Physiologically-based pharmacokinetic modeling of benzo(a)pyrene and the metabolite in humans of different ages.

ABSTRACT

Age-specific differences in the pharmacokinetics of benzo(a)pyrene (BaP) and its metabolite 3-hydroxybenzo(a)pyrene (3-OHBaP) potentially affect time courses of tissue concentration; however, the quantitative impact of these differences is not well characterized. Our objective was to quantify the effect of age-specific differences in physiological and biochemical parameters on the pharmacokinetics of BaP and 3-OHBaP from newborn at birth to adulthood following inhalation exposure. The time courses of BaP and 3-OHBaP were simulated by using a physiologically based pharmacokinetic model with Advanced Continuous Simulation Language (ACSLX). The concentrations of BaP increased with age in the liver but decreased with age in most tissues, urine, and blood. The concentrations of 3-OHBaP were the highest in the newborns. Our results also showed that the concentration of BaP has almost reached a steady state in the kidney, liver, lung, rapidly perfused tissues, slowly perfused tissues, and skin except for adipose tissues. However, the concentration of 3-OHBaP has reached a steady state in all tissues. This study suggests that age-specific parameters have an effect on the pharmacokinetics of BaP and 3-OHBaP. In particular, tissue concentration in the newborns is higher than other age groups, which indicates that the newborns are susceptible to environmental BaP exposure.