The ENDOMIX project: an interdisciplinary approach to understanding how real-life chemical mixtures target the immune system to trigger disease

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 <i>in vitro</i> bioassays, sophisticated organoid and co-culture systems, to <i>in vivo</i> 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 <i>in vitro</i>, <i>in silico</i> and <i>in vivo</i> 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.