A physiologically-based description of the inhalation pharmacokinetics of styrene monomer in rats and humans

Abstract

Abstract : Physiologically-based pharmacokinetic (PB-PK) models describe the body in terms of discrete organs or discrete sets of organs lumped together based on common physiological characteristics. These tissue groups are defined with respect to their volumes and blood flows and to their partition coefficient for test chemical and the biochemical interactions (protein binding/enzymatic metabolism) of the test chemical in the various tissue groups. PB-PK models have potential for extrapolation from one dose level to another, from one route of administration to another, and from the test species to other mammalian species, including humans. The pharmacokinetics of inhaled styrene were previously described in the rat. An attempt to describe these data with a classical compartmental model met with only limited success because of non-linear kinetic behavior at the higher inhaled concentrations (600 and 1200 ppm). In this study we have developed a PB-PK model to describe the kinetics of styrene in rats after either inhalation or after oral dosing. This model explicitly accounts for the non-linear behavior. Secondly, we show the ability to extrapolate from the PB-PK model for the rat to predict styrene inhalation kinetics in humans.