Metabolic effects of Endocrine Disrupting Chemicals: novel testing METhods and adverse outcome pathways

Livrables

An initial press release will be prepared describing the overall goals and ambition of the project and announcing the start of the project. The press release will initially be published on the BfR webpage and will be distributed to all project partners for publication on their individual webpages.

Project brochure

The project brochure within this deliverable will be in folded leaflet format and contain important information similar to what is presented on the website, aimed at presentation of the project e.g. by distribution of the brochure at scientific meetings. An electronic version of the brochure will also be provided on the project website for download; BfR will provide the project partners with printed brochures as required.

Project website for internal access as well as for public access

A website for the project will be generated and made publicly available. The initial website for internal access will serve the purpose of internal data exchange and information (e.g. on scientific events, reporting deadlines, published papers, repository of previous deliverables and reports) and be protected by a password. The publicly available website will contain information on the project goals, partners, current activities and events, recent developments and scientific publications, as well as contact information for stakeholders. Due date: 3/6 and updates

Data management plan

Data management plan is finalised. Availability of the data management plan will guide how research data are to be handled both during the project, and after the project is completed.

A list of potential biomarkers of exposure and effect for EDs

A report detailing the fingerprinting of ED chemical action across a range of omiclevels These fingerprints will be used to predict novel actions biomarkers of ED chemical exposure or effect a proportion of which will be experimentally validated

Report of the Ethical Review
Formation of External Scientific Advisory Board

Members of the External Scientific Advisory Board are appointed by the end of the first project month.

Report describing standardized protocols for in vivo testing of metabolic effects of EDs

The report will describe the recommended protocols for the main in vivo tests to detect harmful metabolic effects of EDs

Database of mitochondrial screening battery data using ED refset1
Validated NR reporter gene assays
Report on testing for ED effects in vulnerable individuals

The report will summarize a protocol for testing metabolic effects of EDs in obese mice Furthermore we shall describe a protocol for testing the metabolic effects of in utero exposure to EDs

Report with potencies of ED reference chemicals
A report of new biomarkers for population studies

Associations of measured ED levels and systemic metabolism by using highthroughput serum nuclear magnetic resonance NMR spectroscopy platform will be made to find new biomarkers for population studies This task needs the information from in vitro and in vivo studies in WP3

A report of the levels of selected EDs and health outcomes

The report consists of the analyzed levels of selected EDs in the study cohorts and literature review about associations of the exposure levels of EDs and health outcomes

Database of expression analysis data of HepaRG treated cells using ED refset1
List of relevant events and stakeholders of the project to be involved in further activities

A list of relevant stakeholders with potential interest in the content and achievements of EDCMET is prepared. Stakeholders are identified based on their role in the field (e.g. regulatory agencies, basic science instituted, industry (see also deliverable 5.10)) and publicly available sources such as scientific publications or conference programs. The list will comprise contact persons, email addresses, affiliations and basic information about background, interests and own previous engagement in the field. The list will be hosted by BfR and will be continuously updated throughout the project.

A report of study protocol for monitoring effects of exposure to EDs in cohort studies

Principles for the study protocol suitable for detecting associations of the health outcomes and exposure to ED related compounds during pregnancy and later in life

Report with the performance based rank-order of tested metabolic ED assays

Report with the performance based rankorder of tested metabolic ED assays

Detailed dissemination and communication plan

Based on the list of the identified stakeholders and their particular interests, a dissemination and communication plan will be established. This document will contain considerations on appropriate communication and dissemination tools (e.g. newsletter, announcement on the project website, and others) to be developed and implemented for further use in the project, in order to ensure optimal interaction with the stakeholders.

Database of NR-cofactor interaction assay battery data using ED refset1

Database of NRcofactor interaction assay battery data using ED refset1

Publications

EDTox: an R Shiny application to predict the endocrine disruption potential of compounds

Auteurs: Sakhteman A, Ghosh A, Fortino V
Publié dans: Bioinformatics, 2022, ISSN 1367-4811
Éditeur: Oxford University Press
DOI: 10.1093/bioinformatics/btac045

The determinants and longitudinal changes in vitamin D status in middle-age: a Northern Finland Birth Cohort 1966 study

Auteurs: Helmi Ikonen, Johanna Lumme, Jussi Seppälä, Paula Pesonen, Terhi Piltonen, Marjo-Riitta Järvelin, Karl-Heinz Herzig, Jouko Miettunen, Maarit Niinimäki, Saranya Palaniswamy, Sylvain Sebert, Marja Ojaniemi
Publié dans: European Journal of Nutrition, Numéro 60/8, 2021, Page(s) 4541-4553, ISSN 1436-6207
Éditeur: Dr. Dietrich Steinkopff Verlag
DOI: 10.1007/s00394-021-02606-z

Nuclear Receptor PXR in Drug-Induced Hypercholesterolemia

Auteurs: Jukka Hakkola; Janne Hukkanen; Mikko Karpale
Publié dans: Cells, Vol 11, Iss 313, p 313 (2022), Numéro 29, 2023, ISSN 2073-4409
Éditeur: MDPI
DOI: 10.3390/cells11030313

Pilot study of exposure of the male population to organophosphate and pyrethroid pesticides in a region of high agricultural activity (Córdoba, Argentina)

Auteurs: Iohanna Filippi; Natalia Bravo; Joan O. Grimalt; Mariana Butinof; Daniel Lerda; Ricardo A. Fernández; Sonia E. Muñoz; María V. Amé
Publié dans: Environmental Science and Pollution Research, Numéro 28, 2021, Page(s) 908-953, ISSN 1614-7499
Éditeur: Springer Science and Business Media LLC
DOI: 10.1007/s11356-021-14397-1

Metabolism-Disrupting Chemicals Affecting the Liver: Screening, Testing, and Molecular Pathway Identification

Auteurs: Kristin Fritsche; Andrea Ziková-Kloas; Philip Marx-Stoelting; Albert Braeuning
Publié dans: International Journal of Molecular Sciences, Numéro 25, 2023, ISSN 1422-0067
Éditeur: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms24032686

When Two Become One: Conformational Changes in FXR/RXR Heterodimers Bound to Steroidal Antagonists

Auteurs: Alejandro Díaz-Holguín, Azam Rashidian, Dirk Pijnenburg, Dr. Glaucio Monteiro Ferreira, Alzbeta Stefela, Dr. Miroslav Kaspar, Prof. Eva Kudova, Prof. Antti Poso, Rinie van Beuningen, Prof. Petr Pavek, Dr. Thales Kronenberger
Publié dans: Chem Med Chem, 2022, ISSN 1860-7187
Éditeur: Wiley-VCH GmbH
DOI: 10.1002/cmdc.202200556

Determinants of accelerated metabolomic and epigenetic aging in a UK cohort

Auteurs: Oliver Robinson, Marc Chadeau Hyam, Ibrahim Karaman, Rui Climaco Pinto, Mika Ala-Korpela, Evangelos Handakas, Giovanni Fiorito, He Gao, Andy Heard, Marjo‐Riitta Jarvelin, Matthew Lewis, Raha Pazoki, Silvia Polidoro, Ioanna Tzoulaki, Matthias Wielscher, Paul Elliott, Paolo Vineis
Publié dans: Aging Cell, Numéro 19/6, 2020, ISSN 1474-9718
Éditeur: Blackwell Publishing Inc.
DOI: 10.1111/acel.13149

Transcriptional and post-transcriptional regulation of the pregnane X receptor: a rationale for interindividual variability in drug metabolism

Auteurs: """Smutny T, Hyrsova L, Braeuning A, Ingelman-Sundberg M, Pavek P"""
Publié dans: Archives of toxicology, Numéro 95, 2020, Page(s) 11-25, ISSN 0340-5761
Éditeur: Springer Verlag
DOI: 10.1007/s00204-020-02916-x

Non-occupational exposure to pesticides and health markers in general population in Northern Finland: Differences between sexes

Auteurs: Saranya Palaniswamy, Khaled Abass, Jaana Rysä, Jon Øyvind Odland, Joan O. Grimalt, Arja Rautio, Marjo-Riitta Järvelin
Publié dans: Environment International, Numéro 156, 2021, Page(s) 106766, ISSN 0160-4120
Éditeur: Pergamon Press Ltd.
DOI: 10.1016/j.envint.2021.106766

Genome-Wide Association Study Identifies Two Novel Loci Associated with Female Stress and Urgency Urinary Incontinence.

Auteurs: Cartwright R, Franklin L, Tikkinen KAO, Kalliala I, Miotla P, Rechberger T, Offiah I, McMahon S, O'Reilly B, Lince S, Kluivers K, Post WM, Poelmans G, Palmer MR, Wessells H, Wong A, Kuh D, Kivimaki M, Kumari M, Mangino M, Spector T, Guggenheim JA, Lehne B, De Silva NMG, Evans DM, Lawlor D, Karhunen V, Männikkö M, Marczak M, Bennett PR, Khullar V, Järvelin M-R, Walley A.
Publié dans: The Journal of urology, Numéro 206, 2021, Page(s) 679-687, ISSN 0022-5347
Éditeur: Elsevier BV
DOI: 10.1097/ju.0000000000001822

Activation of pregnane X receptor induces atherogenic lipids and PCSK9 by a SREBP2‐mediated mechanism

Auteurs: Mikko Karpale, Aki Juhani Käräjämäki, Outi Kummu, Helena Gylling, Tuulia Hyötyläinen, Matej Orešič, Ari Tolonen, Heidi Hautajärvi, Markku J. Savolainen, Mika Ala‐Korpela, Janne Hukkanen, Jukka Hakkola
Publié dans: British Journal of Pharmacology, Numéro 178/12, 2021, Page(s) 2461-2481, ISSN 0007-1188
Éditeur: Wiley-Blackwell
DOI: 10.1111/bph.15433

PXR and 4β-Hydroxycholesterol Axis and the Components of Metabolic Syndrome

Auteurs: Hukkanen J, Hakkola J
Publié dans: Cells, Numéro 9, 2020, Page(s) 2445, ISSN 2073-4409
Éditeur: MDPI
DOI: 10.3390/cells9112445

Metabolic profiles of socio-economic position: a multi-cohort analysis

Auteurs: Oliver Robinson, Alice R Carter, Mika Ala-Korpela, Juan P Casas, Nishi Chaturvedi, Jorgen Engmann, Laura D Howe, Alun D Hughes, Marjo-Riitta Järvelin, Mika Kähönen, Ville Karhunen, Diana Kuh, Tina Shah, Yoav Ben-Shlomo, Reecha Sofat, Chung-Ho E Lau, Terho Lehtimäki, Usha Menon, Olli Raitakari, Andy Ryan, Rui Providencia, Stephanie Smith, Julie Taylor, Therese Tillin, Jorma Viikari, Andrew Wong
Publié dans: International Journal of Epidemiology, Numéro 50/3, 2020, Page(s) 768-782, ISSN 0300-5771
Éditeur: Oxford University Press
DOI: 10.1093/ije/dyaa188

Monitoring temporal trends of dioxins, organochlorine pesticides and chlorinated paraffins in pooled serum samples collected from Northern Norwegian women: The MISA cohort study

Auteurs: Xu S, Hansen S, Rautio A, Järvelin M, Abass K, Rysä J, Palaniswamy S, Huber S, Grimalt JO, Dumas P, Odland JO
Publié dans: Environmental Research, Numéro 204, 2021, Page(s) 111980, ISSN 0013-9351
Éditeur: Academic Press
DOI: 10.1016/j.envres.2021.111980

Metabolism-Disrupting Chemicals and the Constitutive Androstane Receptor CAR

Auteurs: Jenni Küblbeck, Jonna Niskanen, Paavo Honkakoski
Publié dans: Cells, Numéro 9/10, 2020, Page(s) 2306, ISSN 2073-4409
Éditeur: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/cells9102306

Off-target lipid metabolism disruption by the mouse constitutive androstane receptor ligand TCPOBOP in humanized mice

Auteurs: Skoda J, Dohnalova K, Chalupsky K, Stahl A, Templin M, Maixnerova J, Micuda S, Grontved L, Braeuning A, Pavek P
Publié dans: Biochemical pharmacology, Numéro 197, 2022, Page(s) 114905-114905, ISSN 0006-2952
Éditeur: Elsevier BV
DOI: 10.1016/j.bcp.2021.114905

A toxicogenomic data space for system-level understanding and prediction of EDC-induced toxicity

Auteurs: A. Sakhteman; M. Failli; J. Kublbeck; A.L. Levonen; V. Fortino
Publié dans: Environment International, Numéro 156, 2021, Page(s) 106751, ISSN 0160-4120
Éditeur: Pergamon Press Ltd.
DOI: 10.1016/j.envint.2021.106751

The EDCMET Project: Metabolic Effects of Endocrine Disruptors

Auteurs: Jenni Küblbeck, Taina Vuorio, Jonna Niskanen, Vittorio Fortino, Albert Braeuning, Khaled Abass, Arja Rautio, Jukka Hakkola, Paavo Honkakoski, Anna-Liisa Levonen
Publié dans: International Journal of Molecular Sciences, Numéro 21/8, 2020, Page(s) 3021, ISSN 1422-0067
Éditeur: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms21083021

Mother/child organophosphate and pyrethroid distributions

Auteurs: Natalia Bravo, Joan O. Grimalt, Darja Mazej, Janja Snoj Tratnik, Dimosthenis Andreas Sarigiannis, Milena Horvat
Publié dans: Environment International, Numéro 134, 2020, Page(s) 105264, ISSN 0160-4120
Éditeur: Pergamon Press Ltd.
DOI: 10.1016/j.envint.2019.105264

Changes of organochlorine compound concentrations in maternal serum during pregnancy and comparison to serum cord blood composition

Auteurs: Eva Junqué, Sergi Garcia, María Ángeles Martínez, Joaquim Rovira, Marta Schuhmacher, Joan O. Grimalt
Publié dans: Environmental Research, Numéro 182, 2020, Page(s) 108994, ISSN 0013-9351
Éditeur: Academic Press
DOI: 10.1016/j.envres.2019.108994

Urinary cobalt and ferritin in four-years-old children

Auteurs: Eva Junqué, Joan O. Grimalt, Ana Fernández-Somoano, Adonina Tardón
Publié dans: Environmental Research, Numéro 183, 2020, Page(s) 109147, ISSN 0013-9351
Éditeur: Academic Press
DOI: 10.1016/j.envres.2020.109147

Drivers of maternal accumulation of organohalogen pollutants in Arctic areas (Chukotka, Russia) and 4,4′-DDT effects on the newborns

Auteurs: Natalia Bravo, Joan O. Grimalt, Max Chashchin, Valery P. Chashchin, Jon-Øyvind Odland
Publié dans: Environment International, Numéro 124, 2019, Page(s) 541-552, ISSN 0160-4120
Éditeur: Pergamon Press Ltd.
DOI: 10.1016/j.envint.2019.01.049

Mother-child transfer rates of organohalogen compounds up to four years of age

Auteurs: Mercè Garí, Joan O. Grimalt, Esther Vizcaino, Adonina Tardón, Ana Fernández-Somoano
Publié dans: Environment International, Numéro 133, 2019, Page(s) 105241, ISSN 0160-4120
Éditeur: Pergamon Press Ltd.
DOI: 10.1016/j.envint.2019.105241

Organophosphate metabolite concentrations in maternal urine during pregnancy

Auteurs: Natalia Bravo, Soraya Peralta, Joan O. Grimalt, Maria Ángeles Martínez, Joaquim Rovira, Marta Schuhmacher
Publié dans: Environmental Research, Numéro 182, 2020, Page(s) 109003, ISSN 0013-9351
Éditeur: Academic Press
DOI: 10.1016/j.envres.2019.109003

Exposure to low-dose perfluorooctanoic acid promotes hepatic steatosis and disrupts the hepatic transcriptome in mice

Auteurs: Brecht Attema; Aafke W.F. Janssen; Deborah Rijkers; Evert M. van Schothorst; Guido J.E.J. Hooiveld; Sander Kersten
Publié dans: Molecular Metabolism, Numéro 7, 2022, ISSN 2212-8778
Éditeur: Elsevier GmbH
DOI: 10.1016/j.molmet.2022.101602

Organic Air Quality Markers of Indoor and Outdoor PM2.5 Aerosols in Primary Schools from Barcelona.

Auteurs: Barend L. van Drooge; Ioar Rivas; Xavier Querol; Jordi Sunyer; Joan O. Grimalt
Publié dans: International Journal of Environmental Research and Public Health, Numéro 17, 2020, Page(s) 3685, ISSN 1660-4601
Éditeur: MDPI
DOI: 10.3390/ijerph17103685

Evidenced-Based Approaches to Support the Development of Endocrine-Mediated Adverse Outcome Pathways: Challenges and Opportunities

Auteurs: Karine Audouze; Elias Zgheib; Khaled Abass; Khaled Abass; Asma H. Baig; Isabel Forner-Piquer; Henrik Holbech; Dries Knapen; Pim E. G. Leonards; Diana I. Lupu; Saranya Palaniswamy; Arja Rautio; Maria Sapounidou; Olwenn V. Martin
Publié dans: Frontiers in Toxicology, Numéro 3, 2021, ISSN 2673-3080
Éditeur: Frontiers Media S.A
DOI: 10.3389/ftox.2021.787017

Chloro-s-triazines-toxicokinetic, Toxicodynamic, Human Exposure, and Regulatory Considerations.

Auteurs: Khaled Abass; Olavi Pelkonen; Arja Rautio
Publié dans: Current Drug Metabolism, Numéro 22, 2022, Page(s) 645-656, ISSN 1389-2002
Éditeur: Bentham Science Publishers
DOI: 10.2174/1389200222666210701164945

Common maternal and fetal genetic variants show expected polygenic effects on risk of small- or large-for-gestational-age (SGA or LGA), except in the smallest 3% of babies.

Auteurs: Beaumont, R. N., Kotecha, S. J., Wood, A. R., Knight, B. A., Sebert, S., McCarthy, M. I., Hattersley, A. T., Järvelin, M. R., Timpson, N. J., Freathy, R. M., & Kotecha, S.
Publié dans: PLoS genetics, Numéro 16, 2020, Page(s) e1009191-e1009191, ISSN 1553-7390
Éditeur: Public Library of Science
DOI: 10.1371/journal.pgen.1009191

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