Comparison of the use of physiologically based pharmacokinetic model and a classical pharmacokinetic model for dioxin exposure assessments

Claude Emond, Joel E. Michalek, Linda S. Birnbaum, Michael J. DeVito

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1666-1668
Number of pages3
JournalEnvironmental health perspectives
Volume113
Issue number12
DOIs
StatePublished - Dec 2005

Keywords

  • Dioxin
  • Epidemiology
  • PBPK
  • Pharmacokinetic
  • Physiologically based pharmacokinetic model
  • Ranch hand
  • Risk assessment

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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