title: 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.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors: Slovak Medical University, Limbová 14, 83303 Bratislava, Slovakia. Electronic address: sona.wimmerova@szu.sk.
authors: Soňa
authors: S
authors: Wimmerová
authors: Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.176, 3508, TD, Utrecht, The Netherlands. Electronic address: m.vandenberg@uu.nl.
authors: Martin
authors: M
authors: van den Berg
authors: Slovak Medical University, Limbová 14, 83303 Bratislava, Slovakia. Electronic address: jana.chovancova@szu.sk.
authors: Jana
authors: J
authors: Chovancová
authors: Slovak Medical University, Limbová 14, 83303 Bratislava, Slovakia. Electronic address: henrieta.patayova@szu.sk.
authors: Henrieta
authors: H
authors: Patayová
authors: 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.
authors: Todd A
authors: TA
authors: Jusko
authors: Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.176, 3508, TD, Utrecht, The Netherlands. Electronic address: m.vanduursen@uu.nl.
authors: Majorie B M
authors: MB
authors: van Duursen
authors: Slovak Medical University, Limbová 14, 83303 Bratislava, Slovakia. Electronic address: lubica.murinova@szu.sk.
authors: Ľubica
authors: Ľ
authors: Palkovičová Murínová
authors: Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.176, 3508, TD, Utrecht, The Netherlands. Electronic address: rfcanton@gmail.com.
authors: Rocio F
authors: RF
authors: Canton
authors: 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.
authors: Karin I
authors: KI
authors: van Ede
authors: Slovak Medical University, Limbová 14, 83303 Bratislava, Slovakia. Electronic address: tomas.trnovec@szu.sk.
authors: Tomáš
authors: T
authors: Trnovec
mesh_terms: D000328:Adult; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D065633:Cytochrome P-450 CYP1B1 / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System; D004147:Dioxins / Q000097:blood / Q000633:toxicity*; D005260:Female; D005663:Furans / Q000097:blood / Q000633:toxicity*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011078:Polychlorinated Biphenyls / Q000097:blood / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins; D018570:Risk Assessment; D013961:Thyroid Gland / Q000187:drug effects
chemical_list: D004147:Dioxins; D005663:Furans; D000072317:Polychlorinated Dibenzodioxins; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1
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)