Rezultaty
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 brochureThe 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 accessA 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 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 stakeholder workshop to present and discuss the results from the first project phase is organized. If possible, the workshop will take place at the BfR facilities in Berlin, Germany. Organization of the workshop involves compilation of the scientific program, invitation of stakeholders, as well as general conference organization aspects. Stakeholder feedback will be collected, reviewed and used for optimization of the project strategy. A workshop report will be prepared and published as mentioned in the description of deliverable 5.6.
A validated classification system linking ED exposure to adverse outcomeA report detailing the identification of omic-level features that can be used to classify common molecular actions of known ED chemicals. These feature sets will be used to predict novel actions of ED chemicals, a proportion of which will be experimentally validated.
WorkshopJoint meeting for incorporating EDCMET findings
End-of-project workshopA second workshop will be held at the end of the project, again in Berlin, Germany, if organizationally feasible. Organization of the workshop involves compilation of the scientific program, invitation of stakeholders, as well as general conference organization aspects. Major achievements and conclusions will be presented to the stakeholders and feedback will be collected. A workshop report will be prepared and published as mentioned in the description of deliverable 5.6.
A validated molecular modelling approach to identify interactions between proteins and EDsA report detailing the optimal in silico docking protocols for different classes of ED chemical–protein interactions, complete with validation data.
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 ReviewFormation of External Scientific Advisory Board
Members of the External Scientific Advisory Board are appointed by the end of the first project month.
Validation report of the top-performing metabolic ED assay battery using a the reference chemical sets based on WP1 and WP3A binding energy interaction map to explore the quantitative interaction of EDs with proteins, as part of the overall risk assessment model
A report from the proteome-wide screen for ED chemical-protein interactions. For exemplar interactions of each predicted ED chemical class-protein interactions, binding energy interaction maps will be generated
Report describing standardized protocols for in vivo testing of metabolic effects of EDsThe report will describe the recommended protocols for the main in vivo tests to detect harmful metabolic effects of EDs
Database on metabolism related ED pathways that may be further developed into OECD recognized AOPs and on biomarker fingerprints for metabolic disturbanceThis database collects the putative molecular pathways and biomarker fingerprints discovered in WP3 during the project mediating the harmful metabolic effects of EDs.
Database of mitochondrial screening battery data using ED refset1Validated 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 chemicalsA 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 outcomesThe 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
A list of proteins most likely to interact with EDsA report from the proteome-wide screen for ED chemical-protein interactions. A list of predicted interactions will be presented, along with experimental validation data for a proportion of these interactions
Database of expression analysis data of HepaRG treated cells using ED refset1List 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.
Transfer final processed data for long-term storageThis deliverable reports on the storage of the final processed data into databases (e.g. a data repository in CSC IDA-server) for long-term storage. It will summarise the details of the stored data, its quality as well as permanent identifiers of the datasets.
A report of study protocol for monitoring effects of exposure to EDs in cohort studiesPrinciples for the study protocol suitable for detecting associations of the health outcomes and exposure to ED related compounds during pregnancy and later in life
Predictivity and feedback report 2 to WP1 and WP2Predictivity of the in silico and in vitro assays developed in WP1 and WP2 will be tested for selected test compounds using in vivo tests. This final report is public.
A systems toxicology tool to predict emergent metabolic phenotype from ED exposureA report and associated computational model(s) on the development of quasi steady-state Petri net model of the predicted dynamic response to ED chemical exposure. Validation against a training set of known ED chemical effects will be included.
Report with the performance based rank-order of tested metabolic ED assaysReport with the performance based rankorder of tested metabolic ED assays
Detailed dissemination and communication planBased 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 refset1Database of NRcofactor interaction assay battery data using ED refset1
A report/publication of estimation of human health risks of selected EDsA report/publication review the issues associated with human health risk assessment of single/cocktail chemical as well as summary of EDCMET risk assessment results.
Methods submission to supranational organizationsMethods and strategies developed within the course of the project will be identified which are potentially suitable for later regulatory implementation in toxicological testing. Supranational organizations (e.g. JRC, OECD) will be approached and the project results will be communicated in matters of formal validation and future regulatory acceptance. A document summarizing the respective activities will be prepared
Publikacje
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Bioinformatics, 2022, ISSN 1367-4811
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European Journal of Nutrition, Numer 60/8, 2021, Strona(/y) 4541-4553, ISSN 1436-6207
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Jukka Hakkola; Janne Hukkanen; Mikko Karpale
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Cells, Vol 11, Iss 313, p 313 (2022), Numer 29, 2023, ISSN 2073-4409
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MDPI
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10.3390/cells11030313
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Toxicology Reports, Numer 9, 2024, Strona(/y) 750-758, ISSN 2214-7500
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Environmental Science and Pollution Research, Numer 28, 2021, Strona(/y) 908-953, ISSN 1614-7499
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International Journal of Molecular Sciences, Numer 25, 2023, ISSN 1422-0067
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Chem Med Chem, 2022, ISSN 1860-7187
Wydawca:
Wiley-VCH GmbH
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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
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Aging Cell, Numer 19/6, 2020, ISSN 1474-9718
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International Journal of Epidemiology, Numer 50/3, 2020, Strona(/y) 768-782, ISSN 0300-5771
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STAR Protocols, Numer 4, 2024, Strona(/y) 102500, ISSN 2666-1667
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Molecular Metabolism, Numer 76, 2023, Strona(/y) 101779, ISSN 2212-8778
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Frontiers in Public Health, Numer 11, 2023, ISSN 2296-2565
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Cells, Numer 9/10, 2020, Strona(/y) 2306, ISSN 2073-4409
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International Journal of Molecular Sciences, Numer 21/8, 2020, Strona(/y) 3021, ISSN 1422-0067
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