Kinetic management of endocrine disruption: How chemical dynamics shape hormonal systems

Historically, the assessment of endocrine disruption has relied on fixed exposure metrics, neglecting the crucial influence of chemical kinetics on hormonal effects. This review introduces the concept of kinetic management of endocrine disruption, focusing on how factors such as absorption, tissue partitioning, metabolism, and persistence influence the degree, timing, and extent of hormonal interference. We present emerging evidence that highlights how lipophilic accumulation in endocrine organs, the bioactivity of metabolites, and delayed internal release can create a disconnect between the external dose and its biological outcomes. By fusing pharmacokinetics with the dynamics of hormone receptors, feedback regulation, and vulnerabilities specific to different life stages, we propose a holistic framework that combines toxicology, endocrinology, and predictive modeling. This kinetic‒endocrine paradigm opens up significant opportunities for advanced risk assessment, precision in endocrine health safeguarding, and the deliberate creation of safer chemicals and therapeutic solutions. • Understanding endocrine disruption requires focusing on how the body processes chemicals internally. ADME dictate when chemicals interact with hormone systems. • Accumulation in endocrine organs creates internal reservoirs, extending exposure. • Time-dependent internal exposure patterns explain unusual dose-response relationships and developmental sensitivities often seen in endocrine disruption. • Physiologically based pharmacokinetic models quantitatively integrate exposure, distribution, metabolism, and endocrine disruption to predict endocrine outcomes. • Kinetic control framework integrates toxicology, endocrinology, and pharmacokinetic modeling to better understand endocrine hazards and improve environmental health risk assessment.