Testing strategy for the identification of thyroid hormone system disrupting chemicals

Disruption of the thyroid hormone (TH) system during fetal and neonatal life poses a significant risk to human neurodevelopment, yet current regulatory assessments lack sufficiently sensitive and specific endpoints to identify chemicals causing TH system disruption (THSD). The ATHENA project aimed to develop an integrated framework combining in silico, in vitro, and in vivo approaches to improve the identification of substances causing THSD and support their assessment within a regulatory context. This testing strategy emphasizes increased use of the adverse outcome pathways (AOP) framework and read-across approaches to better predict and address adversity. It further provides recommendations for in silico and in vitro test batteries and targeted in vivo investigations to improve identification of chemicals causing THSD. In addition, we propose enhancements to current regulatory practice, including further standardization of test methods, improved integration of human epidemiological and cross-species evidence, and recognition of altered TH concentration in serum and brain in animal studies as predictors of adverse neurodevelopmental outcomes in humans. Collectively, these measures are intended to strengthen chemical hazard assessment and improve protection of human and environmental health through more robust and efficient identification of THSD.