Adult Lead Poisoning

Adult lead poisoning (From up to date - january 2.011)

Adult lead poisoning

Authors

Rose H Goldman, MD, MPH

Howard Hu, ScD, MD Section Editor

Suzanne W Fletcher, MD Deputy Editor

Pracha Eamranond, MD, MPH

Last literature review version 19.1: January 2011 | This topic last updated: February 10, 2011 (More)

INTRODUCTION — Lead poisoning can present with nonspecific signs and symptoms such as abdominal pain, constipation, irritability, difficulty concentrating, and anemia. Clinicians need to consider this diagnosis and know the appropriate tests to order for documenting exposure and assessing for early health effects. It is also now well-established that chronic exposure to modest levels of lead, too low to trigger symptoms, can increase risk for hypertension and accelerated future cognitive decline in adults.

Clinicians need to know how to play a proactive role in early detection and prevention by screening patients known to work in occupations with possible lead exposure, and what actions to take when excessive exposure is found. The costs and consequences of lead poisoning can be entirely prevented by eliminating and decreasing sources of exposures, and by early recognition of elevated lead levels or lead poisoning.

Some of the clinical conditions related to lead poisoning and issues related to lead poisoning in children are presented separately. (See "Clinical aspects, diagnosis, and treatment of the sideroblastic anemias" and "Lead nephropathy and lead-related nephrotoxicity".)

DIMENSIONS OF THE PROBLEM — The true extent of adult lead poisoning in the United States (US) is difficult to measure because of limited data. One source of data is the Centers for Disease Control's (CDC's) Adult Blood Lead Epidemiology and Surveillance (ABLES) program that monitors laboratory reported elevated blood lead levels (BLL) (defined as greater than or equal to 25 mcg/dL) among adults in 38 states [1].

The ABLES surveillance results indicate an overall decrease in the national prevalence of elevated BLL's from 14.0 per 100,000 in 1994 to 7.8 in 2007 [1]. The rate in 2007, however, was slightly more than that in 2006 which was 7.4. Ninety-five percent of the adults with an identified exposure source were exposed at work. These work exposures occurred mainly in battery manufacturing, lead and zinc ore mining, and painting and paper hanging industry subsectors.

The decrease in BLL over the last 15 years might be due to the decline in manufacturing jobs with lead exposure and to prevention measures. However, the rates might also reflect low employer compliance with testing and reporting requirements. The slight increase in rates with ABLES data between 2006 and 2007 might be the result of increased exposures at work or improved testing reporting. Overall, the ABLES data are probably an underestimate because employers may fail to test lead-exposed employees, laboratories may not report results, and not all states report data to ABLES [2].

Data from another source, the National Health and Nutrition Examination Survey (NHANES 1999 to 2002) provides information on the percentage of persons with elevated blood lead levels (here defined as greater than or equal to 10 mcg/dL), and mean lead levels for the US population of different ages, genders, and racial/ethnic populations [3,4]. The NHANES data show a decline in the overall geometric mean blood level for the adult population (greater than 20 years) in the US from approximately 13 mcg/dL in 1976 to 1980, to around 2 mcg/dL or less in 1999 to 2002 [3,4].

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Additionally, the NHANES data show a decrease in the percentage of adults with blood lead levels ≥10 mcg/dL from 3.1 percent (ages 20 to 59) and 6.5 percent (>60 years) in the 1991 to 1994 survey, to 0.7 percent (ages 20 to 59) and 0.8 (age 60) in the 1999 to 2002 survey [3]. The 1999 to 2002 survey also reported higher prevalence rates of elevated blood lead levels in adult males compared to females, and among non-Hispanic blacks and Mexican Americans compared to non-Hispanic whites [3].

Despite these apparent improvements in the US, greater prevention activities, particularly in work environments, will be needed to achieve the US 2010 health objective to reduce to zero the number of adults with blood lead levels ≥25 mcg/dL [5].

Sources of exposure — The majority of adult elevated blood lead levels come from work place exposures (table 1). Lead exposure can occur in numerous work settings, such as manufacturing or use of batteries, pigments, solder, ammunitions, paint, car radiators, cable and wires, some cosmetics, ceramic ware with lead glazes, and tin cans [6]. Primary and secondary lead smelting and refinement are associated with considerable exposure.

An organic form of lead was added to gasoline to raise the octane level and to serve as an "antiknock" agent in the 1920s. It has been estimated that 90 percent of atmospheric lead originated from automobile exhaust and accounted for the increase in environmental lead concentrations observed between the 1930s and 1960s (figure 1) [7,8]. The introduction of lead-free gasoline in the 1980s contributed to a considerable decrease in air lead levels in the US and consequently blood lead levels [7,9]. However, leaded gasoline continues to be used in many parts of the world [10].

The use of lead paint has resulted in lead exposures at work in the construction trades [11] as well as in the home, thereby posing a lead poisoning risk to children [12]. The lead content of paint was unregulated until 1977. It is estimated that about one million construction workers in the US are occupationally exposed to lead [11]. In addition to coating residential properties, lead paint also covers five billion square feet of nonresidential surface area in the US, including 89 percent of the nation's steel bridges [11].

An additional source of lead exposure has been identified as lead dust deposited on radiographs stored in lead-lined boxes. A study performed by the Wisconsin Division of Public health found that patients are at risk for substantial lead exposure during a dental radiograph if the office stores the films in these boxes [13].

In some parts of the US, illegally distilled alcohol ("moonshine") is an important source of lead exposure. As an example, in a study from an emergency department in Atlanta, 8.6 percent of adult patients reported consuming moonshine in the past five years, and the median blood lead level in drinkers of moonshine was significantly higher than in nondrinkers (11.0 versus 2.5 mcg/dL); the percentage of patients with blood lead levels ≥25 mcg/dL was higher as well (25.7 versus 0 percent) [14]. Lead has also been found as an adulterant in marijuana [15].

Lead poisoning has occurred in those taking Ayurvedic medications [16-19] and in those cooking or eating off of lead-glazed tableware and cookware [20]. Litargirio (also known as litharge or lead monoxide), a lead-based powder sold and used in some Hispanic communities as an antiperspirant/deodorant and as a folk remedy, has also caused lead poisoning [21]. Women who reported using herbal supplements had blood lead levels 10 percent higher than non-users, although mean lead levels were low in both groups (<2.0 mcg/dL) [22]. Blood lead levels were about 20 percent higher for those women reporting use of Ayurvedic and/or traditional Chinese medicine herbs, as well as St. John's wort, compared to non-users.

BIOLOGICAL BASIS FOR DISEASE — Inorganic lead is absorbed from the lungs or gastrointestinal tract. In adults, absorption of lead via the respiratory tract is the most significant route of entry, with an average absorption rate of approximately 40 percent [7]. Respiratory exposures can occur with activities such as scraping/sanding/burning leaded paint from surfaces as well as from various smelting/burning processes. Organic (tetraethyl) lead that is found in gasoline can be absorbed via the skin.

The efficacy of gastrointestinal (GI) absorption of lead in adults is about 10 to 15 percent and is increased during fasting when diets are deficient in calcium, iron, phosphorous or zinc. Although GI absorption is not the major route for adults,

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it can be a significant contributor, particularly when working and/or eating in a lead-contaminated environment. GI absorption is the predominate route in children, and is more efficient, estimated to be around 50 percent [7].

Once absorbed, lead is then distributed to the blood, soft tissues, and skeleton. In blood, 99 percent of lead is bound to the erythrocyte and the remaining 1 percent is free in the plasma to exchange with soft tissues (kidney, brain, liver, bone marrow). Lead in blood is excreted via the kidneys and cleared comparatively fast, with a mean half-life of about 30 days if renal function is normal [23]. However, blood clearance can be slower in people with a long history of lead exposure and large bone stores [24].

Lead in the skeleton has a half-life of decades and contains approximately 95 percent of the body burden of lead [23]. Lead can be released from this bone reservoir during times of bone turnover, such as during hyperthyroidism [25], menopause, pregnancy [26], and breast feeding [27].

Lead is a toxic metal that affects many functions and organ systems in humans [6,7]. Some of the biochemical mechanisms of lead toxicity are as follows:

Lead is an electropositive metal. Its high affinity for negatively charged sulfhydryl groups leads to the inhibition of sulfhydryl dependent enzymes such as gamma-aminolevulinic acid dehydratase (ALA-D) and ferrochelatase in heme synthesis [7]. This disruption of hemoglobin synthesis leads to the production of free erythrocyte protoporphyrins that can be measured. Anemia can develop at very high blood lead levels (usually greater than 80ug/dL). In addition, lead inhibition of pyrimidine 5’ nucleotidase can cause degradation of ribosomal RNA in red blood cells that can lead to the appearance of basophilic stippling on a peripheral smear [28].The divalent lead also acts competitively with calcium in several biologic systems, such as mitochondrial respiration and various nerve functions. Lead's interference with several calcium dependent processes and activation of protein kinase C has been implicated as a contributing mechanism in neurotoxicity [7].Lead alters the permeability of the blood brain barrier and accumulates in astroglia, cells essential for maintenance of the neuronal environment [29].Lead can also affect nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) by mechanisms not yet fully understood.Lead has effects on cell membranes, interfering with various energy and transport systems, which may explain effects such as shortened erythrocyte survival time, hemolysis, and renal toxicity [7].Lead promotes generation of superoxide and hydrogen peroxide in human endothelial cells and vascular smooth muscle cells [30], which may explain effects on blood pressure (see 'Clinical manifestations' below).

Evidence is beginning to emerge that some common genetic polymorphisms may predispose individuals to worse responses to lead exposure. As an example, the allele for hemochromatosis (C282Y or H63D), even if in heterozygous carriers without risk for clinical hemochromatosis, has been shown to be associated with worse cognitive declines given the same cumulative exposure to lead [31].

CLINICAL MANIFESTATIONS — Many of the toxic effects of lead are reversible if lead poisoning is identified early. However, high level lead poisoning, or moderate poisoning over long periods, can result in irreversible damage to the central and peripheral nervous systems and kidneys.

Acute exposure — Unrecognized lead poisoning presenting with symptoms of colicky abdominal pain can be misdiagnosed and cause unnecessary gastrointestinal evaluation and abdominal surgery [32].

The manifestations of lead poisoning can vary from individual to individual. There is a general correlation between acute health effects and blood lead levels (figure 2). Severe lead poisoning is seen with blood lead levels generally above 80 mcg/dL. Acute poisoning can present with a number of signs and symptoms, including the following [6,33]:

Abdominal pain ("lead colic")ConstipationJoint painsMuscle achesHeadacheAnorexiaDecreased libidoDifficulty concentrating and deficits in short-term memoryAnemiaNephropathy (Fanconi-type syndrome)A "lead line," a bluish pigmentation seen at the gum-tooth line, is not a sensitive finding, and is the result of a reaction of lead with dental plaque (picture 1).Basophilic stippling on blood smear may be seen (picture 2). However, this is an inconsistent and nonspecific sign of lead poisoning [34].A peripheral neuropathy that frequently manifests with extensor weakness or

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"wrist/ankle drop" due to an axonal degeneration that primarily affects motor nerves [35]. This is seen less frequently since governmental regulations have resulted in lower lead exposures at work.

Chronic exposure — Adults with lower level, chronic or recurrent exposures (blood lead levels in the 30 to 70 mcg/dL range) may be asymptomatic or present with vague nonspecific symptoms such as myalgias, fatigue, irritability, insomnia, anorexia, impaired short-term memory, and difficulty concentrating.

Hypertension — There appears to be an association between blood and bone lead levels and blood pressure, but the magnitude of this effect is uncertain [36-41]. The association between blood lead levels and blood pressure was assessed in a meta-analysis of studies in the general population and in individuals with occupational lead exposure [36]. It was estimated that a two-fold increase in blood lead levels was associated with a small but significant increase in blood pressure of 1.0/0.6 mmHg.

Bone lead, a reflection of cumulative lead exposure, may be more closely associated with the development of hypertension [39,41]. In a report from the Normative Aging Study, it was estimated that an increase from the lowest to the highest quintile of tibial lead was, in a logistic regression model, an independent risk factor for the development of hypertension (OR 1.5) [39]. Blood lead was not an independent risk factor.

Neuropsychiatric effects — Chronic lead exposure has also been associated with a number of other adverse health effects, including:

Declines in neurocognitive functioning [42-45]Psychiatric symptoms (phobic anxiety and hostility) [46]Distal sensory and motor neuropathies [35]Electrocardiographic conduction delays [47]

In addition, elevated lead levels are associated with structural changes in the brain, including white matter lesions and loss of brain volume [48], and increased brain gliosis [49] and electrocardiographic evidence of conduction delays [47] have been described.

Bone lead, which remains for decades, has been shown to be a better predictor than blood levels of long term effects on cognitive function [42,50]. In one of the longest known lead cohort studies available, bone lead level predicted lower cognitive performance over a 22 year period, particularly in workers older than age 55, whereas blood lead levels showed no association [42].

Reproductive effects — In recent decades attention has focused upon the effect of lead on the reproductive system. Lead readily crosses the placenta. Increased number of miscarriages and stillbirths appear to be related to high lead exposures in pregnant women [7]. Reduced birth weight [51] and cognitive impairments [52,53] also have been reported in babies born to mothers with elevated lead in venous blood, cord blood, or bone. Bone lead levels have also been associated with higher maternal blood pressure and higher rates of third-trimester hypertension [54]. Sources of maternal lead exposure may be current, or the result of mobilization from bone stores remaining from past exposures [27,51]. These effects have been seen at levels as low as 10 to 15 mcg/dL. The effect of lead exposure during pregnancy on subsequent neurodevelopment of offspring is most apparent from exposure during the first trimester [55] and heightens the importance of preventing lead exposure as early as possible in pregnancy.

Men with chronic lead exposure (and blood lead levels between 40 and 70 mcg/dL) have been found in some studies to have an increased percent of sperm with abnormal morphology and decreased sperm concentration, total sperm count, and total motile sperm count [56-58], as well as alterations of male endocrine function [59].

Mortality — Chronic exposure with low lead levels (20 to 29 mcg/dL [60], and even less than 10 mcg/dL in one report [61]), has been linked to an increase in mortality. In a nationally representative sample in the US, blood lead levels >10 mcg/dL (median 11.8 mcg/dL) were associated with an increased risk of death from all causes (RR 1.59, 95% CI 1.28-1.98), cardiovascular disease (RR 1.55, 95% CI 1.16-2.07), and cancer (RR 1.69, 95% CI 1.14-2.52) [62].

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In a prospective cohort of 868 lead-exposed men in the Normative Aging Study followed over 8.9 years, those in the highest tertile for bone lead concentration were at higher risk of all-cause mortality (HR 2.5, 95% CI 1.2-5.4) and cardiovascular mortality (HR 5.63, 95% CI 1.7-18.3) [63]. Blood lead level was not associated with mortality in this population.

Other effects — Lead exposure may also affect the kidney and eye. As well, there is some evidence that lead exposure may be carcinogenic.

Lead nephropathy is a potential complication of prolonged high-level lead exposure. In addition, low levels of lead exposure have the potential for lead-related nephrotoxicity. These issues are discussed in detail separately. (See "Lead nephropathy and lead-related nephrotoxicity".)Low-level accumulated lead exposure, at levels commonly experienced by adults in the US, appears to be associated with an increased risk of cataract [64].Some animal studies have found that inorganic lead is carcinogenic, particularly for renal tumors [6]. Epidemiological studies of workers have revealed mixed results regarding increased risks of cancer, and have suffered from lack of quantitative exposure information, information about contribution from smoking, and exposures to other metals. Although the human data are still not conclusive, the US Environmental Protection Agency, the National Toxicology Program of the US Department of Health and Human Services, and the International Agency for Research on Cancer (IARC) determined that there are sufficient data to classify inorganic lead as a probable human carcinogen [65].

There are few studies of the long-term consequences of childhood lead poisoning. However, in a 50-year follow-up of 35 adult survivors of childhood lead poisoning, cognitive dysfunction [66], hypertension [67], and offspring with learning disabilities [68] were more prevalent than in matched adult controls; the adults in this study had been symptomatic in childhood and thus likely had blood lead levels exceeding 60 mcg/dL.

DIAGNOSTIC EVALUATION — The evaluation of the adult with potential lead toxicity involves taking a medical/environmental history to identify potential sources of exposure and symptoms consistent with lead poisoning, looking for signs on physical examination compatible with lead toxicity, documenting and measuring environmental/occupational exposures (when possible), and examining laboratory evidence to confirm excessive lead exposure or organ system damage consistent with lead-related effects [11].

History — The occupational/environmental history includes a job description, products manufactured, potential sources of lead exposure, engineering controls, the appropriate use and maintenance of personal protective equipment, housekeeping practices, smoking and eating at work (which can result in hand-to-mouth exposures), as well as attention to non-work exposures such as hobbies (including such activities as distillation of "moonshine" alcohol) or home repairs (figure 3). (See "Overview of occupational and environmental health".) The timing of the symptoms, changes in frequency or intensity, and relationship to any changes or recent exposure conditions is helpful information. It is also important to note the past history of lead exposure on previous jobs, or childhood lead poisoning.

Laboratory testing — The key clinical monitoring test for diagnosing lead toxicity is the blood lead level. Measuring lead in urine, hair, or other media is not as accurate or reliable. The blood lead level is a good indicator of exposure that has occurred within the previous few weeks. In interpreting the results, it is important to use levels appropriate to adult toxicity, rather than children's (which sometimes are the ranges of concern reported by the testing laboratories).

As discussed below, we tend to recommend chelation for individuals with blood lead levels greater than 80 mcg/dL, and in some symptomatic individuals with levels as low as 50 mcg/dL. (See 'Chelation therapy' below.)

The other core laboratory tests that measure lead effects are the free erythrocyte protoporphyrin (FEP), complete blood count with blood smear morphology, blood urea nitrogen (BUN), serum creatinine, and urinalysis [69,70]:

The free erythrocyte protoporphyrin (FEP) or zinc protoporphyrin (ZPP) both measure the effect of lead on hemoglobin synthesis, and therefore either can be used as an indicator of lead exposure (and effect) over the preceding three-month period (determined by the average 120 day lifespan of the erythrocyte).If either the blood lead or FEP is elevated, then other tests for lead effect on blood (CBC with smear) and the kidneys (serum creatinine, urinalysis) should be performed.

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Blood smear morphology should also be obtained in the setting of anemia. We generally do not perform smear morphology for routine screening (given that abnormalities in the smear would be associated only with high lead levels and are not specific). Smear morphology is required as part of medical surveillance for workers covered by the Occupational Safety Health Administration (OSHA) regulations promulgated in 1978 [69] and for construction workers in 1993 [70]. These guidelines have not been updated. It is important to note that the serum creatinine is not a sensitive indicator of renal damage since it does not rise substantially in patients with normal baseline values until over 50 percent of kidney function is lost. (See "Assessment of kidney function: Serum creatinine; BUN; and GFR" and "Lead nephropathy and lead-related nephrotoxicity".)

Abdominal radiographs, which are often ordered in children to look for evidence of lead ingestion, are not appropriate for adults in whom the route of exposure is more commonly inhalation. (See "Childhood lead poisoning: Clinical manifestations and diagnosis".)

Site of blood sampling — For routine monitoring of occupational exposure to lead, venous blood sampling is preferable to earlobe capillary blood sampling. Surface skin contamination can result in false elevations in the lead level in sampled capillary blood even after the area is cleaned with an alcohol wipe [71].

A single blood lead level reflects both recent exposure to exogenous sources and the release of endogenous lead from bone and soft tissue stores. However, cumulative lead exposure from chronic low-level exposures has been recognized as a cause for concern [72]. It is therefore important to keep a record of repeated measures of blood lead, from which a cumulative blood lead index (CBLI) can be calculated [73]. This parameter has been shown to closely parallel bone lead levels measured by x-ray fluorescence (see 'Other tests' below).

Other tests — Other tests which might be performed depending upon the setting and the patient's symptoms, include:

X-ray fluorescence — Bone lead concentration measured by x-ray fluorescence (XRF) is a relatively new technology that can be used to make rapid, noninvasive measurements of lead in bone [74]. In contrast to blood lead levels, the bone lead concentration reflects cumulative lead exposure, with an estimated half-life of 10 to 30 years [72,75].

XRF measurements have become increasingly standardized in terms of technique and interpretation [73]. However, XRF detection equipment remains available in only a few research centers and tends to be used primarily for research studies.

Neurobehavioral testing — Neurobehavioral testing is indicated in cases in which there is persistent impairment of cognitive function and a history of elevated blood lead levels. Neurobehavioral testing can demonstrate changes in manual dexterity, perceptual motor speed, and memory deficits characteristic of lead poisoning, and can sometimes be helpful in distinguishing from other causes of cognitive dysfunction [43,76].Nerve conduction velocity testing — Nerve conduction velocity testing should be considered when there are persistent symptoms or clinical findings suggestive of the presence of peripheral neuropathy, as well as a history of high blood lead levels, usually above 60 mcg/dL, particularly if persistent for a long time period.

MANAGEMENT — Management of patients with elevated lead levels generally consists of removal of lead exposure and, in cases of high blood lead levels (usually >50 mcg/dL), consideration of chelation therapy. In cases in which chelation therapy is being considered, it would be prudent to consult with a physician with expertise in treating adult lead poisoning.

Reducing lead exposure — Reduction or removal from lead exposure is the key first step in treating all cases of excessive lead absorption. Removal from lead exposure when blood lead levels rise to 50 mcg/dL is mandated under the standards of the US Occupational Safety Health Administration (OSHA) [69]. Removal from lead exposure may be accomplished by transfer to another job in a lead-free area or, if not possible, by removal from work while receiving salary under "medical removal protection." Workers can also be removed at lower levels if the treating clinician believes that the elevated lead level is responsible for adverse health effects.

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There are, however, growing concerns about cumulative effects of long-term exposures (over a working life) resulting in blood levels that remain above 10 to 20 mcg/dL [77]. Although not yet required by regulations, prudent health-based management would involve keeping long-term sustained blood lead concentrations over the working lifetime as low as possible; less than 20 mcg/dL, and ideally below 10 mcg/dL and under 5 mcg/dL for pregnant women [77].

The Centers for Disease Control and Prevention (CDC) set a public health objective to eliminate blood lead levels ≥25 mcg/dL by 2010 [2]. In addition, workers with a blood lead level ≥40 mcg/dL are required by OSHA to have an annual medical evaluation for the adverse effects related to lead exposure.

When elevated blood lead levels are noted, actions can be taken at work to prevent further excessive exposures, such as implementing work practices that generate less lead dust, using engineering controls or personal protection (appropriate respirators, work clothes), hand washing, and other improved clean up practices. Given growing information about subclinical lead effects at blood lead levels less than 40 mcg/dL, efforts should be made to control exposures and get blood lead levels lower when found to be above 20 mcg/dL [60,77]. (See "Lead nephropathy and lead-related nephrotoxicity", section on 'Lead-related nephrotoxicity'.)

When efforts made to control exposures do not result in lowering blood lead levels below 20 mcg/dL, a dilemma arises whether the clinician should advise an asymptomatic worker to leave work entirely to avoid continued low dose exposure and risks of future health effects. There is no simple answer. Removal from work may result in financial losses and hardship, given the lack of current regulatory protection for workers removed in order to protect against future adverse health effects. Different expert groups offer different guidance concerning removal from lead exposure, which may involve removal from the workplace [77,78]. Clinicians will need to address each patient individually, taking into consideration medical history and risk factors, length of time expected to work with lead exposure, and incorporating financial and social factors into the decision.

Chelation therapy — In most cases, removal from exposure is the only therapy needed. However, chelation therapy may more rapidly decrease blood lead levels and relieve acute lead symptoms (such as lead colic). Unfortunately, there are no randomized clinical trials that have proven the efficacy of chelation on clinical outcomes in lead poisoned adults [79]. Some studies have suggested improvement in central nervous system (CNS) symptoms [80] and creatinine clearance [81] with chelation. The decision to treat with chelating agents becomes a judgment call based upon consideration of a number of factors, including presence of lead-related symptoms, current blood lead levels, duration of excessive lead exposure, duration of symptoms, and presence of other underlying medical problems [7,11].

In general, chelation should be initiated for individuals with blood lead levels greater than 100 mcg/dL, and should also be considered for levels between 80-100 mcg/dl in asymptomatic individuals and for blood lead levels between 50 and 80 mcg/dL in individuals with lead-related symptoms [77]. In addition, we sometimes consider chelation in persons with even lower blood lead levels (eg 40 mcg/dL or higher) if they have continued symptoms and elevated blood lead levels after two weeks of removal from exposure. Two chelating agents most commonly used to treat adults are DMSA and CaEDTA.

Chelation with any agent should not be undertaken unless exposure has been definitively curtailed, since its use in the presence of continuing exposure may result in enhanced absorption of lead and worsening, rather than amelioration of toxicity.

DMSA — DMSA (2,3-dimercaptosuccinic acid, succimer) is an oral chelation agent that is approved by the US Food and Drug Administration (FDA) for the treatment of lead-poisoned children, and has also been found effective in adults [82,83]. The recommended dose from the manufacturer is 10 mg/kg three times per day for five days, followed by 10 mg/kg twice per day for two weeks. Although we have found this dosing to be acceptable in treating some adults, the dose can become quite high, especially in heavier adults.

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We have some questions about linearly extrapolating the pediatric dosing schedule to adults. Given the lack of adult treatment data with DMSA, we have also used an adult dosing level of 500 mg twice per day for two weeks as a sensible maximum limit until there are additional clinical data available for adults. The most common adverse side effects include abdominal distress, transient rash, elevated liver transaminase enzymes, and neutropenia.

Calcium EDTA — Calcium disodium ethylenediaminetetraacetate (CaEDTA) is an older chelating agent, introduced in the early 1950's, which must be administered intravenously or intramuscularly, usually for a three to five day chelation period. It increases the urinary excretion of lead through the formation of non-ionizing salts. It is crucial that the calcium disodium EDTA salt be administered, and not the disodium EDTA salt alone which binds calcium and can lead to severe hypocalcemia. Major potential toxicity with CaEDTA is kidney dysfunction. Treatment with CaEDTA should be performed in a hospital setting by clinicians experienced with chelation, in patients with normal renal function, and with careful monitoring of renal and other parameters.

Provocative chelation — Provocative chelation is a mobilization test that has been proposed to give an indirect measure of lead body burden and thereby determine if chelation therapy is indicated. Some medical practices assess lead poisoning by provocative chelation with DMSA or CaEDTA, comparing urinary excretion to reference ranges for non-challenged urine specimens. Studies have failed to establish a valid correlation between prior metal exposure and post-challenge test values. The American College of Medical Toxicology (ACMT) does not support provocative chelation [84].

Ascorbic acid — One study found that the serum ascorbic acid level was inversely related to the blood lead level in adults and children enrolled in the NHANES III study [85]. Animal data are supportive of a chelating effect of ascorbic acid, although human studies have so far yielded inconclusive results. However, case series and small clinical trials using ascorbic acid in doses of 100 mg to 1000 mg per day found a reduction in blood lead levels. Given the benign nature of vitamin C supplementation in modest doses (100 to 1000 mg per day), this may be an attractive adjunct to the management of patients with mild lead toxicity.

Referral — Primary care clinicians may find it advisable to refer patients with elevated blood lead levels, particularly above 20 mcg/dL, to occupational medicine clinicians. These clinicians can not only assist in the diagnosis of lead poisoning, but can also help in arranging for environmental site evaluations and suggesting preventive measures in an effort to avoid both short-term poisoning and long-term health effects. Occupational medicine clinicians can also help with the decision for chelation therapy and then in choosing and administering the appropriate therapy. They can assist in various worker compensation and regulatory issues that arise with cases of work-related lead poisoning. Lastly, the occupational/environmental medicine clinician might be able to help in setting up an appropriate lead surveillance program that is in compliance with various national and local regulations and serve to prevent lead poisoning in the future.

Occupational medicine clinicians can be located by contacting the Association of Occupational and Environmental Clinics (AOEC), a group of occupational medicine clinics (frequently academically affiliated) with board-certified occupational medicine physicians (phone 202-347-4976; internet site: www.aoec.org) or the American College of Occupational and Environmental Medicine Physicians (www.acoem.org).

PREGNANCY AND BREASTFEEDING — In pregnant women, slight elevations in blood lead levels are of high concern because of the potential for adverse effects on the developing fetus which is more susceptible to lead's toxic effects. Even lead levels less than 10 mcg/dL may be of concern in pregnancy in light of studies demonstrating intellectual impairment in children with blood lead concentrations below 10 mcg/dL [86]. (See "Childhood lead poisoning: Clinical manifestations and diagnosis" and "Childhood lead poisoning: Exposure and prevention", section on 'Prenatal exposure'.)

In the US, routine screening of all pregnant women is not warranted given that the prevalence of blood lead levels (BLL) over 5 mcg/dL in pregnant women is less than 1 percent [87,88]. However, the Centers for Disease Control and Prevention (CDC) do recommend blood lead testing for pregnant and lactating women with one or more important risk factors for lead exposure and increased BLLs [87]:

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Recent immigration (from an area where ambient lead contamination is high)Living near point source of lead (eg, lead mines, smelters, battery recycling plants, home remodelling)Pica (ie, compulsive eating of non-food items)Occupational exposures (eg, painters, those exposed to batteries or radiators, living with someone who works in lead industry)Environmental exposures (eg, lead-contaminated soil, water, or food)Use of lead-containing cosmeticsCooking/storing in lead-glazed potteryUse of herbal/alternative medicines (eg, some Chinese herbs, Ayurvedic medicines) (See "Overview of herbal medicine and dietary supplements", section on 'Adverse effects'.)

If BLL during pregnancy is <5 mcg/dL, no follow-up testing indicated. Otherwise, follow-up testing of BLLs during pregnancy depends on the initial BLL (table 2) [87]:

Following pregnancy, levels of lead in breast milk are up to 3 percent of BLLs in the mother (table 3) [87]. Additional monitoring of maternal BLL during breastfeeding depends upon the most recently obtained maternal BLL (table 4).

Providers for pregnant and lactating women with elevated BLL should ensure that the maternal lead level is known by the provider managing the newborn infant. Childhood lead poisoning, including monitoring of neonate and infant BLLs, is discussed elsewhere. (See "Childhood lead poisoning: Exposure and prevention", section on 'Prenatal exposure' and "Childhood lead poisoning: Exposure and prevention", section on 'Breastfeeding'.)

The management of lead exposure in pregnant and lactating women depends on the BLL, which is summarized in a figure (figure 4) [87].

SUMMARY AND RECOMMENDATIONS

Elevated blood lead levels have been defined for epidemiological purposes as greater than or equal to 25 mcg/dL in adults. However, there are also concerns about long term exposures at blood lead levels below this level. Most lead exposure is occupational, associated with manufacturing (table 1). (See 'Dimensions of the problem' above.)Although gastrointestinal absorption is the main route of lead exposure in children, the respiratory tract is the main route in adults. Lead is a toxic metal with a relatively short half life in blood, but a half-life of decades in the bones. It can affect many biologic systems once absorbed into the blood stream (see 'Biological basis for disease' above).Acute clinical manifestations of lead toxicity are varied but include abdominal pain ("lead colic"), joint/muscle aches, short-term memory problems, difficulty concentrating, irritability, anemia (sometimes accompanied by basophilic stippling on blood smear) and nephropathy (see 'Acute exposure' above).Chronic clinical manifestations can be non-specific and similar to acute exposure, but can also include continued decline in neurocognitive function, lead nephropathy, hypertension, and increased risk of all-cause/cardiovascular mortality (see 'Chronic exposure' above).In addition to taking an occupational/environmental history, blood lead level remains the mainstay of diagnosing lead toxicity. Bone lead concentration measured by x-ray fluorescence is a rapid, noninvasive measurement of lead in bone that is becoming increasingly standardized, although availability in most areas is limited. Individualized testing such as neurobehavioral testing depends on specific signs and symptoms of a particular patient (see 'Diagnostic evaluation' above).In most cases of mildly elevated lead levels, removal of the patient from the exposure may be the only therapy indicated. Chelation should be considered for patients with blood lead levels >80 mcg/dL. We also suggest chelation therapy for symptomatic patients with blood levels 50-80 mcg/dL (see 'Management' above).Primary care clinicians may find it advisable to refer patients with elevated blood lead levels, particularly above 20 mcg/dL, to occupational medicine clinicians. (See 'Referral' above.)

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Adult Lead Poisoning