Evaluation of relative effect potencies REPs for dioxin-like compounds to derive systemic or human-specific TEFs to improve human risk assessmentReport as inadecuate




Evaluation of relative effect potencies REPs for dioxin-like compounds to derive systemic or human-specific TEFs to improve human risk assessment - Download this document for free, or read online. Document in PDF available to download.

Archives of Toxicology

, Volume 90, Issue 6, pp 1293–1305

First Online: 09 May 2016Received: 09 February 2016Accepted: 21 April 2016DOI: 10.1007-s00204-016-1724-9

Cite this article as: van Ede, K.I., van Duursen, M.B.M. & van den Berg, M. Arch Toxicol 2016 90: 1293. doi:10.1007-s00204-016-1724-9

Abstract

Toxic equivalency factors TEFs are generally applied for estimating human risk of dioxins and dioxin-like compounds using systemic e.g., blood levels, even though these TEFs are established based on intake doses in rodent studies. This review shows that systemic relative effect potencies REPs can deviate substantially from intake REPs, but are similar to in vitro-derived REPs. Interestingly, the in vitro REPs for 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin HpCDD and 2,3,4,7,8-pentachlorodibenzofuran 4-PeCDF are up to one order of magnitude higher than their in vivo REPs and WHO-TEFs, based on oral intake. In addition, clear species-differences in in vitro REPs were apparent for some congeners. Especially the human-derived REP for polychlorinated biphenyl 126 is one to two orders of magnitude lower than rodent REPs and its current WHO-TEF. Next, suggested adapted systemic or human-specific TEFs for these congeners were applied to calculate changes in systemic TEQ concentrations in studies from the USA, Germany and Japan and compared with either the JECFA TDI or USEPA RfD of TCDD. Overall, the effect of such TEF changes for these three congeners on total TEQ roughly balances each other out in the general population. However, results may be different for situations in which a specific group of congeners dominates. For those congeners that show a distinct deviation between either intake and systemic REPs or between rodent- and human-based in vitro REPs, we propose that especially REPs derived from human-based in vitro models are weighted more heavily in establishing systemic or human-specific TEF values to improve human health risk assessment.

KeywordsDibenzofurans Dioxins Human risk assessment PCBs TEF-concept AbbreviationsAhRAryl hydrocarbon receptor

BEsBiomonitoring Equivalents

DLCDioxin-like compound

GIGastrointestinal

HepG2Human hepatoblastoma cells

HpCDD1,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin

6-HxCDD1,2,3,6,7,8-Hexachlorodibenzo-p-dioxin

9-HpCDF1,2,3,4,7,8,9-Heptachlorodibenzofuran

4-HxCDF1,2,3,4,7,8-Hexachlorodibenzofuran

6-HxCDF1,2,3,6,7,8-Hexachlorodibenzofuran

NTPNational toxicology program

OCDF1,2,3,4,6,7,8,9-Octachlorodibenzofuran

PBMCsPeripheral blood mononuclear cells

PCBPolychlorinated biphenyl

PCB 1263,3′,4,4′,5-Pentachlorobiphenyl

PCDDPolychlorinated dibenzo-p-dioxin

PeCDD1,2,3,7,8-Pentachlorodibenzo-p-dioxin

PCDFPolychlorinated dibenzofuran

1-PeCDF1,2,3,7,8-Pentachlorodibenzofuran

4-PeCDF2,3,4,7,8-Pentachlorodibenzofuran

REPRelative effect potencies

RfDReference dose

TCDD2,3,7,8-Tetrachlorodibenzo-p-dioxin

TCDF2,3,7,8-Tetrachlorodibenzofuran

TEFToxic equivalency factor

TEQToxic equivalency

TDITolerable daily intake

WHOWorld Health Organization

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Author: Karin I. van Ede - Majorie B. M. van Duursen - Martin van den Berg

Source: https://link.springer.com/







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