GSS EU Science Funding Gateway

Bringing together, inter alia, (molecular) epidemiologists, exposure scientists, toxicologists, endocrinologists, health care practitioners and risk assessors, research actions under this topic should focus on the understanding of the impact of exposures at critical life stages as regards development of diseases later in life, focusing on the several health endpoints for which there is currently less information available. The nature of the dose-response relationships and whether effects are threshold-dependent should be addressed in the study designs. Similarities between endocrine systems and certain health outcomes across species should be exploited to improve understanding of functioning of the endocrine system. Finally, research should attempt at identifying predictive biomarkers (e.g. from liquid biopsies such as saliva, urine, blood) that would allow the tracing of endocrine disrupter-mediated health effects in a shorter period of time than normally would be required for epidemiological studies.

Research actions under this topic should provide forward-looking mechanistic information on potential hazards and health risks of exposures to EDCs, through innovative molecular epidemiological, multifactorial models and systems biology approaches, exploiting the use of state of the art non-animal methodologies when relevant, and should include several of the following activities:

• Studying the impact of EDCs on target organs and in multi-organ models, and physiological barriers, such as the placenta, the blood-brain barrier, the blood-saliva barrier, intestinal, pulmonary and immune cells as well as their interaction with microbiota. This should include the provision of a thorough understanding of dose-response relationships;
• Elucidating health endpoints for which insufficient data exist, such as disturbances in the development and functioning of the nervous and cardiovascular systems, the immune system, bone development and disease, obesity, diabetes, hormone-dependent cancers and fertility (e.g. minipuberty, prepuberty and puberty);
• Providing better biological and imaging biomarkers to predict EDC-mediated health outcomes, including the quantitative probabilities of having an adverse effect based on such biomarkers;
• Gaining better insights into the developmental origins of health and disease, especially for those where less data are available. Assessing the occurrence and relevance of multi- and transgenerationally inherited effects, including molecular and epigenetic mechanisms that drive multigenerational effects;
• Gaining better insights into the most sensitive windows of susceptibility, during which exposure are of particular importance for health effects;
• Better understanding of the effects of chemicals and chemical mixtures on the underlying mechanistic crosstalk between endocrine axes, endocrine pathways and other key biological systems, including immune, neurological and metabolic functions;
• Improving the understanding of chemical mixture effects, including with other toxins and at low doses. The role of the microbiome in the activation or detoxification of these chemicals should be explored where relevant.
• Investigating biological effects of realistic mixtures to get a more detailed understanding of the endocrine effectome, taking advantage of computational toxicology and development of up-to-date models;
• Performing comparative analysis between species, assessing similarities to human endocrine system and health outcomes and exploiting non-mammalian species as test organisms, e.g. non-mammalian vertebrates and invertebrates to predict effects or raise concern about potential effects in humans or vice versa;
• Exploiting systems biology approaches in order to understand how exposure to an EDC results in an altered phenotype, a process that implies complex interactions across multiple levels of biological organisation.