Dose-response analyses of the carcinogenic effects of trichloroethylene inexperimental animals

In lifetime bioassays, trichloroethylene (TCE, CAS No. 79-01-6) causes live r tumors in mice following gavage. liver and lung tumors in mice following inhalation, and kidney tumors in rats following gavage or inhalation. Recen tly developed pharmacokinetic models provide estimates of internal, target- organ doses of the TCE metabolites thought responsible for these tumor resp onses. Dose-response analyses following recently proposed methods for carci nogen risk assessment from the U.S. Environmental Protection Agency (U.S. E PA) are conducted on the animal tumor data using the pharmacokinetic dosime ters to derive a series of alternative projections of the potential carcino genic potency of TCE in humans exposed to low environmental concentrations. Although mechanistic considerations suggest action of possibly nonlinear p rocesses, dose-response shapes in the observable range of tumor incidence e vince little sign of such patterns. Results depend on which of several alte rnative pharmacokinetic analyses are used to define target-organ doses. Hum an potency projections under the U.S. EPA linear method based on mouse live r tumors and internal dosimetry equal or somewhat exceed calculations based on administered dose, and projections based on mouse liver tumors exceed t hose from mouse lung or rat kidney tumors. Estimates of the carcinogenic po tency of the two primary oxidative metabolites of TCE-trichloroacetic acid and dichloroacetic acid, which are mouse liver carcinogens in their own rig ht-are also made, but it is not clear whether the carcinogenic potency of T CE can be quantitatively ascribed to metabolic generation of these metaboli tes.