TY - JOUR
T1 - 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
AU - Wimmerová, Soňa
AU - van den Berg, Martin
AU - Chovancová, Jana
AU - Patayová, Henrieta
AU - Jusko, Todd A.
AU - van Duursen, Majorie B.M.
AU - Palkovičová Murínová, Ľubica
AU - Canton, Rocio F.
AU - van Ede, Karin I.
AU - Trnovec, Tomáš
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
KW - Cytochrome P450 (CYP) 1A1 and 1B1
KW - Dioxin-like polychlorinated biphenyl (DL-PCB)
KW - Polychlorinated dibenzo-p-dioxins (PCDDs)
KW - Polychlorinated dibenzo-p-furans (PCDFs)
KW - Relative effect potency (REP)
KW - Toxic equivalency factor (TEF)
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U2 - 10.1016/j.envint.2016.08.016
DO - 10.1016/j.envint.2016.08.016
M3 - Article
C2 - 27588699
AN - SCOPUS:84984620391
SN - 0160-4120
VL - 96
SP - 24
EP - 33
JO - Environment International
JF - Environment International
ER -