Toxicokinetics of isoprene in rodents and humans

A physiological toxicokinetic model (PT model) was developed for inhaled isoprene in mouse, rat and man. Partition coefficients blood:air and tissue:blood were determined in vitro by a headspace method. Parameters of a saturable isoprene metabolism in B6C3F1 mice, Sprague-Dawley rats and volunteers were obtained from gas uptake experiments in closed systems, analyzed by means of a two-compartment model. Incorporation of these parameters into the PT model revealed that isoprene was metabolized not only in the liver but also in extrahepatic organs. Endogenous production of isoprene in man was quantified from experiments with volunteers breathing into a closed system. The PT model was validated for mice, rats and humans by comparing simulated values with data determined by other authors.