TOXICOKINETICS OF ISOPRENE IN RODENTS AND HUMANS

A physiological toxicokinetic model (PT model) was developed for inhal ed isoprene in mouse, rat and man. Partition coefficients blood:air an d tissue:blood were determined in vitro by a headspace method. Paramet ers of a saturable isoprene metabolism in B6C3F(1) mice, Sprague-Dawle y rats and volunteers were obtained from gas uptake experiments in clo sed systems, analyzed by means of a two-compartment model. Incorporati on of these parameters into the PT model revealed that isoprene was me tabolized not only in the liver but also in extrahepatic organs. Endog enous production of isoprene in man was quantified from experiments wi th volunteers breathing into a closed system. The PT model was validat ed for mice, rats and humans by comparing simulated values with data d etermined by other authors.