| Comparison of the Use of a Physiologically Based Pharmacokinetic Model and a Classical Pharmacokinetic Model for Dioxin Exposure Assessments Claude Emond,1,2* Joel E. Michalek,3 Linda S. Birnbaum,2 and
Michael J. DeVito2 1National Research Council, National Academy of Sciences, Washington,
DC, USA; 2Pharmacokinetics Branch, Environmental Toxicology Division,
National Health and Environmental Effects Research Laboratory, Office of Research
and Development, U.S. Environmental Protection Agency, Research Triangle Park,
NC, USA; 3Air Force Research Laboratory, Brooks City-Base, Texas,
USA Abstract
In epidemiologic studies, exposure assessments of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) assume a fixed elimination rate. Recent data suggest a dose-dependent elimination rate for TCDD. A physiologically based pharmacokinetic (PBPK) model, which uses a body-burden-dependent elimination rate, was developed previously in rodents to describe the pharmacokinetics of TCDD and has been extrapolated to human exposure for this study. Optimizations were performed using data from a random selection of veterans from the Ranch Hand cohort and data from a human volunteer who was exposed to TCDD. Assessment of this PBPK model used additional data from the Ranch Hand cohort and a clinical report of two women exposed to TCDD. This PBPK model suggests that previous exposure assessments may have significantly underestimated peak blood concentrations, resulting in potential exposure misclassifications. Application of a PBPK model that incorporates an inducible elimination of TCDD may improve the exposure assessments in epidemiologic studies of TCDD. Key words: dioxin, epidemiology, PBPK, pharmacokinetic, physiologically based pharmacokinetic model, Ranch Hand, risk assessment. Environ Health Perspect 113:1666-1668 (2005) . doi:10.1289/ehp.8016 available via http://dx.doi.org/ [Online 25 August 2005]
Address correspondence to M. DeVito, Pharmacokinetic Branch, MD B143-01, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 USA. Telephone: (919) 541-0061. Fax: (919) 541-4284. E-mail: devito.mike@epa.gov *Current address: Department of Environmental and Occupational Health, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada. This project was funded in part by a cooperative agreement MIPR FQ7624-00-YA085 with the U.S. Air Force and cooperative agreement CR 828790 with the National Research Council, National Academy of Sciences, and performed at the U.S. Environmental Protection Agency (Research Triangle Park, NC, USA) . This document has been reviewed in accordance with U.S. Environmental Protection Agency policy and approved for publication. Approval does not signify that the content necessarily reflects the view and policies of the agency, nor does mention of the trade names or commercial products constitute endorsement or recommendation for use. The authors declare they have no competing financial interests. Received 15 February 2005 ; accepted 25 August 2005. The full version of this article is available for free in HTML or PDF formats. |
