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Robert A. Perkins,¹ Keith W. Ward,² and Gary M. Pollack²

¹Curriculum in Toxicology, School of Medicine, and ²Division of Pharmaceutics, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA

Abstract

We estimated kinetic parameters associated with methanol disposition in humans from data reported in the literature. Michaelis-Menten elimination parameters (V_max = 115 mg/L/hr ; K_m = 460 mg/L) were selected for input into a semi-physiologic pharmacokinetic model. We used reported literature values for blood or urine methanol concentrations in humans and nonhuman primates after methanol inhalation as input to an inhalation disposition model that evaluated the absorption of methanol, expressed as the fraction of inhaled methanol concentration that was absorbed () . Values of for nonexercising subjects typically varied between 0.64 and 0.75 ; 0.80 was observed to be a reasonable upper boundary for fractional absorption. Absorption efficiency in exercising subjects was lower than that in resting individuals. Incorporation of the kinetic parameters and into a pharmacokinetic model of human exposure to methanol, compared to a similar analysis in rodents, indicated that following an 8-hr exposure to 5000 ppm of methanol vapor, blood methanol concentrations in the mouse would be 13- to 18-fold higher than in humans exposed to the same methanol vapor concentration ; blood methanol concentrations in the rat under similar conditions would be 5-fold higher than in humans. These results demonstrate the importance in the risk assessment for methanol of basing extrapolations from rodents to humans on actual blood concentrations rather than on methanol vapor exposure concentrations. Key words: human-animal comparison, methanol, physiologocally based pharmacokinetic model, toxicokinetics. Environ Health Perspect 103: 726-733 (1995)

Address correspndence to G.M. Pollack, Division of Pharmaceutics, School of Pharmacy, CB 7360, University of North Carolina, Chapel Hill, NC 27599-7360 USA.

Received 22 December 1994 ; accepted 10 April 1995.