RACH-Mix

New tools for risk assessment of chemical mixtures

Overview: The primary aim with RACH-Mix was to develop and demonstrate new strategies for risk assessment of mixtures of endocrine disrupting chemicals (EDCs) that complement traditional single compound and additivity methods. The project focused on mixture effects on children’s metabolism and growth, an adverse outcome of high public health concern. The project was built on the results from a previous project (EDC-MixRisk), where we had developed a whole mixture approach, which transforms single chemical regulatory guidelines approaches to a similar strategy for mixtures. In RACH-Mix, we developed further this approach by comparing the whole mixture strategy to single chemical and cumulative approaches based on experimental data produced in the EpiTox lab.

We used human mesenchymal stem cells and zebrafish embryos as model systems, as they fulfill the needs of today’s chemical testing for medium - to high throughput screening and are in line with the 3R principle of animal welfare (Replace, Reduce, and Refine animal testing). In these models, we compared epigenetic signatures of mixture exposure with exposure to single chemicals and linked those signatures to phenotypic outcomes. The metrics obtained with data from these more sensitive models were then compared to the ones based on mouse data obtained in EDC-MixRisk.

This project, on one hand, provided experimental results for developing risk assessment methodology and, on the other hand, contributed to developing more sensitive endpoints for chemical (mixture) testing.

Funding source: Swedish Research Council for Sustainable Developmen (FORMAS)

Responsible researchers: Dr. Polina Lizunkova, Dr. Elin Engdahl, Prof. Joëlle Rüegg

Main collaborators: Prof. Joachim Sturve (University of Gothenburg, Sweden), Prof. Carl-Gustaf Bornehag (Karlstad University, Sweden)