Metal ions as endocrine disruptors

Endocrine-disrupting chemicals have traditionally been conceptualized as organic compounds such as bisphenols, phthalates, and persistent organic pollutants. However, a growing body of experimental, epidemiological, and mechanistic evidence demonstrates that metal ions represent a distinct and underappreciated class of endocrine disruptors. Unlike classical endocrine disruptors that primarily act through receptor agonism or antagonism, metals interfere with endocrine regulation through redox imbalance, displacement of essential cofactors, modulation of hormone synthesis and metabolism, epigenetic remodeling, and disruption of hormone receptor signaling cascades. Metals such as cadmium, arsenic, lead, mercury, chromium, nickel, manganese, cobalt, and vanadium have been shown to alter thyroid, reproductive, adrenal, pancreatic, and steroid hormone systems at environmentally relevant concentrations. Their endocrine effects are often nonlinear, sex-specific, developmentally sensitive, and potentiated by oxidative stress and inflammation. Importantly, metals may act as endocrine disruptors even when systemic concentrations fall below traditional toxicity thresholds, reflecting their capacity to target hormone-sensitive tissues and signaling networks. This review synthesizes current journal evidence on metal-induced endocrine disruption, emphasizing molecular mechanisms, tissue-specific vulnerabilities, redox-endocrine crosstalk, developmental programming, and disease outcomes. We also examine challenges in exposure assessment, the importance of metal speciation and bioavailability, and emerging biomarkers of endocrine disruption. Finally, we discuss regulatory and public health implications, arguing for a paradigm shift that integrates metal chemistry into endocrine risk assessment frameworks.