Lead systemic toxicity: A persistent problem for health

Lead (Pb) has been used by humans since prehistoric times to make tools due to its malleability and durability. The Roman Empire, the Industrial Revolution, and the introduction of Pb in gasoline during the 1920s contributed to increased environmental concentrations. Pb toxicity led to its removal from gasoline after several decades. However, Pb continues to be emitted from various anthropogenic sources, including but not limited to batteries, mining, foundries, smelting, e-waste recycling, and painting. Pb remains an environmental concern, as no established safe concentration for human health has been identified. Children are more susceptible to the absorption and poisoning of Pb. Occupational exposure to Pb poses a significant risk to workers and individuals living near lead industries. The primary routes of exposure are inhalation and ingestion, and bioaccumulation and biomagnification through the food chain are major sources of human exposure. This review aims to provide an overview of Pb and its systemic toxicity of Pb, including its effects on the lungs, blood, liver, kidneys, and nervous, cardiovascular, and reproductive systems. Since Pb is classified as a probable carcinogen for humans, the article also addresses genotoxicity and cancer risk. Furthermore, it reviews the most researched mechanisms of toxicity, including calcium mimicry, oxidative stress, and inflammation, along with other less-studied mechanisms. Nevertheless, the authors emphasize the importance of exploring less examined cells, tissues, and mechanisms to deepen the understanding of Pb toxicity at various concentrations, particularly in cases of chronic low-level Pb exposure, to develop better prevention and treatment strategies for lead poisoning.