Role of Pharmacokinetic Modeling in Risk Assessment: Perchloroethylene (PCE) as an Example

摘要

Available metabolic and pharmacokinetic data on perchloroethylene (PCE) are used as a basis for discussion of the use of such data in quantitative risk assessment. The emphasis is on methodologies for improving risk assessment rather than on the risk assessment of PCE per se. The data available on PCE are sufficient to independently construct a physiologically-based pharmacokinetic (PB-PK) model for each of the three species: humans, rats, and mice. The model is used to convert bioassay-administered doses into metabolized doses for dose-response calculation, to evaluate the effect of various exposure patterns on metabolized dose, and to compare inhalation risk estimates calculated on the basis of inhalation and gavage bioassay data. The advantages and limitations of using PB-PK models in risk assessment are addressed.