CHAPTER 2-52: COBALT

Cobalt is an essential trace metal element in the human diet, being an integral component of Vitamin B₁₂ (cobalamin). It can be found in certain ores with other metals such as nickel, copper or arsenic. It has high melting and boiling points, approximately 1,500°C and 3,000°C, respectively. Cobalt has elemental, organic, and inorganic forms. When combined with tungsten carbide, the material is termed "hard metal" and is used for industrial cutting, drilling, and polishing. Cobalt is also found in jewelry alloys and has ferromagnetic properties making it a useful component in magnets.

Rubratope-57 (Cyanocobalamin Co 57 Capsules) is intended for the diagnosis of pernicious anemia and as a diagnostic adjunct in other defects of intestinal vitamin B12 absorption. Cobalt-60, a radionuclide of cobalt, is used as a source for radiation therapy, in industrial radiography, and in the sterilization of foods and spices, as well as in linear accelerators and leveling devices. Historically, inorganic cobalt salts were used for the treatment of anemia including during pregnancy and were also the cause of "beer drinkers cardiomyopathy" resulting from cobalt additives to beer to stabilize foam. More recently, an excess body burden of cobalt has been linked to failing cobalt alloy metal-on-metal hip joint replacements.

1. Cobalt can exert toxic effects by interacting with a complex array of biological receptors and proteins to stimulate erythropoiesis, foster generation of reactive oxygen species, interfere with mitochondrial function, inhibit thyroidal iodine uptake, and alter calcium homeostasis.

2. Cobalt is considered a possible carcinogen (Class 2B by the International Agency for Research on Cancer).

3. Overdose during pregnancy. There are no reports of overdose in pregnancy. Cobalt had previously been used therapeutically to treat anemia in pregnancy. No fetal anomalies have been reported. A pregnant woman with bilateral metal on metal hips had blood cobalt concentrations of 138 and 143 mcg/L at 7 and 38 weeks gestation, and delivered a healthy male who showed normal development through age 14 weeks.

4. Pharmacokinetics. Cobalt is well absorbed via inhalation and variably absorbed by ingestion. It is distributed in serum, whole blood, liver, kidney, heart and spleen. The major route of elimination is renal, with half-lives on the order of several hours to a week. Lung retention of relatively insoluble cobalt compounds such as cobalt oxide may be prolonged, with pulmonary clearance half-lives of 1–2 years.

1. Ingestion

   1. Acute ingestion of 2.5 g of cobalt chloride by a 6-year-old child caused only abdominal pain. Hemoglobin and electrolytes remained normal.

   2. Chronic doses of 45–90 mg per day were used to induce erythropoiesis in pregnancy, with no reported side effects. Fatal cases of dilated cardiomyopathy were reported among alcoholics who drank an average of 17 glasses of beer per day containing 0.5 ppm of cobalt (range of 0.0–5 ppm).

2. Inhalation of cobalt-containing dust may cause respiratory irritation at air concentrations between 0.002 and 0.01 mg/m³. Concentrations greater than 0.01 mg/m³ may cause "cobalt asthma, " a reactive airway disease and occupational cause of adult onset asthma.

3. Dermal. Doses of 0.7–1.1 mcg/cm² can be released from handling 6% cobalt and 15% cobalt chloride metallic discs.

1. Ingestion

   1. Acute ingestion may cause vomiting and abdominal pain.

   2. Chronic ingestion of cobalt-adulterated beer caused "beer-drinkers' cardiomyopathy." Chronic use may also cause polycythemia.

2. Inhalation

   1. Acute exposure can cause nasal irritation, cough and wheezing.

   2. Chronic inhalation can cause a specific form of interstitial pulmonary fibrosis manifesting as giant cell pneumonitis ("hard metal/diamond polisher's disease"). It can also cause bronchiolitis obliterans and hypersensitivity pneumonitis. Onset of cough and exertional dyspnea may be insidious.

3. Dermal exposure may cause redness, scaling, blistering, formation of papules or pustules, exudation, and excoriation. Chronic exposure leads to fissures, lichenification, and hyperkeratosis. Cobalt is often alloyed in combination with other metals such as nickel and chromium in jewelry, and such alloys are a common cause of allergic contact dermatitis.

4. Metal-on-metal hip prostheses containing cobalt alloys have been associated with hypothyroidism, heart failure, and hearing and visual deficits. Symptoms occurred after an average of 19 months, with whole blood or serum concentrations ranging from 23 to 625 mcg/L.

Is based on a history of exposure and clinical findings consistent with cobalt toxicity.

1. Specific levels. Cobalt can be measured in serum, whole blood or urine.

   1. Serum levels in nonexposed persons are about 0.9 ng/mL (roughly equivalent to ppb).

   2. Urine cobalt levels averaged 0.375 mcg/L in the US population according to the National Health and Nutrition Examination Survey conducted in 2011–2012. Urinary measurements mainly reflect recent exposure, although substantial occupational exposures have produced elevated urinary levels for many weeks. Persons with occupational exposure to cobalt often have urinary cobalt levels that are many times higher than those of the general population.

   3. Metal-on-metal hip prostheses. Patients with nonfailing hip prostheses will have higher cobalt concentrations than nonimplant patients, with whole blood levels of 4–10 mcg/L. Patients with failing cobalt alloy hip replacements generally will have levels greater than 10 mcg/L.

2. Other useful laboratory studies include a complete blood count to evaluate for polycythemia, thyroid studies to evaluate for hypothyroidism, creatinine to evaluate renal clearance ability, transthoracic echocardiogram to evaluate for dilated cardiomyopathy, and patch testing to evaluate allergic contact dermatitis.

3. Occupational inhalation. Pathognomonic multinucleated giant cells may be recovered from bronchoalveolar biopsy or lavage. Pulmonary function tests with and without methacholine and during and when away from work may be helpful in confirming workplace exposure sensitivity. Inhalational challenge with cobalt is the gold standard for diagnosis; however, this requires specialized facilities and is available at only a few centers.

1. Emergency and supportive measures

   1. After inhalational exposure, maintain an open airway, give bronchodilators as needed for wheezing, and assist ventilation if necessary. Once airway hyper-reactivity has been documented, further inhalation exposure to cobalt is contraindicated.

   2. Prevention from further exposure may reverse acute disease, including asthma or allergic contact dermatitis, and prevent the development of chronic disease. Involve public health authorities to determine whether other workers are at increased risk through improper workplace controls.

   3. Treat vomiting with antiemetics and replace volume losses with IV fluids.

   4. Patients with mechanical symptoms (including pain, clicking or effusion) of a failing implanted hip prosthesis should be referred to their orthopedic surgeon for possible replacement. Patients who have no symptoms but have concern for cobalt toxicity can have their cobalt levels evaluated. However, the United Kingdom's Medicines and Healthcare Products Regulatory Agency recommends routine cobalt testing only for patients who are symptomatic or have stemmed metal-on-metal total hip replacements with a femoral head diameter ≥36 mm or Depuy ASR brand prostheses.

2. Specific drugs and antidotes. See chelation under item D, below.

3. Decontamination. Treatment of acute ingestion may include gastric decontamination (such as whole-bowel irrigation or endoscopic removal of cobalt containing magnets) and fluid repletion.

4. Enhanced elimination.

   1. There are no reports of benefit via hemodialysis following cobalt exposure.

   2. Chelation with EDTA, DTPA, and DMSA has been suggested but indications are uncertain. Increased urine levels and apparent clinical improvement were reported with IV EDTA in an 11-year-old following a cobalt-containing magnet ingestion.