ABSTRACT
A physiologically-based pharmacokinetic (PB-PK) model has been developed for dihalomethanes and is especially well suited for its use in risk calculations because it easily supports both dose-route and inter-species extrapolations of kinetic behaviour. The PB-PK model was used to determine target tissue dose from the glutathione pathway in both liver and lung at various exposure concentrations in humans and mice. This chapter develops a PB-PK model for dichloromethane (DCM), considers the model to support a proposed mechanism of DCM carcinogenicity, and compares cancer risk calculated by this model with risk estimated by the more conventional regulatory approaches to the cancer risk assessment. With any PB-PK model, three kinds of data are required: tissue partition coefficients, physiological parameters for the test species, and biochemical constants for binding/metabolism of the chemical in biological tissues. The human PB-PK DCM model can be exercised to predict tissue exposure as a function of the particular environmental exposure concentration.
