Karen Pendergrass is a researcher specializing microbial metallomics and microbiome signatures, with a focus on bridging research and clinical practice. She is the co-founder of several initiatives, including Microbiome Signatures and the Heavy Metal Tested & Certified program, which translate complex science into actionable standards. 
Karen Pendergrass is a researcher specializing microbial metallomics and microbiome signatures, with a focus on bridging research and clinical practice. She is the co-founder of several initiatives, including Microbiome Signatures and the Heavy Metal Tested & Certified program, which translate complex science into actionable standards. What was reviewed?
This review synthesizes current evidence on the mechanisms of lead toxicity across organisms and biological levels, connecting environmental sources to molecular injury pathways relevant to risk management and product standards. It covers exposure routes, global contamination patterns, organ-system effects, and mechanistic drivers such as ion mimicry, mitochondrial dysfunction, oxidative stress, genotoxicity, neuroinflammation, and epigenetic change. The review also summarizes regulatory benchmarks for food, water, soil, and air, and illustrates exposure and injury pathways with several figures. For example, the map on page 3 visualizes Pb concentrations in European topsoils, while the pathway diagram on pages 19–20 outlines inhalation, ingestion, and dermal routes into blood, soft tissue, and bone. The mitochondrial permeability transition pore graphic on page 29 shows how Pb triggers ATP loss and apoptotic factor release.
Who was reviewed?
The authors aggregated about 166 peer-reviewed sources after screening roughly 950 citations across global databases. Evidence spans bacteria, fungi, plants, invertebrates, fish, birds, livestock, and humans, with particular attention to vulnerable human groups such as infants, children, pregnant women, and occupationally exposed adults. The review also integrates international standards bodies and surveillance datasets to contextualize exposure levels and permissible limits.
Most important findings
Lead is a non-essential toxicant with no safe exposure threshold; about 90 percent of body burden is stored in bone for decades. Systemic toxicity affects nervous, cardiovascular, renal, reproductive, hematopoietic, hepatic, and immune systems. Global burden estimates attribute large numbers of deaths and cardiovascular events to lead exposure, with disproportionate impacts in low-income regions. Mechanistically, Pb2+ substitutes for Ca2+, Zn2+, Mg2+, and Fe2+ in proteins and transporters, disrupting signaling, synaptic function, and enzymatic activity. Mitochondria are a sensitive target: Pb impairs electron transport, collapses membrane potential, opens the permeability transition pore, depletes ATP, and amplifies ROS. Oxidative stress and δ-ALA accumulation drive lipid peroxidation and DNA damage; repair pathways are down-regulated and epigenetic marks are altered.
Neurodevelopmental harm occurs below 10 µg/dL, with IQ losses concentrated at the lowest blood-lead ranges. The review highlights exposure from mining, smelting, battery recycling, cookware, plumbing, dust, and contaminated foods. It catalogs typical ranges in water and sediments and notes exceedances in various food categories. A table on page 8 lists maximal permissible levels that align to HTMC scope: food 0.01–3 mg/kg, drinking water 5 µg/L, soil 50–300 mg/kg, and air 0.5 µg/m³.
Key implications
For certification programs like Heavy Metal Tested and Certified (HMTC), three major implications stand out. First, prevention and ALARA framing are justified by the absence of a safe threshold, long bone half-life, and early-life neurodevelopmental sensitivity. Second, finished-product testing is essential because exposure often arises from complex sources, including cookware, ingredients, packaging, and supply-chain, not only raw inputs. Third, priority biomarkers and mechanisms support category-specific limits: neurodevelopmental endpoints for infant foods, cardiovascular and renal risk for adult products, and cumulative body burden considerations for long-shelf-life items.
Citation
Generalova, A., Davidova, S., & Satchanska, G. (2025). The mechanisms of lead toxicity in living organisms. Journal of Xenobiotics, 15, 146. DOI:10.3390/jox15050146
