The Endocrine Society's second Scientific Statement on Endocrine-Disrupting Chemicals (EDCs) provides an updated review of the scientific literature on the effects of EDCs on health and disease. The statement, authored by a team of experts, builds on the first statement published in 2009 and highlights significant advancements in understanding the mechanisms by which EDCs alter gene-environment interactions, particularly during development. The authors emphasize the importance of developmental origins of health and disease (DOHaD) models, which suggest that early-life exposure to EDCs can lead to lifelong health consequences. The statement covers several key areas, including obesity and diabetes, female and male reproduction, hormone-sensitive cancers, prostate and thyroid disorders, and neurodevelopmental and neuroendocrine systems. It reviews the evidence from experimental animal models and epidemiological studies, noting that while there are methodological challenges in drawing broad conclusions, the evidence for the endocrine-related actions of EDCs is robust. The authors also discuss the dose-response characteristics of EDCs, noting that low doses can have significant effects due to the high affinity of hormone receptors and the nonmonotonic dose-response curves observed in many cases. They emphasize the importance of considering both dose and tissue-specific effects when interpreting the results. Finally, the statement offers recommendations for researchers, healthcare providers, and policymakers to minimize further exposures to EDCs, identify new EDCs, and develop interventions to protect public health. The statement underscores the need for continued research to better understand the complex interactions between EDCs and the human body, and to inform regulatory and policy decisions.The Endocrine Society's second Scientific Statement on Endocrine-Disrupting Chemicals (EDCs) provides an updated review of the scientific literature on the effects of EDCs on health and disease. The statement, authored by a team of experts, builds on the first statement published in 2009 and highlights significant advancements in understanding the mechanisms by which EDCs alter gene-environment interactions, particularly during development. The authors emphasize the importance of developmental origins of health and disease (DOHaD) models, which suggest that early-life exposure to EDCs can lead to lifelong health consequences. The statement covers several key areas, including obesity and diabetes, female and male reproduction, hormone-sensitive cancers, prostate and thyroid disorders, and neurodevelopmental and neuroendocrine systems. It reviews the evidence from experimental animal models and epidemiological studies, noting that while there are methodological challenges in drawing broad conclusions, the evidence for the endocrine-related actions of EDCs is robust. The authors also discuss the dose-response characteristics of EDCs, noting that low doses can have significant effects due to the high affinity of hormone receptors and the nonmonotonic dose-response curves observed in many cases. They emphasize the importance of considering both dose and tissue-specific effects when interpreting the results. Finally, the statement offers recommendations for researchers, healthcare providers, and policymakers to minimize further exposures to EDCs, identify new EDCs, and develop interventions to protect public health. The statement underscores the need for continued research to better understand the complex interactions between EDCs and the human body, and to inform regulatory and policy decisions.