Global Burden of Lead Exposure: Integrating Epidemiology, Molecular Mechanisms, and Mitigation Approaches

ABSTRACT Background Lead is a nonessential, toxic heavy metal that causes widespread environmental contamination, affecting humans, animals, plants, and ecosystems. Globally, an estimated 800 million children have blood lead levels (BLLs) above 5 µg/dL. Lead persists in the environment and accumulates in the body, particularly in bone, due to its chemical similarity to calcium. Objectives This review aimed to summarize the prevalence, environmental sources, molecular and cellular mechanisms, dose‐dependent toxic effects, and mitigation strategies related to lead exposure. Methods A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar to identify relevant studies published between 2010 and 2025. Both peer‐reviewed and gray literature were qualitatively synthesized. Results The findings indicated that lead exposure is pervasive, with detectable levels in 100% of participants in EU biomonitoring studies. In the United States, ~590,000 children under 5 years of age had BLLs above 3.5 µg/dL. Lead disrupts essential metal homeostasis, induces oxidative stress, causes mitochondrial dysfunction, disrupts calcium signaling, impairs heme synthesis, and triggers DNA damage, endoplasmic reticulum stress, cell membrane injury, and impaired signal transduction. Experimental studies in mice and chickens demonstrated dose‐dependent accumulation in blood, tissues, and organs, accompanied by significant decreases in Zn, Fe, Mg, and Ca levels and elevated oxidative stress markers. Effective mitigation strategies include regulatory policies, environmental remediation, occupational safety measures, public health education, maternal and child health interventions, food and water safety measures, technological innovations, and continuous monitoring. Conclusion This review showed that lead remains a significant public health threat and underscores the need for targeted and equity‐focused interventions.