Simulation Studies Examining Possible Mechanisms of Trichloroethylene Carcinogenicity.
Final rept. Dec 95-Jan 98,
WASHINGTON UNIV SEATTLE DEPT OF ENVIRONMENTAL HEALTH
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There has been much recent interest regarding methods of evaluating potential human cancer risks associated with trichloroethylene TCE. Stochastic biologically based dose-response BBDR models offer possible means of quantifying these risks. BBDR models have been used to evaluate the effects of cancer initiators and promoters at a cellular level. This paper examines the sensitivity of the Moolgavkar-Venzon-Knudson MVK 2-stage model to variations in model parameters, and the ability of the model to distinguish between initiating and promoting activity of TCE. Maximum-likelihood estimation is used to fit parameters to simulated data sets assuming different carcinogenic mechanisms and low-dose response for TCE. Monte Carlo simulations are used to simulate experimental variability and mechanistic assumptions. Changes in experimental design are evaluated that allow carcinogenic mechanisms to be more clearly distinguished. These analyses provide information regarding uncertainties associated with carcinogenic mechanisms of TCE, and provide possible guidance for laboratory-based toxicological evaluations.