Lead Toxicity

Updated: Jan 16, 2020
  • Author: Pranay Kathuria, MD, FACP, FASN, FNKF; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
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For centuries, lead toxicity has been one of the most significant preventable causes of neurologic morbidity from an environmental toxin. A heavy metal, lead is ubiquitous in our environment but has no physiologic role in biological systems. Lead toxicity is a particularly insidious hazard with the potential of causing irreversible health effects. It interferes with a number of body functions primarily affecting the central nervous, hematopoietic, hepatic and renal system producing serious disorders. Acute toxicity is related to occupational exposure and is quite uncommon. Chronic toxicity on the other hand is much more common.

The ongoing emphasis on abatement of lead environments places added emphasis on occupational exposure to lead (eg, among workers at smelters or battery recycling plants). [1] Such exposure is a continuing problem. Whereas occupational exposure remains an occasional concern, the greatest public health issue related to lead at present is exposure of young children to decaying fragments of leaded paint. More recently, contaminated drinking water has become a cause of childhood lead exposure because of aging infrastructure.

Pediatric lead poisoning

Compared with adult lead poisoning, pediatric lead poisoning is a somewhat newer problem. First reported in the late 1800s in Australia, interest in childhood lead poisoning and its manifold clinical presentations has burgeoned. It should be noted that toxic metals, including lead, can be transmitted from a mother to her child via breast milk. [2]

Lead poisoning is probably the most important chronic environmental illness affecting modern children. Despite efforts to control it and despite apparent success in decreasing incidence, serious cases of lead poisoning still appear in hospital emergency departments (EDs), clinics, and private physicians’ offices.

In children, virtually no organ system is immune to the effects of lead poisoning. Perhaps the organ of most concern is the developing brain. Any disorganizing influence that affects an individual at a critical time in development is likely to have long-lasting effects. Such is the effect of lead on the developing brain. Effects on the brain appear to continue into the teenaged years and beyond. A high index of suspicion is necessary for physicians treating pediatric patients.

The literature suggests that significant insult to the brain of children occurs at very low levels and that medical intervention with chelation fails to reverse such effects. [3, 4, 5, 6, 7]



The major mechanism of lead toxicity is due to increased generation of reactive oxygen species (ROS) and interference with generation of antioxidants. Lead causes the generation of ROS like hydroperoxide, hydrogen peroxide, and singlet oxygen. ROS are stabilized by glutathione in the body.  Ninety percent of glutathione in the cell exists in reduced form and 10% in oxidative form, and it typically acts as an antioxidant defense mechanism. Glutathione stabilizes ROS, and after being converted (oxidizing) to glutathione disulfide, it is reduced back to GSH by glutathione reductase. Lead inactivates glutathione by binding to GSH’s sulfhydryl group, which causes GSH replenishment to become inefficient, thereby increasing oxidative stress. Lead also interferes with the activity of other antioxidant enzymes including superoxide dismutase and catalase. The increase in oxidative stress leads to cell membrane damage due to lipid peroxidation. Lead blocks the activity of 5-aminolevulinic acid dehydratase and leads to hemoglobin oxidation, which along with the lipid peroxidation can result in red cell hemolysis. [8]

Lead entering the intravascular space binds quickly to red blood cells. Lead has a half-life of approximately 30 days in the blood, from where it diffuses into the soft tissues, including the kidneys, brain, liver, and bone marrow.

Lead then diffuses into bone and is stored there for a period that corresponds to a half-life of several decades. Increased bone turnover with pregnancy, menopause, lactation, or immobilization can increase blood lead levels. Estimations of blood lead levels are more useful for diagnosing acute lead poisoning, whereas the extent of past lead exposure can be estimated by determining the body burden of lead on the basis of results from the edetate (EDTA) calcium disodium (CaNa2 EDTA) lead mobilization test.

Lead is primarily excreted in urine and bile, but the elimination rate varies, depending on the tissue that absorbed the lead. The kidney excretes lead by means of glomerular filtration and tubular secretion. Lead has bidirectional transport across the tubular epithelium. The clearance of lead ranges from 1 to 3 mL/min and is relatively independent of kidney function.

The effects of lead poisoning on the brain are manifold and include delayed or reversed development, permanent learning disabilities, seizures, coma, and even death. The long-term effect of lead exposure is maximal during the first 2 or 3 years of life, when the developing brain is in a critical formative stage.




The most significant lead exposure in adults usually occurs at the workplace, whereas for children, other forms of environmental exposure are more important. Although lead toxicity can occur after a single event, it is usually a result of chronic exposure.

Workplace exposure

Sites and occupations associated with lead exposure include pipe cutting, lead mining and ore crushing, lead and copper smelting, welding operations, construction, the rubber industry, the plastic industry, radiator repair, battery manufacturing, soldering of lead products, the printing industry, glass manufacture, organic lead production, solid waste combustion, frit manufacture, and paint and pigment manufacture. Persons employed in these occupations may also expose family members to lead by transporting lead dust from the workplace to their homes.

Other environmental exposure

Exposure from lead-based paint was significant among children in the past. Although lead was banned from use in residential paint, it continues to be used in nonresidential settings, and as a result of its past use, lead paint can still be found in many older homes.

Leaded gasoline contaminates the atmosphere. Although lead has been removed from gasoline in Western countries, leaded gasoline continues to be used in the developing world. Huffing of leaded gasoline (ie, deeply inhaling fumes to achieve a “high”) could also cause poisoning.

Food has been an important source of lead exposure. Surface contamination of homegrown vegetables, storage cans with lead solder seams (banned in 1991), and kitchenware are sources of lead contamination in food. Strong animal evidence suggests that malnutrition is highly significantly associated with increased levels of blood lead. [9]

Water is an important source of lead poisoning. Lead from the atmosphere may contaminate bodies of water [10]  and equally important, the leaching of lead from water pipes may cause poisoning. Although use of lead pipes (largely replaced by copper or polyvinyl pipes) has declined considerably since the 1950s, old public water systems continue to have networks that include lead piping. Because the use of lead-based soldering of copper pipes was permitted until 1986, homes with copper plumbing may also have substantial lead in the water. In May 2015, at least 28 children under the age of five were killed by drinking stream water contaminated with lead in Nigeria's Niger state. [11]

One of the worst public waterworks failures occurred in Flint, Michigan causing widespread lead poisoning. In 2014, Flint changed sourcing water from Lake Huron to the Flint River to save money. The corrosion-control treatments required by the Environmental Protection Agency were not followed for unknown reasons and increased amounts of chlorine were added to the water due to bacterial contamination. This made the water very corrosive and caused leaching of lead from the aging water system pipes. In six of nine city wards, the water in 20% to 32% of the homes had a lead concentration greter than15 μg per liter. The 90th percentile was 25 μg per liter, and in some samples the lead concentration exceeded 1000 μg per liter (www.FlintWaterStudy.org). [4] The incidence of children with elevated blood lead concentrations (greater than the reference value of 5 μg per deciliter) increased from 2.4% to 4.9% between 2013 and 2015. The increase was greatest, from 4.0% to 10.6%, among children in neighborhoods with the highest lead concentrations in water. [12]

Some hobbies are associated with exposures to lead. These hobbies may include making bullets, making fishing-weights, soldering, indoor firearm shooting, and remodeling older homes.

Soil contaminated with lead can be an important source of lead exposure. Such soil contamination may occur surrounding lead smelters and around older homes with deterioration of exterior surfaces.

Moonshine ethanol (ie, illegally distilled corn whiskey) made in lead-containing vessels, such as discarded automobile radiators, has been associated with lead poisoning and even local epidemics. [13]

Topical agents that contain lead, such as kohl and surma, may be ingested accidentally.

Several reports exist of lead poisoning that develops as the result of absorption of lead from retained bullet or shrapnel fragments. Bullets located in areas bathed by fluids are more likely to dissolve, while those embedded in soft tissues are likely to be walled off by inflammation.

An incidental finding of bullet or shrapnel fragments on an x-ray should prompt consideration of possible elevated lead levels, though most of these cases occur only with intra-articular fragments. Of particular concern is a retained bullet in the spine, an area where removal is often considered too dangerous to attempt. [14]

Familial factors

Frequently, 1 or 2 children in a family develop more lead poisoning than other siblings. This observation may be related to age, activity, or genetics. Identical twins seem to have concordant lead levels and biologic evidence of lead’s effects, but this is less likely to be the case with fraternal twins.

For further information on etiology, see Pathophysiology and Etiology of Lead Toxicity.



United States statistics

Children are more likely than adults to have elevated blood lead levels (BLLs). More hand-to-mouth behavior and better gastrointestinal absorption of lead are some factors contributing to higher BLLs in children. In fact, lead poisoning is said to be the most common environmental illness of children in the United States. The incidence varies with age, socioeconomic status, the population of a given community, race, and the age of the home.

No blood level of lead is safe. In 1991, the CDC defined BLLs of ≥10 µg/dL as the "level of concern" for children aged 1–5 years. However, in May 2012, the CDC accepted the recommendations of its Advisory Committee on Childhood Lead Poisoning Prevention that the term "level of concern" be replaced with an upper reference interval value defined as the 97.5th percentile of BLLs in US children aged 1–5 years from two consecutive cycles of NHANES (National Health and Nutritional Examination Survey). The current upper reference interval value of the 97.5th percentile of the distribution of the combined 2007–2008 and 2009–2010 cycles of NHANES was calculated as 5 µg/dL. [15]

There has been a remarkable decline in BLLs in children over the past 30 years. Data from the 1976–1980 cycle of NHANES indicated that an estimated 88% of children aged 1–5 years had BLLs ≥10 µg/dL. Since then, the percentage has fallen sharply, to 4.4% during 1991–1994 (NHANES III), to 1.6% during 1999–2002, and to 0.8% during 2007–2010. [16] The percentage of children aged 1–5 years with BLLs ≥5 µg/dL from the 2007–2010 NHANES cycle was 2.6% or approximately 535,000 US children. Despite progress in reducing BLLs among children in this age group overall, long-standing disparities persist. The geometric mean BLLs (GM BLLs) among younger children, those belonging to poor families, and those enrolled in Medicaid were significantly higher compared with their older, more affluent counterparts, while the GM BLLs for non-Hispanic black children were significantly higher compared with either non-Hispanic white or Mexican American children.

Generally, adults develop lead poisoning as the result of an occupational exposure or from exposure through a hobby.

Adult Blood Lead Epidemiology and Surveillance (ABLES) is a program that works with states to accurately measure trends in work-related adult BLLs, to better target interventions and prevent lead exposures. The National Institute for Occupational Safety and Health (NIOSH) in 2015 designated 5 µg/dl of whole blood, in a venous blood sample, as the reference BLL for adults. A BLL ≥5 µg/dL is considered abnormal. The US Occupational Safety and Health Administration (OSHA) Lead Standards require workers to be removed from lead exposure when BLLs are equal or greater than 50 µg/dL (construction industry) or 60 µg/dL (general industry) and allow workers to return to work when the BLL is less than 40 µg/dL.

Data from the NHANES show that the average BLL (geometric mean) of all adults in the United States in 2009–2010 was 1.2 µg/dL. Over the last 18 years, a 54% decrease in the national prevalence rates of BLL ≥25 μg/dL has been documented using ABLES surveillance data. In 1994, the rate was 14.0 employed adults per 100,000; in 2011, the rate was reduced to 6.4. In 2010, 40 state ABLES programs that provided data reported 31,081 adults with BLLs ≥10 μg/dL. Among these, 8,793 had BLLs ≥25 μg/dL, and 1,388 had BLLs ≥40 μg/dL. Overall, the national prevalence rate of BLLs ≥10 μg/dL declined from 26.6 adults per 100,000 employed in 2010 (among 37 states) to 20.4 in 2013 (among 29 reporting states). [17]

The highest numbers of workers exposed to lead with BLLs of 25 µg/dL or greater included employees in the storage battery manufacturing and lead and zinc ore mining industries, according to the ABLES report. [18]

International statistics

Lead poisoning has been reported in almost every country on earth. Blood lead levels are higher in developing countries because of continued use or later phaseout of leaded gasoline and paint. Occupational exposure in these countries is higher as well. In particular, the old “iron-curtain” countries had less strict guidelines for occupational and environmental exposures than other places in the world; thus, exposures there were common.

Age-related demographics

Young children who are independently mobile are at greatest neurologic risk from chronic exposure to low or moderate levels of lead. From the time children are able to crawl until they enter school, they are at risk of ingesting lead-containing dust. Although this sometimes is associated with pica and intentional ingestion of paint chips, lead poisoning often occurs without such behavior. Children may also be at risk for lead toxicity if folk remedies are used or if their parents, siblings, or caregivers are involved in lead-related occupations.

Children younger than 3 years are at the greatest risk for lead poisoning. This is because these children are most likely to put things containing lead into their mouths and because their brains are rapidly developing and are most vulnerable to any disorganizing influence. However, physicians and other health care professionals must be aware that lead poisoning can occur in children of any age.

Adults are now believed to be affected at a lower level of exposure than was once assumed. This has sparked renewed interest in occupational exposure to lead and its consequences. Careful attention must be paid to the occupations of adults who present with uncommon peculiar symptoms and signs.

Sex-related demographics

Because of occupational exposures, men have higher lead levels than women. No sex difference in incidence is reported in children.

Racial differences in incidence

Although no compelling evidence exists that any particular race is biologically predisposed to lead toxicity, covariant conditions such as poor nutrition and lower socioeconomic status clearly are associated with chronic lead poisoning.

Certain populations, such as African American children and new immigrants living in homes with decaying lead-based paint in low-income urban centers, are at increased risk of lead poisoning. The NHANES III data have shown higher lead levels among non-Hispanic blacks and Mexican Americans. Whether this translates into a higher incidence of lead nephropathy among these persons is not known.

Overall, black non-Hispanic children appear to have the greatest risk of developing lead poisoning. The NHANES figures for 1997 reveal a prevalence rate of 21.9% among black non-Hispanic children living in homes built before 1946, a rate of 13.7% in those living in homes built in 1946-1973, and a rate of 3.4% in those living in homes built subsequent to 1973.

This compares to a prevalence of 13%, 2.3%, and 1.6% among Mexican-American children and 5.6%, 1.4%, and 1.5% among white non-Hispanic children living in homes built before 1946, living in homes built in 1946-1973, and living in homes built subsequent to 1973, respectively.

An analysis of trends in blood lead levels over the past 20 years shows that, although the overall geometric mean blood lead level in children has dropped dramatically, disparities still exist, causing increased risk to certain populations. The factors of living in older housing, poverty, age, and being non-Hispanic black places a child at risk for elevated blood lead levels. [19]



Essentially, 2 syndromes of lead poisoning exist, depending on exposure: one syndrome is associated with acute or subacute high-level lead exposure, and the other is associated with chronic low-level lead exposure.

With exposure to high levels of lead, patients develop lethargy, progressing to coma and seizures. Death is uncommon with appropriate medical management. Long-term sequelae depend on the duration, as well as the amount, of exposure. Acute lead nephropathy is usually completely reversible with chelation therapy. Deaths may result from the elevated intracranial pressure (ICP) associated with lead encephalopathy.

With chronic exposure to low or moderate levels of lead, subacute symptoms develop. Patients with chronic lead nephropathy may have a progressive decline in kidney function and eventually require renal replacement therapy.

Mortality related to lead toxicity is rare today. However, morbidity remains common. Because lead is an enzymatic poison, it perturbs multiple essential bodily functions, producing a wide array of symptoms and signs.

Adults generally do not develop central effects but may develop distal motor neuropathies. Some reports document an increase in depressive disorders, aggressive behavior, and other maladaptive affective disorders in adult patients with lead poisoning. Men with lead poisoning tend to have lower sperm counts and may experience frank impotence; women have an increase in miscarriages and smaller babies.

In the pediatric population, fatalities associated with lead encephalopathy were reported in the 1960s. Today, with aggressive management of ICP, these deaths are preventable. Occasional cases of acute lead encephalopathy still occur, and these often result in severe neurologic damage. Mounting evidence suggests that lead poisoning in childhood produces a long-term problem with learning, intelligence, and earning power. Asymptomatic lead poisoning has a far better prognosis.


Patient Education

In cooperation with local health departments, the physician should educate families about the following:

  • Causes and effects of lead poisoning

  • Relationship between blood lead level and anticipated medical or neuropsychological problems

  • Importance of follow-up or serial blood lead level determinations to monitor effects of treatment and environmental lead abatement

  • Identifying and eliminating possible sources of lead exposure

  • Increased lead absorption in patients with iron-deficiency anemia

  • Local resources about lead exposure and treatment

All patients must be educated in lead avoidance. The termination of exposure to lead is imperative. In particular, workers should be educated regarding the health risks of lead and sources that may cause poisoning.

A good, substantial diet is important; lead absorption is increased when a diet rich in fats is consumed. Also, diets low in iron, calcium, and vitamin C increase the likelihood of lead absorption and resultant lead poisoning. Dietary fiber helps promote good peristalsis and decreases the opportunity for lead absorption; thus, at least 15 g of dietary fiber is suggested for children each day.