OBERON · An integrative strategy of testing systems for identification of EDs related to metabolic disorders

Exposure to chemical substances that can produce endocrine disrupting effects represents one of the most critical public health threats nowadays. In line with the regulatory framework implemented within the European Union to reduce the levels of endocrine disruptors (EDs) for consumers, new and effective methods for ED testing are needed. The OBERON project will build an integrated testing strategy (ITS) to detect EDs-related metabolic disorders by developing, improving and validating a battery of test systems. It will be based on the concept of an integrated approach for testing and assessment (IATA). OBERON will combine 1) experimental methods (in vitro e.g. on 2D and 3D human-derived cells and tissues, and in vivo i.e. in zebrafish at different stages), 2) high throughput omics technologies, 3) epidemiology and human biomonitoring studies and 4) advanced computational models (in silico and systems biology) on functional endpoints related to metabolism. Such interdisciplinary framework will help at deciphering EDs based on mechanistic understanding of toxicity by providing and making available more effective alternative test methods relevant for human health that are in line with regulatory needs. Data generated in OBERON will also allow the development of novel Adverse Outcome Pathways (AOPs). The assays will be pre-validated in order to select the test systems that will show acceptable performance in terms of relevance for the second step of the validation process, i.e. the inter-laboratory validation as ring tests. Therefore, the aim of the OBERON project is to support the OECD conceptual framework for testing and assessment of EDs by developing specific assays not covered by the current tests, and to propose an IATA approach for ED-related metabolic disorders detection, which will be submitted to the JRC and OECD community.