Characterisation of chlorinated, brominated and mixed halogenated dioxins, furans and biphenyls as potent and as partial agonists of the Aryl hydrocarbon receptor

The Aryl hydrocarbon receptor (AhR) binds a variety of chlorinated and brominated dioxins, furans and biphenyls. Mixed halogenated variants have been recently identified in food at significant levels but full characterisation requires potency data in order to gauge their impact on risk assessment. R...

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Main Authors:	Wall, Richard J., Fernades, Alwyn, Rose, Martin, Bell, David R., Mellor, Ian R.
Format:	Article
Language:	English
Published:	Elsevier 2015
Online Access:	http://eprints.nottingham.ac.uk/34985/ http://eprints.nottingham.ac.uk/34985/ http://eprints.nottingham.ac.uk/34985/ http://eprints.nottingham.ac.uk/34985/1/Wall%20et%20al%202015.pdf

id	nottingham-34985
recordtype	eprints
spelling	nottingham-349852017-10-13T04:19:01Z http://eprints.nottingham.ac.uk/34985/ Characterisation of chlorinated, brominated and mixed halogenated dioxins, furans and biphenyls as potent and as partial agonists of the Aryl hydrocarbon receptor Wall, Richard J. Fernades, Alwyn Rose, Martin Bell, David R. Mellor, Ian R. The Aryl hydrocarbon receptor (AhR) binds a variety of chlorinated and brominated dioxins, furans and biphenyls. Mixed halogenated variants have been recently identified in food at significant levels but full characterisation requires potency data in order to gauge their impact on risk assessment. Rat H4IIE and human MCF-7 cells were treated with various mixed halogenated ligands. Antagonist properties were measured by treating cells with various concentrations of TCDD in the presence of EC25 of the putative antagonist. Measurement of CYP1A1 RNA was used to quantify the potency of agonism and antagonism. The PXDDs were found to be slightly less potent than the corresponding fully chlorinated congeners with the exception of 2-B,3,7,8-TriCDD which was 2-fold more potent than TCDD. PXDFs and non-ortho-PXBs were found to be more potent than their chlorinated congeners whilst several mono-ortho-substituted PXBs were shown to have partial agonistic properties. REPs were produced for a range of mixed halogenated AhR-activating ligands providing a more accurate estimation of potency for risk assessment. Several environmentally abundant biphenyls were shown to be antagonists and reduce the ability of TCDD to induce CYP1A1. The demonstration of antagonism for AhR ligands represents a challenge for existing REP risk assessment schemes for AhR ligands. Elsevier 2015-03 Article PeerReviewed application/pdf en cc_by http://eprints.nottingham.ac.uk/34985/1/Wall%20et%20al%202015.pdf Wall, Richard J. and Fernades, Alwyn and Rose, Martin and Bell, David R. and Mellor, Ian R. (2015) Characterisation of chlorinated, brominated and mixed halogenated dioxins, furans and biphenyls as potent and as partial agonists of the Aryl hydrocarbon receptor. Environment International, 76 . pp. 49-56. ISSN 1873-6750 http://www.sciencedirect.com/science/article/pii/S0160412014003572 doi:10.1016/j.envint.2014.12.002 doi:10.1016/j.envint.2014.12.002
repository_type	Digital Repository
institution_category	Local University
institution	University of Nottingham Malaysia Campus
building	Nottingham Research Data Repository
collection	Online Access
language	English
description	The Aryl hydrocarbon receptor (AhR) binds a variety of chlorinated and brominated dioxins, furans and biphenyls. Mixed halogenated variants have been recently identified in food at significant levels but full characterisation requires potency data in order to gauge their impact on risk assessment. Rat H4IIE and human MCF-7 cells were treated with various mixed halogenated ligands. Antagonist properties were measured by treating cells with various concentrations of TCDD in the presence of EC25 of the putative antagonist. Measurement of CYP1A1 RNA was used to quantify the potency of agonism and antagonism. The PXDDs were found to be slightly less potent than the corresponding fully chlorinated congeners with the exception of 2-B,3,7,8-TriCDD which was 2-fold more potent than TCDD. PXDFs and non-ortho-PXBs were found to be more potent than their chlorinated congeners whilst several mono-ortho-substituted PXBs were shown to have partial agonistic properties. REPs were produced for a range of mixed halogenated AhR-activating ligands providing a more accurate estimation of potency for risk assessment. Several environmentally abundant biphenyls were shown to be antagonists and reduce the ability of TCDD to induce CYP1A1. The demonstration of antagonism for AhR ligands represents a challenge for existing REP risk assessment schemes for AhR ligands.
format	Article
author	Wall, Richard J. Fernades, Alwyn Rose, Martin Bell, David R. Mellor, Ian R.
spellingShingle	Wall, Richard J. Fernades, Alwyn Rose, Martin Bell, David R. Mellor, Ian R. Characterisation of chlorinated, brominated and mixed halogenated dioxins, furans and biphenyls as potent and as partial agonists of the Aryl hydrocarbon receptor
author_facet	Wall, Richard J. Fernades, Alwyn Rose, Martin Bell, David R. Mellor, Ian R.
author_sort	Wall, Richard J.
title	Characterisation of chlorinated, brominated and mixed halogenated dioxins, furans and biphenyls as potent and as partial agonists of the Aryl hydrocarbon receptor
title_short	Characterisation of chlorinated, brominated and mixed halogenated dioxins, furans and biphenyls as potent and as partial agonists of the Aryl hydrocarbon receptor
title_full	Characterisation of chlorinated, brominated and mixed halogenated dioxins, furans and biphenyls as potent and as partial agonists of the Aryl hydrocarbon receptor
title_fullStr	Characterisation of chlorinated, brominated and mixed halogenated dioxins, furans and biphenyls as potent and as partial agonists of the Aryl hydrocarbon receptor
title_full_unstemmed	Characterisation of chlorinated, brominated and mixed halogenated dioxins, furans and biphenyls as potent and as partial agonists of the Aryl hydrocarbon receptor
title_sort	characterisation of chlorinated, brominated and mixed halogenated dioxins, furans and biphenyls as potent and as partial agonists of the aryl hydrocarbon receptor
publisher	Elsevier
publishDate	2015
url	http://eprints.nottingham.ac.uk/34985/ http://eprints.nottingham.ac.uk/34985/ http://eprints.nottingham.ac.uk/34985/ http://eprints.nottingham.ac.uk/34985/1/Wall%20et%20al%202015.pdf
first_indexed	2018-09-06T12:32:17Z
last_indexed	2018-09-06T12:32:17Z
_version_	1610861392575856640

Characterisation of chlorinated, brominated and mixed halogenated dioxins, furans and biphenyls as potent and as partial agonists of the Aryl hydrocarbon receptor

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