Refinement of Risk Analysis Procedures for Trichloroethylene Through the Use of Monte Carlo Method in Conjunction with Physiologically Based Pharmacokinetic Modeling.

摘要

This study refines risk analysis procedures for trichloroethylene (TCE) using a physiologically based pharmacokinetic (PBPK) model in conjunction with the Monte Carlo method. The Monte Carlo method is used to generate random sets of model parameters, based on the mean, variance, and distribution types. The procedure generates a range of exposure values for human excess lifetime cancer risk of lxl0 (exp-6), based on the upper and lower bounds and the mean of a 95% confidence interval. Risk ranges were produced for both ingestion and inhalation exposures. Results are presented in a graphical format to reduce reliance on qualitative discussions of uncertainty. A sensitivity analysis of the model was also performed. This method produced acceptable TCE exposures, for total amount TCE metabolized, greater than the Environmental Protection Agency's (EPA) by a factor of 23 for inhalation and a factor of 1.6 for ingestion. Sensitive parameters identified were the elimination rate constant, alveolar ventilation rate, and cardiac output. This procedure quantifies the uncertainty related to natural variations in parameter values. Its incorporation into risk assessment could be used to promulgate, and better present, more realistic standards.... Risk analysis, Physiologically based pharmacokinetics, Pbpk, Trichloroethylene, Monte carlo method.