Comparison of intake and systemic relative effect potencies of dioxin-like compounds in female rats after a single oral dose

Karin I. Van Ede*, Patrik L. Andersson, Konrad P.J. Gaisch, Martin Van Den Berg, Majorie B.M. Van Duursen

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Risk assessment for mixtures of dioxin-like compounds uses the toxic equivalency factor (TEF) approach. Although current WHO-TEFs are mostly based on oral administration, they are commonly used to determine toxicity equivalencies (TEQs) in human blood or tissues. However, the use of "intake" TEFs to calculate systemic TEQs in for example human blood, has never been validated. In this study, intake and systemic relative effect potencies (REPs) for 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126), 2,3′,4,4′,5-pentachlorobiphenyl (PCB-118) and 2,3,3′,4, 4′,5-hexachlorobiphenyl (PCB-156) were compared in rats. The effect potencies were calculated based on administered dose and liver, adipose or plasma concentrations in female Sprague-Dawley rats 3 days after a single oral dose, relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Hepatic ethoxyresorufin-O-deethylase activity and gene expression of Cyp1a1, 1a2, 1b1 and aryl hydrocarbon receptor repressor in liver and peripheral blood lymphocytes were used as endpoints. Results show that plasma-based systemic REPs were generally within a half log range around the intake REPs for all congeners tested, except for 4-PeCDF. Together with our previously reported systemic REPs from a mouse study, these data do not warrant the use of systemic REPs as systemic TEFs for human risk assessment. However, further investigation for plasma-based systemic REPs for 4-PeCDF is desirable.

Original languageEnglish
Pages (from-to)637-646
Number of pages10
JournalArchives of Toxicology
Volume88
Issue number3
DOIs
Publication statusPublished - 1 Mar 2014
Externally publishedYes

Keywords

  • Dibenzofurans
  • Dioxins
  • PCBs
  • Systemic REPs
  • TEF concept

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