Novel Effect biomarkers for MEtabolic disruptorS: evidence on health Impacts to answer science and policy needS

Endocrine-disrupting chemicals (EDCs) disturb lipid and glucose metabolism in several metabolically active organs such as liver and pancreas besides being able to interfere with many aspects of hormonal action. There is accumulating evidence linking EDCs or their mixtures with an increased incidence of obesity, atherosclerosis, and type 2 diabetes. Developmental exposure to EDCs can exert life-long, even transgenerational effects and affects the susceptibility to many diseases. However, the metabolic effects of EDCs are still poorly understood and the lack of mechanistic data and predictive models of adverse metabolic outcomes of EDCs hinders their risk assessment. The “Novel Effect biomarkers for MEtabolic disruptorS: evidence on health Impacts to science and policy needS” (NEMESIS) consortium brings together experts in toxicology, medicine, risk assessment, and social sciences and humanities to respond to the unmet regulatory needs of EDCs within silico, in vitro, in vivo, epidemiological and systems biology data on EDC-mediated metabolic effects in multifactorial models. We will assess mechanistic data on metabolic disruption in liver and pancreas and how EDCs or their mixtures affect the microbiota, enhanced with data on dose-response relationships and the causality of these actions. In addition, NEMESIS will provide human exposure data of EDCs and explore effect biomarkers for metabolic disruption. NEMESIS’ results will improve assessment of metabolic endpoints in testing guidelines and adopt alternative models to animal testing. Adverse Outcome Pathways (AOP)s and Integrated Approaches to Testing and Assessment (IATA) approaches will be developed to assess adverse metabolic effects of EDCs and improve the risk assessment towards a more holistic approach. Citizens are engaged from the beginning of the project to develop effective risk communication practices on EDCs and to maximize the science-to-policy impact of NEMESIS together with relevant stakeholders.