Simulation Studies Examining Possible Mechanisms of Trichloroethylene Carcinogenicity.

Abstract

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.

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Document Details

Document Type
Technical Report
Publication Date
Mar 01, 1998
Accession Number
ADA341080

Entities

People

  • Elaine M. Faustman
  • Georg E. Luebeck
  • Robert C. Lee
  • Scott M. Bartell
  • William Griffith

Organizations

  • University of Washington

Tags

DTIC Thesaurus Topics

  • Air Force
  • Alkenes
  • Cell Division
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Computational Science
  • Data Science
  • Data Sets
  • Environmental Health
  • Experimental Design
  • Information Science
  • Maximum Likelihood Estimation
  • Monte Carlo Method
  • Risk Analysis
  • Simulations
  • Test And Evaluation

Readers

  • Computational Modeling and Simulation
  • Groundwater Contamination Remediation.
  • Toxicology/Environmental Toxicology