Metabolic effects of Endocrine Disrupting Chemicals: novel testing METhods and adverse outcome pathways (EDCMET)
Endocrine disrupting chemicals (EDs) are classically known as compounds which exert adverse effects by interfering with hormone-related signalling pathways. The concept of endocrine disruption has recently been extended to metabolic alterations which may result in diseases such as obesity, diabetes and fatty liver disease, which constitute an increasing health concern word wide.
Currently, there are no validated methods to assess the metabolic effects of EDs. To address this unmet need and other gaps in the context of ED testing, the European Union has funded eight projects on the overarching topic ‘New testing and screening methods to identify endocrine disrupting chemicals’ within the Horizon 2020 (H2020) framework. One of these projects is EDCMET (‘Metabolic effects of Endocrine Disrupting Chemicals: novel testing METhods and adverse outcome pathways’). The project is running from 01/01/2019 until 12/31/2023 and is coordinated by Prof. Dr. Anna-Liisa Levonen from the University of Eastern Finland. Project partners from eight European countries will contribute to achieving the scientific goals of EDCMET.
The objective of the EDCMET project is to develop validated in silico, in vitro and in vivo methods assessing metabolic effects of EDs, with a focus on energy and fat metabolism and nuclear receptors regulating these processes. Thorough understanding of the mechanisms leading to adverse metabolic effects of EDs is presently lacking. EDCMET will apply the adverse outcome pathway (AOP) paradigm to identify molecular initiating events (MIE) and predict the emergent adverse biological phenotype. The project brings together scientists with different expertise to meet the common goal to improve the currently available testing methods. EDCMET utilizes a wide variety of methodologies, ranging from computational methods, cell culture systems and up-to-date animal models, to epidemiological data, in order to associate the exposure to chemicals to ED-related metabolic effects.
Within EDCMET, Faculty of Pharmacy at Charles University will participate in development of cellular screening method for interaction testing of potential endocrine disruptors with nuclear receptors (WP2). In addition, we will work on animal models for analysis of hormonal and metabolic interference of endocrine disruptors (WP3).
Database on metabolism related ED pathways that may be further developed into OECD recognized AOPs and on biomarker fingerprints for metabolic disturbance
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