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标题：Comparison of Intake and Systemic Relative Effect Potencies of Dioxin-like Compounds in Female Mice after a Single Oral Dose
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作者：Karin I. van Ede ; Patrik L. Andersson ; Konrad P.J. Gaisch 等
期刊名称：Environmental Health Perspectives
印刷版ISSN：0091-6765
电子版ISSN：1552-9924
出版年度：2013
卷号：121
期号：7
页码：847-853
DOI：10.1289/ehp.1206336
出版社：OCR Subscription Services Inc
摘要：Background: Risk assessment for mixtures of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) is performed using the toxic equivalency factor (TEF) approach. These TEF values are derived mainly from relative effect potencies (REPs) linking an administered dose to an in vivo toxic or biological effect, resulting in “intake” TEFs. At present, there is insufficient data available to conclude that intake TEFs are also applicable for systemic concentrations (e.g., blood and tissues). O b jective: We compared intake and systemic REPs of 1,2,3,7,8-pentachlorodibenzodioxin (PeCDD), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), 3,3´,4,4´,5-pentachlorobiphenyl (PCB‑126), 2,3´,4,4´,5-pentachlorobiphenyl (PCB‑118), and 2,3,3´,4,4´,5-hexachlorobiphenyl (PCB‑156) in female C57BL/6 mice 3 days after a single oral dose. Methods: We calculated intake REPs and systemic REPs based on administered dose and liver, adipose, or plasma concentrations relative to TCDD. Hepatic cytochrome P450 1A1–associated ethoxyresorufin-O-deethylase (EROD) activity and gene expression of Cyp1a1, 1a2 and 1b1 in the liver and peripheral blood lymphocytes (PBLs) were used as biological end points. R esults: We observed up to one order of magnitude difference between intake REPs and systemic REPs. Two different patterns were discerned. Compared with intake REPs, systemic REPs based on plasma or adipose levels were higher for PeCDD, 4-PeCDF, and PCB‑126 but lower for the mono-ortho PCBs 118 and 156. C onclusions: Based on these mouse data, the comparison between intake REPs and systemic REPs reveals significant congener-specific differences that warrants the development of systemic TEFs to calculate toxic equivalents (TEQs) in blood and body tissues.
关键词：dibenzofurans; dioxins; PCBs; PCDDs; PCDFs; polychlorinated biphenyls; systemic REPs; TEF concept.