A pharmacokinetic model of styrene inhalation with the fugacity approach

The physiologically based pharmacokinetic model of J. C. Ramsey and M. E. Andersen (1984, Toxicol. Appl. Pharmacol. 73, 159-175) of styrene inhalation in rats, with extrapolation to humans, was reformulated with the chemical equilibrium criterion of fugacity instead of concentration to describe compartment partitioning. Fugacity models have been used successfully to describe environmental partitioning processes which are similar in principle to pharmacokinetic processes. The fugacity and concentration models are mathematically equivalent and produce identical results. The use of fugacity provides direct insights into the relative chemical equilibrium partitioning status of compartments, thus facilitating interpretation of experimental and model data. It can help to elucidate dominant processes of transfer, reaction and accumulation, and the direction of diffusion. Certain model simplifications become apparent in which compartments which remain close to equilibrium may be grouped. Maximum steady-state tissue concentrations for a known exposure may be calculated readily. It is suggested that pharmacokinetic fugacity models can complement conventional concentration models and may facilitate linkage to fugacity models describing environmental sources, pathways, and exposure routes.