Physiologically-based pharmacokinetic models in risk and exposure assessment

Pharmacokinetic non-linearities occur between different doses and between different species. Physiologically based pharmacokinetic models are accurate tools for taking these non-linearities into account. Dichloromethane and perchloroethylene are two examples discussed in this paper. For dichloromethane the pharmacokinetic non-linearity factor results in a greater delivered dose than would be predicted from linear relationships as the dose increases. For perchloroethylene the opposite holds true. In addition a brief illustration of the use of pharmacokinetic models as tools for interpreting biomarker data is provided.