Differential relative effect potencies of some dioxin-like compounds in human peripheral blood lymphocytes and murine splenic cells

被引:10
作者
van Ede, Karin I. [1 ]
Gaisch, Konrad P. J. [1 ]
van den Berg, Martin [1 ]
van Duursen, Majorie B. M. [1 ]
机构
[1] Univ Utrecht, Inst Risk Assessment Sci, NL-3584 CM Utrecht, Netherlands
关键词
Dibenzodioxins; Dibenzofurans; Lymphocytes; PCBs; REPs; Risk assessment; TOXIC EQUIVALENCY FACTORS; RAT PRIMARY HEPATOCYTES; POLYCHLORINATED-BIPHENYLS; AROMATIC-HYDROCARBONS; CYTOCHROME-P450; 1A1; MONONUCLEAR-CELLS; GENE-EXPRESSION; DOSE-RESPONSE; HEPG2; CELLS; INDUCTION;
D O I
10.1016/j.toxlet.2014.01.026
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Human risk assessment for dioxin-like compounds is typically based on the concentration measured in blood serum multiplied by their assigned toxic equivalency factor (TEF). Consequently, the actual value of the TEF is very important for accurate human risk assessment. In this study we investigated the effect potencies of three polychlorinated dibenzo-p-dioxins (PCDDs), six polychlorinated dibenzofurans (PCDFs) and 10 polychlorinated biphenyls (PCBs) relative to the reference congener 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) in in vitro exposed primary human peripheral blood lymphocytes (PBLs) and mouse splenic cells. REPs were determined based on cytochrome P450 (CYP) 1111, 181 and aryl hydrocarbon receptor repressor (AhRR) gene expression as well as CYP1A1 activity in human PBLs and Cyp1a1 gene expression in murine splenic cells. Estimated median human REPs for 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (1234678-HpCDD), 2,3,4,7,8,pentachlorodibenzofuran (23478-PeCDF), 1,2,3,4,7,8-hexachlorodibenzofuran (123478-HxCDF) and 1,2,3,4,7,8,9-heptachlorodibenzofuran (1234789-HpCDF) were with 0.1, 1.1, 1 and 0.09, respectively, significantly higher compared to those estimated for mouse with REPs of 0.05, 0.45, 0.09 and 0.04, respectively. Opposite to these results, the estimated median human REP of 3,3,4,4',5 -pentachlor obiphenyl (PCB 126), was with 0.001 30-fold lower compared to the mouse REP of 0.03. Furthermore, human REPs for 1234678-HpCDD, 23478-PeCDF, 123478-HxCDF, 1234789-HpCDF and PCB 126 were all outside the I half log uncertainty range that is taken into account in the WHO-assigned TEFs. Together, these data show congener- and species-specific differences in REPs for some, but not all dioxin-like congeners tested. This suggests that, more emphasis should be placed on human-tissue derived REPs in the establishment of a TEF for human risk assessment. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:43 / 52
页数:10
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