New Scoping Document on in vitro and ex vivo Assays for the Identification of Modulators of Thyroid Hormone Signalling

Abstract

Complete document available on OLIS in its original formatThis document and any map included herein are without prejudice to the status of or sovereignty over any territory, to the delimitation of international frontiers and boundaries and to the name of any territory, city or area. About the OECDThe Organisation for Economic Co-operation and Development (OECD) is an intergovernmental organisation in which representatives of 34 industrialised countries in North and South America, Europe and the Asia and Pacific region, as well as the European Commission, meet to co-ordinate and harmonise policies, discuss issues of mutual concern, and work together to respond to international problems. Most of the OECD's work is carried out by more than 200 specialised committees and working groups composed of member country delegates. Observers from several countries with special status at the OECD, and from interested international organisations, attend many of the OECD's workshops and other meetings. Committees and working groups are served by the OECD Secretariat, located in Paris, France, which is organised into directorates and divisions. This publication was developed in the IOMC context. The contents do not necessarily reflect the views or stated policies of individual IOMC Participating Organisations.The Inter-Organisation Programme for the Sound Management of Chemicals (IOMC) was established in 1995 following recommendations made by the 1992 UN Conference on Environment and Development to strengthen co-operation and increase international co-ordination in the field of chemical safety. The Participating Organisations are FAO, ILO, UNDP, UNEP, UNIDO, UNITAR, WHO, World Bank and OECD. The purpose of the IOMC is to promote co-ordination of the policies and activities pursued by the Participating Organisations, jointly or separately, to achieve the sound management of chemicals in relation to human health and the environment. FOREWORDThis new scoping document aims at bringing forward relevant in vitro and ex vivo thyroid assays to the attention of OECD member countries, to provide recommendations for their development/use, and also, to identify aspects/blocks of the thyroid signalling pathways that are not covered and would require further development of thyroid assays. ACRONYMS, ABBREVIATIONS AND DEFINITIONS ADMEAbsorption, distribution, metabolism and excretion AhR aryl hydrocarbon receptor AMA Amphibian Metamorphosis Assay (OECD TG 231) AOP adverse outcome pathway AOP is a sequence of events from the exposure of an individual or population to a chemical substance through a final adverse (toxic) effect at the individual level (for human health) or population level (for ecotoxicological endpoints). AR androgen receptorAssay An experimental system that can be used to obtain a range of information from chemical properties through the adverse effects of a substance. The terms 'assay' and 'test method' may be used interchangeably for wildlife as well as for mammalian studies (OECD, 2005) Indicators of Hormonal activit...

High-throughput screening and chemotype-enrichment analysis of ToxCast phase II chemicals evaluated for human sodium-iodide symporter (NIS) inhibition

“…Instead, thyroid target sites primarily include TH synthesis, secretion, transport, and metabolism ( Ferrari et al, 2017 ; Hornung et al, 2015 ; Maurício Martins da et al, 2018 ; Murk et al, 2013 ; Pearce et al, 2013 ). For this reason, there has been a recent global effort to develop and implement the use of high throughput screening (HTS) assays to expand the coverage of molecular targets of thyroid-disrupting chemicals ( Dong and Wade, 2017 ; Murk et al, 2013 ; OECD, 2017 ). The current project is part of a joint effort between the U.S. EPA's Endocrine Disruptor Screening Program (EDSP) and Office of Research and Development (ORD) to expedite the use of HTS and computational toxicology to evaluate chemicals under the Agency's regulatory purview for thyroid-disrupting activity.…”

Candidate Proficiency Test Chemicals to Address Industrial Chemical Applicability Domains for in vitro Human Cytochrome P450 Enzyme Induction

“…In addition to mediating detoxification, CAR, PXR and AhR have been implicated in the regulation of a broader range of physiological functions ( Kretschmer and Baldwin 2005 ; Wang and Tompkins 2008 ; Yi, Fashe et al, 2020 ), where dysregulation can lead to adverse effects ( Hakkola, Bernasconi et al, 2018 ) and receptor and CYP induction have well documented roles for instance in inflammation ( Christmas, 2015 ; Rubin, Janefeldt et al, 2015 ), cholestasis, steatosis ( Gomez-Lechon, Jover et al, 2009 ), hepatotoxicity ( Woolbright and Jaeschke 2015 ), carcinogenesis ( De Mattia, Cecchin et al, 2016 ; Pondugula, Pavek et al, 2016 ; Fucic, Guszak et al, 2017 ), and thyroid disruption ( OECD 2006 ; OECD 2014 ). Thus, in these cases, induction of specified CYP enzymes may serve as a biomarker for key events associated with adverse health effects.…”

“…Here we have also given some examples of immediate applications of the assay for the OECD Conceptual Framework for Endocrine Disruptors, and for the OECD IATA for non-genotoxic carcinogens. There will also be necessary applications to other complex human health IATAs, including that for thyroid disruption ( OECD, 2014 ), and metabolic disruption ( Legler, Zalko et al, 2020 ).…”