Analysis of respiratory exchange of methanol in the lung of the monkey using a physiological model. Toxicol Sci 53

A physiologically based pharmacokinetic (PBPK) model was developed for the monkey, to account for fractional systemic uptake of inhaled methanol vapors in the lung. Fractional uptake of inhaled [14C]-methanol was estimated using unreported exhaled breath time course measurements of [14C]-methanol from the D. C. Dorman et al. (1994, Toxicol Appl Pharmacol. 128, 229–238) lung-only exposure study. The cumulative amount of [14C]-meth-anol exhaled was linear with respect to exposure duration (0.5 to 2 h) and concentration (10 to 900 ppm). The model estimated that forty to eighty-one percent of the of inhaled [14C]-methanol deliv-ered to the lung was taken into systemic circulation in female Cynomolgus monkeys exposed for two h to 10–900 ppm of [14C]-methanol. There was no apparent trend between the percent of inhaled [14C]-methanol absorbed systemically and the [14C]-meth-anol exposure concentration. Model simulations were conducte