Physiologically Based Pharmacokinetic Modeling of the Lactating Rat and NursingPup: A Multiroute Exposure Model for Trichloroethylene and its Metabolite, Trichloroacetic Acid

摘要

A physiologically based pharmacokinetic (PB-PK) model was developed to describetrichloroethylene (TCE) kinetics in the lactating rate and nursing pup. The lactating dam was exposed to TCE either by inhalation or by ingestion in drinking water. The nursing pup's exposure to TCE was by ingestion of maternal milk containing TCE. The kinetics of trichloroacetic acid (TCA), a metabolite of TCE, were described in the lactating dam and developing pup by a hybrid one-compartment model. The lactating dam's exposure to TCA was from metabolism of TCE to TCA. The pup's exposure to TCA was from metabolism of TCE ingested in suckled milk and from direct ingestion of TCA in maternal milk. For the PB-PK model, partition coefficients (PCs) were determined by vial equilibration, and metabolic constants for TCE oxidation, by gas uptake methods. Keywords: Trichloroethylene, Trichloroacetic acid, Lactation, PB-PK Modeling, Inhalation, Drinking water. (JS)