Development of a Probabilistic Model for Trichloroethylene-Induced Liver Cancer. T. W. Simon, US Environmental Protection Agency, Atlanta, GA
A two-stage clonal growth model of cancer induction was coupled to a previously developed physiologically-based pharmacokinetic model for trichloroethylene to examine the dose-response relation for hepatic cancer in humans. The coupling between the two models was defined by three aspects. First, a metabolite of trichloroethylene was assumed to bind weakly to hepatocyte DNA. Second, trichloroethylene or its metabolism inflamed liver cells, and the cells were targeted for destruction by the immune system. Third, trichloroacetic acid, a major metabolite of trichloroethylene, was directly toxic to hepatocytes. The first coupling aspect was assumed to produce cancer by a genotoxic mechanism. The second and third coupling aspects increased cell proliferation in the liver. The model used a combination of measured and assumed distributions. For all model parameters, the distributions were based on human data. A large number of iterations of the model will be performed and used to develop a cancer potency factor for trichloroethylene-induced liver cancer.
This work does not reflect the policies of the US Environmental Protection Agency.
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