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 |
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| Institution: | 1. Slovak Medical University, Limbová 14, 83303 Bratislava, Slovakia;2. Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.176, 3508, TD, Utrecht, The Netherlands;3. Departments of Public Health Sciences and Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA;1. Laboratory of Aquatic Toxicology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Selangor, Malaysia;2. School of Veterinary Medicine, Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA;3. Centre of Excellence for Environmental Forensics, Faculty of Environmental Studies, Universiti Putra Malaysia, 43400, UPM, Selangor, Malaysia;4. Department of Environment and Resource Studies, Canadian Water Network, Canadian Rivers Institute, University of Waterloo, Canada;1. Hokkaido University Center for Environmental and Health Sciences, Kita 12, Nishi 7, Kita-ku, Sapporo 060-0812, Japan;2. Osaka Occupational Health Service Center, Japan Industrial Safety and Health Association, 2-3-8, Tosabori, Nishi-ku, Osaka 550-0001, Japan;3. Department of Environmental Health and Toxicology, Division of Environment Health, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunincho, Shinjuku-ku, Tokyo 169-0073, Japan;4. Asahikawa Medical University for Department of Health Science, E2-1-1-1, Midorigaoka, Asahikawa, Hokkaido 078-8510, Japan;1. Advisory Committee on Protection of the Sea, London, UK;2. Department of Oceanography, University of Hawai''i at Mānoa, Honolulu, HI, USA;1. School of Social and Community Medicine, University of Bristol, Bristol, UK;2. Department of Environmental and Occupational Health and Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA, USA;1. Institute of Clinical Physiology, National Research Council, Pisa, Italy;2. S.C. Epidemiologia e Statistica - Sez. Registro Tumori - ASL Taranto, Italy |
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| Abstract: | BackgroundIn 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.ObjectivesWe 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.MethodsWe 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.ResultsWe 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).ConclusionsREPs 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. |
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