Persistent lead neurotoxicity as a consequence of global regulatory failure and trade-driven exposure inequities

Abstract Background The global phase-out of leaded gasoline, completed in 2021, is widely regarded as a major public health success. However, this achievement has fostered policy complacency, while legacy reservoirs and emerging exposure vectors continue to sustain a persistent neurotoxic burden. Low- and middle-income countries (LMICs) remain disproportionately affected due to enforcement constraints, informal recycling economies, and trade dynamics that externalise toxic risks. Objective This critical narrative review integrates regulatory drivers of persistent lead exposure with molecular mechanisms of neurotoxicity to identify actionable leverage points for elimination. Methods Peer-reviewed studies, surveillance reports, and case investigations published between 2015 and 2026 were synthesised. Evidence was organised across three domains: regulatory and enforcement gaps, contemporary environmental and consumer exposure pathways, and neurobiological mechanisms. Results Lead exposure has shifted from historical fuel emissions to complex sources embedded in global trade and informal economies. Regulatory blind spots persist in high-income settings, while LMICs face enforcement challenges shaped by survival-based incentives. Exposure continues through contaminated soil, dust, water systems, food, and consumer products. Mechanistically, lead (Pb²⁺) acts as a calcium-mimetic neurotoxicant that crosses the blood-brain barrier, disrupts NMDA-dependent synaptic plasticity, and promotes mitochondrial dysfunction and apoptosis, contributing to long-term cognitive and economic harm. Conclusion Persistent lead neurotoxicity reflects governance failure rather than scientific uncertainty. Eliminating exposure requires closing export loopholes, strengthening enforcement, formalising informal sectors through realistic incentives, and shifting from secondary screening to primary prevention.