Trace Element Toxicity

Laboratory Testing

Laboratory testing to detect trace elements for toxicity is typically indicated in cases of a known or suspected source of exposure and corresponding symptoms.

Aluminum

Aluminum has no known biological function but is widespread in the environment and in food. The typical dietary intake of aluminum is normally completely eliminated from the blood by the kidneys. Patients with renal failure are at particular risk for aluminum toxicity due to a reduced ability to filter aluminum from the blood. Patients undergoing dialysis are at increased risk for aluminum exposure from aluminum-contaminated dialysate water or aluminum-containing phosphate binders.  To assess chronic exposure, urine samples should be collected 1 to 2 days after removal from the source of exposure.  Contamination of specimens during collection is an important consideration for aluminum testing, as many common blood collection tools have rubber stoppers made using aluminum silicate. 

Arsenic

Arsenic is a nonessential element. Arsenic is present in the environment in several forms; some forms are toxic and others are nontoxic. Syndromes of arsenic toxicity can present as acute, chronic, or latent. Arsenic exposure can be detected through urine and blood. Urine testing is sensitive for low-level arsenic exposure, and urine is the preferred specimen type to detect acute exposure.  Total urinary arsenic measurements can overestimate exposure to toxic forms of arsenic, as unmetabolized, nontoxic organic arsenic, which is typically contained in certain seafoods, is eliminated through urine.  Elevated total urine arsenic results should be fractionated to differentiate between toxic inorganic forms and relatively nontoxic organic forms. Blood arsenic testing is used for the detection of recent exposure (<24 hours since exposure) and large-dose poisoning only.  Arsenic has a half-life of <4 hours in blood; therefore, blood is the least useful specimen for detecting exposure. 

Beryllium

Acute exposure to beryllium is rare and typically presents as chemical pneumonitis. Chronic industrial exposure, which is caused by inhaling insoluble beryllium compounds, can cause chronic beryllium disease (CBD), or berylliosis. 

Serum beryllium testing measures the amount of beryllium in serum and can confirm exposure to beryllium; however, serum beryllium has a biological half-life of 2-8 weeks, so test results do not indicate the extent of exposure or how recently the patient was exposed.  Although a serum beryllium test can confirm exposure, a diagnosis of CBD requires that the following three criteria be met:

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

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. 

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

Cadmium

Cadmium has a long biological half-life of more than 26 years.  Cadmium is not only toxic in moderate amounts, but it also counteracts several necessary minerals. 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. ^,  The amount of cadmium in blood can be used to determine acute toxicity or recent exposure. ^,  For employees occupationally exposed to cadmium, the Occupational Safety and Health Administration (OSHA) has set standards for monitoring that include 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.

Chromium

Chromium exists in many forms; the most common forms are chromium (0), chromium (III), and chromium (VI). Chromium (VI) is a known carcinogen and can cause ulcers, anemia, and lung cancer. ^,  Urine chromium concentrations that exceed normal levels indicate recent occupational exposure or environmental exposure but not body burden. ^, 

The FDA recommends chromium metal ion testing be considered in symptomatic individuals with metal-on-metal hip joint replacements because such joint replacements may release metal debris. The FDA does not currently recommend testing if there are no symptoms of chromium toxicity and the hip is functioning properly with normal radiographs.  The United Kingdom Medicines and Healthcare Products Regulatory Agency (UK MHRA) recommends annual testing for all individuals with such joint replacements.  Whole blood is the recommended specimen type for this testing, and repeat testing is recommended to monitor changes in chromium levels. Although there is no accepted cutoff value for this testing, significantly elevated concentrations of chromium or increases in concentrations of chromium should prompt further investigation.

Cobalt

To determine recent, acute cobalt exposure, urine cobalt measurements are best, given that most cobalt is eliminated in urine 2-8 days after ingestion. ^,  Serum, plasma, whole blood, or erythrocytes may be used to assess occupational exposure or toxic ingestion with a multicompartmental half-life in serum and whole blood. ^, ,  Whole blood is the specimen type recommended by the FDA to evaluate for metal ion release from metal-on-metal joint arthroplasty.  The FDA’s and the UK MHRA’s recommendations for monitoring cobalt levels in patients with metal-on-metal hip replacements are the same as the recommendations described in the Chromium section. ^, 

Copper

Copper imbalance is associated with diseases such as Wilson disease (excess copper body burden) and Menkes disease (reduced copper bioavailability). ^,  For diagnostic testing recommendations specific to Wilson disease, refer to the ARUP Consult Wilson Disease topic.

Iron

For testing recommendations specific to iron deficiency anemia, refer to the ARUP Consult Iron Deficiency Anemia topic. For testing and monitoring of iron overload as a result of hemochromatosis, refer to the ARUP Consult Hemochromatosis topic. For testing for beta (β)-thalassemia, a common cause of secondary iron overload, refer to the ARUP Consult Thalassemias topic.

Lead

Lead poisoning or lead toxicity generally occurs either in childhood or as a result of occupational exposure. For more information about lead testing, refer to the ARUP Consult Lead Poisoning topic.

Manganese

Laboratory testing for manganese status is complicated by individual variability and the rapid rate of manganese clearance from the body. ^,  Serum or urine manganese measurements are the most commonly used markers to determine manganese status, but they are not sensitive indicators of deficiency and are only responsive to severe depletion. ^,  Blood or serum manganese testing can be helpful in combination with imaging to determine excessive exposure. 

Mercury

Mercury has three forms: methylmercury compounds (which accumulate in the food chain), inorganic mercury compounds, and elemental mercury. The specific form of mercury accumulated corresponds with the source of exposure (e.g., methylmercury from seafood, inorganic mercury from paint or ayurvedic medicine). Symptoms of toxicity depend on the form, route of exposure, and duration. 

Total mercury can be measured in blood or urine, but these specimen types do not enable differentiation between exposure to organic, inorganic, and elemental mercury.  Organic mercury exposure is more strongly correlated with total mercury concentrations in red blood cells or hair in populations in which methylmercury is the primary source of exposure to mercury.  Inorganic mercury can be measured in whole blood, plasma, or urine and is more prevalent in urine total mercury measurements. Demethylation of organic mercury can lead to inorganic mercury in blood and urine, making it difficult to distinguish between exposure to organic and inorganic forms of mercury solely based on total mercury measurements in blood or urine.  Urine total mercury measurements can be used to monitor treatment for mercury toxicity. 

Nickel

Serum and urine nickel measurements are the most useful biomarkers for assessing recent nickel exposure.  Hair and nail testing has been used to assess past nickel exposure.  Some nickel compounds are poorly soluble and difficult to detect through laboratory testing.

Thallium

Thallium has a biological half-life of 3.3 days and can be detected in both blood and urine. Urine thallium testing is the suggested test for assessing thallium exposure, especially chronic and occupational exposure.  Blood thallium measurements are useful for acute exposure.