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USING MULTIPLE SETS OF OBSERVED DATA TO ESTIMATE METABOLIC RATE PARAMETERS IN A PBPK MODEL FOR CCL CONTAMINANTS
Citation:
Kenyon, E M., C. K. Kovach, AND P. Schaefer. USING MULTIPLE SETS OF OBSERVED DATA TO ESTIMATE METABOLIC RATE PARAMETERS IN A PBPK MODEL FOR CCL CONTAMINANTS. Presented at 2004 Toxicology and Risk Assessment conference, Cincinnati, OH, April 26-30, 2004.
Description:
The poster describes the application of parameter estimation methods using multiple sets of observed data to determine parameters for PBPK models used for studies in risk assessment for exposure to chemicals from the Candidate Contaminant List (CCL) created by the U.S EPA. The work is based on studies conducted at the U.S.EPA (NHEERL) using an in vivo gas uptake system to generate data to estimate rates of metabolism for 1,1-dichloropropene and 2,2-dichloropropane (C.T. Mitchell, et al., 2004). The objective is to show the benefit of using simultaneously multiple sets of data that represent multiple animals per exposure level and multiple exposure levels. This method results in improved metabolic rate parameter estimates for the PBPK model. The estimate of variability of the parameters in addition to the point estimate allows for a much better risk assessment as the metabolic rate parameters are often the critical determinants of target tissue concentration of toxicologically active chemicals and hence information concerning their variability is valuable for risk assessment. The computer simulation and analysis was performed using acslXtreme, a commercial-of-the-shelf product with specific enhancements for toxicology and risk assessment.
Disclaimer: The information presented in this poster does not reflect policies of the U.S. EPA.