Engineering and Architecture
Marta Schuhmacher Ansuategui
Universitat Rovira i Virgili
Nanoscience, Materials and Chemical Engineering
Integration of techniques to evaluate the human risk to long term at low level exposure to mixtures (Long-Low-Mixtures)
Although the knowledge that link environmental contamination to disease is quite extended, there is a lack of established causality for developing the respective Adverse Outcome Pathways (AOPs), taking into account cumulative exposure. The AOP framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes.To improve the knowledge is necessary to integrate different disciplines as including environmental and exposure modelling, recent advances in toxicology (including in vitro, in vivo and in silico aspects) with a special focus on omics technologies and bioinformatics, as well as environmental epidemiology.
The objective of the project is to improve chemical risk assessment related to co-exposure to mixtures of chemicals. To do that the project will assess the long-term health risk of this co-exposure to these chemicals by understanding how these compounds induce molecular and biochemical pathways that may interact to lead to the final adverse outcome.
Chosen chemicals will be those with widespread uses in industrial and consumer goods the EU population is co-exposed to several of them often, albeit at relatively low doses (i.e. bisphenols, (chlorinated) flame retardants, perfluorinated compounds, and phthalate exposure).
Biological data will be obtained from a cohort of pregnant women that is composed of more than 150 pair’s mother-child. The evidences indicate that some chemicals can affect the different levels of epigenetic control if the exposure occurs during “two critical windows of exposure”, the prenatal and the early life period.
Environmental exposure will be measured by means of diverse technologies like sensors and questionnaires . Besides the internal exposure will be measured by analyzing the concentration of toxins in human blood, urine and breast milk.
In vitro assays and, possibly, multi-omics data will be used to link key events quantitatively to other key events or an adverse outcome based on realistic conditions of co-exposure to multiple chemicals.
Physiologically based pharmacokinetic modeling will be used to predict the pharmacokinetic behavior of these chemicals and their mixtures in human body. This model will be integrated with a physiologically dynamic model that describes the kinetics of both, the chemicals and biomolecules, help us to understand the dynamic and steady-state behaviors of molecular pathways under perturbed condition.
Expected results. Stronger scientific confidence in key event relationships will result in the development of quantitative models for associating low, environmentally relevant exposure of mixtures to adverse outcomes. This will lead to improved chemical risk assessment of frequently occurring chemical coexposures following and even advancing the AOP guidelines of the OECD.
Results will be communicated, disseminated and exploited to the different stakeholders to reduce public health risks.
37.5 hours a week
|This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 713679|