1) Cobalt-56 (half-life of 78.8 days)
2) Cobalt-57 (half-life of 271 days)
3) Cobalt-58 (half-life of 70.8 days)
4) Cobalt-60 (half-life of 5.27 years)

a) ETIOLOGY: In the early to mid 1960's, breweries in the United States, Europe and Canada added cobalt (1.0-1.5 ppm) to beer as a foam stabilizer (ASTDR, 1992). (This practice has been discontinued). Cardiomyopathy was reported in heavy beer drinkers who consumed large quantities (8-25 pints/day) of cobalt foam stabilized beer (Gosselin et al, 1984; Kurppa et al, 1984; Alexander, 1972) (ASTDR, 1992).
b) PREDISPOSITION: Dietary deficiencies of protein or vitamins or pre-existing alcoholic cardiomyopathy may have been partially responsible for the development of cardiomyopathy, as the estimated amounts of cobalt consumed were less than dosages given for the treatment of refractory anemias (Barceloux, 1999; Gosselin et al, 1984; Shaper, 1979; Alexander, 1972).
c) SIGNS/SYMPTOMS: Pericardial effusions were common in "beer drinker's cardiomyopathy" (Harbison, 1998) (Alexander, 1972). Hypotension and peripheral cyanosis were common terminal findings (Clayton & Clayton, 1994).
d) Uremic cardiomyopathy may also be related to elevated serum cobalt levels (Lins & Pehrrson, 1976; Curtis et al, 1976).
e) Cases of cardiomyopathy, some fatal, in patients with industrial exposure have been described (Harbison, 1998; (Kennedy et al, 1981; Goldhaber, 1983), and 5 cases of "allergic cardiomyopathy" have been described in cobalt workers (Kennedy et al, 1981; Jarvis et al, 1992). However, the relationship of cardiomyopathy to hard metal work remains poorly established. A review of beer drinker's cardiomyopathy and other reports of cobalt-related disease failed to confirm the existence of occupational cobalt-induced cardiomyopathy (Seghizzi et al, 1994).
f) CASE REPORT: Cardiomyopathy, with cardiomegaly and congestive heart failure, was reported in an 11-year-old boy following suspected chronic or sub-acute ingestion of cobalt containing magnets (40% cobalt by weight) materials (Henretig & Shannon, 1998).
g) CASE REPORT: A 56-year-old man, who underwent a total hip replacement with a ceramics-on-ceramics implant, received a hip replacement revision, with a metal implant containing cobalt, chromium, and titanium, approximately 3 years after the original replacement. Twenty months later, he experienced a hip dislocation due to 40% abrasion of the metal head, and the metal implant was removed. An echocardiogram revealed a large pericardial effusion with signs of a cardiac tamponade and left ventricle hypertrophy, and a chest radiograph indicated cardiomegaly. In addition, the patient had also developed severe sensorimotor polyneuropathy of the upper and lower extremities and severe sensorineural deafness. Laboratory analysis revealed serum cobalt and chromium concentrations of 506 mcg/L (normal 0.9 mcg/L) and 14.3 mcg/L (normal less than 0.5 mcg/L), respectively. Following symptomatic therapy and antidotal treatment with administration of DMPS, the patient's symptoms improved, although deafness continued to persist (Pelclova et al, 2012).
h) CASE REPORT: A 46-year-old man underwent a ceramic-on-ceramic left total hip replacement. Five years later, he fractured the ceramic liner after falling, and subsequently underwent revision surgery replacing the ceramic components with a polyethylene acetabular liner and a cobalt-chromium femoral head. Approximately 6 months postoperatively, the patient reported severe fatigue and anorexia, resulting in a 10 kg weight loss, as well as left hip pain. The initial diagnosis was hypothyroidism, as well as a subsequent diagnosis of heterotopic ossification affecting the left total hip replacement. However, he continued experiencing worsening fatigue and dyspnea. Two months later, he was admitted with dilated cardiomyopathy, left ventricular failure, and pericardial effusion, with subsequent development of cardiogenic shock requiring an intra-aortic balloon pump for cardiac support. Whole blood cobalt levels were elevated, with a peak concentration of 6521 mcg/L (laboratory reference range 0.032 to 0.290 mcg/L). Despite removal of the hip prosthesis and cobalt chelation therapy, with a decrease in serum cobalt levels to 2618 mcg/L over two weeks, he continued to deteriorate clinically, with worsening cardiac function (ie, left ejection fraction less than 10% (normal minimum: 55%) and development of renal, liver, and respiratory failure. The decision was made to withdraw advanced life support, and he subsequently died approximately 3 weeks following removal of the cobalt components and 16 months following the original revision surgery (Zywiel et al, 2013).
i) CASE REPORT: A 60-year-old woman presented with signs and symptoms of congestive heart failure (CHF) and a history of bilateral hip replacement. An echocardiogram revealed left ventricular ejection fraction of 25% to 30% with normal left ventricular size and thickness, and moderate pericardial effusion. Following removal of 650 mL of fluid via pericardiocentesis, the patient was discharged on a beta-blocker, ACE inhibitor, and diuretic therapy. Over the next 4 months, her cardiovascular status declined significantly leading to hospitalization for CHF. A cardiac MRI indicated a left ventricular ejection fraction of 14% with normal left ventricular size and thickness. There was also reduced systolic function in her right ventricle and T2 images suggested edema. Further history of the patient revealed that she had a metal-on-metal hip prosthesis. Serum cobalt and chromium levels were between 200 and 300 ng/mL (reference range less than 1 ng/mL) and 80.3 ng/mL (reference range less than 1 ng/mL), respectively. Histopathology of the myocardium, following an endomyocardial biopsy, revealed increased interstitial fibrosis and hypertrophic myocytes, and electron microscopy showed increased lipid and degenerated lipid deposits with minimal mitochondrial changes, all of which suggested cobalt cardiomyopathy. Cardiogenic shock developed and the patient was stabilized with extracorporeal membrane oxygenation therapy, followed by biventricular assist device placement and replacement of the metal hip prosthesis with a ceramic hip; however, she subsequently died following development of a stroke postoperatively (Khan et al, 2015).
j) CASE REPORT: A 51-year-old woman, who underwent total hip arthroplasty and 2 subsequent revisions, presented to the hospital in congestive heart failure. Prior to presentation, she had been diagnosed with obstructive sleep apnea and severe sensorineural hearing loss. An echocardiogram, performed at hospital admission, revealed severe global left ventricular systolic dysfunction with concentric hypertrophy. Laboratory data revealed hypothyroidism and polycythemia with a hemoglobin level of 188 g/L. Because of her hip arthroplasty, a blood cobalt level was obtained and measured at 1351.4 mcg/L. An emergent implant revision was performed, and repeat cobalt levels, obtained on post-operative days 2 and 6, were 326 and 242 mcg/L, respectively. However, her serum lactate level was elevated at greater than 3 mEq/L. At her 3 month follow-up as an outpatient, repeat laboratory data revealed a plasma cobalt level of 116.5 mcg/L, a hemoglobin level of 138 g/L, and a lactate level of 2.4 mEq/L (the upper limit of normal). A repeat echocardiogram showed cardiovascular improvement with a systolic ejection fraction of 45%. There was also improvement in her hearing as evidenced by audiometry testing, and her thyroid function appeared to be stable (Austin et al, 2015).

a) Three syndromes have been described after occupational exposure to "hard metal," a mixture of tungsten carbide and cobalt: 1) allergic occupational asthma 2) hypersensitivity pneumonitis or alveolitis and 3) pulmonary fibrosis(Hathaway et al, 1996). Patients may present with a combination of asthma and alveolitis (Van Cutsem et al, 1987). Alveolitis and fibrosis represent two extremes of a continuum of effects. Pure alveolitis may occur initially, followed by a mixed picture after repeated attacks, and finally by development of irreversible fibrosis (Cugell et al, 1990). Acute cobalt induced pulmonary conditions include the upper respiratory tract symptoms of rhinitis and asthma. Sub-acute and chronic effects occur primarily in the bronchial parenchyma. These are manifested as pulmonary fibrosis, alveolitis and chronic interstitial fibrosis (ILO, 1998).
b) PULMONARY FINDING/LONG-TERM OCCUPATIONAL STUDY: In a 13-year follow-up study the influence of cobalt exposure on lung function was studied in a cobalt-producing plant. Approximately 122 workers had lung function tests that were evaluated longitudinally. The primary finding of this study was that cobalt exposure, as reflected by cobalturia, contributed to a decline in FEV(1) over time only in workers that were cigarette smokers. Overall, the decline was relatively small (Verougstraete et al, 2004).
c) HARD METAL LUNG DISEASE/CASE REPORT: A 34-year-old life-long nonsmoking man presented with a 2-year history of progressive shortness of breath, increased sputum production and cough. He had a 15-year history of exposure to tungsten carbide dust as a machinist sharpening tungsten carbide blades. Mild clubbing and diffuse end-inspiratory crackles were present on physical examination. High-resolution chest CT demonstrated bilateral lobular areas of ground glass attenuation and centrilobular nodules throughout the lung parenchyma with no zonal predominance. Lung biopsy showed a patchy pattern of interstitial fibrosis and chronic inflammation. He was treated with corticosteroids and removed from the environment. A repeat CT 7 months later demonstrated reduction in the centrilobular nodularity and significant improvement in the patchy lobular areas of ground glass (Dunlop et al, 2005).

a) ETIOLOGY: An interstitial fibrotic pulmonary process has been described among "hard metal" workers (Hathaway et al, 1996; Sprince et al, 1984). This disease rarely occurs after exposure to cobalt alone, but rather after exposure to hard metal, a combination of tungsten and cobalt with small amounts of titanium, tantalum and vanadium oxides (Barceloux, 1999). Fibrosis results from repeated attacks of alveolitis. Diamond polishers working with cobalt grinding disks and other compounds (Lahaye et al, 1984) and detonation welders (CDC, 1992) are also at risk.
b) LONG-TERM STUDY: In a study of Finnish cobalt production workers, the findings concurred with previous studies. Workers exposed for more than 10 years in a cobalt plant did not develop hard metal disease or fibrosing alveolitis. As expected the workers did have a higher incidence of asthma as compared to the control group. The authors concluded that cobalt production did not cause serious chronic effects (with the exception of asthma) on the respiratory tract of non-smoking workers (Oksa et al, 2003).
c) SIGNS/SYMPTOMS: Mild alveolar diffusion defects may be seen in the early stages or with mild disease (Bech et al, 1962). Symptoms have included either nonproductive cough or cough with scanty mucoid sputum production, dyspnea on exertion, tachypnea, clubbing of the fingertip, and crackles on chest examination (Barceloux, 1999; Hathaway et al, 1996; Clayton & Clayton, 1994; Sprince et al, 1984; Coates & Watson, 1971).
d) DIAGNOSIS: Pulmonary function tests become abnormal early in the course of the disease, usually with a restrictive pattern of impairment (Barceloux, 1999; Hathaway et al, 1996); (Davison et al, 1983). Chest x-rays reveal progressive nodular and linear densities, emphysema, and shrinking of the lungs (Hathaway et al, 1996) (Harbison, 1998).
e) ONSET: This disease is not often seen in patients with less than 10 years of exposure (Hathaway et al, 1996).
f) PROGNOSIS

a) SIGNS/SYMPTOMS: Wheezing, cough, and shortness of breath which seem to be an allergic response may occur in workers exposed to cobalt (Hathaway et al, 1996; Coates & Watson, 1971). Diamond polishers working with cobalt grinding disks are also at risk (Gheysens et al, 1985). Chest discomfort or pain may occur (Plunkett, 1976).
b) ONSET: These symptoms usually have not been noted until after 6 to 48 months of exposure. Patients have not been reported to progress to interstitial pulmonary fibrosis (Hathaway et al, 1996), but may develop concurrent hypersensitivity pneumonitis (Cugell et al, 1990). Bronchoconstriction may progress as the working day goes on (Gheysens et al, 1984). It usually develops after 4 to 6 hours, with worsening in early evening. Complete relief of symptoms usually follows removal from exposure (Harbison, 1998).
c) MECHANISM: Of 9 patients with hard metal asthma, 4 had cobalt-specific IgE antibodies, suggesting a humoral mechanism (Shirakawa et al, 1989). Cobalt acts as a hapten and conjugates with serum albumin, producing T-cell-mediated hypersensitivity, which is thought to be the mechanism of some cases of cobalt asthma, contact dermatitis, and hypersensitivity pneumonitis (Kusaka et al, 1989). Some authors believe that pure cobalt dust rarely produces this syndrome and that other components of hard metal alloys or perhaps something unique to the alloy itself is responsible (Lison, 1996).
d) DIAGNOSIS: Cobalt-induced occupational asthma may be suspected with a history of wheezing, dyspnea, and chest tightness at work or home, with no or fewer symptoms on weekends or holidays, and obstructive changes in pulmonary function tests (WIlk-Rivard & Szeinuk, 2001). Confirmation of cobalt hypersensitivity has been performed using RAST testing, inhalation challenge with 1% cobalt chloride, and patch testing (Shirakawa et al, 1989).
e) LONG-TERM STUDY: In a study of Finnish cobalt production workers, the findings concurred with previous studies. Workers exposed for more than 10 years in a cobalt plant did not develop hard metal disease or fibrosing alveolitis. As expected the workers did have a higher incidence of asthma as compared to the control group. The authors concluded that cobalt production did not cause serious chronic effects (with the exception of asthma) on the respiratory tract of non-smoking workers (Oksa et al, 2003).

a) SIGNS/SYMPTOMS: Attacks of fever, anorexia, and shortness of breath and cough occur during work exposure and improve when removed from exposure. Repeated episodes are common, with persistent and progressively severe shortness of breath (Barceloux, 1999; Cugell et al, 1990).
b) ONSET: The latency between initiation of occupational exposure and diagnosis of interstitial lung disease ranged from 4 to 16 years in a series of 7 subjects (Sprince et al, 1988).
c) DIAGNOSIS: Chest roentgenogram often shows a fine reticulonodular pattern. This may clear after the early attacks. Persistent reduction in lung volume, restrictive impairment, decreased diffusing capacity, and increased static elastic recoil occur (Cugell et al, 1990). Histologic features include intra-alveolar desquamation of large vacuolated mononuclear cells. Lung biopsy or bronchoalveolar lavage often reveals unusual multinucleated giant cells (Barceloux, 1999; Sundaram et al, 2001).
d) PREVALENCE: The overall prevalence of interstitial disease (hypersensitivity pneumonitis) among 1039 active hard metal workers was 0.7%, although 10.9% had evidence of obstructive airway disease (occupational asthma). The relative risk of asthma was 2.1 times for cobalt exposures exceeding 50 mcg/m(3) (Sprince et al, 1988).
e) GOODPASTURE'S SYNDROME: A case of Goodpasture's syndrome is reported following exposure to hard metal dust with presenting signs of interstitial lung disease with pulmonary hemorrhage (Lechleitner et al, 1993).

a) GUINEA PIGS developed rapidly fatal acute pneumonitis following intratracheal or inhalation cobalt exposure (Proctor & Hughes, 1978; Hathaway et al, 1991).

a) CASE REPORT: Numbness of the feet occurred in a 53-year-old man, who experienced deterioration of a metal femoral head following hip arthroplasty and subsequently developed cobalt poisoning. The numbness gradually resolved after the area of soft tissue and bone was cleaned with jet-lavage and all prosthetic components were removed and replaced with a cemented total hip prosthesis (Steens et al, 2006).
b) CASE REPORT: A 60-year-old man with a revised right hip cobalt-chromium alloy arthroplasty, presented to a medical toxicology clinic 11 months postoperatively with a 6- to 7-month history of numbness of his extremities that required a wheelchair for ambulation. Following his revised arthroplasty, the patient also developed other symptoms including hypothyroidism, decreased binocular vision, and decreased hearing. Physical examination after presentation revealed severe vision loss (20/800 bilaterally) due to optic neuropathy, and an inability to walk. Laboratory data indicated a serum chromium level of 54 ng/mL, a serum cobalt level of 1096.5 ng/mL, and a urine cobalt level of greater than 1600 mcg/L. An implant revision was performed, and within 2 days, his vision and neuropathy improved significantly. Repeat laboratory data, obtained 3 weeks and 6 weeks postoperatively, revealed serum chromium levels of 42.7 and 19.5 ng/mL and serum cobalt levels of 346 and 98.8 ng/mL. Two months postoperatively, the patient continued to show improvement in his vision and his peripheral neuropathy, no longer requiring a wheelchair, although hearing aids were still necessary (Leikin et al, 2015).

a) CASE REPORT: A 56-year-old man, who initially received a total hip replacement with a ceramics-on-ceramics implant, experienced paresthesias in his feet and toes and difficulty walking approximately 14 months after receiving a hip replacement revision, with a metal implant containing cobalt, chromium, and titanium. Twenty months after the hip replacement revision, evaluation of the metal implant indicated 40% abrasion of the metal head, and the metal implant was removed. The paresthesias had progressed to severe sensorimotor polyneuropathy of his upper and lower extremities with hypotonia, decreased muscle mass, and diminished or absent deep tendon reflexes. Laboratory analysis revealed serum cobalt and chromium concentrations of 506 mcg/L (normal 0.9 mcg/L) and 14.3 mcg/L (normal less than 0.5 mcg/L), respectively. Following antidotal therapy with DMPS, the patient's symptoms improved (Pelclova et al, 2012).

a) Cobalt has epileptogenic properties when surgically applied directly to the cerebral cortex in experimental animals (Hartman et al, 1974).

a) Seizures have NOT been reported in experimental animals exposed to cobalt by any other route or in exposed humans.

a) Ingestion or inhalation of cobalt causes nausea, vomiting, diarrhea, and colicky abdominal pain from local irritation (ITI, 1995; Plunkett, 1976; Henretig & Shannon, 1998).

a) CASE REPORT: Goodpasture's syndrome was reported in one patient with occupational exposure to hard metal dust.

a) Hematuria has been described following chronic dust exposure (EPA, 1985).

a) RATS: Adult male rats chronically fed 265 ppm of cobalt in the diet developed testicular damage with deterioration of cellular architecture and decreased testicular volume (Mollenhauer et al, 1985). These changes may not have been a primary response to cobalt (Mollenhauer et al, 1985).

a) METABOLIC ACIDOSIS has been reported in patients with cobalt-induced cardiomyopathy and shock (Kennedy et al, 1981; Alexander, 1972).
b) CASE REPORT: Persistent metabolic acidosis was reported in an 11-year-old boy following probable chronic or sub-acute ingestion of cobalt containing magnets (40% by weight). After surgical removal of the magnets, the acidosis persisted until chelation therapy with calcium disodium EDTA. The boy had presented to the emergency department with cardiomegaly, hepatomegaly, hypothyroid goiter, tachycardia, tachypnea; he was normotensive (Henretig & Shannon, 1998).

a) Chronic ingestion of large amounts has produced elevated red blood cell counts (EPA, 1985; Alexander, 1972).
b) CASE REPORT: Polycythemia was reported in an 11-year-old mentally retarded boy following suspected ingestion of cobalt materials. Serum laboratory values were reported as follows: Hgb 19.2 g/dL, Hct 54.6%, WBC 6600 (normal differential), and platelets 288,000 (Henretig & Shannon, 1998).

a) CASE REPORT: Acute ingestion of 2.5 grams of cobalt chloride by a 6-year-old child resulted in neutropenia (Mucklow et al, 1990).

a) CASE REPORT: A case of Goodpasture's Syndrome was reported with laboratory tests revealing a significant leukocytosis, microhematuria, and later macrohematuria. Bronchoalveolar lavage revealed a massive increase in neutrophils (Lechleitner et al, 1993).

a) An erythematous, papular, pruritic, "measle-like" red spotty rash may occur, usually in areas of skin subject to friction such as the sides of the neck, flexor surfaces of elbows, and ankles (EPA, 1985; Hathaway et al, 1996) (ACGIH, 1991) (Plunkett, 1976).
b) Systemic exposure (ingestion, dental or loosened orthopedic prostheses) has been reported to induce sensitivity, causing local dermatitis over the area of the prosthesis or generalized dermatitis, and/or to exacerbate cobalt-induced contact dermatitis at a site distant from the site of exposure (Steens et al, 2006; Lygre, 2002; Veien & Kaaber, 1979; Glendenning, 1971; Munro-Ashman & Miller, 1976). Stainless steel does not contain cobalt and can be used in patients with isolated cobalt allergy (Menne & Maibach, 1987). Disulfiram-treated patients can experience a flare-up of cobalt dermatitis (Menne, 1985).
c) CROSS-REACTIONS: This allergic dermatitis may be a result of cross-reactions due to hapten similarities between cobalt, chromium, and nickel (Harbison, 1998).

a) Eczematous rashes described in some cement workers may be due to the cobalt content of the cement (Clayton & Clayton, 1994), although American cements may not contain measurable amounts of cobalt (Perone et al, 1974).
b) CASE REPORT: A case of generalized eczema resulting from a systemic contact dermatitis was reported in a patient with a static orthopedic implant which contained 65% cobalt and to which the patient had a positive patch skin test reaction (Merle et al, 1992).

a) Perioral contact dermatitis and delayed hypersensitivity orofacial granulomas have been reported in children who sucked pens, presumably due to the cobalt naphthenate accelerator in the plastic; positive patch tests to cobalt were demonstrated (Bruynzeel, 1987; Pryce & King, 1990).

a) CASE REPORT: Tungsten coating small cobalt particles were found in nodules adhering to the underlying skin following a history of shrapnel hitting the skin of an adult male during use of a saw. The nodules had been present for 5 years before he sought medical advise. Lymphocyte transformation tests were positive for cobalt and negative for tungsten. Lymphocytoma cutis was diagnosed (Miyamoto et al, 1997).

a) Allergic contact dermatitis has been reported in cobalt exposed workers (Julander et al, 2009; Minamoto et al, 2002; Dickel et al, 2001).
b) PATCH TESTING: Standard patch test materials include 1% (10,000 ppm) cobalt chloride in petrolatum and 1% cobalt chloride in water. The aqueous solution is more sensitive. No reactions to 1 ppm were demonstrated in a small series of sensitized patients (Allenby & Basketter, 1989). Allergic reactions to metallic cobalt appear to be frequent in patients with a positive patch test to cobalt chloride in petrolatum (Olivarius & Menne, 1992).
c) CASE REPORT: A 39-year-old woman experienced generalized urticaria, eczematous skin lesions, and swelling of her face, lips, and tongue following chronic occupational exposure to blue paint containing cobalt chloride. Patch testing with cobalt chloride was positive, and the cobalt-specific IgE level in the patient's serum was 2.97 International Units/mL. Following a challenge test, involving 30 minutes of painting with cobalt chloride-containing paint, the patient developed an anaphylactic reaction. She recovered following administration of intravenous corticosteroids (Krecisz et al, 2009).
d) CASE REPORT: An 84-year-old woman, who had undergone a cobalt-chromium right hip replacement, developed a pruritic eczematous rash, initially localized around the right hip scar, approximately 5 months after surgery. The dermatitis gradually became generalized and persistent, refractory to treatment with corticosteroids, antihistamines, a mentholated emollient, and an ultraviolet B light. Patch testing revealed a positive reaction to cobalt. Serum cobalt and chromium levels were 967 nmol/L (normal, less than 20 nmol/L) and 442 nmol/L (normal, less than 100 nmol/L), respectively. In addition to the dermatitis, the patient also developed short term memory loss, all of which was suspected to be related to cobalt toxicity secondary to the hip replacement. The patient underwent hip revision surgery, with removal of the cobalt-chromium prosthesis and replacement with a titanium-polyethylene prosthesis. Three months later, the patient gradually recovered with a decrease in her serum cobalt levels and resolution of her dermatitis. However, due to numerous surgeries and hospitalizations, the patient had lost a significant amount of functional capacity (Wong & Nixon, 2014).

a) Patients have been described who developed local tissue reactions and pain around the sites of total hip arthroplasties with implantation of cobalt-chrome-molybdenum femoral head prostheses. Several of these patients had positive patch tests for hypersensitivity to cobalt (Jones et al, 1975).

a) Chronic ingestion of large amounts of cobalt in association with "beer drinker's cardiomyopathy" has produced goiter (thyroid hyperplasia) and hyperthyroidism (EPA, 1985; Clayton & Clayton, 1994).
b) CASE REPORT: An 11-year-old mentally retarded boy presented to the emergency department with a goiter and thyroid tests which revealed a low thyroxine (2.4 mcg/dL, normal 5 to 11 mcg/dL) and an elevated TSH (26 mcmol/mL, normal 0.4 to 4.8 mcmol/mL). His thyroid hormone profile was consistent with primary hypothyroidism presenting as goiter. Cobalt toxicity was diagnosed because of a history of pica (in this case, ingestion of 40% by weight cobalt containing magnets)(Henretig & Shannon, 1998).

a) In RABBITS, high doses destroy the pancreatic islet alpha cells, resulting in temporary blood sugar elevations (Clayton & Clayton, 1994). This effect has not been reported in exposed humans.

a) CASE REPORT - A 31-year-old woman with severe cobalt-induced pulmonary fibrosis delivered a normal full term infant. Throughout the pregnancy, supplemental oxygen was required during exercise due to deterioration of respiratory capacity (Ratto et al, 1988).

a) Occupational exposure to cobalt has been associated with miscarriages in Finland. This study did not track exposure levels and exposures were mixed (Hemminki, 1983).

a) Human fetal liver contained less than 10 percent of the level of cobalt in adult liver (Widdowson, 1972). Cobalt may be available to the fetus (Agranovskaia, 1967), and placental, maternal, and cord blood levels of cobalt all correlated (Baglan, 1974), suggesting the lack of a placental barrier to cobalt.

a) Cobalt has caused various effects in the fetus in experimental animal studies. Post-natal developmental defects in rats exposed to cobaltous chloride included reduced weight gain (Shepard, 1985), increased resorptions (with cobaltic chloride) (Garban, 1984), and interference with fetal bone development (Domingo, 1985; Wide, 1984).

a) Listed as: Cobalt
b) Carcinogen Rating: 2A

a) Listed as: Cobalt metal (without tungsten carbide)
b) Carcinogen Rating: 2B

a) Listed as: Cobalt metal (with tungsten carbide)
b) Carcinogen Rating: 2A

a) DERMAL PATCH TESTING may be useful to diagnose cobalt allergic dermatitis. False positive results of cobalt patch testing may, however, be obtained (Fischer & Rystedt, 1985).

a) PULMONARY FUNCTION TESTING is useful for the diagnosis and monitoring of interstitial lung disease. Reduced FVC, near normal FEV1, and elevated FEV1/FVC ratios may be early signs of ventilatory impairment (Lichtenstein et al, 1975). Significant reduction in vital capacity may be seen (Coates & Watson, 1971).
b) With possible cobalt inhalation, allergen challenge testing could be useful in the diagnosis of cobalt-induced allergic reactive airway disease (Gheysens et al, 1985).

a) May be indicated in patients with suspected cobalt-induced cardiomyopathy. Echocardiograms could be useful to detect the presence of possible pericardial effusions.

a) OCCUPATIONAL SURVEILLANCE: Medical surveillance of workers exposed to processes using fine cobalt dust may include periodic review of symptoms, spirometry, diffusing capacity measurement, and chest radiographs (CDC, 1992).
b) BRONCHOALVEOLAR LAVAGE: Demonstration of multinucleated giant cells in lavage fluid is consistent with cobalt-induced hypersensitivity pneumonitis, alveolitis, or early fibrosis (Cugell et al, 1990).

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Pericardiocentesis could be indicated if sufficient pericardial effusion has accumulated to cause symptomatic cardiac filling deficits.

a) One suggested regimen for cobalt poisoning is: 4 milligrams per kilogram intramuscularly (not more than 300 milligrams per dose) every 4 hours for the first day; then every 6 hours for the second day; then 3 times daily for approximately 7 days (Plunkett, 1976; ITI, 1995).
b) AN ALTERNATE (AND MOST LIKELY PREFERABLE) REGIMEN

a) Some animal data have suggested that calcium EDTA (Calcium versenate) may be useful in cobalt poisoning (Clayton & Clayton, 1994; Llobet et al, 1986) although it has not been reported to be efficacious in treating either cobalt-induced myocardial or respiratory disease, and its indications for use are unclear.
b) One patient with cobalt-beer cardiomyopathy was treated with a one-week course of calcium EDTA three years following cobalt ingestion, but no cobalt was recovered in the urine (Alexander, 1972).
c) As no patients with cobalt-beer cardiomyopathy were treated acutely, the possible efficacy of calcium EDTA remains unknown in this setting (Alexander, 1972).

a) While calcium EDTA has been suggested as a possible therapy for cobalt poisoning, no dosing recommendations have been reported. The following dosing regimen is extrapolated from that for lead poisoning.
b) Calcium EDTA may be administered either deep intramuscularly or intravenously at a dose of 50 to 75 milligrams per kilogram per 24 hours for a 5 day course (not to exceed 500 milligrams per kilogram of body weight per 5 day course).
c) An interval of two days with no calcium EDTA administration should separate multiple 5 day courses.
d) For intravenous administration, calcium EDTA should be diluted with isotonic dextrose or normal saline solution to a final concentration of less than 0.5 percent and administered either as a continuous infusion or in 3 to 6 divided doses per 24 hours with each dose infused slowly over 15 to 20 minutes.
e) Calcium EDTA should also be given in 3 to 6 divided doses if administered intramuscularly.

a) CASE REPORT: A 56-year-old man, who initially received a total hip replacement with a ceramics- on-ceramics implant, developed cardiomyopathy, severe sensorimotor polyneuropathy of the upper and lower extremities, and severe sensorineural deafness approximately 20 months after receiving a hip revision with a metal implant containing cobalt, chromium, and titanium. Evaluation of the implant revealed 40% abrasion of the metal head and the implant was removed. Laboratory analysis revealed serum cobalt and chromium concentrations of 506 mcg/L (normal less than 0.9 mcg/L) and 14.3 mcg/L (normal less than 0.5 mcg/L), respectively. Unithiol (DMPS; 1,3 dimercaptopropane-1-sulfonate) was initiated at a dose of 14 mg/kg for 6 days, then reduced to 4 mg/kg for 5 days. Treatment was interrupted due to the presence of a mild skin rash, and then restarted 1 month later with 4 mg/kg unithiol for 4 days with additional antihistamine treatment. Total unithiol dose was 10 g (5 packages). The patient's symptoms improved, although his deafness continued to persist. Repeat laboratory data revealed a decrease in the serum cobalt concentration of approximately 26% (130 mcg/L). The patient's pre-treatment urine cobalt concentration was 138.6 mcg/mL and his urine cobalt concentration, measured approximately 9 days after beginning unithiol therapy, was 305 mcg/L. The accelerated elimination of cobalt suggests that unithiol therapy may be helpful as an antidote for treatment of severe cobalt toxicity; however, further studies are warranted (Pelclova et al, 2012).
b) DMPS/INDICATIONS: Chelating agent for heavy metal toxicities associated with arsenic, bismuth, copper, lead and mercury (Blanusa et al, 2005).
c) DMPS/DOSING
d) SOURCES

a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.

a) ALBUTEROL

a) Consider systemic corticosteroids in patients with significant bronchospasm.
b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).

a) DIPHENHYDRAMINE

a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).

a) EPINEPHRINE

a) OXYGEN: 5 to 10 liters/minute via high flow mask.
b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).

a) CARDIAC MONITOR: All complicated cases.
b) IV ACCESS: Routine in all complicated cases.

a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.

a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).

a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.

a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).

a) Administer beta2 adrenergic agonists. Consider use of inhaled ipratropium and systemic corticosteroids. Monitor peak expiratory flow rate, monitor for hypoxia and respiratory failure, and administer oxygen as necessary.

a) 2.5 to 5 milligrams diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response, administer 2.5 to 10 milligrams every 1 to 4 hours as needed OR administer 10 to 15 milligrams every hour by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.5 milligram by nebulizer every 30 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).

a) 0.15 milligram/kilogram (minimum 2.5 milligrams) diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.25 to 0.5 milligram by nebulizer every 20 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).

a) The incidence of adverse effects of beta2-agonists may be increased in older patients, particularly those with pre-existing ischemic heart disease (National Asthma Education and Prevention Program, 2007). Monitor for tachycardia, tremors.

a) Consider systemic corticosteroids in patients with significant bronchospasm. PREDNISONE: ADULT: 40 to 80 milligrams/day in 1 or 2 divided doses. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 or 2 divided doses (National Heart,Lung,and Blood Institute, 2007).

a) A patient with uremic cardiomyopathy was found to have a serum cobalt of 0.24 parts per billion (falling to 0.07 parts per billion after hemodialysis and 0.10 parts per billion after renal transplantation) compared to levels of between 0.02 and 0.06 parts per billion in normal controls (Lins & Pehrrson, 1976).
b) The average non-exposed adult human has a cobalt plasma concentration of 0.006 to 0.007 micrograms per deciliter (Linder, 1984).
c) Blood cobalt levels in normal subjects range from 0.6 to 1.8 micrograms per liter, while those in dialysis patients treated with cobalt ranged from 3.1 to 138 micrograms per liter (Curtis et al, 1976).

a) A 14-year-old patient who packed 3 empty gelatin capsules with a mixture of three parts sodium chloride and one part cobalt chloride obtained from a home chemistry set developed serum cobalt levels of 7.8 micrograms per deciliter at 12 hours and 0.7 micrograms per deciliter at 22 hours after ingestion. No serious toxicity occurred in this case (Everson et al, 1988).
b) A 6-year-old who ingested 2.5 g cobalt chloride obtained from a chemistry set developed serum and whole blood levels of 7,230 nanomoles/liter and 4,020 nanomoles/liter respectively at 7 hours postingestion. No serious toxicity except for mild neutropenia occurred (Mucklow, 1990).

1) Cobalt
b) Adopted Value

B) NIOSH REL and IDLH Values for CAS7440-48-4 (National Institute for Occupational Safety and Health, 2007):
C) Carcinogenicity Ratings for CAS7440-48-4 :
D) OSHA PEL Values for CAS7440-48-4 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

a) 100-200 mg/kg
b) 100 mg/kg -- arteriolar or venous dilation, changes in blood and liver

a) 6171 mg/kg -- general depressed activity, ataxia, gastrointestinal hypermotility, diarrhea

a) 200 mg/m(3) for 17W-I -- arteriolar or venous dilation, changes in respiratory and urinary system