ST Beer BSc
    SM Bradberry BSc MB MRCP
    WN Harrison PhD CChem MRSC

    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

    Copper carbonate is produced commercially for veterinary use. Copper
    carbonate hydroxide is formed by the action of air and water on
    elemental copper. Variable amounts of copper carbonate hydroxide and
    copper sulphate are used in the fungicide "Burgundy mixture".


    Direct copper carbonate poisoning is rare.

    Chronic inhalation of copper containing pesticides produces pulmonary
    and hepatic toxicity. Copper contact sensitivity is recognized.



         -    May irritate skin. Contact dermatitis is recognized.


         -    Copper carbonate is an eye irritant.


         -    There are no reports of copper carbonate poisoning following
         -    Very small ingestions (milligrams) are likely to cause only
              nausea and vomiting.

    Moderate/substantial ingestions:

         -    Nausea, vomiting and a metallic taste followed by abdominal
              pain and diarrhoea may be expected. Secretions may be


         -    Chronic occupational inhalation of copper-sulphate
              containing fungicides has caused 'Vineyard sprayer's lung'
              with progressive dyspnoea, cough and wheeze, micronodular
              and reticular opacities on chest X-ray (which may coalesce)
              and a restrictive lung function defect. Other features
              include hepatic copper-containing granulomas,
              hypergammaglobulinaemia, myalgia and profound malaise.
              Similar features might be expected among those working with
              "Burgundy mixture".



    1.   Irrigate with copious lukewarm water.
    2.   Copper irritant dermatitis and contact sensitivity are managed
         most effectively by discontinuing exposure.


    1.   Irrigate immediately with lukewarm water or preferably saline for
         at least 10 minutes.
    2.   Application of local anaesthetic may be required for pain relief
         and to overcome blepharospasm to allow thorough decontamination.
    3.   Ensure no particles remain lodged in the conjunctival recesses.
    4.   Corneal damage may be detected by the instillation of
    5.   If symptoms do not resolve rapidly or if there are abnormal
         examination findings, refer for an ophthalmological opinion.


    1.   Symptomatic and supportive measures are usually all that are
    2.   Although based on cases of acute copper sulphate ingestions,
         whole blood copper concentrations correlate well with the
         severity of poisoning they should always be interpreted in
         conjunction with the clinical features. Chuttani et al (1965)
         suggested severe complications (liver or renal damage or
         hypovolaemic shock) were unlikely in those with whole blood
         copper concentrations less than 4 mg/L but this is not
         universally true (Wahal et al, 1976; Hantson et al, 1996).
    3.   Chelation therapy is unlikely to be appropriate and its value is
         unproven. Discussion with an NPIS physician is recommended.
    4.   Check full blood count and liver profile if chronic exposure is


         -    Acute copper salt inhalation will produce pulmonary
              irritation. There are no case reports specific to this
              compound. Chronic copper sulphate inhalation causes a
              granulomatous hypersensitivity response.
              Arrange for chest X-ray and lung function tests. Seek
              specialist advise from a NPIS physician.


    Bentur T, Koren G, McGuigan M, Spielberg SP.
    An unusual skin exposure to copper; clinical and pharmacokinetic
    Clin Toxicol 1988; 26: 371-80.

    Gleason RP.
    Exposure to copper dust.
    Am Ind Hyg Assoc J 1968; 29: 461-2.

    Knobeloch L, Ziarnik M, Howard J, Theis B, Farmer D, Anderson H,
    Proctor M.
    Gastrointestinal upsets associated with ingestion of copper-
    contaminated water.
    Environ Health Perspect 1994; 102: 958-61.

    Mülendahl KE, Lange H.
    Copper and childhood cirrhosis.
    Lancet 1994; 344: 1515-6.

    Spitalny KC, Brondum J, Vogt RL, Sargent HE, Kappel S.
    Drinking-water-induced copper intoxication in a Vermont family.
    Pediatrics 1984; 74: 1103-6.

    Terry RF.
    Excess copper in a local water supply.
    Med J Aust 1996; 165: 296.

    WHO/World Health Organization.
    Guidelines for drinking-water quality. 2nd ed. Vol 1. Recommendations.
    Geneva: World Health Organization, 1993.

    Wyllie J.
    Copper poisoning at a cocktail party.
    Am J Public Health 1957; 47: 617.

    Substance name

         Copper (II) carbonate

    Origin of substance

         Copper carbonate is manufactured commercially.
                                                 (HSDB, 1997)


         Carbonic acid, copper (II) salt
         Copper monocarbonate
         Cupric carbonate
         Xanthic acid, copper (II) salt          (RTECS, 1997)

    Chemical group

         A compound of copper, a group 1B transition metal (d block)

    Reference numbers

         CAS            1184-64-1
         RTECS          FF9500000                (RTECS, 1997)
         UN             NIF

    Physicochemical properties

    Chemical structure
         CuCO3                                   (HSDB, 1997)

    Molecular weight
         123.55                                  (RTECS, 1997)

    Physical state at room temperature


         Odourless                               (HSDB, 1997)




    Autoignition temperature

    Chemical interactions
         Copper salts and nitromethane may spontaneously form explosive
         Dangerous acetylides may be formed from copper salts.
         Salts of copper promote the decomposition of hydrazine.
         Solutions of sodium hypobromite are decomposed by the powerful
         catalytic action of cupric ions.        (HSDB, 1997)

    Major products of combustion

    Explosive limits


    Boiling point


    Vapour pressure

    Relative vapour density

    Flash point



         In poultry and animal feeds as an absorbable source of copper.
         Anthelmintic aid in sheep.              (HSDB, 1997)

    Hazard/risk classification


    Substance name

         Copper (II) carbonate hydroxide

    Origin of substance

         Occurs in nature as the mineral malachite.
         Prepared by adding CuSO4 solution to Na2CO3solution.
         Another form of basic copper carbonate, 2CuCO3.Cu(OH)2, occurs
         in nature as the mineral azurite or chessylite.
         In hard water copper carbonate hydroxide is the final
         precipitation product of dissolved copper.
                                                 (MERCK, 1996; DOSE, 1993)


         Basic copper carbonate
         Cupric subcarbonate
         Bremen blue
         Bremen green                            (MERCK, 1996)

    Chemical group

         A compound of copper, a group 1B transition metal (d block)

    Reference numbers

         CAS            12069-69-1
         RTECS          GL6910000                (RTECS, 1997)
         UN             NIF

    Physicochemical properties

    Chemical structure
         CuCO3.Cu(OH)2                           (MERCK, 1996)

    Molecular weight
         221.11                                  (SAX'S, 1996)

    Physical state at room temperature
         Solid                                   (MERCK, 1996)

         Green to blue powder or dark green crystals
                                                 (MERCK, 1996)




         Soluble in dilute acids and ammonia. Practically insoluble in
         alcohol and water.                      (MERCK, 1996)

    Autoignition temperature

    Chemical interactions

    Major products of combustion
         Acrid smoke and fumes.                  (SAX'S, 1996)

    Explosive limits


    Boiling point
         Decomposes at 200°C                     (SAX'S, 1996)

         4.0 at 20°C                             (SAX'S, 1996)

    Vapour pressure

    Relative vapour density

    Flash point



         In the manufacture of other copper salts.
         As a fungicide.
         In pyrotechnics.
         In sweetening of petrol sour crude stock.
         As paint and varnish pigment.
         In animal and poultry feeds.
         As a treatment for copper deficiency in ruminants.
                                                 (MERCK, 1996)

    Hazard/risk classification



    Copper forms two divalent carbonates, copper carbonate (CuCO3) and
    copper carbonate hydroxide (CuCO3.Cu (OH)2).

    Copper carbonate is a commercially manufactured copper salt. There are
    no reports of intoxication from exposure to copper carbonate.

    Copper carbonate hydroxide, commonly known as verdigris, is formed
    naturally by the action of moist air on elemental copper (MERCK,
    1996). It is also a constituent of fungicides, such as Burgundy
    mixture, formed by the reaction of aqueous copper sulphate and sodium
    carbonate. In hard water areas copper carbonate hydroxide is the final
    precipitation product of dissolved copper ions.


    Cellular damage and cell death may result from excess copper
    accumulation. This is likely when copper-metallothionein binding and
    copper clearance from the cell are blocked.

    Metallothionein is a cysteine rich low molecular weight (6500 Da)
    metal-binding protein which is important in heavy metal
    detoxification, metal ion storage, and in the regulation of normal
    cellular Cu(II) (and Zn(II)) metabolism. It is also thought to be a
    free radical scavenger, playing a protective role in oxidative stress.
    Metallothionein is found in both intra and extracellular compartments.
    It is known to bind zinc, cadmium, copper, mercury and silver (in
    increasing order of affinity) and its gene transcription is greatly
    enhanced upon exposure of cells to these metals. High metallothionein
    concentrations are also induced in the liver by physical and chemical
    stress, infection and glucocorticoids.

    It is proposed that free Cu(I) (from Cu(II) reduction) binds to
    intracellular sulphydryl groups and inactivates enzymes such as
    glucose-6-phosphate dehydrogenase and glutathione reductase (Dash,
    1989). In addition copper may interact with oxygen species (e.g.
    superoxide anions and hydrogen peroxide) and catalyze the production
    of reactive toxic hydroxyl radicals.

    Copper(II) ions can oxidize haem iron to form methaemoglobin.


    Absorption and distribution

    There are no toxicokinetic data specific to copper carbonate.

    Although copper carbonate hydroxide is practically insoluble in water
    its solubility in dilute acid may facilitate gastrointestinal

    Strickland et al (1972) suggested a mean copper absorption of 57 per
    cent (range 40 to 70 per cent) following oral administration of
    0.4-4.5 mg copper (as copper acetate) to four volunteers. An early
    human study suggested a maximum blood copper concentration was reached
    within some two hours after oral copper chloride administration
    (1.5-12 mg copper) (Earl et al, 1954).

    Copper transport across the intestinal mucosa following ingestion is
    facilitated by cytosolic metallothionein. In blood, copper is
    initially albumin-bound and transported via the hepatic portal
    circulation to the liver where it is incorporated into caeruloplasmin
    (an alpha globulin synthesized in hepatic microsomes) (Britton, 1996).
    Some authors have noted a secondary rise in the serum copper
    concentration following acute copper sulphate ingestion (Singh and
    Singh, 1968) and this may be due to release of the
    copper-caeruloplasmin complex from the liver. Ninety-eight per cent of
    copper in the systemic circulation is caeruloplasmin-bound.

    Copper is distributed to all tissues with the highest concentrations
    in liver, heart, brain, kidneys and muscle. Intracellular copper is
    predominantly metallothionein-bound. Kurisaki et al (1988) reported
    copper in the lungs, liver, kidney, blood, bile and stomach (33.7,

    35.1, 41.4, 13.8, 2.8, and 2988 µg/g wet weight respectively)
    following ingestion of some 10 g copper sulphate in a 58 year-old
    male. Although copper in the liver and kidneys was metallothionein
    bound, pulmonary copper was not, possibly because copper had entered
    the lung via aspiration.

    Copper can penetrate the erythrocyte membrane. In acute copper
    sulphate poisoning this occurs quite rapidly as indicated by the
    markedly higher whole blood than serum copper concentration within the
    first few hours after ingestion (Singh and Singh, 1968). In a series
    of 40 cases of acute copper sulphate ingestion Singh and Singh (1968)
    noted that haemolysis (secondary to erythrocyte copper uptake)
    occurred typically 12-24 hours post poisoning, suggesting that red
    cell copper accumulation is maximal around this time.

    Studies among vineyard sprayers provide evidence of haematogenous
    dissemination of inhaled copper sulphate (Villar, 1974; Pimentel and
    Menezes, 1977). Copper sulphate can also be absorbed through the skin
    giving rise to systemic effects (Holtzman et al, 1966; Pande and
    Gupta, 1969).

    Copper can cross the placenta.


    Caeruloplasmin renders free copper innocuous with subsequent excretion
    via a lysosome-to-bile pathway. This process is essential to normal
    copper homeostasis and provides a protective mechanism in acute copper
    poisoning. An impaired or overloaded biliary copper excretion system
    results in hepatic copper accumulation, as occurs in patients with
    Wilson's disease and in copper poisoning.

    Renal copper elimination is normally low (Tauxe et al (1966) retrieved
    less than one per cent of an injected dose in the urine over 72 hours)
    but is likely to increase in acute copper poisoning. For example, a
    child who ingested three grams copper sulphate had increased urine
    copper concentrations (maximum 2.8 - 3.0 mg/L) for three weeks post
    poisoning (Walsh et al, 1977).

    In a series of 40 cases of acute copper sulphate ingestion increased
    whole blood copper concentrations were noted up to ten days post
    poisoning with values returning to normal over 17 hours to seven days
    (Singh and Singh, 1968).

    The whole-body half-life of copper has been estimated as approximately
    four weeks (Strickland et al, 1972).


    Dermal exposure

    There are no reports of acute dermal copper carbonate exposure. Copper
    contact and irritant dermatitis are recognized (see Copper monograph).

    Ocular exposure

    Verdigris dropped or dusted on the eye caused immediate irritation and
    conjunctival inflammation. The reaction subsided following irrigation
    of the eye with no permanent damage (Grant and Schuman, 1993).


    There are no reports of acute copper carbonate ingestion. Abdominal
    pain, diarrhoea, nausea and vomiting, headaches and dizziness have
    been reported following ingestion of copper contaminated water
    (Spitalny et al, 1984; Knobeloch et al, 1994). This is discussed in
    detail in the Copper monograph.


    Occupational exposure to copper fumes may cause upper respiratory
    tract irritation and sometimes symptoms of metal fume fever. These
    complaints are, however, typically encountered in those working in the
    copper industry for prolonged periods (see Copper monograph).


    Dermal exposure

    A number of cases of green staining of the hair have been reported
    following exposure to water containing high copper concentrations,
    presumably due to the precipitation of copper carbonate hydroxide on
    exposure to air.

    Parish (1975) noted that cases of green hair among copper workers have
    been reported since 1882. In these cases it was generally accepted
    that the copper staining was "from without and not within the hair"
    (Parish, 1975).

    Cooper and Goodman (1975) reported a "minor epidemic" of green hair in
    girls from a state college following the introduction of fluoride to
    the town water supply. Low pH water leaching copper from piping was a
    possible cause of the colouration. The authors noted that individuals
    with blonde hair were affected mainly, although green discolouration
    would not be as apparent in dark haired individuals. However,
    Goldsmith and Holmes (1975) noted that, independent of any copper
    effect, artificial hair bleaching may lead to green discolouration on
    exposure to chlorinated water.

    A hair copper concentration of 466 mg/kg (normal 4-128 mg/kg) was
    measured in a six year-old boy who developed green hair following
    repeated bathing in a swimming pool (Lampe et al, 1977). In another
    case of "green hair" in a five year-old girl (Lampe et al, 1977),
    water analysis revealed a copper concentration of 0.9 mg/L. Hair
    returned to normal following daily alternate washing with acidic and
    basic shampoos. The source of small amounts of copper in the swimming
    pool water was likely to be algicide residue or copper leached from

    Nordlund et al (1977) described two nursing students who acquired
    green discolouration to blonde hair following a four to six week stay
    in a university dormitory where they washed their hair daily. Analysis
    of one student's hair revealed a copper concentration of 1042 ppm
    (normal 17-38 ppm) and the copper concentration from the dormitory
    water source was noted to range from 0.41 to 4 ppm (normal 0.25 ppm).
    A faulty electrical connection to the copper water pipes was thought
    to have resulted in increased amounts of dissolved copper in the water

    Copper contact sensitivity has been described and is discussed in the
    Copper monograph.


    Gastrointestinal toxicity

    A 15 month-old infant who presented with failure to thrive and
    diarrhoea was found to have a serum copper concentration increased to
    2.9 mg/L which was attributed to the consumption of contaminated
    domestic water (copper concentration 0.8 mg/L) for three months.
    Resolution of symptoms and substantial weight gain accompanied removal
    from exposure. The child also received a five week course of oral
    d-penicillamine 75 mg tds which was associated initially with an
    increased urine copper concentration (Salmon and Wright, 1971). The
    water copper concentration reported in this case is well below the
    provisional guideline value for drinking water of 2 mg/L (WHO, 1993)
    which is defined as "the concentration of a constituent that does not
    result in any significant risk to health ........ over a lifetime of
    consumption" (IPCS, 1996). This child must have had "abnormal
    sensitivity to the metal" as the authors emphasized for copper
    intoxication to occur. Wilson's disease was excluded by serum
    caeruloplasmin assay and liver biopsy but another defect of copper
    metabolism is possible.


    Indian childhood cirrhosis (ICC) is a frequently fatal disease
    affecting children (mean age 18 months) in rural areas of India and is
    caused by massive hepatic copper accumulation (Pandit and Bhave, 1983;
    Pandit and Bhave, 1996). A high dietary copper intake, due to copper
    leaching into milk from brass cooking vessels, is the most important
    aetiological factor (Pandit and Bhave, 1983; Pandit and Bhave, 1996).

    The milk protein casein has been shown to avidly bind copper and serve
    as an effective metal ion carrier from brass to the infant (O'Neill
    and Tanner, 1989). Fortunately the previously high incidence of ICC,
    accounting for 10 per cent paediatric mortality in some Indian
    hospitals (Pandit and Bhave, 1983), has been reduced dramatically by
    an effective health education campaign aimed at maximizing breast
    feeding and avoiding the use of copper-containing cooking utensils
    (Pandit and Bhave, 1996). ICC is now rare.

    Although a high dietary copper intake is undoubtedly the main cause of
    ICC, the observed male preponderance and familial occurrence suggests
    an inherited predisposition (Pandit and Bhave, 1996). Further support
    for a genetic component in at least some cases of paediatric
    copper-induced cirrhosis comes from reports of an ICC-like condition
    among children in Western countries who have had a high, but not
    massive, dietary copper intake (Mühlendahl and Lange, 1994).

    A large-scale epidemiological survey in Massachusetts in 1993
    concluded that a moderately increased domestic water copper
    concentration alone does not cause liver disease (Scheinberg and
    Sternlieb, 1994). In this study none of the 135 deaths occurring
    between 1969 and 1991 in children under six years-old in three towns
    with the highest tapwater copper concentration (8.5-8.8 mg/L) of any
    "medium size" USA town, were attributed to any form of liver disease.

    In conclusion it appears that idiopathic childhood cirrhosis is a
    multifactorial disease which requires increased copper ingestion
    superimposed on an inherited defect of copper metabolism to be
    manifest fully.

    A 15 month-old infant fed with copper-contaminated water (copper
    concentration 0.8 mg/L) for three months developed transiently
    increased liver enzyme activities in association with features of
    gastrointestinal and neurological toxicity (Salmon and Wright, 1971).
    As discussed above this child must have been predisposed to copper
    toxicity since the water copper concentration was not particularly

    Walker-Smith and Blomfield (1973) described a 14 month-old infant who
    died six weeks after presenting with clinical and histopathological
    features of cirrhosis. The child had been bottle fed with
    copper-contaminated water from an acidic private supply running
    through domestic copper pipes (water copper concentration 6.75 mg/L).
    A slightly low plasma caeruloplasmin concentration and raised urinary
    copper excretion were consistent with Wilson's disease although the
    acute presentation at such a young age suggested concomitant
    abnormally high copper exposure was aetiologically significant.


    Hypotonia, photophobia and "behaviour change" were noted in a young
    child who presented with failure to thrive and was found to have an
    increased serum copper concentration (2.9 mg/L) attributed to chronic

    copper intoxication from a domestic water supply (Salmon and Wright,


    "Burgundy mixture" is a fungicide containing variable amounts of
    copper carbonate hydroxide and copper sulphate. Although there are no
    reports of adverse effects from the use of this mixture, features
    similar to those from exposure to copper sulphate in "Bordeaux
    mixture" may be expected (see Copper sulphate monograph). Copper
    poisoning due to occupational inhalation of such fungicides presents
    as "Vineyard sprayers lung" which, although primarily a pulmonary
    disease, may involve systemic granuloma formation.

    Pulmonary toxicity

    Characteristic presenting features of "Vineyard sprayer's lung"
    include weakness, anorexia, fever, myalgia, progressive dyspnoea,
    wheeze and a dry productive cough (Pimentel and Marques, 1969; Villar,
    1974; Pimentel and Menezes, 1975; Stark, 1981). Symptoms may resolve
    following prolonged absence from work, reappearing on return to work
    (Pimentel and Marques, 1969; Villar, 1974). Examination findings
    include cyanosis, finger clubbing and diffuse crackles and wheeze on
    auscultation of the lung fields (Villar, 1974; Pimentel and Menezes,
    1975; Stark, 1981).

    Chest X-ray findings typically include increased pulmonary markings
    with diffuse bilateral micronodular and reticular opacities sometimes
    with areas of consolidation (Pimentel and Marques, 1969; Villar, 1974;
    Pimentel and Menezes, 1975). Enlarged hilae, pleural effusion and
    areas of calcification have been noted (Villar, 1974; Stark, 1981).
    These findings initially are mainly in the lower lung fields, but may
    progress to the upper zones with formation of large opacities from
    confluence of the shadows (Villar, 1974; Stark, 1981).

    Lung function tests usually reveal a restrictive defect (Pimentel and
    Marques, 1969; Villar, 1974; Pimentel and Menezes, 1975). Arterial
    blood gases may show a respiratory alkalosis and hypoxia (Pimentel and
    Menezes, 1975).

    In a study by Plamenac et al (1985) copper containing macrophages were
    identified in the sputum of 64 and 42 per cent respectively of smoking
    (n=9) and non-smoking (n=16) vineyard workers (all with normal chest
    X-rays) compared to none of 51 controls (smokers n=21, non-smokers
    n=30, all non-vineyard workers). Morning expectoration was more common
    among vineyard workers than controls suggesting an effect on the
    respiratory epithelium as well as the lung parenchyma. Eosinophilia
    was present in the sputum samples from 42 per cent of vineyard workers
    compared to ten per cent of controls, suggesting an allergic reaction
    to the Bordeaux mixture (Plamenac et al, 1985).

    Lung biopsies from vineyard sprayers have revealed non-specific
    inflammation and intra-alveolar copper-containing macrophages,
    copper-containing granulomas of the alveolar septum with fibro-hyaline
    nodules, which sometimes also contain copper (Pimentel and Marques,
    1969; Villar, 1974; Stark, 1981). A notable similarity between
    copper-induced nodules and silicotic nodules has been emphasized
    (Pimentel and Marques, 1969; Stark, 1981). Thoracotomy may show
    characteristic blue-green patchy colouration of the visceral pleura (a
    phenomenon not observed in any other pathological lung condition)
    which often coalesce (Pimentel and Marques, 1969; Villar, 1974;
    Plamenac et al, 1985).

    Established "Vineyard sprayer's lung" carries a poor long-term
    prognosis although there may be partial resolution of radiological
    abnormalities following removal from exposure (Pimentel and Marques,
    1969). More typically progressive respiratory failure ensues (Pimentel
    and Menezes, 1975), often associated with cor pulmonale (see below)
    (Stark, 1981). Pimentel and Menezes (1975) reported fatal spontaneous
    bilateral pneumothoraces in a 57 year-old man who developed "Vineyard
    sprayer's lung" after using Bordeaux mixture for three years. Autopsy
    revealed pulmonary fibrosis with numerous copper-containing blue
    nodules and lower lobe emphysema (Pimentel and Menezes, 1975).

    Stark (1981) suggested that the duration of copper sulphate exposure
    before the clinical disease is produced is usually at least five
    years, though most workers are occupationally exposed for far longer.
    Diagnosis is complicated by the fact that the disease may remain
    subclinical for several years following removal from exposure (Villar,
    1974). Progression may be accelerated by the presence of pulmonary
    infection. Moreover, presenting features are not dissimilar to those
    of tuberculosis which itself may predispose to "Vineyard sprayer's

    It is proposed that the incidence of bronchial carcinoma is increased
    among those with "Vineyard sprayer's lung" (Villar, 1974; Stark, 1981)
    (see Carcinogenicity).

    Occupational exposure to dusts and fumes of copper salts has been
    reported to cause nasal mucosal congestion and occasionally nasal
    septum perforation but no original data have been identified
    (Scheinberg, 1983).

    Although upper respiratory tract irritation and metal fume fever are
    cited as "common complaints" of copper workers (Cohen, 1979) original
    case data are scarce. Metal fume fever is more typically associated
    with zinc oxide inhalation (see Zinc monograph).

    Employees complained of head stuffiness, "common cold" symptoms and
    "sensations of chills or warmth" a few weeks after commencing copper
    plate polishing (Gleason, 1968). Analysis of settled dust revealed
    "major" amounts of copper and "minor" amounts of aluminium; air copper
    concentrations ranged from 0.030 - 0.120 mg/m3. Following dust

    control via exhaust ventilation copper concentrations were reduced to
    less than 0.008 mg/m3 air, and symptoms resolved.


    Biopsy and autopsy findings from patients with "Vineyard sprayer's
    lung" in association with pulmonary lesions include hepatomegaly,
    copper-containing granulomas (histiocytic or sarcoid-type), Kupffer
    cell proliferation with copper inclusions, peri/intralobular fibrosis
    and idiopathic portal hypertension (Pimentel and Menezes, 1975;
    Pimentel and Menezes, 1977). Micronodular cirrhosis (sometimes
    complicated by oesophageal varices and splenomegaly) and "fatty
    change" have also been observed but may be at least partly
    alcohol-induced (Pimentel and Menezes, 1975; Pimentel and Menezes,
    1977). Copper sulphate is proposed as the cause of the lesions
    observed following deposition in the reticuloendothelial cells of the
    liver (Pimentel and Menezes, 1977). Copper accumulation in hepatocytes
    and abnormal liver function tests do not typically accompany these
    histological findings (Pimentel and Menezes, 1975).


    Increased erythrocyte sedimentation rates, IgA and IgG concentrations
    have been reported in association with the pulmonary features of
    "Vineyard sprayer's lung" (Villar, 1974). Hypergammaglobulinaemia is
    consistent with the likely immunological basis for this condition.

    Cardiovascular toxicity

    Cor pulmonale may ensue as a complication of "Vineyard sprayer's lung"
    with typical features of tachycardia, a raised jugular venous
    pressure, cardiomegaly, a right ventricular heave and summation
    gallop, and evidence of right heart strain on the electrocardiogram
    (Stark, 1981).


    Severe pulmonary manifestations of "Vineyard sprayer's lung" with
    fever may be accompanied by confusion (Pimentel and Menezes, 1975).

    A recent population based case control study among 144 Parkinsonian
    patients and 464 controls in Detroit identified a significant
    (p<0.05) association between Parkinson's disease and more than 20
    years occupational exposure to copper (Gorell et al, 1977). Chronic
    manganese exposure was independently significantly associated with
    this disorder. The neurological hazards of chronic metal exposure
    require further clarification.

    Musculoskeletal toxicity

    Joint and muscle pain with weakness has been described in association
    with the characteristic pulmonary features of "Vineyard sprayer's
    lung" (Pimentel and Marques, 1969; Villar, 1974; Pimentel and Menezes,

    Metabolic disturbances

    Hypoalbuminaemia is noted frequently in patients chronically
    debilitated with "Vineyard sprayer's lung" (Villar, 1974; Pimentel and
    Menezes, 1975).


    Copper-containing renal granulomas have been reported at autopsy in a
    patient with "Vineyard sprayer's lung" (Villar, 1974).

    Oral toxicity

    Superficial green staining of the teeth was reported in a 21 year-old
    brass foundry worker after 10 months exposure to fumes containing
    approximately 75 per cent copper (Donoghue and Ferguson, 1996). The
    authors suggested the staining was attributed to copper adherence from
    the brass fume and its subsequent conversion to copper carbonate.


    Dermal exposure

    Following acute exposure irrigate the affected area with lukewarm
    water. Particular care is required if copper carbonate has been in
    prolonged contact, with broken skin since systemic copper uptake is
    then possible.

    Copper contact sensitivity or irritant dermatitis are managed most
    effectively by discontinuing exposure.

    Ocular exposure

    Irrigate immediately with lukewarm water or preferably saline for at
    least 10 minutes. A local anaesthetic may be indicated for pain relief
    and to overcome blepharospasm. Ensure removal of any particles lodged
    in the conjunctival recesses. The instillation of fluorescein allows
    detection of corneal damage. Seek ophthalmological advice if there are
    any significant findings on examination and in those whose symptoms do
    not resolve rapidly.


    Effective management of copper carbonate ingestion primarily involves
    symptomatic and supportive care. Gastrointestinal decontamination is
    most unlikely to favourably influence outcome and should only be
    considered within the first hour after a potentially life threatening
    ingestion. Liver function assessment is important, especially in
    children, if chronic excess copper ingestion is suspected. In these
    circumstances the serum copper concentration is likely to be
    increased. The role of chelating agents is discussed below.


    The priority following copper salt inhalation is removal from exposure
    and administration of oxygen by face-mask if there is respiratory
    distress. A chest X-ray should be performed if there are abnormal
    examination findings; metal fume fever may be accompanied by transient
    ill-defined opacities which typically resolve uneventfully. The
    possibility of a granulomatous pulmonary and possibly systemic
    reaction should be considered following chronic exposure.


    Animal studies

    The application of dimercaprol-containing ointments or the injection
    of aqueous dimercaprol into the eyes of animals with experimentally
    induced copper injury was of no benefit (Grant and Schuman, 1993).

    d-Penicillamine, triethylenetetramine dihydrochloride (trien) and DMPS
    each administered in a dose of 50 µmol/kg intraperitoneally daily for
    five days were the most effective chelating agents in increasing
    copper excretion in the urine (p<0.01) in copper-poisoned rats fed a
    high copper diet for 20 days prior to chelation (Planas-Bohne, 1979).
    Faecal copper excretion was unaffected. Other workers have
    demonstrated enhanced renal copper elimination following parenteral
    DMPS and DMSA (Maehashi et al, 1983).

    Rana and Kumar (1983) suggested oral sodium calciumedetate (1g/kg
    daily for ten days) could limit histopathological renal damage in rats
    fed oral copper sulphate 0.1 g/kg daily for 20 days prior to chelation
    therapy. Protection against copper-induced hepatic and renal lesions
    was observed also in mice administered intraperitoneal DMPS 132 mg/kg
    20 minutes after intraperitoneal copper sulphate 10 mg/kg
    (approximately the LD50) (Mitchell et al, 1982).

    DMPS was the most effective antidote in protecting against
    copper-induced mortality in copper sulphate-intoxicated mice (10 mg/kg
    intraperitoneally, LD50 8.7 mg/kg) administered intraperitoneal
    antidotes 20 minutes post dosing at a 10:1 molar ratio antidote:
    copper sulphate. Mice were observed for two weeks or until death. The
    survival ratio following DMPS was 25/30, compared to 7/30, 5/15, 4/15,
    3/15, 3/15 for d-penicillamine, triethylene- tetramine, sodium
    calciumedetate, DMSA and dimercaprol respectively (p <0.0001 for DMPS
    compared to all chelating agents except triethylenetetramine,
    p<0.0005) (Jones et al, 1980).

    Henderson et al (1985) investigated the effect of single and repeated
    doses of chelating agents on copper toxicity. Copper intoxicated mice
    (10-130 mg/kg subcutaneously) were given single doses of dimercaprol
    10 mg/kg or N-acetylcysteine 200 mg/kg, 30 minutes post dosing. With a
    single dose of chelating agent, the calculated LD50 (± SE) was
    significantly (p<0.05) increased from 54.7 ± 10 mg/kg in control mice
    to 95.2 ± 22 mg/kg and 87 ± 14 mg/kg in mice treated with dimercaprol

    or NAC respectively. The chelating agents were even more effective
    (p<0.05) in copper-poisoned mice (40-170 mg/kg subcutaneously)
    treated with repeated doses of chelating agent: dimercaprol 10 mg/kg,
    N-acetylcysteine 200 mg/kg or d-penicillamine 50 mg/kg every hour for
    five hours, with calculated LD50 values of 60.5 ± 12 mg/kg, 150.3 ±
    35 mg/kg, 139.4 ± 8 mg/kg and 91.4 ± 16 mg/kg for controls,
    dimercaprol, NAC and d-penicillamine treated mice respectively.

    d-Penicillamine, 52 mg/kg daily for six days, significantly (p<0.05)
    enhanced urinary copper excretion in four copper-poisoned sheep (given
    20 mg/kg copper sulphate intraruminally daily for 35 days) (Botha et
    al, 1993). Under the same conditions triethylenetetramine failed to
    increase urinary copper excretion although the authors suggested this
    might have been related to specific features of ruminant metabolism.
    There is some evidence that polyamines structurally related to
    triethylenetetramine (e.g. 2,3,2-tetramine) have a more potent
    cupruretic action (Borthwick et al, 1980) but experience with these
    agents is limited (Twedt et al, 1988).

    Diethyldithiocarbamate (DDC) chelates copper but the lipophilic
    chelate accumulates in tissues, especially the brain (Iwata et al,
    1970; Jasim et al, 1985), suggesting it may be an unsuitable antidote
    in copper poisoning. It has been suggested that DDC modifies the
    permeability of cell membranes and the blood brain barrier to copper
    (Allain and Krari, 1993).

    Clinical studies

    Wilson's disease

    Wilson's disease, characterized by decreased biliary copper excretion
    traditionally has been treated with d-penicillamine which serves to
    increase urinary copper elimination (Scheinberg et al, 1987). Adverse
    reactions to d-penicillamine are not uncommon and frequently are
    immunologically rather than toxicologically-induced including
    nephrotic syndrome, systemic lupus erythematosus (Walshe, 1982), white
    cell dyscrasias, thrombocytopenia, haemolytic anaemia (Walshe, 1982)
    and urticaria (Walshe, 1968). Anorexia, nausea and vomiting are
    described (Walshe, 1968). In animal studies penicillamine induces
    hepatic metallothionein (Heilmaier et al, 1986) which may disrupt the
    body distribution of other trace elements. Adverse effects occur in up
    to 10 per cent of patients receiving penicillamine and may necessitate
    treatment withdrawal (Walshe, 1982). Thus, in recent years,
    alternative agents have been investigated.

    Sunderman et al (1963) advocated parenteral and/or oral DDC in the
    management of Wilson's disease but evidence that this antidote
    enhances cerebral copper uptake limits its usefulness (see above).

    Walshe (1982) demonstrated increased urine copper elimination,
    symptomatic improvement and resolution of basal-ganglia abnormalities
    on CT brain scan among 20 patients with Wilson's disease treated with
    triethylenetetramine. These authors suggested triethylenetetramine as

    an effective drug for the treatment and maintenance of patients with
    Wilson's disease at all stages of the illness. Others concur with this
    view (Dubois et al, 1990; Morita et al, 1992) although there are
    potential hazards of triethylenetetramine therapy, notably
    sideroblastic anaemia (Perry et al, 1996).

    Although zinc sulphate has been utilized as alternative therapy to
    penicillamine in patients with Wilson's disease (Hoogenraad and Van
    den Hamer, 1983; Van Caillie-Bertrand et al, 1985; Veen et al, 1991),
    this treatment is unsuitable for acute copper poisoning as the
    mechanism of benefit is reduced gastrointestinal copper absorption.

    DMPS 200 mg bd increased urine copper elimination in a patient with
    Wilson's disease (Walshe, 1985).

    Acute poisoning

    There are no clinical data regarding the use of any chelating agent in
    copper carbonate poisoning.

    d-Penicillamine, the standard therapy for Wilson's disease, has been
    utilized in copper poisoning (Holtzman et al, 1966; Jantsch et al,
    1984/85; Hantson et al, 1996) but without confirmed evidence of
    enhanced urinary copper excretion. Intramuscular dimercaprol
    (Fairbanks, 1967; Jantsch et al, 1984/85; Schwartz and Schmidt, 1986;
    Hantson et al, 1996) and intravenous sodium calciumedetate (Holleran,
    1981; Agarwal et al, 1975) have also been employed but again without
    confirmed benefit.

    A five year-old child with copper intoxication following repeated
    application of copper sulphate crystals to skin burns received a 12
    day course of d-penicillamine 250 mg qds (Holtzman et al, 1966). Six
    hour urine copper excretion on the first day of chelation was 1000 µg,
    with a maximum value of 2000 µg/6h some 24 hours later. No pre- or
    post-chelation copper excretion data were given.

    Jantsch et al (1984/85) advocated the use of chelation therapy with
    dimercaprol and d-penicillamine following their experience with a
    patient who survived the alleged ingestion of 250 g copper sulphate. A
    single intramuscular dimercaprol dose 4 mg/kg was administered within
    the first ten hours (time not specified) followed by oral
    d-penicillamine 250 mg qds for at least seven days. The only 24 hour
    urine copper excretion measured "after initiation of chelation
    therapy" was 8160 µg (time not specified) with no pre- or
    post-chelation data presented. This case was unusual in that despite
    massive copper sulphate ingestion the patient developed no features of
    severe gastrointestinal irritation (save initial vomiting), no
    haemolysis or oliguria.

    Walsh et al (1977) administered intramuscular dimercaprol 2.5 g/kg
    (?2.5 mg/kg) plus 12.5 g/kg (?12.5 mg/kg) "edetic acid" four hourly to
    an 18 month-old child, commencing five hours after ingestion of 3 g
    copper sulphate. The urine copper concentration from a two hour
    collection was 500 µg/L on the second day, increasing to 3000 µg/L on
    day 12. The chelating agent was then switched to d-penicillamine 250
    mg daily for one month with a gradual fall in urine copper excretion.
    Unfortunately urine volumes were not stated and no pre-chelation
    measurements were possible.

    Hantson et al (1996) recently treated an 86 year-old woman with acute
    copper sulphate poisoning with intramuscular dimercaprol 4 mg/kg qds
    and oral d-penicillamine 250 mg qds, both commenced within four hours
    of poisoning. Urine copper elimination was not enhanced and chelation
    was discontinued after 48 hours following onset of renal failure.
    These authors concluded that "available clinical and toxicokinetic
    data do not support the benefits of chelation in addition to
    supportive therapy" in acute copper (and zinc) sulphate poisoning.

    Alkaline diuresis

    Muthusethupathi et al (1988) advocated forced alkaline diuresis in
    copper sulphate poisoning. In 103 copper sulphate-poisoned patients in
    whom gastric lavage followed by forced alkaline diuresis were
    instituted immediately, the incidence of renal failure was claimed to
    be substantially lower (14.6 per cent) than in other similar series.
    However, no copper excretion data were reported, and it is possible
    that prompt fluid resuscitation with correction of hypovolaemia played
    an important role in patient recovery (Muthusethupathi et al, 1988).


    Haemodialysis for five hours in a 41 year-old female failed to remove
    copper when instituted 12 hours after the ingestion of 280 mL
    dissolved copper sulphate (Agarwal et al, 1975). The patient had
    already undergone gastric lavage, had received intravenous sodium
    calciumedetate (1g) and a blood transfusion but died on the sixth
    hospital day after developing septicaemia, hepatic and renal failure.

    Peritoneal dialysis

    Cole and Lirenman (1978) reported a two year old child who had
    ingested some 30 mL super-saturated copper sulphate solution and
    underwent peritoneal dialysis for the management of renal failure.
    Copper extraction into the dialysate was enhanced markedly by the
    addition of salt-poor albumin 25 g/L. Over a 40 hour dialysis period
    (between 17 and 57 hours post ingestion) 0.7 mg copper was removed in
    17 litres dialysate compared to 9.1 mg copper removed in 24 litres
    during dialysis with added albumin between 57 and 117 hours. The
    authors advocated albumin-enriched peritoneal dialysis in the
    management of copper poisoning complicated by acute renal failure. It
    should be noted, however, that the child consumed at least 2.7 g
    copper so that the amount removed by dialysis, even with albumin, was

    Enhancing elimination: Conclusions and recommendations

    1.   There are no controlled clinical data regarding the use of
         chelating agents in copper carbonate poisoning.

    2.   Animal data suggest DMPS may be the most effective antidote in
         copper poisoning, though DMPS was administered within 20 minutes
         of copper dosing in these studies. DMPS has a more favourable
         adverse effect profile than dimercaprol and d-penicillamine
         although these are alternatives if DMPS is not available. DMPS
         usually is given orally or parenterally in a dose of 30 mg/kg
         body weight per day. Side effects are infrequent but have
         included allergic skin reactions, nausea and vertigo (Aposhian,
         1983). Discussion of individual cases with an NPIS physician is

    3.   There is insufficient evidence to advocate alkaline diuresis in
         the management of acute copper poisoning.

    4.   The role of haemodialysis and peritoneal dialysis is limited to
         the management of renal failure.

    Measurement of copper and caeruloplasmin concentrations in
    biological fluids

    Although whole blood copper concentrations correlate well with the
    severity of copper poisoning following acute ingestion, they should
    always be interpreted in conjunction with the clinical features.
     Serum copper concentrations are less useful in acute intoxication
    (Chuttani et al, 1965). In 20 patients who ingested copper sulphate,
    mean (± SD) whole blood copper concentrations were lower (2.9 ± 1.3
    mg/L) in those with only gastrointestinal symptoms compared to those
    who developed jaundice, renal failure or shock (mean whole blood
    copper 8.0 ± 4.0 mg/L). The number of patients in each group was not

    Among 65 cases of acute copper sulphate poisoning, Wahal et al (1976)
    observed that although patients who developed complications had higher
    whole blood, red cell and plasma copper concentrations than
    uncomplicated cases, the difference was not statistically significant
    (p>0.05). No correlation was found betwen plasma copper
    concentrations and prognosis. However, whole blood copper
    concentrations greater than 1.2 mg/L were associated generally with
    the development of complications. The four fatalities reported, who
    were admitted within 6-8 hours of ingestion, had whole blood
    concentrations of at least 2.1 mg/L.

    Serum caeruloplasmin concentration estimation has been suggested as a
    useful prognostic indicator in cases of acute copper sulphate
    poisoning. There are no data for copper carbonate. Wahal et al (1978)
    observed significantly higher (p<0.001) serum caeruloplasmin
    concentrations in uncomplicated cases of copper sulphate poisoning
    than in those with complications (gastrointestinal haemorrhage,

    jaundice, renal impairment, delirium or coma). Values less than 35
    mg/dL within 24 hours of poisoning or less than 44 mg/dL beyond 72
    hours post ingestion were associated with the development of

    Increased urine copper excretion (preferably as a 24 hour collection)
    will be present in any moderate or severe case of copper poisoning.
    The main value of this measurement is to monitor the effect of
    chelation therapy.


    Infants are at increased risk of excess copper accumulation during the
    first three months of life since their hepatic copper stores are
    significantly higher than in adults. This is due to the presence of
    fetal copper-binding protein which enables the fetal liver to
    accumulate sufficient copper to maintain body stores despite the
    relatively lower copper content of breast milk (Walker-Smith and
    Blomfield, 1973).


    Close attention to personal hygiene and the use of appropriate
    protective equipment are of primary importance among those
    occupationally exposed to copper.

    Twenty-four hour urine copper excretion is a useful screening
    procedure if copper intoxication is suspected but the source of
    exposure is unclear. However, when collected in an occupational
    setting great care must be taken to avoid sample contamination. Serum
    or whole blood copper concentrations may be useful if exogenous copper
    contamination of urine samples is suspected (Cohen, 1979). It should
    be remembered that impaired biliary copper excretion from any cause
    will lead to increased renal copper elimination.

    Pre-employment screening for Wilson's disease may be indicated in
    those occupationally exposed to copper.

    Normal copper concentrations in biological fluids

    Plasma/serum: 0.7-1.3 mg/L (Weatherall et al, 1996).
    Whole blood: 1.6-2.7 mg/L (Chuttani et al, 1965).
    Urine: Less than 60 µg/24h (Weatherall et al, 1996).


    Occupational exposure standard

    Copper: Long-term exposure limit (8 hour TWA reference period) fume
    0.2 mg/m3; dusts and mists 1 mg/m3 (Health and Safety Executive,



    There are no human carcinogenicity data for copper carbonate.

    There is no conclusive evidence that copper is carcinogenic in humans
    (Aaseth and Norseth, 1986). However, it is proposed that patients with
    "Vineyard sprayer's lung" are at a greater risk than the general
    population of developing bronchial carcinoma (Villar, 1974; Stark,
    1981). When originally reported in Europe, lung cancers in vineyard
    workers were attributed to the arsenic content of some fungicides, but
    in Portugal arsenic fungicides have never been used in the vineyards
    (Villar, 1974).

    Among 14 smoking vineyard workers Plamenac et al (1985) noted atypical
    squamous metaplasia in four cases and suggested copper as an
    aetiologic agent.

    In a review of liver disease among 30 vineyard sprayers who had used
    Bordeaux mixture for three to 45 years (mean 18 years), Pimentel and
    Menezes (1977) observed one case of hepatic angiosarcoma. The authors
    suggested copper-induced sinusoidal cell proliferation as a possible
    trigger of tumour development.

    Musicco et al (1988) reported a significant (p=0.006) increase in the
    incidence of brain gliomas among farmers occupationally exposed to
    insecticides or fungicides (often commercial copper sulphate
    preparations), but concluded these were associated probably with
    exposure to alkyl urea (known neurogenic carcinogens) in the


    There are no reprotoxicity data for copper carbonate.

    In a controlled study Barash et al (1990) investigated the teratogenic
    potential of copper releasing intrauterine devices (IUD) on the
    developing human embryo. No malformations or copper deposits were
    observed in the organs/placentae of copper IUD-exposed embryos (n=11)
    examined between seven and 12 weeks gestation. The results from the
    small study suggest that copper releasing IUDs have no observed
    negative effects on the developing embryo.

    Copper sulphate is teratogenic in several animal species (Bologa et
    al, 1992).

    Genotoxicity (for copper)

    Copper induced sister chromatid exchanges in human peripheral
    lymphocytes (DOSE, 1993).

    Fish toxicity (for copper)

    Chronic, partial chronic and early life stage toxicity tests were
    carried out on bluegill sunfish, bluntnose minnow, king salmon,
    fathead minnow and brook trout. The study duration was 30-60 days
    post-hatch. Under hard water conditions for fat head minnow the lowest
    observed effect concentration (LOEC) - no observed effect
    concentration (NOEC) was 33-15 µg/L and for the bluntnose minnow 18-4
    µg/L. The reproduction part of the life cycle gave the most sensitive

    In a chronic study (30-60 days post-hatch) with fathead minnow and
    bluegill sunfish, in soft water conditions LOEC-NOEC range was 40-11
    µg/L, fry survival was the most sensitive response. A partial chronic
    study (30-60 days post-hatch) the LOEC-NOEC for brook trout was 17-9
    µg/L, fry growth and survival were the most sensitive responses.
    LC50 (96 hr)  Oreochromis niloticus 1.06 mg/L.

    LC50 (96 hr) rainbow trout 0.253 mg/L.

    LC50 (48 hr) larvae of flat fish  Paralichthys olivaceus 0.36 mg/L

    The fertilized eggs of  Cyprinus carpio (108 hr) were exposed to 10,
    50, 70 and 100 ppb copper. Survival of developing eggs, hatchlings,
    hatching and hatchability percentage decreased with increasing
    concentration. Deformities observed were formation of blisters, curved
    tail, stunted growth, circulatory failure, enlargement of the
    pericardial sac, deformed head region, underdeveloped fins and
    deformed vertebral column.

    Rainbow trout exposed to a number of combinations of copper, water
    hardness and pH showed reduced growth rate during the first 10 days,
    followed by partial or complete recovery. The lethal concentration of
    copper to rainbow trout was not affected by alkalinity at 10-50 ppm in
    soft water, however, the toxicity doubled by the same alkalinity
    change in hard water. Synergism between pH value and copper toxicity
    was observed (DOSE, 1993).

    EC Directive on Drinking Water Quality 80/778/EEC

    Copper: EC advisory level for drinking water, 100 µg/L at source of
    supply; 3000 µg/L after standing in piping for 12 hours (DOSE, 1993).

    WHO Guidelines for Drinking Water Quality

    Copper: Provisional guideline value 2 mg/L (WHO, 1993).


    ST Beer BSc
    SM Bradberry BSc MB MRCP
    WN Harrison PhD CChem MRSC

    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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    See Also:
       Toxicological Abbreviations