In vivo metabolic interactions of benzene and toluene.

The metabolic interactions of benzene and toluene co-exposure were investigated in male Fischer rats. A closed recirculated exposure system was used to obtain inhalation uptake curves for individual chemicals as well as for a mixture of the two compounds. Pharmacokinetic parameters for benzene and toluene individually were determined in previous experimental studies. These values were incorporated into a physiologically based pharmacokinetic model which simulated the inhalation uptake process for both chemicals simultaneously. An optimal fit to the uptake curves for simultaneous exposure was obtained by adjusting the metabolic interaction terms for each chemical. Mutual suppression of metabolism was apparent. Toluene more effectively inhibited benzene metabolism than the reverse. This simulation approach for analyzing gas uptake data provided a method to determine the metabolic interactions occurring upon inhalation exposure to two different chemicals. Such analyses will prove useful in improving predictive toxicokinetic models.