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.

Autor: Wimmerová S; Slovak Medical University, Limbová 14, 83303 Bratislava, Slovakia. Electronic address: sona.wimmerova@szu.sk., van den Berg M; Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.176, 3508, TD, Utrecht, The Netherlands. Electronic address: m.vandenberg@uu.nl., Chovancová J; Slovak Medical University, Limbová 14, 83303 Bratislava, Slovakia. Electronic address: jana.chovancova@szu.sk., Patayová H; Slovak Medical University, Limbová 14, 83303 Bratislava, Slovakia. Electronic address: henrieta.patayova@szu.sk., Jusko TA; Departments of Public Health Sciences and Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. Electronic address: todd_jusko@urmc.rochester.edu., van Duursen MB; Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.176, 3508, TD, Utrecht, The Netherlands. Electronic address: m.vanduursen@uu.nl., Palkovičová Murínová Ľ; Slovak Medical University, Limbová 14, 83303 Bratislava, Slovakia. Electronic address: lubica.murinova@szu.sk., Canton RF; Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.176, 3508, TD, Utrecht, The Netherlands. Electronic address: rfcanton@gmail.com., van Ede KI; Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.176, 3508, TD, Utrecht, The Netherlands. Electronic address: K.I.vanEde@uu.nl., Trnovec T; Slovak Medical University, Limbová 14, 83303 Bratislava, Slovakia. Electronic address: tomas.trnovec@szu.sk.
Jazyk: angličtina
Zdroj: Environment international [Environ Int] 2016 Nov; Vol. 96, pp. 24-33. Date of Electronic Publication: 2016 Aug 31.
DOI: 10.1016/j.envint.2016.08.016
Abstrakt: 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.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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