SM Bradberry BSc MB MRCP
    ST Beer BSc

    National Poisons Information Service
    (Birmingham Centre),
    West Midlands Poisons Unit,
    City Hospital NHS Trust,
    Dudley Road,
    B18 7QH

    This monograph has been produced by staff of a National Poisons
    Information Service Centre in the United Kingdom.  The work was
    commissioned and funded by the UK Departments of Health, and was
    designed as a source of detailed information for use by poisons
    information centres.

    Peer review group: Directors of the UK National Poisons Information


    Toxbase summary

    Type of product

    Used in alloys, magnets, in the production of tungsten carbide, in
    catalysts, pigments and enamels.


    Cobalt and its salts are relatively non toxic by ingestion. Most cases
    of cobalt toxicity relate to occupational skin contact or inhalation.



         -    Cobalt is a topical irritant and a well recognised cause of
              occupational contact dermatitis.
         -    Cobalt sensitivity may be the cause of metal prosthesis
         -    Simultaneous allergies to nickel and cobalt are frequent.
         -    Orofacial granulomatosis has been described in association
              with delayed cobalt hypersensitivity.


         -    Nausea, vomiting, abdominal pain. A transient neutropenia
              occurred in a six year old child who ingested 2.5 g cobalt
         -    Congestive cardiomyopathy has been reported after the
              consumption of large quantities of beer to which cobalt had
              been added as a foam stabiliser and in those receiving oral
              cobalt therapy in the treatment of anaemia.


         -    Pulmonary toxicity following chronic cobalt exposure is
              associated typically with the hard metal (tungsten carbide)
              industry. Symptoms usually arise after several years and may
              manifest as pneumoconiosis (with dyspnoea and cough
              secondary to interstitial fibrosis), an allergic alveolitis
              or occupational asthma.
         -    Corpulmonale may complicate hard metal pneumoconiosis.
         -    There are occasional reports of cobalt cardiomyopathy
              following occupational exposure.



         -    Removal from exposure is the priority. Remember the cobalt
              source may not be immediately apparent e.g. in prostheses.


    1.   Supportive care only. Replace fluids and electrolytes as
    2.   Gastrointestinal decontamination is not necessary.
    3.   Check the full blood count.
    4.   If chronic cobalt ingestion is suspected consider the possibility
         of cobalt cardiomyopathy and check thyroid function to exclude
    5.   Collect blood and urine for cobalt concentration determination in
         symptomatic patients. Cobalt assays are not widely available.
         Check with NPIS.


    Acute inhalation:
    1.   Remove from exposure and treat symptomatically.

    Chronic inhalation:
    1.   Asthmatic symptoms respond to conventional measures.
    2.   Established pulmonary fibrosis generally has a poor prognosis.
         Cyclophosphamide may have a role but seek specialist advice from
         the NPIS.


    Alexander CS.
    Cobalt-beer cardiomyopathy. A clinical and pathologic study of twenty-
    eight cases.
    Am J Med 1972; 53: 395-417.

    Cugell DW.
    The hard metal diseases.
    Clin Chest Med 1992; 13: 269-79.

    Curtis JR, Goode GC, Herrington J, Urdaneta LE.
    Possible cobalt toxicity in maintenance hemodialysis patients after
    treatment with cobaltous chloride: a study of blood and tissue cobalt
    concentrations in normal subjects and patients with terminal renal
    Clin Nephrol 1976; 5: 61-5.

    Manifold IH, Platts MM, Kennedy A.
    Cobalt cardiomyopathy in a patient on maintenance haemodialysis.
    BMJ 1978; 2: 1609.

    Mucklow ES, Griffin SJ, Delves HT, Suchak B.
    Cobalt poisoning in a 6-year-old.
    Lancet 1990; 335: 981.

    Pryce DW, King CM.
    Orofacial granulomatosis associated with delayed hypersensitivity to
    Clin Exp Dermatol 1990; 15: 384-6.

    Sullivan JF, Egan JD, George RP.
    A distinctive myocardiopathy occurring in Omaha, Nebraska: clinical
    Ann NY Acad Sci 1969; 156: 526-43. 

    Substance name


    Origin of substance

         Naturally occurring in ores.            (DOSE, 1993)


         Super cobalt
         Cobalt-59                               (DOSE, 1993)

    Chemical group

         A transition metal (d block) element

    Reference numbers

         CAS            7440-48-4                (DOSE, 1993
         RTECS          GF8750000                (RTECS, 1996)
         UN             NIF

    Physico-chemical properties

    Chemical structure
         Cobalt, Co                              (DOSE, 1993)

    Molecular weight
         58.93                                   (DOSE, 1993)

    Physical state at room temperature

         Silvery-grey                            (HSDB, 1996)

         Odourless                               (HSDB, 1996)



         Solubility in water:<1 mg/ml at 19°C.
                                                 (DOSE, 1993)
         Soluble in dimethyl sulphide, ethanol and acetone.
                                                 (HSDB, 1996)

    Autoignition temperature

    Chemical interactions
         Contact of cobalt dust with strong oxidizers may cause fire and
         explosions. Cobalt will react violently and sometimes explosively
         with fused ammonium nitrate.            (HSDB, 1996)
         At ambient or slightly elevated temperatures cobalt powder will
         react violently with bromine pentafluoride, ignition often
         occurring.                              (NFPA, 1986)
         Pyrophoric cobalt decomposes acetylene in cold and becomes
         incandescent.                           (NFPA, 1986)
         Glowing or white incandescence occurs when nitryl fluoride is
         passed over cobalt at mild warming temperatures.
                                                 (HSDB, 1996)

    Major products of combustion

    Explosive limits

         Fire potential moderate when exposed to heat of flame.
                                                 (HSDB, 1996)

    Boiling point
         2870°C                                  (DOSE, 1993)

         8.92 at 20°C                            (DOSE, 1993)

    Vapour pressure
         0 Pa at 20°C                            (HSDB, 1996)

    Relative vapour density

    Flash Point



         Cobalt is used widely as an alloying ingredient together with
         nickel, chromium, molybdenum and other elements. These alloys are
         utilised in jet aircraft, gas turbines and other equipment
         operating at high temperatures.
         Cobalt is an important constituent of magnets.
         Cobalt is the binder employed in the production of tungsten
         carbide which, due to its toughness and shock resistance, is used
         in drill bits and machine tools.
         60Co, the artificially produced radioisotope is sometimes used
         in place of x-rays to inspect the internal structure of
         Cobalt oxide is used in the glass and ceramic industries as a
         pigment, and for enamelling purposes.
         Cobalt catalysts are used in many industrial reactions; cobalt
         hydrocarbonyl may be used as a catalyst in organic reactions.
                                                 (PATTY, 1994)

    Hazard/risk classification

    Index no.   027-001-00-9
    Risk phrases
         R42/43 - May cause sensitisation by inhalation and skin contact.
    Safety phrases
         Xn; S(2-)22-24-37 - Harmful. Keep out of reach of children. Do
         not breathe dust. Avoid contact with the skin. Wear suitable
    EEC no.   231-158-0                          (CHIP2, 1994)


    Cobalt is a relatively rare element that usually exists in association
    with nickel, silver, lead, copper and iron ores. Occupational exposure
    to cobalt dust occurs mainly in the tungsten carbide industry but has
    been reported also in diamond polishers (Lahaye et al, 1984) and
    dental technicians (Sherson et al, 1990). It is an essential dietary
    trace element as a component of vitamin B12 (cyanocobalamin), each
    molecule of the vitamin containing one atom of cobalt.

    Cigarettes contain cobalt but most of this is in the paper of the butt
    which contains approximately 4 µg cobalt compared to 0.4 µg in the
    cigarette. Linnainmaa and Kiilunen (1997) estimated that the butt
    paper cobalt from 100 cigarettes would need to be absorbed to achieve
    cobalt uptake equivalent to eight hours exposure to 0.05 mgCo/m3.


    Cobalt interacts with sulphydryl groups to impair thiol-enzyme
    activities (Alexander, 1972). In  in-vitro studies cobalt causes DNA
    damage and induces the formation of reactive oxygen species in the
    presence of hydrogen peroxide (Beyersman and Hartwig, 1992).

    Cobalt is immunogenic and may act as a hapten in the induction of
    bronchial and dermal hypersensitivity (Sjögren et al, 1980). Evidence
    for an autoimmune mechanism in hard-metal lung disease is suggested by
    the recurrence of disease in a single transplanted lung despite no
    evidence of cobalt in the donated organ (Frost et al, 1993).

    In a dog model cobalt myocardial toxicity was characterized by
    vacuolation and loss of myofibers (Sandusky et al, 1981a) with
    histochemical evidence of severe mitochondrial damage (Sandusky et al,
    1981b). This is probably related to cobalt-thiol group interaction
    causing citric acid cycle malfunction (Jarvis et al, 1992).

    The erythropoietic effect of cobalt is attributed to increased
    erythropoietin release from damaged renal cells (Alexander, 1972). In
    cobalt pneumoconiosis non-respiratory symptoms of constitutional upset
    are thought to be due to the release of a tumour necrosis factor
    (Rolfe et al, 1992).



    Cobalt can be absorbed orally, by inhalation and dermal exposure
    (Domingo, 1989; Scansetti et al, 1994). Cobalt and iron share the same
    transport mechanism within the small intestine such that cobalt
    ingestion competitively inhibits iron uptake. The extent of intestinal
    cobalt absorption after ingestion depends on the dose with only some
    20 per cent of a large ingestion being absorbed (Domingo, 1989). Some
    inhaled cobalt undergoes mucociliary clearance while particles which
    reach the distant pulmonary tree are taken up predominantly by
    macrophages (Evans et al, 1993).


    The normal body burden of cobalt is about 1.1 mg. Approximately 43 per
    cent is in muscle with some 14 per cent in bone and the remainder in
    other soft tissues (Domingo, 1989).


    Cobalt which reaches the systemic circulation is eliminated
    predominantly in urine with a variable but small amount excreted in
    bile (Domingo, 1989). Following acute occupational cobalt exposure the
    urinary elimination of cobalt is rapid for the first 24 hours followed
    by a slower excretion phase lasting several weeks (Alexandersson,

    1988). A small proportion of retained cobalt has a biological
    half-life of several years (Elinder and Friberg, 1986).



    Cobalt salts are relatively non-toxic but ingestion may lead to
    gastrointestinal and rarely transient haematological disturbance (see

    Gastrointestinal toxicity

    A six year-old boy developed nausea and vomiting after swallowing a
    drink to which he had added about 2.5 g cobalt chloride from a crystal
    growing set (Mucklow et al, 1990). The serum cobalt concentration some
    seven hours post ingestion was 434 µg/L (normal range <1 µg/L) but he
    made a full recovery.

    Everson et al (1988) reported a 14 year-old female who vomited but was
    otherwise asymptomatic following ingestion of a small (undetermined)
    amount of cobalt chloride from her brother's chemistry set. The serum
    cobalt concentration 12 hours post ingestion was 78 µg/L.


    A six year old boy who ingested 2.5 g cobalt chloride (Mucklow et al
    1990) developed a transient neutropenia (1.7 x 109/L) but recovered


    Dermal exposure

    Cobalt is a topical irritant (Fischer and Rystedt, 1985) and a well
    recognised cause of occupational contact dermatitis which has been
    described in hard metal workers (Cugell, 1992), printers, builders
    (Kiec-Swierczynska, 1990; Irvine et al, 1994) and employees in the
    rubber (Foussereau and Cavelier, 1988) and glass-fibre-reinforced
    plastics (Tarvainen et al, 1993) industries. Cobalt sensitivity may
    also be caused by exposure to jewellery, metal buttons, plastics and
    domestic detergents (Castiglioni et al, 1992). Photosensitization to
    cobalt has been reported (Camarasa and Alomar, 1981; Manciet et al,

    Cobalt contact allergy is an important cause of metal prosthesis
    failure with joint loosening and dislocation, local bone resorption
    and fractures (Jones et al, 1975). There may be an associated
    dermatitis which can spread beyond the primary irritation site (Merle
    et al, 1992). A widespread allergic vasculitis due to cobalt
    sensitivity from a cobalt alloy prosthesis has also been described
    (Munrow-Ashman and Miller, 1976). Dental prostheses containing cobalt

    also have caused local irritation with gingivitis and stomatitis in
    addition to a remote dermatitis (Hildebrand et al, 1989).

    A 56 year-old woman developed intense pain and burning of the lips,
    with oedema and erosive lesions following implantation of a dental
    prosthesis in the superior dental arch. The prosthesis was mainly
    composed of a methylacrylate containing cobalt, chromium and nickel. A
    series of patch tests revealed an isolated strong positivity for
    cobalt chloride. This was the first report in which hypersensitivity
    to cobalt in a dental prosthesis was suggested as a possible cause of
    erosive oral lichen planus (Torresani et al, 1994).

    Simultaneous allergies to nickel and cobalt are frequent (Burden and
    Eedy, 1991) and there is some evidence for a mutual enhancing effect
    of contact sensitization to one metal in the presence of the other
    (Domingo, 1989).  The administration of disulfiram in the treatment of
    ethanol abuse has led to an exacerbation of cobalt dermatitis
    presumably via diethyldithiocarbamate (a disulfiram metabolite)
    chelation and mobilization of cobalt in a manner similar to that
    reported in nickel sensitive subjects (Menné, 1985).

    Pryce and King (1990) described a patient with orofacial
    granulomatosis in association with delayed cobalt hypersensitivity
    suggesting that this condition is allergy - based. The source of
    cobalt was traced to plastic pens and crayons which the patient sucked
    frequently.  Tattoos containing cobalt have also initiated a
    granulomatous reaction (Ro and Lee, 1991).


    Gastrointestinal toxicity

    Gastrointestinal symptoms similar to those occurring after acute
    cobalt salt ingestion have also complicated chronic therapy. A 35
    year-old woman with anaemia treated with cobalt chloride 25 mg qds
    complained of nausea, vomiting and weight loss in addition to the
    neurological symptoms described below (Schirrmacher, 1967).

    Cardiovascular toxicity

    Congestive cardiomyopathy has been reported in people who drank large
    quantities of beer to which cobalt had been added as a foam stabilizer
    (Morin et al, 1967; Kesteloot et al, 1968; Sullivan et al, 1969) and
    in those receiving oral cobalt therapy (Manifold et al, 1978).

    In a study of 28 cases of cobalt beer cardiomyopathy (Alexander, 1972)
    symptoms of cardiac failure were of fairly abrupt onset (mean duration
    at presentation 10 weeks) and variable severity with five deaths from
    cardiogenic shock and a full physical recovery in only 11 patients.
    Cardiomegaly, a pericardial effusion and polycythemia were present in
    the majority with pleural effusion in 11 cases though radiological
    evidence of pulmonary oedema "characteristically ..... was absent".
    Profound lactic acidosis was a prominent feature in severe cases.

    Electrocardiographic abnormalities included p pulmonale or p mitrale,
    axis (usually right) deviation and acute ischaemic changes in the
    precordial leads typically associated with raised plasma cardiac
    enzyme concentrations. Electron microscopy of myocardial tissue from
    these patients showed extensive myofibril degeneration with abnormal
    mitochondria containing electron-dense bodies believed to incorporate
    cobalt. It is probable that alcohol and malnutrition contributed to
    the cardiotoxicity observed in these and other cases since the
    absolute quantities of cobalt ingested often were small (up to 10 mg
    daily) (Kesteloot et al, 1968; Alexander, 1972).

    Curtis et al (1976) described a haemodialysis patient who died three
    months after "a course" of cobalt chloride. At post mortem the
    myocardial cobalt concentration was 1.65 µg/g, some 25-80 times
    greater than myocardial cobalt concentrations in haemodialysis
    patients who had not received cobalt. These authors noted that renal
    failure haemodialysis patients treated with oral cobalt chloride had
    significantly higher (p=0.001) blood cobalt concentrations than
    patients who had not received cobalt thus identifying renal failure
    patients as an 'at risk' group for cobalt toxicity (see below). In
    another report a 17 year-old girl on maintenance haemodialysis died
    from rapidly progressive dilated cardiomyopathy after nine months
    cobalt chloride therapy (25 mg bd) for anaemia. At necropsy the
    myocardial cobalt concentration was 8.9 µg/g (Manifold et al, 1978).


    After six months treatment with cobalt-chloride 25 mg qds for anaemia
    a 35 year-old woman developed limb paraesthesiae, an unsteady gait,
    impaired hearing and dizzy spells in addition to nausea, vomiting and
    weight loss (Schirrmacher, 1967). Clinical examination confirmed
    bilateral nerve deafness, absent ankle reflexes and impaired vibration
    sense which all resolved with four months of cobalt withdrawal.


    Chronic ingestion of excess cobalt causes polycythaemia which in the
    past led to its use in the treatment of anaemia (Manifold et al,
    1978).  A 13 month-old child developed persistent anaemia with
    polycythaemia and cardiomegaly in addition to hypothyroidism (see
    below) and hypertrichosis following treatment of iron deficiency for
    one year with a commercial iron-cobalt preparation. At the end of the
    treatment period the serum cobalt concentration was 59 µg/L. The
    haematological abnormalities and hypothyroidism resolved when the
    treatment was stopped, with some improvement in cardiac size and a
    fall in the serum cobalt concentration to 6.8 µg/L and 1.4 µg/L at
    four and 12 months respectively (Bianchi et al, 1989).

    Endocrine toxicity

    Cobalt inhibits the iodination of tyrosine and goitre is a recognised
    side-effect of cobalt therapy (Schirrmacher, 1967). A 13 month-old
    baby developed clinical and biochemical hypothyroidism after treatment
    of iron deficiency for one year with a commercial iron-cobalt
    preparation. The endocrine abnormality resolved when treatment was
    withdrawn (Bianchi et al, 1989).

    Ocular toxicity

    Following treatment of pancytopenia with 73 g oral cobalt chloride
    over two and a half years, a patient developed abnormal choroidal
    perfusion and optic atrophy. Vision did not deteriorate further
    following cessation of therapy (Licht et al, 1972).


    Pulmonary toxicity

    Pulmonary toxicity following chronic cobalt exposure is associated
    typically with the hard metal (tungsten carbide in a cobalt matrix)
    industry (Auchincloss et al, 1992) but similar problems have been
    reported in diamond polishers using cobalt-coated discs (Lahaye et al,
    1984; Nemery et al, 1990) and in a dental technician (Sherson et al,
    1990). Lung disease in the hard metal industry is more common among
    workers exposed to ionized cobalt (dissolved in machine coolants) than
    in those exposed to dry (non-ionized) cobalt dusts even though the
    dust-exposed group usually work in the highest ambient air cobalt
    concentrations (Cugell, 1992).

    There is some debate concerning whether cobalt exposure alone is
    sufficient to cause pulmonary fibrosis.  In-vitro and animal studies
    suggest there is no relationship between cellular cobalt uptake and
    cellular toxicity (Lison and Lauwerys, 1994) and cobalt workers
    frequently are exposed to several other potential toxins (including
    tungsten carbide, iron, silica and diamond) (Swennen et al, 1993).
    While Gennart and Lauwerys (1990) observed a significantly increased
    incidence (p<0.05) of restrictive spirometry and respiratory symptoms
    in workers exposed for more than five years to cobalt dust in a plant
    producing diamond-cobalt circular saws compared to non cobalt-exposed
    factory workers, Swennen et al (1993) found no difference in
    ventilatory performance, lung volumes or carbon monoxide diffusion
    capacity between 82 cobalt refinery workers and controls even though
    the cobalt workers complained more frequently of wheeze and dyspnoea.

    Hard metal pneumoconiosis

    Chronic cobalt (and tungsten carbide) inhalation is associated
    typically with "hard metal" pneumoconiosis characterized by
    interstitial fibrosis (primarily of the lower zones) and a restrictive
    ventilatory defect. Patients usually present with exertional dyspnoea,
    cough and sometimes chest tightness (Bech et al, 1962). There may be

    associated constitutional symptoms of fever, weight loss or general
    malaise (Coates and Watson, 1971; Balmes, 1987; Migliori et al, 1994).
    In one study of 12 tungsten carbide workers the mean duration of
    exposure before the onset of respiratory symptoms was 12 years with a
    range of 1 month to 28 years (Coates and Watson, 1971). Inspiratory
    crackles are the earliest physical sign (Rochat et al, 1987) but
    finger clubbing, cyanosis and eventually corpulmonale may ensue.

    Chest x-ray findings vary greatly (Cugell et al, 1990) but usually
    show increased linear markings and small nodular opacities in the
    lower (and mid) zones with later cardiomegaly and features of
    pulmonary hypertension (Bech et al, 1962).

    Many patients develop a form of pulmonary fibrosis complicated by
    atypical intraalveolar giant cells (Davison et al, 1983; Rochat et al,
    1987; Cugell, 1992) which can be demonstrated in bronchoalveolar
    lavage fluid (Forni, 1994). Forni (1994) suggested that a persistently
    high bronchoalveolar lavage eosinophil count despite steroid therapy
    and cessation of exposure carried an unfavourable prognosis in
    patients with hard metal lung disease.

    Several fatalities from hard metal pneumoconiosis have been reported
    (Della-Torre et al, 1990; Figueroa et al, 1992). Nemery et al (1990)
    described a 52 year-old diamond polisher who died less than one year
    after a diagnosis of interstitial lung disease. He continued work
    without specific treatment until three months before death when he
    required continuous oxygen and systemic steroids. At autopsy there was
    evidence of extensive fibrosis with interstitial giant cells. The lung
    cobalt concentration was 2.1 µg/g. The authors suggested that oxygen
    therapy may have exacerbated this man's deterioration via
    cobalt-induced hydroxyl free radical formation.

    Allergic alveolitis

    An allergic alveolitis has been described in hard-metal workers with
    cough, dyspnoea and flu-like symptoms associated with bilateral
    crackles, radiographic small nodular infiltrates and a restrictive
    lung function defect (Sjögren et al, 1980; Cugell, 1992). These
    abnormalities may reverse if exposure ceases but with continued cobalt
    inhalation irreversible fibrosis is likely (Cugell, 1992).

    Occupational asthma

    Hard metal workers may develop occupational asthma with cough, wheeze
    and dyspnoea that characteristically improves during week-ends and
    holidays (Sprince et al, 1988; Cugell, 1992). Similar symptoms have
    been described in diamond workers exposed to cobalt in polishing discs
    (Gheysens et al, 1985).

    In a study of 703 hard metal workers Kusaka et al (1996a) identified
    age (>40 years), atopy and cobalt exposure as risk factors for
    asthma. Surprisingly, low airborne cobalt concentrations (below 50
    µg/m3) posed a greater risk of hard metal asthma than did higher air
    cobalt concentrations (Kusaka et al, 1996a) although the observed
    deterioration in ventilatory function seemed to be related to duration
    of cobalt exposure (Kusaka et al, 1996b). There was no significant
    difference in asthma prevalence between those exposed to the elemental
    (dust) or ionised (mist) metal (Kusaka et al, 1996a).

    Cobalt asthma is associated in some, but not all, cases with
    circulating cobalt-specific IgE and generalised bronchial
    hyperresponsiveness (Coates and Watson 1971; Sjögren et al, 1980;
    Kusaka et al, 1989; Shirakawa et al, 1989; Cugell, 1992). Respiratory
    cross-reactivity between cobalt and nickel has also been described
    (Shirakawa et al, 1990).

    Cardiovascular toxicity

    Patients with fulminant hard metal pneumoconiosis may, after several
    years, develop cor pulmonale with clinical and radiographic features
    of pulmonary hypertension and right heart failure (Bech et al, 1962).

    Cobalt cardiomyopathy is most frequently associated with chronic
    excess cobalt ingestion (see above) but an identical syndrome has been
    reported occasionally in those occupationally exposed (Barborik et al,
    1972; Jarvis et al, 1992).

    Kennedy et al (1981) reported fatal cardiogenic shock in a 48 year-old
    hard metal worker following routine vagotomy and pyloroplasty for
    duodenal ulceration. The patient, who had handled tungsten carbide and
    cobalt dust for four years, initially developed signs of
    cardiovascular compromise during the operation and gradually
    deteriorated without evidence of ischaemic heart disease. At
    post-mortem the heart was dilated with extensive myocardial fibrosis
    and a myocardial cobalt concentration of 7 µg/g (normal range


    Jordan et al (1990) reported significantly impaired attention
    (p<0.05) and verbal (p<0.001) memory in 12 hard metal workers
    exposed to tungsten carbide and cobalt (as dust and dissolved in an
    organic solvent) compared to healthy unexposed controls. However, all
    members of the study group had "pulmonary manifestations" of hard
    metal disease which may have affected performance.

    A patient occupational exposed (mainly via inhalation) to cobalt dust
    for 20 months developed bilateral optic atrophy and bilateral nerve
    deafness. Fourteen months after stopping work visual activity improved
    and hearing returned to normal (Meecham and Humphrey, 1991).


    Lechleitner et al (1993) reported Goodpasture's syndrome in a 26
    year-old hard metal worker with severe interstitial lung disease and
    fulminant glomerulonephritis. The role of heavy metal exposure in the
    aetiology of this case is not known though the authors proposed
    cobalt-induced ß-cell activation or exposure of pulmonary basement
    membrane antigens as possible disease mechanisms.


    Dermal exposure

    Removal from exposure is the priority. It is important to remember
    that the cobalt source may not be immediately apparent, for example,
    when in a dental or other prosthesis. The role of chelation therapy in
    cobalt contact sensitivity is discussed below.


    Removal from exposure is the principle requirement. The possibility of
    cobalt cardiotoxicity should be remembered in those in whom exposure
    is chronic. Asthmatic symptoms respond to conventional measures
    (Pisati and Zedda, 1994). Established pulmonary fibrosis has a
    generally poor prognosis although there are reports of substantial
    improvement following removal from the workplace (Zanelli et al,
    1994). The role of blood and urine cobalt concentration measurements
    is discussed below (Medical Surveillance).



    Gastric lavage is unnecessary as cobalt ingestion produces only low
    acute oral toxicity and there is no evidence that oral activated
    charcoal reduces gastrointestinal cobalt absorption.

    Supportive measures

    Following acute cobalt salt ingestion supportive care is usually all
    that is required with intravenous fluid replacement if vomiting is
    severe. Plasma creatinine, urea and electrolytes and full blood count
    should be measured. If chronic cobalt toxicity is suspected a thorough
    cardiovascular and neurological (including fundoscopy) assessment
    should be undertaken. Thyroid function tests should be performed. The
    role of chelation therapy is discussed below (Antidotes). The presence
    of cobalt in blood and urine confirms exposure but blood and urine
    concentrations require careful interpretation (see Medical
    Surveillance) and these assays are not widely available.



    Aposhian (1983) reported early animal studies published in the Chinese
    literature in 1965 which showed that DMSA (4 mmol/kg, route not
    stated) increased the LD50 of cobalt chloride-poisoned mice some
    three times.

    Four of ten mice administered 1.8 mmol/kg intraperitoneal cobalt
    chloride (a dose exceeding the LD95 immediately followed by
    intraperitoneal DMSA 3.4 mmol/kg survived two weeks (Llobet et al,
    1986). Under these experimental conditions DMSA was a less effective
    cobalt chelator than calcium EDTA or DTPA (diethylenetriamine-
    pentacetic acid) (see below).


    Llobet et al (1986) reported a 70 per cent two week survival rate in
    mice administered intraperitoneal DTPA (3.1 mmol/kg) immediately
    following intraperitoneal loading with 1.8 mmol/kg cobalt chloride (a
    dose in excess of the LD95).

    Calcium EDTA

    All mice administered intraperitoneal cobalt chloride at doses
    approximating to the LD50-LD95 (0.6-1.8 mmol/kg), immediately
    followed by 4.3 mmol/kg intraperitoneal calcium EDTA (ethylenediamine
    tetraacetic acid) survived two weeks with significantly increased
    urine cobalt elimination in the 24 hours post antidote administration
    (Llobet et al, 1986).

    Allenby and Basketter (1989) found that a positive patch test reaction
    to one per cent aqueous cobalt chloride was abolished in five out of
    six subjects by the concomitant application of an equimolar EDTA

    No cobalt was recovered in the urine of a patient with cobalt
    cardiomyopathy who received a one week course of calcium EDTA (and
    penicillamine, doses not stated) but treatment was not instituted
    until three years after cobalt ingestion (quantity not stated)
    (Alexander, 1972). The use of topical EDTA in cobalt dermatitis is
    discussed above (dermal exposure).


    Balmes (1987) reported a 28 year-old lady with aggressive hard metal
    pneumoconiosis unresponsive to prednisolone (40-60 mg daily) who
    clinically improved significantly after two months of low-dose
    (25 mg bd) cyclophosphamide therapy.


    In a patient with uraemic cardiomyopathy and a high serum cobalt
    concentration (0.24 ppb), Lins and Pehrsson (1976) reported reduced
    cardiac size in association with a fall in the serum cobalt
    concentration to 0.07 ppb during haemodialysis. However no cobalt
    dialysis clearance data or details of dialysis duration were given.


    Patients with renal failure are at risk of cobalt toxicity if
    administered oral cobalt containing pharmaceuticals (Curtis et al,
    1976); these preparations are not available in the UK.


    Regular monitoring of workplace airborne cobalt concentrations (Sala
    et al, 1994), strict attention to personal hygiene (Scansetti et al,
    1994) and periodic assessment for pulmonary or dermatological symptoms
    are important in the prevention of cobalt toxicity. The recommended
    maximum exposure limit (eight-hour time weighted average 1995) in the
    UK for cobalt is 0.1 mg/m3 (Health and Safety Executive, 1995).

    Some studies suggest that airborne cobalt concentrations are
    frequently underestimated (Auchincloss et al, 1992; Mosconi et al,
    1994) and other workers recently have reported average cobalt airborne
    concentrations in a hard metal factory greatly exceeding the
    recommended occupational exposure limit (Kumagai et al, 1996).
    Furthermore, significant reductions in FEV1 and FVC have been
    observed in workers exposed to airborne cobalt concentrations lower
    than 50 µg/m3 (Nemery et al, 1992).

    Sjögren et al (1980) noted that the development of cobalt contact
    dermatitis often preceded pulmonary disease and suggested that those
    with a positive cobalt patch test should be removed immediately from
    exposure. However, in another study only two of nine hard metal
    workers sensitive to inhaled cobalt had a positive cobalt patch test
    (Kusaka et al, 1986).

    Abnormal clinical findings should be investigated conventionally with
    particular attention to establishing a temporal relationship to
    workplace exposure in those with possible occupational asthma or
    alveolitis. The presence of cobalt-specific IgE in plasma or cobalt
    particles in bronchoalveolar lavage fluid or lung biopsy tissue may be

    Increased blood and urine cobalt concentrations are frequently
    encountered in hard metal workers (Ichikawa et al, 1985; Stebbins et
    al, 1992) but are more useful as grouped rather than individual data
    (Sabbioni et al, 1994) and their significance requires careful

    In workers exposed to cobalt dust in a plant producing diamond-cobalt
    saws urine cobalt concentrations reflected recent rather than
    cumulative cobalt exposure (Gennart and Lauwerys, 1990). Lison et al
    (1994) concluded that while urine and blood cobalt concentrations
    correlate reasonably well with recent exposure to soluble forms of
    cobalt (as in hard metal powders) the same is not true following
    exposure to insoluble cobalt oxide.

    No evidence of hard a metal pneumoconiosis or significantly excess
    heart disease was found in controlled study of 49 workers exposed to
    cobalt and cobalt oxides despite the presence of high urine cobalt
    concentrations (mean 340 g/L) (Morgan, 1983).


    Maximum exposure limit

    Long-term exposure limit (8 hour TWA reference period)
    0.1 mg/m3 (Health and Safety Executive, 1995).



    Animal studies suggest cobalt and its compounds are carcinogenic.
    While several studies have confirmed that hard metal workers exhibit
    excess lung cancer mortality, there is no strong evidence that cobalt
    or its compounds are carcinogenic in man (IARC, 1991). Assessment of
    human cancer risk is often confounded by simultaneous tobacco
    consumption, exposure to nickel and arsenic and small study population
    numbers (Mur et al, 1987; Jensen and Tüchsen, 1990).

    Mur et al (1987) observed an excess mortality form lung cancer
    (standardized mortality ratio = 4.66) in 1143 workers employed between
    1950-1980 in a cobalt and sodium producing plant; smoking habits in
    the study population were not assessed. Further follow-up from 1981-88
    failed to show a relationship between lung cancer and cobalt exposure
    (Moulin et al, 1993).

    Lasfargues et al (1994) reported a significantly higher mortality from
    lung cancer among 709 hard metal workers (employed for at least one
    year) compared to controls, though the study was too small to be


    There is no conclusive evidence regarding the reprotoxicity of cobalt
    (Reprotox, 1996). Ratto et al, (1988) reported a successful pregnancy
    in a 31 year-old woman despite severe cobalt pneumoconiosis requiring
    systemic steroids and cyclophosphamide.


    Salmonella typhimurium TA98, TA102, TA1535, TA1537 with metabolic
    activation negative; TA98, TA1537 without metabolic activation

    Induced DNA strand breaks in human diploid fibroblasts and Chinese
    hamster ovary cells in vitro.

    In vivo rats 0.005 mg/kg cobalt metal in drinking water caused no
    mutagenic effects (DOSE, 1993).

    Fish toxicity

    LC50 (96 hr) fathead minnow 92 mg/L

    Rainbow trout tolerated 7 day exposure to 30 mg (Co)/L. Lethal limit
    35 mg (Co)/L (DOSE, 1993).

    EC Directive on Drinking Water Quality 80/778/EEC



    SM Bradberry BSc MB MRCP
    ST Beer BSc

    National Poisons Information Service (Birmingham Centre),
    West Midlands Poisons Unit,
    City Hospital NHS Trust,
    Dudley Road,
    B18 7QH

    This monograph was produced by the staff of the Birmingham Centre of
    the National Poisons Information Service in the United Kingdom. The
    work was commissioned and funded by the UK Departments of Health, and
    was designed as a source of detailed information for use by poisons
    information centres.

    Date of last revision


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