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

  • Molecular Toxicology
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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.

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Acknowledgments

This work was financially supported by the European Union Seventh Framework Project SYSTEQ under grant agreement number FP7-ENV-226694. The compounds were purchased by The Dow Chemical Company (Michigan, USA) and donated to the SYSTEQ consortium. The authors thank Helma Avezaat, Sabine Versteeg, Anja van der Sar, Ron Timmermans, Sandra Nijmeijer, Esmée Janssen, Wouter de Wilde, Maarke Roelofs and Sture Bergek for excellent technical assistance. The authors gratefully thank Dr. Lesa Aylward for all the helpful discussions.

Conflict of interest

The purchase of the compounds was financially made possible by The Dow Chemical Company. However, the authors had complete freedom to design, conduct, interpret and publish the research. The authors KE, PA, KG, MB and MD declare no conflict of interest.

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Authors and Affiliations

  1. Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80177, 3508 TD, Utrecht, The Netherlands

    Karin I. van Ede, Konrad P. J. Gaisch, Martin van den Berg & Majorie B. M. van Duursen

  2. Department of Chemistry, Umeå University, Umeå, Sweden

    Patrik L. Andersson

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  1. Karin I. van Ede
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  2. Patrik L. Andersson
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  3. Konrad P. J. Gaisch
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  4. Martin van den Berg
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  5. Majorie B. M. van Duursen
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Correspondence to Karin I. van Ede.

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van Ede, K.I., Andersson, P.L., Gaisch, K.P.J. et al. Comparison of intake and systemic relative effect potencies of dioxin-like compounds in female rats after a single oral dose. Arch Toxicol 88, 637–646 (2014). https://doi.org/10.1007/s00204-013-1186-2

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  • DOI: https://doi.org/10.1007/s00204-013-1186-2

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