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MEETING ABSTRACT Open Access Endocrine Disrupting Compounds do we need to consider thyroid hormones? Mechanism-based testing strategy using in vitro approaches for identification of thyroid hormone disrupting chemicals Arno C Gutleb From 4th Congress of the Polish Thyroid Association 2013 Lodz, Poland. 11-13 April 2013 The thyroid hormone (TH) system is involved in many important physiological processes, including regulation of energy metabolism, growth and differentiation, development and maintenance of brain function, thermo- regulation, osmo-regulation, and axis of regulation of other endocrine systems, sexual behaviour and fertility, cardiovascular function. Therefore, concern about TH dis- ruption (THD) has resulted in strategies being developed to identify THD chemicals (THDC). Information on potential of chemicals causing THD is typically derived from animal studies. However, for most chemicals, this information is often limited or even unavailable. It is also unlikely that animal experiments will be performed for all THD relevant chemicals in the near future for ethical, financial and practical reasons. In addition, typical animal experiments often do not provide information on the mechanism of action of THDC, making it harder to extra- polate results across species. Relevant effects may not be identified in animal studies when the effects are delayed, life stage specific, not assessed by the experimental para- digm (e.g., behaviour) or only occur when an organism has to adapt to environmental factors by modulating TH levels. Therefore, in vitro and in silico alternatives to iden- tify THDC and quantify their potency are needed. THDC have many potential mechanisms of action, including altered hormone production, transport, metabolism, receptor activation and disruption of several feed-back mechanisms. In vitro assays are available for many of these endpoints, and the application of modern -omicstechnologies, applicable for in vivo studies can help to reveal relevant and possibly new endpoints for inclusion in a targeted THDC in vitro test battery. Within the frame- work of the ASAT initiative (Assuring Safety without Ani- mal Testing), an international group consisting of experts in the areas of thyroid endocrinology, toxicology of endo- crine disruption, neurotoxicology, high-throughput screening, computational biology, and regulatory affairs has reviewed the state of science [1] for (1) known mechanisms for THD plus examples of THDC; (2) in vitro THD tests currently available or under development related to these mechanisms; and (3) in silico methods for estimating the blood levels of THDC. Based on this scien- tific review, the panel recommends a battery of test meth- ods to be able to classify chemicals as of less or high concern for further hazard and risk assessment for THD. Published: 5 April 2013 Reference 1. Murk AJ, Rijntjes E, Blaauboer BJ, Clewell R, Crofton KM, Dingemans MM, David Furlow J, Kavlock R, Köhrle J, Opitz R, Traas T, Visser TJ, Xia M, Gutleb AC: Mechanism-based testing strategy using in vitro approaches for identification of thyroid hormone disrupting chemicals. Toxicol In Vitro . doi:10.1186/1756-6614-6-S2-A20 Cite this article as: Gutleb: Endocrine Disrupting Compounds do we need to consider thyroid hormones? Mechanism-based testing strategy using in vitro approaches for identification of thyroid hormone disrupting chemicals. Thyroid Research 2013 6(Suppl 2):A20. Centre de Recherche Public Gabriel Lippmann, Luxembourg Gutleb Thyroid Research 2013, 6(Suppl 2):A20 http://www.thyroidresearchjournal.com/content/6/S2/A20 © 2013 Gutleb; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Endocrine Disrupting Compounds – do we need to consider thyroid hormones? Mechanism-based testing strategy using in vitro approaches for identification of thyroid hormone disrupting

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MEETING ABSTRACT Open Access

Endocrine Disrupting Compounds – do we needto consider thyroid hormones? Mechanism-basedtesting strategy using in vitro approaches foridentification of thyroid hormone disruptingchemicalsArno C Gutleb

From 4th Congress of the Polish Thyroid Association 2013Lodz, Poland. 11-13 April 2013

The thyroid hormone (TH) system is involved in manyimportant physiological processes, including regulationof energy metabolism, growth and differentiation,development and maintenance of brain function, thermo-regulation, osmo-regulation, and axis of regulation ofother endocrine systems, sexual behaviour and fertility,cardiovascular function. Therefore, concern about TH dis-ruption (THD) has resulted in strategies being developedto identify THD chemicals (THDC). Information onpotential of chemicals causing THD is typically derivedfrom animal studies. However, for most chemicals, thisinformation is often limited or even unavailable. It is alsounlikely that animal experiments will be performed for allTHD relevant chemicals in the near future for ethical,financial and practical reasons. In addition, typical animalexperiments often do not provide information on themechanism of action of THDC, making it harder to extra-polate results across species. Relevant effects may not beidentified in animal studies when the effects are delayed,life stage specific, not assessed by the experimental para-digm (e.g., behaviour) or only occur when an organismhas to adapt to environmental factors by modulating THlevels. Therefore, in vitro and in silico alternatives to iden-tify THDC and quantify their potency are needed. THDChave many potential mechanisms of action, includingaltered hormone production, transport, metabolism,receptor activation and disruption of several feed-backmechanisms. In vitro assays are available for many ofthese endpoints, and the application of modern ‘-omics’

technologies, applicable for in vivo studies can help toreveal relevant and possibly new endpoints for inclusion ina targeted THDC in vitro test battery. Within the frame-work of the ASAT initiative (Assuring Safety without Ani-mal Testing), an international group consisting of expertsin the areas of thyroid endocrinology, toxicology of endo-crine disruption, neurotoxicology, high-throughputscreening, computational biology, and regulatory affairshas reviewed the state of science [1] for (1) knownmechanisms for THD plus examples of THDC; (2) in vitroTHD tests currently available or under developmentrelated to these mechanisms; and (3) in silico methods forestimating the blood levels of THDC. Based on this scien-tific review, the panel recommends a battery of test meth-ods to be able to classify chemicals as of less or highconcern for further hazard and risk assessment for THD.

Published: 5 April 2013

Reference1. Murk AJ, Rijntjes E, Blaauboer BJ, Clewell R, Crofton KM, Dingemans MM,

David Furlow J, Kavlock R, Köhrle J, Opitz R, Traas T, Visser TJ, Xia M,Gutleb AC: Mechanism-based testing strategy using in vitro approachesfor identification of thyroid hormone disrupting chemicals. Toxicol InVitro .

doi:10.1186/1756-6614-6-S2-A20Cite this article as: Gutleb: Endocrine Disrupting Compounds – do weneed to consider thyroid hormones? Mechanism-based testing strategyusing in vitro approaches for identification of thyroid hormonedisrupting chemicals. Thyroid Research 2013 6(Suppl 2):A20.

Centre de Recherche Public – Gabriel Lippmann, Luxembourg

Gutleb Thyroid Research 2013, 6(Suppl 2):A20http://www.thyroidresearchjournal.com/content/6/S2/A20

© 2013 Gutleb; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.