ERGO: Breaking Down the Wall between Human Health and Environmental Testing of Endocrine Disrupters
Language English Country Switzerland Media electronic
Document type Journal Article, Review
Grant support
825753
Horizon 2020 Framework Programme
PubMed
32331419
PubMed Central
PMC7215679
DOI
10.3390/ijms21082954
PII: ijms21082954
Knihovny.cz E-resources
- Keywords
- AOP, IATA, OECD, adverse outcome pathway, biomarkers, cross-species extrapolation, endocrine disruption, integrated approach to testing and assessment, test guideline, thyroid hormone disruption,
- MeSH
- Biomarkers MeSH
- Biological Assay * methods MeSH
- Species Specificity MeSH
- Endocrine Disruptors adverse effects analysis MeSH
- Endocrine System drug effects metabolism MeSH
- Risk Assessment MeSH
- Health Impact Assessment MeSH
- Humans MeSH
- Environmental Monitoring * methods MeSH
- Workflow MeSH
- Data Warehousing MeSH
- Health Plan Implementation MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Biomarkers MeSH
- Endocrine Disruptors MeSH
ERGO (EndocRine Guideline Optimization) is the acronym of a European Union-funded research and innovation action, that aims to break down the wall between mammalian and non-mammalian vertebrate regulatory testing of endocrine disruptors (EDs), by identifying, developing and aligning thyroid-related biomarkers and endpoints (B/E) for the linkage of effects between vertebrate classes. To achieve this, an adverse outcome pathway (AOP) network covering various modes of thyroid hormone disruption (THD) in multiple vertebrate classes will be developed. The AOP development will be based on existing and new data from in vitro and in vivo experiments with fish, amphibians and mammals, using a battery of different THDs. This will provide the scientifically plausible and evidence-based foundation for the selection of B/E and assays in lower vertebrates, predictive of human health outcomes. These assays will be prioritized for validation at OECD (Organization for Economic Cooperation and Development) level. ERGO will re-think ED testing strategies from in silico methods to in vivo testing and develop, optimize and validate existing in vivo and early life-stage OECD guidelines, as well as new in vitro protocols for THD. This strategy will reduce requirements for animal testing by preventing duplication of testing in mammals and non-mammalian vertebrates and increase the screening capacity to enable more chemicals to be tested for ED properties.
AquaTT Olympic House Pleasants Street D08 H67X Dublin Ireland
BASF SE Experimental Toxicology and Ecotoxicology 67098 Ludwigshafen Germany
Centre for Organismal Studies University of Heidelberg 69120 Heidelberg Germany
Department of Biology University of Southern Denmark 5230 Odense M Denmark
Department of Environmental Science Aarhus University 4000 Roskilde Denmark
German Environment Agency Section IV2 3 Chemicals 06844 Dessau Roßlau Germany
Graduate School of Nanobioscience Yokohama City University Yokohama 236 0027 Japan
Matthiessen Consultancy Dolfan Barn Beulah LD5 4UE UK
RECETOX Faculty of Science Masaryk University Kamenice 5 625 00 Brno Czech Republic
Zebrafishlab Department of Veterinary Sciences University of Antwerp 2610 Wilrijk Belgium
See more in PubMed
Bopp S., Nepelska M., Halder M., Munn S. Expert Survey on Identification of Gaps in Available Test Methods for Evaluation of Endocrine Disruptors. JRC; Ispra, Italy: 2017. Technical Report.
BIPRO. DHI. Directorate-General for Environment (European Commission) INERIS. RAMBOLL Environ . Temporal Aspects in the Testing of Chemicals for Endocrine Disrupting Effects (in Relation to Human Health and the Environment) EU Publications; Brussel, Belgium: 2018.
European Commission. Risk & Policy Analysts Limited (RPA) wca Environment . Setting Priorities for Further Development and Validation of Test Methods and Testing Approaches for Evaluating Endocrine Disruptors. EU Publications; Brussel, Belgium: 2018.
EURION EURION Cluster Webpage 2020. [(accessed on 15 April 2020)]; Available online: https://eurion-cluster.eu.
Holzer G., Morishita Y., Fini J.B., Lorin T., Gillet B., Hughes S., Tohme M., Deleage G., Demeneix B., Arvan P., et al. Thyroglobulin Represents a Novel Molecular Architecture of Vertebrates. J. Biol. Chem. 2016;291:16553–16566. doi: 10.1074/jbc.M116.719047. PubMed DOI PMC
Holzer G., Roux N., Laudet V. Evolution of ligands, receptors and metabolizing enzymes of thyroid signaling. Mol. Cell. Endocrinol. 2017;459:5–13. doi: 10.1016/j.mce.2017.03.021. PubMed DOI
Mengeling B.J., Wei Y., Dobrawa L.N., Streekstra M., Louisse J., Singh V., Singh L., Lein P.J., Wulff H., Murk A.J., et al. A multi-tiered, in vivo, quantitative assay suite for environmental disruptors of thyroid hormone signaling. Aquat. Toxicol. 2017;190:1–10. doi: 10.1016/j.aquatox.2017.06.019. PubMed DOI PMC
Pickford D.B. Screening chemicals for thyroid-disrupting activity: A critical comparison of mammalian and amphibian models. Crit. Rev. Toxicol. 2010;40:845–892. doi: 10.3109/10408444.2010.494250. PubMed DOI
Power D.M., Elias N.P., Richardson S.J., Mendes J., Soares C.M., Santos C.R.A. Evolution of the thyroid hormone-binding protein, transthyretin. Gen. Comp. Endocrinol. 2000;119:241–255. doi: 10.1006/gcen.2000.7520. PubMed DOI
Rivetti C., Allen T.E., Brown J.B., Butler E., Carmichael P.L., Colbourne J.K., Dent M., Falciani F., Gunnarsson L., Gutsell S., et al. Vision of a near future: Bridging the human health-environment divide. Toward an integrated strategy to understand mechanisms across species for chemical safety assessment. Toxicol. Vitro. 2020;62:104692. doi: 10.1016/j.tiv.2019.104692. PubMed DOI
McArdle M., Freeman E.L., Staveley J., Ortego L., Coady K., Weltje L., Weyers A., Wheeler J.R., Bone A.J. Critical Review of Read-Across Potential in Testing for Endocrine-Related Effects in Vertebrate Ecological Receptors. Environ. Toxicol. Chem. 2020;39:739–753. doi: 10.1002/etc.4682. PubMed DOI PMC
Gore A.C., Chappell V.A., Fenton S.E., Flaws J.A., Nadal A., Prins G.S., Toppari J., Zoller R.T. EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals. Endocr. Rev. 2015;36:E1–E150. doi: 10.1210/er.2015-1010. PubMed DOI PMC
Korevaar T.I., Muetzel R., Medici M., Chaker L., Jaddoe V.W., de Rijke Y.B., Steegers A.P., Visser J., White T., Tiemeier H., et al. Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: A population-based prospective cohort study. Lancet Diabetes Endocrinol. 2016;4:35–43. doi: 10.1016/S2213-8587(15)00327-7. PubMed DOI
Grandjean P., Landrigan P.J. Neurobehavioural effects of developmental toxicity. Lancet Neurol. 2014;13:330–338. doi: 10.1016/S1474-4422(13)70278-3. PubMed DOI PMC
USEPA America’s Children and the Environment Health/Neurodevelopmental Disorders/Third Edition, Updated August 2017. [(accessed on 15 April 2020)]; Available online: https://www.epa.gov/sites/production/files/2017-07/documents/neurodevelopmental_updates_0.pdf.
Gee D. Late Lessons from Early Warnings: Science, Precaution, Innovation. European Environment Agency; Copenhagen, Denmark: 2013.
Woodruff T.J., Zota A.R., Schwartz J.M. Environmental Chemicals in Pregnant Women in the United States: NHANES 2003–2004. Environ. Health Perspect. 2011;119:878–885. doi: 10.1289/ehp.1002727. PubMed DOI PMC
Bellanger M., Demeneix B., Grandjean P., Zoeller R.T., Trasande L. Neurobehavioral Deficits, Diseases, and Associated Costs of Exposure to Endocrine-Disrupting Chemicals in the European Union. J. Clin. Endocrinol. Metab. 2015;100:1256–1266. doi: 10.1210/jc.2014-4323. PubMed DOI PMC
Middelbeek R.J., Veuger S.A. Letter to the Editor: Re: Neurobehavioral Deficits, Diseases, and Associated Costs of Exposure to Endocrine-Disrupting Chemicals in the European Union. J. Clin. Endocrinol. Metab. 2015;100:L52–L53. doi: 10.1210/jc.2015-2010. PubMed DOI PMC
Trasande L., Zoeller R.T., Hass U., Kortenkamp A., Grandjean P., Myers J.P., Di Gangi J., Bellanger M., Hauser R., Legler J., et al. Estimating Burden and Disease Costs of Exposure to Endocrine-Disrupting Chemicals in the European Union. J. Clin. Endocrinol. Metab. 2015;100:1245–1255. doi: 10.1210/jc.2014-4324. PubMed DOI PMC
Rovida C., Longo F., Rabbit R.R. How are Reproductive Toxicity and Developmental Toxicity Addressed in REACH Dossiers? ALTEX-Altern. Anim. Exp. 2011;28:273–294. PubMed
Rovida C. Food for Thought ... Why No New In Vitro Tests Will Be Done for REACH by Registrants. ALTEX-Altern. Anim. Exp. 2010;27:175–183. doi: 10.14573/altex.2010.3.175. PubMed DOI
OECD . The OECD Conceptual Framework for Testing and Assessment of Endocrine Disrupters (as Revised in 2012) Nordic Council of Ministers; Copenhagen, Denmark: 2012.
Salmina E.S., Wondrousch D., Kühne R., Potemkin V.A., Schüürmann G. Variation in predicted internal concentrations in relation to PBPK model complexity for rainbow trout. Sci. Total Environ. 2016;550:586–597. doi: 10.1016/j.scitotenv.2016.01.107. PubMed DOI
OECD . Guidance Document 150 on Standardised Test Guidelines for Evaluating Chemicals for Endocrine Disruption (2018 Version) Organisation for Economic Cooporation and Development; Paris, France: 2018.
Marelli F., Persani L. How zebrafish research has helped in understanding thyroid diseases. F1000Research. 2017;6:2137. doi: 10.12688/f1000research.12142.1. PubMed DOI PMC
Sachs L.M., Buchholz D.R. Frogs model man: In vivo thyroid hormone signaling during development. Genesis. 2017;55:10. doi: 10.1002/dvg.23000. PubMed DOI
Opitz R., Maquet E., Huisken J., Antonica F., Trubiroha A., Pottier G., Janssens V., Costagliola S. Transgenic zebrafish illuminate the dynamics of thyroid morphogenesis and its relationship to cardiovascular development. Dev. Biol. 2012;372:203–216. doi: 10.1016/j.ydbio.2012.09.011. PubMed DOI
Raldua D., Thienpont B., Babin P.J. Zebrafish eleutheroembryos as an alternative system for screening chemicals disrupting the mammalian thyroid gland morphogenesis and function. Reprod. Toxicol. 2012;33:188–197. doi: 10.1016/j.reprotox.2011.09.001. PubMed DOI
Lohr H., Hammerschmidt M. Zebrafish in Endocrine Systems: Recent Advances and Implications for Human Disease. In: Julius D., Clapham D.E., editors. Annual Review of Physiology. Volume 73. Annual Reviews; Palo Alto, CA, USA: 2011. pp. 183–211. PubMed
Lazcano I., Orozco A. Revisiting Available Knowledge on Teleostean Thyroid Hormone Receptors. Gen. Comp. Endocrinol. 2018;265:128–132. doi: 10.1016/j.ygcen.2018.03.022. PubMed DOI
Marelli F., Carra S., Agostini M., Cotelli F., Peeters R., Chatterjee K., Persani L. Patterns of thyroid hormone receptor expression in zebrafish and generation of a novel model of resistance to thyroid hormone action. Mol. Cell. Endocrinol. 2016;424:102–117. doi: 10.1016/j.mce.2016.01.020. PubMed DOI
Baumann L., Ros A., Rehberger K., Neuhauss S.C., Segner H. Thyroid disruption in zebrafish (Danio rerio) larvae: Different molecular response patterns lead to impaired eye development and visual functions. Aquat. Toxicol. 2016;172:44–55. doi: 10.1016/j.aquatox.2015.12.015. PubMed DOI
Cavallin J.E., Ankley G.T., Blackwell B.R., Blanksma C.A., Fay K.A., Jensen K.M., Kahl M.D., Knapen D., Kosian P.A., Poole S.T., et al. Impaired swim bladder inflation in early life stage fathead minnows exposed to a deiodinase inhibitor, iopanoic acid. Environ. Toxicol. Chem. 2017;36:2942–2952. doi: 10.1002/etc.3855. PubMed DOI PMC
Grandel H., Schulte-Merker S. The development of the paired fins in the Zebrafish (Danio rerio) Mech. Dev. 1998;79:99–120. doi: 10.1016/S0925-4773(98)00176-2. PubMed DOI
Houbrechts A.M., Vergauwen L., Bagci E., Heijlen M., Kulemeka B., Hyde D.R., Knapen D., Darrasd V.M. Deiodinase knockdown affects zebrafish eye development at the level of gene expression, morphology and function. Mol. Cell. Endocrinol. 2016;424:81–93. doi: 10.1016/j.mce.2016.01.018. PubMed DOI
Sharma P., Grabowski T.B., Patino R. Thyroid endocrine disruption and external body morphology of Zebrafish. Gen. Comp. Endocrinol. 2016;226:42–49. doi: 10.1016/j.ygcen.2015.12.023. PubMed DOI
Bagci E., Heijlen M., Vergauwen L., Hagenaars A., Houbrechts A.M., Esguerra C.V., Blust R., Darras V.M., Knapen D. Deiodinase Knockdown during Early Zebrafish Development Affects Growth, Development, Energy Metabolism, Motility and Phototransduction. PLoS ONE. 2015;10:22. doi: 10.1371/journal.pone.0123285. PubMed DOI PMC
Heijlen M., Houbrechts A.M., Bagci E., Van Herck S.L., Kersseboom S., Esguerra C.V., Blust R., Visser T.J., Knapen D., Darras V.M. Knockdown of Type 3 Iodothyronine Deiodinase Severely Perturbs Both Embryonic and Early Larval Development in Zebrafish. Endocrinology. 2014;155:1547–1559. doi: 10.1210/en.2013-1660. PubMed DOI
Reider M., Connaughton V.P. Effects of Low-Dose Embryonic Thyroid Disruption and Rearing Temperature on the Development of the Eye and Retina in Zebrafish. Birth Defects Res. Part B Dev. Reprod. Toxicol. 2014;101:347–354. doi: 10.1002/bdrb.21118. PubMed DOI
Reider M., Connaughton V.P. Developmental Exposure to Methimazole Increases Anxiety Behavior in Zebrafish. Behav. Neurosci. 2015;129:634–642. doi: 10.1037/bne0000087. PubMed DOI
Community X. Xenopus Community White Paper 2016. [(accessed on 15 April 2020)];2016 Available online: http://www.xenbase.org.
Sater A.K., Moody S.A. Using Xenopus to understand human disease and developmental disorders. Genesis. 2017;55:14. doi: 10.1002/dvg.22997. PubMed DOI
Grimaldi A., Buisine N., Miller T., Shi Y.B., Sachs L.M. Mechanisms of thyroid hormone receptor action during development: Lessons from amphibian studies. Biochim. Biophys. Acta-Gen. Subj. 2013;1830:3882–3892. doi: 10.1016/j.bbagen.2012.04.020. PubMed DOI
Duarte-Guterman P., Navarro-Martin L., Trudeau V.L. Mechanisms of crosstalk between endocrine systems: Regulation of sex steroid hormone synthesis and action by thyroid hormones. Gen. Comp. Endocrinol. 2014;203:69–85. doi: 10.1016/j.ygcen.2014.03.015. PubMed DOI
Boas M., Feldt-Rasmussen U., Skakkebæk N.E., Main K.M. Environmental chemicals and thyroid function. Eur. J. Endocrinol. 2006;154:599–611. doi: 10.1530/eje.1.02128. PubMed DOI
Cooper R.L., Zorrilla L.M. Comprehensive Toxicology. 3rd ed. Elsevier; Oxford, UK: 2018. 4.12—The Hypothalamic-Pituitary-Thyroid A; pp. 230–275.
Mondal S., Raja K., Schweizer U., Mugesh G. Chemistry and Biology in the Biosynthesis and Action of Thyroid Hormones. Angew. Chem. Int. Ed. 2016;55:7606–7630. doi: 10.1002/anie.201601116. PubMed DOI
OECD . Test No. 319B: Determination of in Vitro Intrinsic Clearance Using Rainbow Trout Liver S9 Sub-Cellular Fraction (RT-S9) OECD Publishing; Paris, France: 2018. DOI
Picou F., Fauquier T., Chatonnet F., Richard S., Flamant F. Minireview: Deciphering Direct and Indirect Influence of Thyroid Hormone with Mouse Genetics. Mol. Endocrinol. 2014;28:429–441. doi: 10.1210/me.2013-1414. PubMed DOI PMC
United States Environmental Protection Agency . Estimation Programs Interface Suite™ for Microsoft® Windows, v. 4.11. United States Environmental Protection Agency; Washington, DC, USA: 2012.
ADC/Percepta ACD/Labs 2015 Release (Build 2726 27 November 2014) [(accessed on 15 April 2020)];2015 Available online: www.acdlabs.com.
Kühne R., Ebert R.-U., Schüürmann G. Chemical Domain of QSAR Models from Atom-Centered Fragments. J. Chem. Inf. Model. 2009;49:2660–2669. doi: 10.1021/ci900313u. PubMed DOI
Schüürmann G., Ebert R.-U., Kühne R. Quantitative Read-Across for Predicting the Acute Fish Toxicity of Organic Compounds. Environ. Sci. Technol. 2011;45:4616–4622. doi: 10.1021/es200361r. PubMed DOI
