Novel Testing Strategies for Endocrine Disruptors in the Context of Developmental NeuroToxicity (ENDpoiNTs)
ProjectClear evidence supports associations between endocrine disrupting chemical (EDC) exposure and impaired neurodevelopment. Yet, current hazard assessment of EDCs does not address developmental neurotoxicity. This is due to lack of scientific knowledge on how endocrine disruption is linked to developmental neurotoxicity (DNT).
Thus there is an urgent need for novel testing and screening tools to address ED-induced DNT, based on new scientific knowledge. This calls for rapid advances in basic research as well as in the development of screening and testing tools close to the end-users. ENDpoiNTs will address this need by i) integrating advanced expertise in the EDC and DNT fields, two so far rather independent toxicology communities, and ii) continuous interaction with European and international key stakeholders. By combining state-of-the-art in silico and in vitro tools, innovative experimental designs and technologies, and advanced biostatistics on human epidemiological and biomonitoring data, ENDpoiNTs will 1) Generate the necessary scientific insights on the correlative and causal links between endocrine disruption and DNT; 2) Develop predictive in silico tools for chemical screening using machine learning and combination of evidence; 3) Develop and validate in vitro tools for chemical screening and testing that address sex- and species differences; 4) Develop novel molecular endpoints for existing animal-based test guidelines by integrating in vitro, in vivo, and human omics data with behavioural outcomes; 5) Ensure human relevance by linking experimental and epidemiological evidence; 6) Develop an integrated testing approach based on the developed in silico, in vitro, and in vivo assays and molecular markers; 7) Ensure regulatory relevance by developing strategies for implementation of these tools and endpoints into regulatory frameworks. In this way, ENDpoiNTs will meet the scientific, regulatory, and societal needs for improved hazard and risk assessment of EDCs
Thus there is an urgent need for novel testing and screening tools to address ED-induced DNT, based on new scientific knowledge. This calls for rapid advances in basic research as well as in the development of screening and testing tools close to the end-users. ENDpoiNTs will address this need by i) integrating advanced expertise in the EDC and DNT fields, two so far rather independent toxicology communities, and ii) continuous interaction with European and international key stakeholders. By combining state-of-the-art in silico and in vitro tools, innovative experimental designs and technologies, and advanced biostatistics on human epidemiological and biomonitoring data, ENDpoiNTs will 1) Generate the necessary scientific insights on the correlative and causal links between endocrine disruption and DNT; 2) Develop predictive in silico tools for chemical screening using machine learning and combination of evidence; 3) Develop and validate in vitro tools for chemical screening and testing that address sex- and species differences; 4) Develop novel molecular endpoints for existing animal-based test guidelines by integrating in vitro, in vivo, and human omics data with behavioural outcomes; 5) Ensure human relevance by linking experimental and epidemiological evidence; 6) Develop an integrated testing approach based on the developed in silico, in vitro, and in vivo assays and molecular markers; 7) Ensure regulatory relevance by developing strategies for implementation of these tools and endpoints into regulatory frameworks. In this way, ENDpoiNTs will meet the scientific, regulatory, and societal needs for improved hazard and risk assessment of EDCs