Relative effect potency estimates of dioxin-like activity for dioxins, furans, and dioxin-like PCBs in adults based on cytochrome P450 1A1 and 1B1 gene expression in blood

Soňa Wimmerová, Martin van den Berg, Jana Chovancová, Henrieta Patayová, Todd A. Jusko, Majorie B.M. van Duursen, Ľubica Palkovičová Murínová, Rocio F. Canton, Karin I. van Ede, Tomáš Trnovec*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Background In the risk assessment of PCDDs, PCDFs, and dioxin-like (DL) PCBs, regulatory authorities support the use of the toxic equivalency factor (TEF)-scheme derived from a heterogeneous data set of the relative effect potency (REPs) estimates. Objectives We sought to determine REPs for dioxin-like compounds (DLCs) using expression of cytochrome P450 (CYP) 1A1 and 1B1 mRNA in human peripheral blood mononuclear cells representing two different pathways. Methods We used a sex and age adjusted regression-based approach comparing the strength of association between each DLC and the cytochrome P450 (CYP) 1A1 and 1B1 mRNA expression in 320 adults residing in an organochlorine-polluted area of eastern Slovakia. Results We calculated REPs based on CYP1A1 expression for 4 PCDDs, 8 PCDFs, and 1 PCB congener, and based on CYP1B1 expression for 5 PCDFs and 11 PCB congeners. REPs from CYP1A1 correlated with REPs previously derived from thyroid volume (ρ = 0.85; p < 0.001) and serum FT4 (ρ = 0.77; p = 0.009). The 13 log REPs from CYP1A1 correlated with log WHO-TEFs (r = 0.63; p = 0.015) and 11 log PCB REPs with PCB consensus toxicity factors (CTFs) for compounds with WHO-TEFs (r = 0.80; p = 0.003). The complete set of derived 56 log REPs correlated with the log CTFs (r = 0.77; p = 0.001) and log WHO-TEFs (r = 0.81; p < 0.001). Conclusions REPs calculated from thyroid and cytochrome P450 endpoints realistically reflect human exposure scenarios because they are based on human chronic and low-dose exposures. While the CYP 1A1 seems more suitable for toxicity evaluation of PCDD/Fs, the CYP 1B1 is more apt for PCDFs and PCBs and reflects different pathways.

Original languageEnglish
Pages (from-to)24-33
Number of pages10
JournalEnvironment International
Volume96
DOIs
Publication statusPublished - 1 Nov 2016
Externally publishedYes

Keywords

  • Cytochrome P450 (CYP) 1A1 and 1B1
  • Dioxin-like polychlorinated biphenyl (DL-PCB)
  • Polychlorinated dibenzo-p-dioxins (PCDDs)
  • Polychlorinated dibenzo-p-furans (PCDFs)
  • Relative effect potency (REP)
  • Toxic equivalency factor (TEF)

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