Understanding how endocrine disruptors and chemical mixtures of concern target the immune system to trigger or perpetuate disease

Project Information

ENDOMIX

Grant agreement ID: 101136566

DOI

10.3030/101136566

EC signature date 13 November 2023

Start date 1 January 2024

End date 31 December 2027

Funded under

• Health

Total cost

€ 6 488 875,00

EU contribution

€ 6 488 875,00

Coordinated by

HELMHOLTZ-ZENTRUM FUR UMWELTFORSCHUNG GMBH - UFZ
Germany

Periodic Reporting for period 1 - ENDOMIX (Understanding how endocrine disruptors and chemical mixtures of concern target the immune system to trigger or perpetuate disease)

Reporting period: 2024-01-01 to 2025-06-30

Summary of the context and overall objectives of the project

Endocrine-disrupting chemicals (EDCs) are present in the environment and in everyday products such as plastics, food packaging and cosmetics as well as in food and drinking water. By mimicking hormones, EDCs interfere with the normal functioning of the body’s endocrine system potentially leading to long-term health effects like impaired reproductive function, metabolic disorders and cancers. Although we are exposed to EDCs and chemical mixtures throughout our lives, a significant gap in our understanding of their impact on human health, especially on the immune system, and underlying mechanisms remains. Thus, the ENDOMIX project takes an innovative approach to identify associations and casualties between exposure to EDC mixtures and adverse health outcomes in European populations across different life stages.
By combining high-throughput in vitro bioassays, sophisticated organoid and co-culture systems, in vivo models and in silico data, ENDOMIX will identify novel biomarkers and patterns of exposure that are easy to measure, available for big sample sizes, and indicative of health endpoints. Finally, knowledge graphs to summarise the complexity of obtained biomechanistic information will be built to support the creation of network models and facilitate rapid risk assessment. The knowledge generated by ENDOMIX will provide an essential evidence base for policy-making and actionable recommendations to reduce the risk of EDC exposure and encourage health-promoting behaviours.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the first reporting period, significant strides were made in advancing our understanding of how complex mixtures of EDCs impact human health. A major scientific milestone was the compilation of a comprehensive list of prioritised chemicals that may influence the immune response, forming the basis for designing representative exposure mixtures across Europe. The project launched several epidemiological and meta-analyses using data from European cohorts. These analyses uncover associations between chemical exposures and health outcomes such as allergies, inflammation, and epigenetic changes. OMICs data were generated across cohorts, laying the groundwork for future analyses linking chemical exposure to molecular patterns and health outcomes. In parallel, several in vitro test systems were set up to investigate immune cells shifts and changes in phenotypes and function after exposure to EDC mixtures. Barrier models and organoid systems were developed to study chemical translocation and potential impacts on health.
These achievements during the first project period highlight the significant progress of the ENDOMIX project towards its main objectives to provide a unique new evidence base on the health impact of EDC exposure.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

In the first reporting period, ENDOMIX has made significant contributions that go beyond the current state of the art. A major achievement was the identification and prioritisation of 7,874 chemicals with endocrine-disruptive and immunomodulatory potential, based on bioactivity data and exposure modelling. From this, 30 representative chemicals across five major groups were selected for mixture testing. Mixtures were prepared at physiologically relevant concentrations and distributed to partners for use in in vitro systems. Advanced immune assays were established to assess how these mixtures affect immune cell populations, phenotypes, and functions. Early results show measurable effects at real-life exposure levels.
Innovative in vitro models were developed, including placental co-cultures, gut-liver systems, and immune cell assays, enabling mechanistic studies of mixture effects. Notably, new trophoblast spheroids and blood-placenta barrier models were established to assess chemical translocation and morpho-functional impacts, with potential applications in studying pregnancy-related disorders and physiological changes that may relate to long-term impact on the offspring. A novel flow cytometry panel was also developed to assess immune cell distribution in human sperm, opening new avenues for investigating EDC-related infertility.
ENDOMIX evaluated EDC exposure data from multiple European life course cohorts to investigate immune-mediated health outcomes during critical periods of development. In this context, the consortium published a study that linked prenatal exposure to phthalates and BPA mixtures with eczema and IgE levels in children.
Large-scale, multi-cohort studies were launched to explore causal links between chemical exposures and health outcomes across the life course, including allergies, inflammation, and DNA methylation. These efforts are supported by cross-omics integration and mechanistic insights into, for example, microbiota-mediated pathways, positioning ENDOMIX at the forefront of environmental health research.

ENDOMIX Strategy

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