Quantitative Evaluation of the Matabolic Interactions between Trichloroethylene and 1,1-Dichloroethylene In vivo Using Gas Uptake Methods

摘要

Quantitative Evaluation of the Metabolic Interactions between Trichloroethylene and 1,1-Dichloroethylene in Vivo Using Gas Uptake Methods. Gas uptake simulation methods were used to determine kinetic constants for trichloroethylene (TCE) and 1,1-dichloroethylene (1,1-DCE) metabolism in vivo in male Fischer 344 rats. Both are metabolized by single, saturable, oxidative pathways with high-affinity substrate binding. The allometrically scaled maximum velocities (Vmaxc) for TCE and 1,1-DCE were, respectively, 11 nd 7.5 mg/hr (i.e., 84 and 77 micro/hr). Gas uptake studies were also conducted with three mixed atmosphere exposures with the following initial concentrations in parts per million: 500 (1.1-DCE):200 (TCE); 500 (1,1-DCE):500 (TCE); and 2000 (1,1-DCE):500 (TCE). Mixture uptake curves were described by a system of equations in which a full physiologically based pharmacokinetic (PB-PK) model was provided for each chemical and each was regarded as an inhibitor of the other's metabolism.