An analysis of exposure rate effects for benzene using a physiologically based pharmacokinetic model

A new physiological pharmacokinetic model was used to explore the effect of exposure rate on the rate of formation of several crucial metabolites of benzene. Metabolite formation was compared following exposure to benzene over the course of an 8-hr workday and following a single exposure for 15 min. These exposures were based on the permissible exposure limit and short-term exposure limit of the benzene standard set by the Occupational Safety and Health Administration. The model was parametrized using in vitro and in vivo experimental data on benzene toxicokinetics and metabolism. Ranges, rather than fixed values, were assigned to the parameters. Model predictions show that the amounts of hydroquinone, catechol, and muconaldehyde formed in the body following a peak exposure to 32 ppm of benzene over 15 min are on average 20% higher than those formed following an equivalent dose of 1 ppm over an 8-hr period. The health consequences of these findings and the implications for policy concerning short-term exposure limits are discussed.