Perchlorate exposure and human health: Integrating biomonitoring evidence, thyroid mechanisms, and risk assessment

Perchlorate (ClO₄^-), a persistent environmental contaminant originating from industrial activities, propellants, fireworks, and fertilizers, has emerged as a global public health concern due to its widespread occurrence in water, soil, and food matrices. Human exposure occurs primarily through contaminated drinking water and dietary intake, with vulnerable populations including pregnant women, fetuses, neonates, and iodine-deficient individuals. This review provides an integrated synthesis of environmental occurrence, human exposure pathways, toxicokinetics, and mechanistic disruption of thyroid function. Perchlorate is rapidly absorbed and eliminated (urinary half-life ∼6-8 h), making urinary biomonitoring a reliable indicator of recent exposure. At the mechanistic level, perchlorate competitively inhibits iodide uptake via the sodium-iodide symporter (NIS), thereby reducing thyroid hormone synthesis (T₄ and T₃) and potentially increasing TSH levels. Such disruption may have critical implications for neurodevelopment and long-term endocrine health, particularly in susceptible populations. We critically evaluate current epidemiological evidence, highlight inconsistencies in regulatory thresholds across jurisdictions, and identify major knowledge gaps regarding chronic low-dose exposure and mixture effects with other NIS inhibitors such as nitrate and thiocyanate. Given ongoing environmental contamination and climate-related changes influencing water resources, harmonized regulatory approaches and improved risk assessment frameworks are urgently needed to protect vulnerable populations.