EDC-MixRisk project has started its final year. It is time to take stock on what has been accomplished in the project so far as well as to take a look at the progress and key results at this stage.

The overall concept underpinning EDC-MixRisk is that early life exposure to EDC mixtures induces changes in the organism that underlie increased susceptibility to diseases during the entire life span. Three health domains are addressed in the project (growth and metabolism, neurodevelopment, and sexual development).

In the epidemiological module, mixtures of EDCs are identified, exposure to which is associated to adverse health outcomes in the three domains. These mixtures are subsequently composed and tested in different experimental systems relevant for the respective health outcomes. To test mixtures that are composed based on epidemiological data is a novel strategy to tackle the mixture issue. The experimental data are then on one hand, integrated into the risk assessment methods developed in the project, and, on the other hand, used to refine the biostatistical analyses. Two sets of mixtures have been established for metabolism and growth (G), neurodevelopment (N) and sexual development (S). The mixtures are based on data from the Swedish mother-child pregnancy cohort SELMA.

In the experimental module, mixtures 0 and 1 are tested in various animal and cell models to identify molecular actions of the mixtures that could underlie their adversity. Results obtained in mice, tadpoles, zebrafish, and cell models show that mixtures 0 for all the health domains induce negative effects on the molecular, cellular, and organismal level. In some of the assays, effects were observed even at the lowest concentrations tested, which correspond to the actual levels of the SELMA mothers.

Interestingly, the mixtures disrupted common signalling pathways in cell and in animal models, which enabled us to link the molecular effects to adverse outcomes such as increased adipose tissue, behavioural changes, and disruption of sexual organ development. Selected single chemicals were also tested and their effects compared to the mixtures. In most cases, the single compounds did not have an effect at concentrations comparable to the mixtures.

An important part of the project is the improvement of the regulatory risk assessment of mixtures as well as science-to-policy interaction. Three different novel mixture risk assessment methods have been established and are now being elaborated on by conducting case studies using EDC-MixRisk and published data.

The EDC-MixRisk approach of identifying EDC mixtures associated with adverse health outcomes in a pregnancy cohort, preparing artificial mixtures of the bad actors for toxicological testing and using the experimental data for risk assessment is a novel approach and one of the major outcomes of the project. More specifically, this proof-of-concept, will enable more systematic integration of epidemiological and experimental evidence into mixture risk assessment strategies.

By applying the novel approach, which is based on real life exposure data, we could find a higher rate of pregnant women at risk when compared with more traditional models of additivity. This adds to the evidence that cocktail effects of manmade chemicals are not properly taken into account in risk assessment and management of chemicals. More systematic approaches are needed, both in terms of science and regulations. The improved testing strategies and risk assessment methodologies developed in the project are important for the regulatory processes to protect public health and to avoid hazardous chemicals, whether they come in mixtures or as single substances.

Read the full summary of the project progress here.