Uncertainties in Trichloroethylene Pharmacokinetic Models
Understanding the pharmacokinetics of a chemical¯its absorption, distribution, metabolism, and excretion in humans and laboratory animals ¯ is critical to the assessment of its human health risks. For trichloroethylene (TCE), numerous physiologically-based pharmacokinetic (PBPK) models have been developed to predict the concentrations of TCE and its metabolities in the body. However, as described in the U.S. Environmental Protection Agency's (EPA) 2001 external review draft, Trichloroethylene Health Risk Assessment: Synthesis and Characterization. (EPA/600/P-01/002A August 2001), predictions of several of these mathematical models have differed up to 10-fold. This perspective provides a brief overview of rhe unxcertainties in thePBPK modeling of TCE and its metabolities, drawn from EPA's recent TCE issue papers (URL:http://cfpub.epa.gov/neca/cfm/recorddisplay.cfm?deid=117502, and a forthcoming EnvironmentalHealth Perspectives (EHP) mimi-monograph on TCE written by EPA scientists. Recent and ongoing efforts to improve the PBPK models for TCE have focused on understanding the extent to which differences in each model's structure, parameters, and underlying data each contribute to their differing predictions. In addition, the National Academy of Sciences (NAS), in their ongoing project on key issues in TCE health risks, has been asked to provide further guidance on addressingthese uncertainties, with the hope that a single, integrated PBPK model can be developed for use in EPA's revised health risk assessment of TCE.