Abstract:
The purpose of this study was to characterize the toxicokinetics of toluene in men and women under the influence of rest and exercise, using a person-specific, physiologically-based toxicokinetic (PBTK) model. Ten men and 10 women were exposed to deuterated toluene under both exercise and resting exposures for 2 hours. A person-specific model using subject-specific values for ventilation rate, cardiac output, blood/air partition coefficient, body weight, and fraction of adipose tissue was used to model the blood and exhaled breath data. The maximum velocity of metabolism by the lung (Vmaxlc) and the post-exposure fraction of cardiac output to adipose tissue, slowly perfused tissues and highly perfused tissues were fitted to the data. Comparing exercise and resting exposures, there were no differences in clearance, half-life or terminal volume of distribution. However, the peak toluene blood concentrations, and AUC were approximately 3 times higher for the exercise exposures. Comparing men and women, no difference in clearance, half-life or volume of distribution for the exercise exposures was found. However, in the resting exposures, Vmaxlc was higher for the men, clearance was higher for men, and half-life was longer for women (all p<0.05). These differences may be due to a higher rate of extraheptic metabolism in men and a higher adipose tissue fraction in women. After adjusting for body weight, clearance was not statistically different, but volume of distribution for the women was significantly higher. Our findings suggest that women may be more at risk of the chronic effects to toluene exposure compared to men. Such findings may prove valuable when determining regulatory standards for worker health and safety.