Endocrinology · 2012 · 1.2K citations · 44 references
PharmacyEndocrinologyToxicologyDevelopmental ToxicologyMechanisms Of ToxicityToxicodynamicsDevelopmental EndocrinologyEndocrine DisruptionEndocrine ToxicityEndocrine Toxicity ManagementEndocrine-disrupting ChemicalsRisk Assessment For Developmental ToxicantsDevelopmental Endocrine ToxicityDevelopmental Exposure To Endocrine-disrupting ChemicalsEndocrine Disruption In WildlifeEndocrine SecretionEndocrine-disrupting Chemical EffectsLow-dose EffectsMechanisms Of Endocrine DisruptionTissue-specific Hormone Action
Endocrine‑disrupting chemicals are exogenous agents that interfere with hormone synthesis, secretion, or action, and their effects depend on developmental stage, tissue specificity, and life‑cycle regulation, making static toxicity guidelines inadequate for risk assessment. The authors propose applying fundamental endocrinology principles to identify EDCs, emphasize the critical role of developmental exposure and low‑dose potency, and recommend enhancing the Endocrine Disruptor Screening Program accordingly. They recommend integrating core endocrinology principles—such as developmental timing and dose–response relationships—into the screening program to better detect and manage complex EDC effects.
An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action. The potential for deleterious effects of EDC must be considered relative to the regulation of hormone synthesis, secretion, and actions and the variability in regulation of these events across the life cycle. The developmental age at which EDC exposures occur is a critical consideration in understanding their effects. Because endocrine systems exhibit tissue-, cell-, and receptor-specific actions during the life cycle, EDC can produce complex, mosaic effects. This complexity causes difficulty when a static approach to toxicity through endocrine mechanisms driven by rigid guidelines is used to identify EDC and manage risk to human and wildlife populations. We propose that principles taken from fundamental endocrinology be employed to identify EDC and manage their risk to exposed populations. We emphasize the importance of developmental stage and, in particular, the realization that exposure to a presumptive "safe" dose of chemical may impact a life stage when there is normally no endogenous hormone exposure, thereby underscoring the potential for very low-dose EDC exposures to have potent and irreversible effects. Finally, with regard to the current program designed to detect putative EDC, namely, the Endocrine Disruptor Screening Program, we offer recommendations for strengthening this program through the incorporation of basic endocrine principles to promote further understanding of complex EDC effects, especially due to developmental exposures.
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