hum ans and nonhuman primates after methanol inhalation as input to an inh alation disposition model that evaluated the absorption of methanol, e xpressed as the fraction of inhaled methanol concentration that was ab sorbed (Phi) Values of Phi for nonexercising subjects typically varied between 0.64 and 0.75; 0.80 was observed ed to be a reasonable upper boundary for functional absorption. Absorption efficiency in exercisin g subjects was lower than that in resting individuals. Incorporation o f the kinetic parameters and Phi into a pharmacokinetic model of human exposure to methanol, compared to a similar analysis in rodents, indi cated that following an 8-hr exposure to 5000 ppm of methanol vapor, b lood methanol concentrations in the mouse would be 13- to 18-fold high er than in humans exposed to the same methanol vapor concentration; bl ood methanol concentrations in the rat under similar conditions would be 5-fold higher than in humans. These results demonstrate the importa nce in the risk assessment For methanol of basing extrapolations from rodents to humans on actual blood concentrations rather than on methan ol vapor exposure concentrations.