The true impact of endocrine disrupting chemicals (EDCs) on human health is far from being understood. Humans are exposed to mixtures of chemicals throughout their lives, yet regulations and most studies focus on individual chemicals. ENDOMIX takes a novel approach to identifying associations and causality between EDCs and adverse health outcomes by focusing on exposure to mixtures of EDCs over the life course, including windows of susceptibility, using human biomonitoring data from several European cohorts. We will model and measure how real-life EDC mixtures act together and target the immune system to initiate, trigger or maintain disease. Health effects will be investigated using pioneering methodologies ranging from high-throughput in vitro bioassays, sophisticated organoid and co-culture systems, to in vivo models. In combination, they will provide valuable information on mechanistic pathways and transgenerational effects of EDC exposure. We aim to identify biomarkers and patterns of chemical exposures that are easy to measure, available for large cohorts and indicative for adverse health outcomes. We will use in vitro, in silico and in vivo data to strengthen causal inference using a weight-of-evidence approach. Moreover, using novel text mining methods, we will create knowledge graphs to capture and summarize the complexity of biomechanistic information, which aids rapid risk assessments and the creation of network models. The knowledge generated by ENDOMIX will provide an evidence base for policy-making and also reach people of all ages to raise awareness of the risks of EDC exposure and encourage health-promoting behaviors.

Department of Cell Toxicology Helmholtz Centre for Environmental Research UFZ Leipzig Saxony 04318 Germany

Department of Ecotoxicology Helmholtz Centre for Environmental Research UFZ Leipzig Saxony 04318 Germany

Department of Environmental Immunology Helmholtz Centre for Environmental Research UFZ Leipzig Saxony 04318 Germany

Department of Molecular Toxicology Helmholtz Centre for Environmental Research UFZ Leipzig Saxony 04318 Germany

Department of Neonatal and Intensive Care Division of Neonatology Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands

Department of Nursing Faculty of Nursing and Chiropody University of Valencia Valencia Spain

Department of Pediatrics Erasmus MC University Medical Center Rotterdam The Netherlands

Epidemiology and Environmental Health Joint Research Unit FISABIO Universitat Jaume 1 Universitat de València Valencia Spain

European Institute for Biomedical Imaging Research Vienna Austria

Fraunhofer Institute for Biomedical Engineering IBMT Sulzbach Germany

Generation R Study Group Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands

German Center for Child and Adolescent Health partner site Leipzig Dresden Leipzig Germany

German Federal Institute for Risk Assessment Dept Food Safety Berlin 10589 Germany

Institute for Global Health ISGlobal Barcelona Spain

Institute for Risk Assessment Sciences Utrecht University Utrecht The Netherlands

MRC Centre for Environment and Health School of Public Health Imperial College London London UK

RECETOX Faculty of Science Masaryk University Brno South Moravian Region Czech Republic

Spanish Consortium for Research on Epidemiology and Public Health Madrid Spain

Univ Rennes Inserm EHESP Institut de Recherche en Santé Environnement et Travail UMR_S 1085 Rennes France

University Grenoble Alpes Inserm U 1209 CNRS UMR 5309 Environmental Epidemiology Applied to Development and Respiratory Health Team Institute for Advanced Biosciences Grenoble France

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