Trace Elements - Deficiency and Toxicity

Aluminum

Exposure to aluminum from food, water, and dermal contact (eg, antiperspirants and sunscreen lotion) is low. Intake of aluminum is greatest from aluminum-containing remedies, including antacids and antidiarrheal and antiulcerative medications. Aluminum accumulates in the skeleton and lungs, but the brain and nervous system are most affected by excess amounts. A typical dietary intake of aluminum is normally completely eliminated from the blood by the kidneys, but patients with renal failure are at particular risk for aluminum toxicity due to a reduced ability to filter aluminum from the blood.

Indications for Testing

Patients with a known or suspected source of exposure and corresponding symptoms should be tested for aluminum exposure. Patients undergoing dialysis are at increased risk for aluminum exposure from contaminated dialysate water or aluminum-containing phosphate binders; however, the Kidney Disease: Improving Global Outcomes (KDIGO) organization recommends precautions to avoid aluminum intoxication.  Nonaluminum-containing treatments and procedures are available.

Laboratory Testing

Diagnosis

Serum

Serum aluminum levels best reflect recent exposure. Serum is the preferred specimen type for routine screening and to assess patients for toxicity due to dialysis. Serum levels in healthy individuals range from 1-3 µg/L.  A serum aluminum level >50.0 µg/L is consistent with overload and may correlate with toxicity.

Urine

Aluminum levels in urine are more appropriate for determining chronic exposure.

Monitoring

KDIGO no longer recommends regular monitoring of serum or plasma aluminum levels. However, KDIGO does recommend avoiding long-term use of aluminum-containing phosphate binders in patients with chronic kidney disease, stages 3-5D, and use of aluminum-contaminated dialysate in patients with chronic kidney disease, stage 5D. 

Antimony

Antimony is not an essential nutrient for human function. The general population can be exposed to low levels in air, water, or food, or from polyethylene terephthalate water bottles and fire retardants.  Workers in the antimony industry (involved with production of fire retardants, glass, hard alloys, etc.) are at risk for higher, toxic levels of exposure. Exposure can cause delayed growth in children, dermatitis and inflammatory lesions, pulmonary damage, myocardial damage, and gastrointestinal irritation.

Indications for Testing

Individuals with a known or suspected source of exposure and corresponding symptoms should be tested for antimony exposure.

Laboratory Testing

Diagnosis

Blood

Blood antimony levels predominantly reflect recent exposure and are most useful in the diagnosis of acute poisoning. Blood concentrations in unexposed individuals rarely exceed 3 µg/L.

Urine

Although most people in the United States have a small amount of antimony in their urine, high levels in blood or urine indicate recent exposure to an amount greater than normal. 

Hair

Antimony levels in hair are not a reliable indicator of exposure. 

Arsenic

Arsenic exists in toxic and nontoxic forms. Nontoxic arsenic, or organic arsenic, is found in seawater and in several foods, notably shellfish and dark-meat fish. Inorganic arsenic is highly toxic; it is most readily found in pesticides and wood preservatives but is also used in glass and ceramic production and in some pharmaceuticals. Children are more susceptible to toxins due to their higher metabolic rate, developing nervous system, and increased hand-to-mouth behavior; they are also less able to methylate arsenic. Additionally, arsenic is known to cross the placenta and accumulate in the fetus. Syndromes of arsenic toxicity can present as acute, chronic, or latent. Appropriate specimen choice and testing are important for a successful diagnosis.

Indications for Testing

Acute arsenic exposure is characterized by vomiting, diarrhea, abdominal pain, and, in extreme cases, numbness, tingling, muscle cramps, and death. Chronic exposure (≥5 years of exposure) causes changes in skin pigmentation, skin lesions, and hard patches on hands and bottoms of feet. Individuals with known or suspected exposure and associated symptoms should be tested.

Criteria for Diagnosis

A person is diagnosed with arsenic exposure when urinary arsenic levels are >50 µg/L in a random urine collection or >50 µg total for 24-hour urine collection.  In patients with elevated urine arsenic levels, testing must differentiate the amounts of organic and inorganic arsenic.  The American Conference of Governmental Industrial Hygienists (ACGIH) Biological Exposure Index (BEI)  for arsenic in urine is 35 µg/L; the BEI for arsenic is based on the sum of inorganic and methylated arsenic species.

Laboratory Testing

Diagnosis

Urine

Urine testing is sensitive for low-level arsenic exposure, and urine is the preferred specimen to detect acute exposure due to the short half-life of arsenic in the blood.  Concentrations of methylated arsenic species in urine peak 40-60 hours after ingestion and return to baseline after 6-20 days. A 24-hour urine arsenic level is useful for the detection of chronic exposure. Elevated results should be fractionated to differentiate between toxic, inorganic forms and relatively nontoxic, organic forms.

Blood

Blood arsenic testing is used for the detection of recent exposure (<24 hours since exposure) and large-dose poisoning only. In blood, the half-life of inorganic arsenic species is 4-6 hours, and the half-life of methylated arsenic species is 20-30 hours. Arsenic binds to hemoglobin, and, as a result, hemoglobin contains three times more arsenic than plasma.

Other

Hair or nail testing can detect chronic or past exposures of >3 weeks and is most useful to determine time of exposure. However, hair is a poor specimen type to assess arsenic exposure at low or moderate levels and can become contaminated by arsenic-containing water.

Beryllium

Beryllium is a poisonous earth metal that inhibits the alkaline phosphatase, acid phosphatase, phosphoglycerate mutase, hexokinase, and lactate dehydrogenase enzyme systems in the body. Exposure through food and water is not clinically significant, owing to the low level of exposure and the limited absorption of beryllium by the stomach and intestines.  However, chronic industrial exposure, which occurs from inhaling insoluble beryllium compounds through the respiratory tract, can cause chronic beryllium disease (CBD), or berylliosis. CBD is a potentially fatal respiratory condition that is diagnosed with a beryllium lymphocyte proliferation test (BeLPT) and biopsy.   Acute exposure is rare but can happen from an industrial explosion. Beryllium is used in nuclear weapons, spacecraft, circuit boards, dental bridges, and sports equipment, among other applications. Beryllium chloride (soluble compound) has a pulmonary half-life of 20 days, and beryllium oxide (insoluble compound) has a pulmonary half-life of about 1 year. Beryllium compounds are classified as a Group 1 human carcinogen by the International Agency for Research on Cancer (IARC). 

Indications for Testing

Patients with a known or suspected source of exposure and corresponding symptoms should be tested for beryllium exposure. Common symptoms include shortness of breath, dry cough, chest pain, and fatigue.

Laboratory Testing

Diagnosis

Although a serum beryllium test can confirm an exposure, a diagnosis of CBD requires that the following three criteria be met :

• Appropriate history of exposure
• A positive blood or bronchoalveolar lavage (BAL) BeLPT
• Granulomatous inflammation on lung biopsy

Beryllium Lymphocyte Proliferation

The BeLPT identifies beryllium sensitization; the result of this test can help predict CBD but alone is not diagnostic for CBD. The test can be performed with either blood or fluid from BAL. Testing can be used in asymptomatic individuals with chronic exposure to beryllium or in symptomatic individuals with a history of beryllium exposure. Patients with an elevated number of cells (lymphocytes) are sensitized to beryllium and are at greater risk for developing CBD.

Serum

Serum beryllium testing measures the amount of beryllium in serum and can confirm an exposure to beryllium; however, serum test results do not indicate the extent of exposure or how recently the patient was exposed.

Monitoring

Patients who are diagnosed with CBD require lifelong follow-up with serial arterial blood gases, chest x-rays, and pulmonary function tests; those with beryllium sensitization in the absence of CBD should undergo periodic evaluation but do not need treatment. 

Bismuth

Bismuth is a metal that is often formulated into a salt used in medications to treat vomiting, diarrhea, and ulcers. It is also used in ceramic and glass manufacturing and in the production of alloys and castings. Toxicity resulting from ingestion, although rare, mostly affects the kidneys, liver, and bladder.

Indications for Testing

Individuals with a known or suspected source of exposure and corresponding symptoms should be tested for bismuth exposure.

Laboratory Testing

Diagnosis

Blood

Bismuth exposure can be evaluated by blood or urine testing, but whole blood is a better indicator of bismuth exposure because bismuth is normally rapidly excreted in urine.  A blood bismuth concentration <5 µg/dL is a normal level and is rarely associated with symptoms. 

Cadmium

Cadmium is a heavy metal used in the production of batteries, plastics, metal plating, and for pigments. Most cadmium exposure is occupational, but outbreaks can occur as an effect of mining pollution. Cadmium is not only toxic in moderate amounts but also counteracts several necessary minerals.  Cadmium damages the kidneys, lungs, and bones, and increases the risk of developing lung cancer. 

Indications for Testing

Individuals with a known or suspected source of exposure and corresponding symptoms should be tested for cadmium exposure.

Laboratory Testing

Diagnosis

The Occupational Safety and Health Administration (OSHA) recommends a panel that includes both blood and urine cadmium testing as well as a test for beta-2-microglobulin in urine.  Because many collection materials (rubber catheters and colored plastic containers) contain cadmium, it is important to use trace-free collection equipment. See Trace Elements Specimen Collection Guide for ARUP Laboratories’ metals-free collection requirements.

Urine

Urinary cadmium concentrations have been shown to accurately reflect the amount of cadmium stored in the body and can indicate both recent and past exposure.   Urine specimens are recommended for the assessment of chronic exposure.

Blood

The amount of cadmium in blood can be used to determine acute toxicity or recent exposure.  

Chromium

Chromium exists in many forms; the most common are chromium (0), chromium (III), and chromium (VI). Chromium (III) is considered an essential nutrient with low toxicity, but its necessity is unproven.   It is believed to help in the metabolism of sugar, protein, and fat. However, chromium (VI), a known carcinogen, is toxic and can cause ulcers, anemia, and lung cancer. In industrial settings, chromium is used in the manufacturing of steel, in dyes, and for chrome plating, leather tanning, and wood preserving.

Indications for Testing

Deficiency

Although a state of chromium deficiency has not been clinically defined  and explicit symptoms are limited, individuals at increased risk for deficiency are the elderly, pregnant women, and those with DM. Patients with DM have reduced tissue levels and may have altered chromium metabolism. Studies have shown that chromium supplements can improve glucose and insulin metabolism in those with DM but that the effect of supplementation is limited in those without DM.  Additionally, strenuous exercise, infection, and physical trauma can increase chromium losses.

Toxicity

Symptomatic patients with a known or suspected source of exposure should be tested. Patients with metal-on-metal joint replacements, in particular, are at risk for release of metal debris, which can cause periprosthetic soft tissue reactions and chromium and cobalt toxicity and can result in neurologic impairment, cardiomyopathy, and hypothyroidism. See Monitoring.

Laboratory Testing

Diagnosis

Chromium levels can be tested in blood, urine, and hair, but testing does not predict health outcomes because dietary chromium biomarkers are inconclusive.  Chromium concentrations that exceed normal levels indicate recent excessive exposure or dietary intake but not body burden. 

Blood

Whole blood is useful for assessing chromium deficiency or overload and is the specimen type recommended by the U.S. Food and Drug Administration (FDA) for evaluating metal ion release from metal-on-metal joint arthroplasty. 

Red Blood Cells

Chromium in red blood cells (RBCs) can be used to investigate or monitor potential chromium exposure and is preferred when assessing hexavalent chromium exposure.

Serum/Plasma

Concentration of chromium in serum is one of the most common indicators of chromium status,  whether deficiency or overload. Serum and plasma are appropriate specimen types to evaluate metal ion release from metal-on-metal joint arthroplasty. Elevated plasma chromium levels may be a good indicator of exposure and indicate recent dietary intake. 

Urine

The level of chromium in urine is one of the most common indicators of chromium status  and may be used to monitor short-term exposure (other than that from metal-on-metal joint implants).

Monitoring

The FDA recommends that cobalt and chromium metal ion testing be considered in symptomatic patients with metal-on-metal hip replacements.  Although the FDA found insufficient evidence to recommend testing in asymptomatic patients,  the United Kingdom Medicines and Healthcare products Regulatory Agency (UK MHRA) recommends testing for every patient with metal-on-metal hip replacements on the following schedule :

• Symptomatic patients: annually while the device remains implanted
• Asymptomatic patients with all stemmed total hip replacements or resurfacing devices without a 10A Orthopaedic Data Evaluation Panel (ODEP) rating: annually for the first 5 years, twice a year to 10 years, and three times a year thereafter
• Asymptomatic patients with resurfacing devices with 10A ODEP rating: at the first year, once at 7 years, and three times a year thereafter

There is no accepted cutoff value for a whole blood metal level that either predicts outcome or indicates revision is necessary; however, the UK MHRA suggests that a measurement of ≥7 ppb (119 nmol/L cobalt or 134.5 nmol/L chromium) in one or both metals indicates the need for further investigation. 

Cobalt

Cobalt, a component of vitamin B₁₂, is a natural element that is essential for blood and DNA production and nerve health. In excess, however, it negatively affects the lungs and heart. Dietary cobalt toxicity is rare; toxicity is more likely to occur in an occupational setting where cobalt is released into the air in high concentrations. Exposure can also be caused by metal-on-metal arthroplasty and athletic salts. Cardiomyopathy is common, especially in heavy beer drinkers with excess cobalt, given that cobalt interacts with ethanol, but the mechanism of action is not fully elucidated. Industrially, cobalt is used in the manufacturing of magnets, tools, aircraft engines, and hip and knee prostheses.

Indications for Testing

Symptomatic patients with a known or suspected source of exposure should be tested. Patients with metal-on-metal joint replacements, in particular, are at risk for release of metal debris, which can cause periprosthetic soft tissue reactions and chromium and cobalt toxicity and can result in neurologic impairment, cardiomyopathy, and hypothyroidism. See Monitoring.

Laboratory Testing

Diagnosis

Blood

Either whole blood or erythrocytes may be used to assess occupational exposure or toxic ingestion. Whole blood is the specimen type recommended by the FDA for evaluating metal ion release from metal-on-metal joint arthroplasty.  Elevated cobalt levels in RBCs indicate long-term exposure. 

Serum/Plasma

Serum or plasma can be used to assess occupational exposure or toxic ingestion. Most serum/plasma cobalt tests measure free ionized cobalt and free and protein-bound soluble cobalt; elevated concentrations indicate recent exposure.  Serum and plasma are appropriate specimen types for evaluating metal ion release from metal-on-metal joint arthroplasty.

Urine

Urine cobalt measurements are best for determining recent, acute exposure, given that the majority of cobalt is eliminated in urine 2-8 days after ingestion. 

Monitoring

The FDA recommends cobalt and chromium metal ion testing be considered in symptomatic patients with metal-on-metal hip replacements.  Although the FDA found insufficient evidence to recommend testing in asymptomatic patients,  the UK MHRA recommends testing for every patient with metal-on-metal hip replacements on the following schedule :

• Symptomatic patients: annually while the device remains implanted
• Asymptomatic patients with all stemmed total hip replacement or resurfacing devices without a 10A ODEP rating: annually for the first 5 years, twice a year to 10 years, and three times a year thereafter
• Asymptomatic patients with resurfacing devices with 10A ODEP rating: at the first year, once at 7 years, and three times a year thereafter

There is no accepted cutoff value for a whole blood metal level that either predicts outcome or indicates revision is necessary; however, the UK MHRA suggests that a measurement of ≥7 ppb (119 nmol/L cobalt or 134.5 nmol/L chromium) in one or both metals indicates the need for further investigation. 

Copper

Copper is present throughout the environment and is used for wires and pipes, in brass and bronze fixtures, and as a textiles preservative. Although copper is dietarily necessary in a small amount for healthy nerves, bones, and collagen, ingesting or breathing in too much can cause vomiting and diarrhea, or nose and throat irritation, or damage to the liver and kidneys.

Excess copper body burden may also result from an inherited disorder called Wilson disease, which causes copper to accumulate in the liver and brain rather than being eliminated through bile and can be fatal if untreated. Conversely, Menkes disease is a genetic disorder that reduces copper bioavailability, resulting in symptoms of deficiency.

Indications for Testing

Deficiency

Individuals with symptoms of copper deficiency, including slow growth (especially in young children), anemia, and osteopenia, should be considered for copper deficiency testing. Patients who have had bariatric surgery are at increased risk for symptoms of nutrient deficiencies.

Toxicity

Individuals with progressive neurologic dysfunction, especially in association with liver disease, should be tested for copper excess that may be related to Wilson disease, unless a source of exposure is known.

Laboratory Testing

Diagnosis

A combination of copper, free copper (direct), and ceruloplasmin testing is preferred to diagnose conditions of copper overload in symptomatic patients or individuals with a family history of Wilson disease. For diagnostic testing recommendations specific to Wilson disease, see the ARUP Consult Wilson Disease topic.

Serum/Plasma

The concentration of copper in serum/plasma is a traditional marker for copper status; levels are decreased in severe copper deficiency. But the serum/plasma copper concentration may not be a reliable marker for mild deficiency, given that circulating concentrations are affected by age, infection, inflammation, cancer, and pregnancy.  In cases of copper overload, serum ceruloplasmin is usually low, and free copper (direct) is usually high. Serum free (direct) copper testing is preferred to monitor response to copper-reducing therapies.

Ceruloplasmin

Ceruloplasmin is a protein in the blood that carries copper and is a traditional marker for copper status. But like serum/plasma copper levels, ceruloplasmin copper concentrations may be affected by conditions other than deficiency. Testing of ceruloplasmin may be used as an initial screening test in Wilson disease or copper transport disorders, in conjunction with urine copper and serum/plasma copper levels.

Urine

Testing either a random urine collection or a 24-hour urine collection may be useful to assess copper overload, but test validity is subject to interindividual variability. 

Liver

The concentration of copper in liver may also provide information on copper status and is especially useful when related serum or urine assessments are inconclusive. Levels of copper in liver are increased in Wilson disease. 

Red Blood Cells

Testing in red blood cells (RBCs) may be useful for exposure monitoring or investigation, but this testing is not recommended for clinical diagnosis of copper deficiency or overload. Copper concentrations in erythrocytes reflect the intracellular stores and general homeostasis of copper.

Iodine

Iodine is an essential nutritional element for proper thyroid function and development. Deficiency can cause goiter in adults and brain damage and mental retardation in children and fetuses. Excess iodine is typically excreted from the body, so toxic levels are usually a result of drugs, radioactive iodine uptake tests, and iodine-containing sterilizers.

Indications for Testing

Individuals with signs of either deficiency or excess iodine should be considered for testing. Dysfunction of the thyroid gland is a principle indicator.

Laboratory Testing

Diagnosis

Urine

The majority of excess iodine is excreted in urine, making urine iodine testing ideal for determining nutritional status, especially across populations. Because iodine intake varies from day to day, 24-hour urine testing is a more accurate measure and preferred over random urine testing; however, the accuracy of 24-hour urine testing is affected by low protein intake and high creatinine output. 

Serum

Serum testing is recommended for determining iodine excess and monitoring overload in patients on iodine-containing medications. For testing specific to thyroid function, see the ARUP Consult Thyroid Disease Testing page.

Iron

Iron is distributed throughout the body, mainly into hemoglobin and also ferritin and hemosiderin, and transferred from organ to organ by a complex called transferrin. Iron deficiency occurs more frequently than any other micronutrient deficiency.  Signs and symptoms of iron deficiency anemia appear when body stores are depleted. Acute toxicity is characterized by constipation, vomiting, and diarrhea and is more likely to occur in children. Chronic toxicity is most likely a result of hereditary hemochromatosis. 

Indications for Testing

Individuals with signs of either iron deficiency or excess should be considered for testing. The most common indicator of deficiency is anemia and its corresponding symptoms:

• Fatigue
• Shortness of breath
• Pallor
• Dizziness
• Fainting

Hemochromatosis is characterized by the classic triad of symptoms:

• Bronzing of skin
• Cirrhosis
• DM

Laboratory Testing

Diagnosis

Several laboratory testing options are available to help identify iron deficiency or overload. For testing recommendations specific to iron deficiency anemia, see the ARUP Consult Iron Deficiency Anemia topic. For testing and monitoring of iron overload as a result of hemochromatosis, see the ARUP Consult Hemochromatosis topic. For testing for beta (β)-thalassemia, the most common cause of secondary iron overload, see the ARUP Consult Thalassemias topic.

Serum Iron

A serum iron measurement indicates the amount of iron bound to serum transferrin and does not include iron contained in serum as free hemoglobin. Serum iron concentrations are often decreased in patients with iron deficiency anemia as well as in those with inflammatory disorders; however, concentrations naturally decrease throughout the day, so results require careful interpretation. Levels are elevated in patients with iron-loading disorders and after iron intake.

Total Iron-Binding Capacity

Total iron-binding capacity is a measurement of the greatest amount of iron that transferrin can bind. In patients with iron deficiency, transferrin saturation, determined by the ratio of plasma iron to total iron-binding capacity, is low because synthesis increases to maximize iron delivery.

Transferrin

Serum transferrin may be a better biomarker than iron-binding capacity because it is not affected by inflammatory diseases, which can yield false-negative results.

Soluble Transferrin Receptor

Soluble transferrin receptor testing can distinguish between iron deficiency anemia and anemia of chronic disease and can identify iron deficiency anemia in patients with inflammatory conditions in whom ferritin is increased.  The soluble transferrin receptor test result is also a useful marker because it corresponds more closely with the depletion and normalization of iron stores. 

Ferritin

Serum ferritin is an acute phase reactant, and concentrations are affected by inflammation, alcohol use,  and obesity. However, in the absence of inflammation, measurement of serum ferritin is the most powerful test for iron deficiency. 

Erythrocyte Zinc Protoporphyrin

Erythrocyte zinc protoporphyrin is an indicator of abnormal heme synthesis and is helpful in primary screening for basic iron deficiency; in combination with soluble transferrin receptor testing, it is particularly useful for monitoring iron supplement therapy. 

Other Testing

Liver tissue testing can be useful to confirm hepatic iron overload, particularly in individuals with hemochromatosis and no common HFE gene variants, but less invasive iron testing should be used as an initial approach to diagnosis. Similarly, bone marrow staining can be used to assess iron status by examining the amount of hemosiderin in the reticulum cells. 

Lead

Lead poisoning or lead toxicity generally occurs either in childhood or because of occupational exposure. Lead exposure in children can result in critical conditions, including brain damage, nervous system damage, developmental delay, and hearing and speech problems. 

In adults, lead exposure can cause adverse reproductive outcomes in women, hypertension, renal damage, and cognitive dysfunction. 

Lead poisoning can also disturb heme synthesis and cause symptoms similar to those of porphyrin disorders, including abdominal pain, nausea, and rapid heart rate. Aminolevulinic acid, erythrocyte porphyrin, and zinc protoporphyrin can be used as biomarkers to differentiate a lead poisoning effect.  See the ARUP Consult Porphyrias topic for testing specific to porphyrin disorders.

Indications for Testing

Testing is appropriate for adults with a risk of exposure, known exposure, or suspected occupational exposure. Children at greater risk include those who are younger than 6 years and those who live in older housing; children of some racial and ethnic groups are also at higher risk.  

Laboratory Testing

Diagnosis

Blood

The best way to measure lead exposure is with a venous blood lead test. 

Blood from capillaries is recommended for the initial screening in pediatric populations. A safe blood lead level (BLL) has not been identified for children. Confirmatory testing should be performed within 3 months for children with a BLL above the reference value or as soon as possible if the BLL is ≥45 µg/dL. 

Management is recommended for adults with a BLL ≥5 µg/dL. 

Urine

Urine lead testing may be useful to assess chronic lead exposure or in monitoring chelation therapy, but blood is the preferred specimen for routine lead exposure testing.

Screening

The CDC recommends targeted screening of children at a higher risk of exposure (eg, due to housing and other risk factors). Medicaid-enrolled children are required to be tested at 12 months and at 24 months, or as late as 72 months for those not previously screened for lead exposure. 

The American Academy of Pediatrics recommends risk assessment or screenings as appropriate at 6, 9, 12, and 18 months and annually from 2-6 years of age. 

The U.S. Preventive Services Task Force (USPSTF) found insufficient evidence to recommend or discourage screening of elevated BLLs in asymptomatic pregnant individuals and asymptomatic children younger than 6 years of age. 

Monitoring

Children with a BLL ≥3.5 µg/dL should be monitored until environmental conditions are resolved. 

Lead-exposed workers should have a baseline BLL determined at job placement and be monitored based on BLL (recommendations vary between health authorities and states)  :

• <10 µg/dL
  • Perform BLL test every 2 months for the first 6 months after placement or after being placed in a higher-exposure task, then every 6 months.
  • If BLL increases ≥5 µg/dL, evaluate exposure and increase monitoring frequency if necessary; repeat testing can be considered every 3 months until the BLL is <5 µg/dL based on the California Department of Public Health recommendations.
  • Individuals with a BLL of 5-9 µg/dL who are pregnant or may become pregnant should reduce lead exposure until two consecutive BLLs are <5 µg/dL.
• 10-19 µg/dL
  • Perform BLL test every 2 months.
  • Evaluate exposure and consider removal from exposure.
  • If three BLL test results are <10 µg/dL, test every 6 months.
• ≥20 µg/dL
  • If BLL is ≥30 µg/dL, immediately remove from exposure.
  • If BLL remains 20-29 µg/dL after 4 weeks, remove from exposure.
  • Perform monthly testing of BLLs.
  • If two monthly tests report a BLL of <15 µg/dL, consider a return to work.

Magnesium

Symptomatic magnesium deficiency is rare, but people with gastrointestinal disease, type 2 DM, and alcohol dependence are at risk for magnesium inadequacy. Insufficient levels are associated with high blood pressure, osteoporosis, and migraines.  The kidneys eliminate any excess dietary magnesium in urine, but the use of supplements, notably laxatives and antacids that contain magnesium, can cause toxicity, resulting in low blood pressure, nausea, urine retention, and possible cardiac arrest. Hypermagnesemia refers to an abnormally high level of magnesium, specifically in serum. In clinical practice, it is most often caused by treatment for preeclampsia or eclampsia in pregnant women.  Hypermagnesemia can also occur in patients with renal failure, milk-alkali syndrome, or tumor lysis syndrome. Hypomagnesemia is common in hospitalized patients and in patients with acute or chronic illness.

Indications for Testing

Testing for magnesium status should be performed in conjunction with a clinical assessment. Indications for magnesium testing include:

• Hypocalcemia
• Hypokalemia
• Cardiac disorders

Laboratory Testing

Diagnosis

Serum/Plasma

Serum magnesium concentration is the most common and available method to measure magnesium status; it is preferred for routine screening. It does not, however, correlate with total body stores or concentrations in tissue. 

Blood

Erythrocyte measurements may be useful to assess tissue stores of magnesium, but no test alone is considered satisfactory to assess magnesium status.

Urine

Urine measurements may provide information on magnesium status, but no test alone is considered satisfactory to assess status. 

Manganese

Manganese is an essential trace element found in most foods, but excess can cause brain damage. Manganese is often used in pesticides and steel manufacturing and as a fuel additive. Occupational exposure poses a risk for nervous system damage, neurologic effects such as bradykinesia (slow movement), and lung irritation.

Indications for Testing

Individuals with a known or suspected source of exposure and corresponding symptoms should be tested for manganese exposure.

Laboratory Testing

Diagnosis

Most laboratory testing is limited in measuring past exposure, given that manganese is excreted from the body within days. 

Blood

Both whole blood testing and erythrocyte testing may be useful as reasonable indicators of recent, active manganese exposure and modest indicators to identify exposed and nonexposed individuals. Whole blood is recommended for monitoring potential manganese accumulation from total parenteral nutrition. However, erythrocyte testing is preferred for detecting long-term, low-dose manganese exposure. Although whole blood tests yield more accurate results than plasma or serum tests, some patients with normal whole blood manganese levels have abnormal magnetic resonance images. 

Serum/Plasma

Serum and plasma tests are believed to assess dietary manganese intake but typically indicate only dramatic variations in intake.  Serum testing is not recommended for the assessment of manganese body stores.

Urine

Urine testing has limited utility for determining manganese exposure; it is most reliable only for severe depletion. 

Mercury

Mercury has three forms: organic mercury compounds (which accumulate in the food chain), inorganic mercury compounds, and elemental mercury. All three forms can accumulate in the kidneys, brain, and central nervous system. Symptoms of toxicity depend on the form, route of exposure, and duration of exposure and include changes in skin pigmentation, headaches, nausea and vomiting, and thrombocytopenia.   Mercury has several industrial applications, including use in thermometers, dental fillings, and vaccines.

Indications for Testing

Individuals with a known or suspected source of exposure and corresponding symptoms should be tested for mercury exposure. Fish consumption can elevate total whole blood mercury concentrations.  Clinical presentation after toxic exposure to organic mercury may include dysarthria, ataxia, and constricted vision fields with mercury blood concentrations of 20-50 µg/L.

Criteria for Diagnosis

An elevated whole blood or urinary mercury concentration is diagnostic for mercury exposure. A total whole blood mercury concentration ≥10 µg/L or a urinary mercury concentration ≥10 µg/L indicates an unusual level of exposure in a person with no known occupational exposure to mercury. 

A study involving data from the CDC, the U.S. Environmental Protection Agency, and the American Conference of Governmental Industrial Hygienists  took into account both occupational exposure and food ingestion and suggested a blood mercury limit of 10.0 μg/L and a urine mercury limit of 19.8 nmol Hg/mmol creatinine.  Clinical intervention is recommended in patients with blood mercury concentrations ≥40 μg/L. 

Laboratory Testing

Diagnosis

Urine

Urinary mercury levels predominantly reflect acute or chronic elemental or inorganic mercury exposure but not organic mercury exposure; organic mercury is eliminated in the stool and not in urine.   A 24-hour urine specimen is preferred for testing.  Urine concentrations in unexposed individuals are typically <10 µg/L, and levels up to 20 µg/L are not associated with symptoms.  Urine concentrations of 30-100 µg/L from a 24-hour collection may be associated with subclinical neuropsychiatric symptoms and tremors, and concentrations >100 µg/L can be associated with overt neuropsychiatric disturbances and impaired kidney function. Urine is especially useful for monitoring chelation therapy.  Because mercury accumulates in the kidneys, mercury-urine concentrations may also be a better indicator of kidney burden  than concentrations in blood or hair.

Blood

Blood can be used to evaluate exposure to mercury of any form. Both dietary and nonoccupational exposure to organic mercury may contribute to an elevated total mercury result. The blood mercury concentration predominantly reflects recent exposure and is most useful in the diagnosis of acute poisoning, given that mercury has a half-life in blood of 3 days. Blood concentrations in unexposed individuals are usually <10 µg/L, but concentrations up to 20 µg/L are considered normal.  A blood concentration ≥50 μg/L is considered the threshold for symptoms of toxicity. 

Nickel

Food is the most common source of nickel exposure, but exposure can also occur from handling nickel-containing coins, jewelry, and electronic devices. Up to 20% of the population is sensitive to nickel and subject to an allergic reaction that manifests as a skin rash. Higher-level exposure can occur from contact with nickel-processing industries. Nickel carbonyl, used in petroleum refining, is a highly toxic chemical. Symptoms of occupational exposure include chronic bronchitis, reduced lung function, inability to oxygenate blood, and lesions on organs. Soluble nickel compounds are more easily detected by testing than are less soluble compounds. 

Indications for Testing

Measurement of nickel is not recommended in asymptomatic individuals or individuals with a low likelihood of exposure.

Laboratory Testing

Diagnosis

Urine

Because absorbed nickel is primarily excreted in urine, this is the preferred specimen type for assessing exposure. 

Serum

Serum nickel levels may be useful for follow-up testing after an elevated urine nickel result.

Selenium

Selenium is a required element for antioxidant balance, thyroid hormones, and immunity ; however, excess can cause selenosis, which is characterized by nerve damage. The range for normal selenium levels is small.  Selenium is used in the electronics and glass industries and as a pigment. Up to 20% of patients who undergo bariatric surgery have selenium deficiency postoperatively.

Indications for Testing

Individuals with signs or symptoms of either selenium deficiency or overload should be considered for selenium status testing. Patients who have had bariatric surgery are at an increased risk for symptoms of nutrient deficiencies.

Laboratory Testing

Diagnosis

Urine

Urine selenium is the preferred indicator of selenium status, given that excess selenium is excreted in urine.

Serum/Plasma

Because selenium is transported to the organs in plasma and increases quickly with intake, plasma or serum is used most often to evaluate short-term dietary consumption. 

Blood

Erythrocyte testing is most appropriate to assess selenium tissue stores, but urine testing is preferred to evaluate deficiency or toxicity.

Thallium

Thallium has no physiologic function in humans. Most thallium exposure is a result of food consumption, cigarette smoking, or workplace inhalation. Thallium is used in electronic devices and for semiconductors.

Indications for Testing

Individuals with a known or suspected source of exposure and corresponding symptoms should be tested for thallium exposure.

Laboratory Testing

Diagnosis

Urine

The majority of thallium is excreted in urine. Thallium can be detected in urine as soon as 2 hours postexposure and for as long as 1-2 months afterwards.  Urine testing can be useful in assessing both acute and chronic thallium exposure. It has also been the suggested specimen type for occupational monitoring of thallium exposure; however, no threshold levels are currently available for urine thallium measurements. 

Blood

Blood thallium measurements are useful for assessing acute exposure due to a short half-life of 2-4 days in the blood.

Zinc

Zinc is present in air, soil, water, and all foods, as well as many commercial products. In small quantities, it is an essential nutritional element for metabolism, immunity, and the cell life cycle; in large quantities, it can cause abdominal pain (from acute exposure) or secondary hypocupremia (from chronic exposure). Zinc overload can also suppress the absorption of copper. 

Indications for Testing

There is no clear indication for zinc status assessment ; however, individuals with signs or symptoms of either zinc deficiency (particularly slow growth in children) or overload can be considered for zinc status testing.

Laboratory Testing

Diagnosis

Serum/Plasma

Serum zinc is the most frequently used biomarker for zinc status, particularly acute deficiency. However, serum testing is limited in its ability to detect marginal deficiency and is affected by daily fluctuations of zinc and inflammation caused by other diseases. 

Urine

Urine zinc is an insensitive biomarker, but it may be helpful as an indicator of acute toxicity. Urinary excretion correlates to body stores. 

Red Blood Cells

Testing in RBCs has limited utility as an indicator of deficiency. Zinc concentrations in erythrocytes reflect the intracellular stores and general homeostasis of zinc.