A Pharmacokinetic Model of Inhaled Methanol in Humans and Comparison to Methanol Disposition in Mice and Rats

Abstract

(Perkins et al., submitted). Elimination via the lungs (after exposure) and the kidney is theoretically a small fraction of total methanol elimination (8,11) and modeled well in both rat and mouse without being specifically included (10). In both the rat and mouse, the systemic disposition of methanol was similar after oral (PO), intravenous (IV), or inhalation administration (Perkins et al., submitted).To assess risk to the human conceptus based on extrapolation from rodent data, it is desirable to begin with comparisons of blood methanol concentrations rather than with the ambient methanol vapor concentration; as demonstrated in rodents, blood concentrations can vary substantially between species exposed to the same ambient methanol concentration. Blood toxicant levels are a more relevant determinant of systemic effects (such as teratogenicity) than are ambient environmental toxicant concentrations (12). Because of the well-established species differences in the acute toxicity of methanol between primates and nonprimates (1), the primate is the model of choice for both kinetic and toxicologic studies of methanol, and only data obtained from human and nonhuman primates in the published literature were used in this study. Numerical values presented in tables were preferred to values that were scaled from charts or graphs, although the majority of data were scaled. Many of the data were reported as methanol concentrations in urine rather than in blood. It has been shown that blood methanol concen-

Defining a tolerable concentration of methanol in alcoholic drinks

“…Correspondingly, a blood level of 5 mg/dl for any period might then be taken as the maximum ''safe'' level, i.e., one unlikely to be associated with toxic effects. 10,12,19,22 23 Literature review to obtain pharmacokinetic model…”