SM Bradberry BSc MB MRCP

    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 pigments, wood preservatives, catalysts, fertilizers,
    corrosion inhibitors and deodorants.


    Zinc sulphate is a gastrointestinal irritant. An early report
    (Brennan, 1855) described recovery after ingesting 112 g although
    fatalities secondary to gastrointestinal haemorrhage could follow
    significantly smaller ingestions.

    A 72 year-old female died after the inadvertent intravenous
    administration of 7.4 g zinc sulphate (Brocks et al, 1977).



         -    Zinc sulphate is a skin and eye irritant.
         -    Zinc contact sensitivity has been described.


         -    There are no reports of zinc sulphate inhalation although
              the salt would irritate the respiratory tract.


         -    Zinc sulphate ingestion causes gastrointestinal irritation.
              Headache and dizziness are also described. Features are
              generally less severe than following zinc chloride ingestion
              although fatalities have occurred (Mackintosh, 1900).
         -    Chronic excess zinc sulphate ingestion may induce reversible
              anaemia and leucopenia, transient irritability, tremor and
              seizures. These neurological features occurred in a
              premature infant inadvertently given excess zinc sulphate
              supplements (Tasic et al, 1982).


         -    Inadvertent excess zinc sulphate in a parenteral nutrition
              solution has been associated with nausea, vomiting, anaemia,
              thrombocytopenia and elevated amylase activity.



    1.   Decontaminate with soap and water.
    2.   Symptomatic and supportive measures should be dictated by the
         patient's condition.


    1.   Irrigate with copious lukewarm water or 0.9 per cent saline for
         at least ten minutes.
    2.   A topical anaesthetic may be required for pain relief and to
         overcome blepharospasm.
    3.   Ensure removal of particles lodged in the conjunctival recesses.
    4.   The instillation of fluorescein allows detection of corneal
    5.   Seek ophthalmological advice if any significant abnormality is
         detected on examination and in those whose symptoms do not
         resolve rapidly.


    1.   Remove from exposure.
    2.   Institute symptomatic and supportive measures as dictated by the
         patient's condition.
    3.   See zinc oxide monograph for management of "metal fume fever".


    Minor ingestions:

    1.   Patients with features of mild gastrointestinal upset require
         only supportive care.
    2.   Gastric lavage or other gut decontamination procedures are

    Substantial ingestions:

    1.   Most patients will vomit spontaneously. Gastric lavage or other
         gut decontamination procedures are not likely to improve outcome.
    2.   Symptomatic and supportive measures with adequate fluid
         resuscitation are paramount.
    3.   Endoscopic examination may be required.
    4.   Save blood and urine for zinc concentration estimations.
    5.   Monitor the blood count and biochemical profile including serum
         amylase activity.
    6.   The value of chelation therapy following zinc ingestion has not
         been confirmed. Discuss with NPIS if patient is symptomatic.


    Brennan P.
    Poisoning by sulphate of zinc.
    Lancet 1855; 2: 52-3.

    Brocks A, Reid H, Glazer G.
    Acute intravenous zinc poisoning.
    Br Med J 1977; 212: 1390-1.

    Burkhart KK, Kulig KW, Rumack B.
    Whole-bowel irrigation as treatment for zinc sulfate overdose.
    Ann Emerg Med 1990; 19: 1167-70.

    Mackintosh GD.
    A fatal case of poisoning with zinc sulphate: necropsy.
    Br Med J 1900; 2: 1706-7.

    Tasic V, Gordova A, Delidzhakova M, Kozhinkova N.
    Zinc toxicity.
    Pediatrics 1982; 70: 661.

    Substance name

         Zinc sulphate

    Origin of substance

         Treatment of roasted ore concentrates, scrap, leach from flue
         dust, or zinc chemical sludges with sulphuric acid to produce
         zinc sulphate monohydrate.              (HSDB, 1996)


         Bufopto zinc sulphate
         Op-thal - zin
         Sulphuric acid, zinc salt (I:I)
         Verazinc white copperas
         White vitriol
         Zinc vitriol                            (DOSE, 1994)

    Chemical group

         A compound of zinc, a group II B (d block) transition element.

    Reference numbers

         CAS            7733-02-0                (DOSE, 1994)
         RTECS          ZH5260000                (RTECS, 1996)
         UN             NIF

    Physicochemical properties

    Chemical structure
         ZnSO4                                   (DOSE, 1994)

    Molecular weight
         161.43                                  (DOSE, 1994)

    Physical state at room temperature
         Solid                                   (MERCK, 1996)

         Colourless                              (SAX'S, 1996)

         Odourless                               (MERCK, 1996)


         Aqueous solution is acid to litmus; pH about 4.5
                                                 (MERCK, 1996)

         Water: 965 g/L at 20°C (heptahydrate).
         Soluble in ethanol, methanol and glycerol.
                                                 (DOSE, 1994; HSDB, 1996)

    Autoignition temperature

    Chemical interactions
         Insoluble sulphates are formed with strontium, calcium, lead and
         barium salts. Mercury and silver form slightly soluble salts.
         Zinc sulphate has dehydrating action on methylcellulose
         suspensions which leads to precipitation of methylcellulose,
         tannins, acacia and proteins.           (HSDB, 1996)

    Major products of combustion
         Toxic fumes of zinc oxide and sulphur oxides.
                                                 (SAX'S, 1996)

    Explosive limits

         Non combustible.                        (HSDB, 1996)

    Boiling point
         The hydrate loses water above 280°C. Decomposes above 500°C.
                                                 (MERCK, 1996)

         3.74 at 15°C                            (SAX'S, 1996)

    Vapour pressure
         7999.32 Pa at 700°C                     (OHM/TADS, 1997)

    Relative vapour density

    Flash point

         When heated to decomposition it emits toxic fumes of sulphur
         oxides and zinc oxide.                  (HSDB, 1996)


         Pigments in paints.
         In wood preservatives.
         In fertilizers and animal feeds.
         Corrosion inhibitor.
         Deodorant.                              (DOSE, 1994)

    Hazard/risk classification

    Index no.  030-006-00-9
    Risk phrases
         Xi; R36/38. Irritating to eyes and skin.
    Safety phrases
         S(2-) S22-25. Keep out of reach of children. Do not breathe dust.
         Avoid contact with eyes
    EEC No: 231-793-3                            (CHIP2, 1994)


    Zinc is an essential trace element required for the function of over
    200 metallo-enzymes, including alkaline phosphatase and carbonic
    anhydrase. Zinc also plays a critical role in the regulation of DNA
    and RNA synthesis (via interaction with DNA binding proteins), in
    hormone-receptor interactions and in the 'second-messenger' system of
    cellular signal transduction (Walsh et al, 1994).

    Dietary zinc supplements usually are prescribed as zinc sulphate. In
    addition zinc sulphate has been advocated in the treatment of acne
    vulgaris (Michaėlsson et al, 1977), venous leg ulcers (Hallböök and
    Lanner, 1972), Wilson's disease (Gill et al, 1994; Hoogenraad, 1995)
    and leprosy (Mahajan et al, 1994). Eye drops containing zinc sulphate
    (0.25 per cent) are used in the treatment of excessive lacrimation
    (Joint Formulary Committee, 1997).


    Acute zinc sulphate intoxication has occurred in several reports of
    deliberate ingestion (Burkhart et al, 1990; Hantson et al, 1996) and
    chronic poisoning has resulted from excess oral zinc supplementation
    (Hoffman et al, 1988; Ramadurai et al, 1993). Zinc toxicity is also an
    occasional complication of parenteral nutrition (Brocks et al, 1977;
    Faintuch et al, 1978).


    Excess body zinc interacts with free thiol groups on macromolecules,
    so blocking the active sites of enzymes, co-enzymes and membrane
    receptors. Zinc contributes to normal immunological function and
    excess zinc (300 mg daily for six weeks to 11 volunteers) has been
    associated with impaired immune and inflammatory responses (Chandra,



    Zinc sulphate exposure occurs primarily via ingestion.
    Gastrointestinal zinc absorption is a function of a cysteine-rich
    intestinal protein (CRIP) which sequesters zinc within enterocytes
    prior to active transport into plasma (Hempe and Cousins, 1992; Walsh
    et al, 1994). Metallothionein contributes to zinc homeostasis at
    higher exposures, primarily via retaining excess zinc within mucosal
    cells which are subsequently shed into the intestinal lumen (Hempe and
    Cousins, 1992). Zinc absorption is affected by diet; it is inhibited
    by calcium, phosphorus and phytates and facilitated by dietary protein
    (Hunt et al, 1991). In one study less than 15 per cent of dietary zinc
    was absorbed from a high phytate diet compared to 40 per cent from a
    diet with a high animal protein content (Sandstrom, 1995).

    In ten healthy volunteers Nčve et al (1991) observed a peak serum zinc
    concentration some 2-3 hours after ingestion of 45 mg zinc sulphate.

    Zinc salts may be absorbed through the skin, typically as zinc oxide
    in medicated dressings (Hallmans, 1977; Agren, 1990).


    Most intravascular zinc is contained within erythrocytes. Plasma zinc
    is bound predominantly to albumin (approximately 80 per cent) and
    other proteins (such as alpha2-macroglobulin) for distribution to
    tissues. Excess zinc is stored as a metallothionein complex, mainly in
    the liver (Abdel-Mageed and Oehme, 1990; IPCS, 1996).

    Some 90 per cent of total body zinc is in muscle and bone (Wastney et
    al, 1986).

    Appreciable amounts of zinc are found also in the kidney, lung, spleen
    and brain (IPCS, 1996).

    Zinc crosses the placenta slowly and is found in breast milk (Agency
    for Toxic Substances and Disease Registry, 1997).


    Most ingested zinc is eliminated in faeces via bile, pancreatic fluid
    and intestinal mucosal cells, with up to ten per cent appearing in
    urine (Abdel-Mageed and Oehme, 1990). Zinc is also eliminated in
    sweat. The kidneys do not play an important role in regulating total
    body zinc (IPCS, 1996).

    The whole-body zinc half-life is some 5-16 months (IPCS, 1996).


    Dermal exposure

    Zinc sulphate is a skin irritant (Lansdown, 1991) but there are no
    human case reports of significant toxicity.

    Ocular exposure

    Zinc sulphate (0.25 per cent solution) is used as an astringent in eye
    drops for the treatment of excessive lacrimation. Adverse effects via
    this application are not reported although historically the use of 20
    per cent zinc sulphate solutions in the treatment of dendritic
    keratitis led to the formation of white flecks on the lens
    ("glaukomflecken") (Grant and Schuman, 1993).


    Gastrointestinal toxicity

    Zinc sulphate is a gastrointestinal irritant. Brennan (1855) reported
    a young man who developed severe diarrhoea, vomiting and abdominal
    pain but fully recovered after ingesting 112 g zinc sulphate.

    Mackintosh (1900) reported a fatal (not quantified) zinc sulphate
    ingestion. Necropsy showed intense haemorrhagic gastrointestinal
    inflammation. Another patient suffered acute gastrointestinal
    haemorrhage requiring an eight unit blood transfusion after taking 440
    mg zinc sulphate daily for one week (Moore, 1978).

    A 16 year-old boy vomited several times but developed no other signs
    after ingesting 2.5 g (Burkhart et al, 1990).

    An 86 year-old woman began coughing and vomiting blue/green liquid
    some 15 minutes after ingesting 3g each of zinc sulphate and copper
    sulphate (Hantson et al, 1996). An endoscopy less than four hours post
    ingestion revealed diffuse gastric inflammation . The initial plasma

    zinc concentration was 19.8 mg/L (normal 0.9 - 1.2 mg/L). The
    patient's clinical course was complicated by acute renal failure,
    cardiac failure and a chemical pneumonitis requiring inotropic support
    and mechanical ventilation but she fully recovered over 20 days with
    no sequelae. Chelation therapy (intramuscular dimercaprol and oral
    d-penicillamine) was given during the first two days although this was
    not associated with significantly increased urine zinc elimination
    (see Antidotes).

    Brown et al (1964) described nausea, vomiting, abdominal pain and
    bloody diarrhoea some 20 minutes to ten hours after eating and
    drinking foods stored in galvanized containers. Similar symptoms plus
    a metallic taste were reported by students who consumed a punch stored
    overnight in partially corroded galvanized vessels (Lapham et al,
    1983). In these cases elemental zinc and zinc oxide were the original
    zinc sources although consumed as soluble zinc salts.


    A premature infant with zinc deficiency was inadvertently given excess
    zinc sulphate supplements (the route of administration, dose and
    duration of therapy were not stated). Irritability, tremor and
    seizures accompanied an increased serum zinc concentration to 2.2 mg/L
    (normal range 0.8 - 1.3 mg/L) (Tasic et al, 1982).

    Headache and dizziness accompanied the gastrointestinal effects caused
    by the ingestion of zinc-contaminated punch (Lapham et al, 1983).


    The elderly woman described above (Hantson et al, 1996) who ingested a
    mixture of the sulphates of copper and zinc developed a transiently
    prolonged prothrombin time (23 seconds) with no associated increase in
    hepatic transaminase activities. She fully recovered over 20 days.


    Anaemia secondary to gastrointestinal haemorrhage may complicate
    significant zinc sulphate ingestion (Moore, 1978).

    Endocrine toxicity

    Brandao-Neto et al (1990) suggested that zinc may have an inhibitory
    effect on the synthesis and secretion of cortisol but this is

    Pulmonary toxicity

    An 86 year-old woman developed a chemical pneumonitis due to partial
    aspiration of an ingested mixture of zinc and copper sulphate (3g of
    each) (Hantson et al, 1996) (see above). She fully recovered over 20


    Gastrointestinal toxicity

    Acute-on-chronic zinc intoxication occurred in seven patients
    receiving total parenteral nutrition solutions which accidentally
    contained zinc sulphate 100 mg/L (Faintuch et al, 1978). Six patients
    developed increased amylase activities (peak activities 557-1850 Klein
    units; normal range 130-310) (Faintuch et al, 1978).

    Another patient who received excess zinc sulphate (7.4 g) in error
    over 60 hours as part of a parenteral nutrition regime (Brocks et al,
    1977) developed diarrhoea, vomiting and increased amylase activity
    with evidence of cardiovascular, hepatic and renal toxicity (see
    below) and died on the 47th day with bronchopneumonia. The peak serum
    zinc concentration was 41.8 mg/L.


    Following intravenous administration of 7.4 g zinc sulphate, a 72
    year-old woman developed anaemia and thrombocytopenia (Brocks et al,
    1977). The cause of these features was not completely clear; no bone
    marrow or gastrointestinal autopsy findings were included in the


    Cholestatic jaundice was observed in the patient who was inadvertently
    administered 7.4 g zinc sulphate intravenously (Brocks et al, 1977).


    A 72 year-old woman developed oliguria immediately following the
    inadvertent administration of 7.4 g zinc sulphate via parenteral
    nutrition. She remained oliguric despite therapy with frusemide and
    intravenous fluids; haemodialysis was instituted when the blood urea
    concentration was 61 mmol/L. Acute tubular necrosis was present at
    autopsy (Brocks et al, 1977).

    Cardiovascular toxicity

    Hypotension, pulmonary oedema and cardiac arrhythmias (not specified)
    were reported in a 72 year-old woman following intravenous
    administration of 7.4 g zinc sulphate over 60 hours (Brocks et al,
    1977). She also developed multi-organ failure and sepsis and died on
    the 47th day.


    Dermal exposure

    Skin sensitization to zinc sulphate has been reported (BIBRA Working
    Group, 1989) but no original case data were identified in the English



    Chronic excess zinc sulphate ingestion may induce reversible anaemia
    and leukopenia secondary to a relative copper deficiency (Prasad et
    al, 1978; Patterson et al, 1985; Simon et al, 1988). The mechanism is
    probably zinc-induced intestinal metallothionein synthesis with
    increased metallothionein-copper binding and reduced copper
    bioavailability via sequestration in the intestinal mucosa.

    Ramadurai et al (1993) reported a 36 year-old lady who presented with
    sideroblastic anaemia and neutropenia having taken 600 mg zinc
    sulphate daily for three years as a health food supplement. On
    admission the serum zinc concentration was 2.2 mg/L (normal range
    0.6-1.3 mg/L) but this and the haematological abnormalities returned
    to normal within four months of zinc supplement withdrawal.

    Similar clinical pictures were observed in two patients prescribed 660
    mg zinc sulphate daily in the treatment of intractable coeliac disease
    (Porter et al, 1977) and apthous ulcers (Hoffman et al, 1988).

    Metabolic effects

    Chronic excess zinc supplementation has been associated with adverse
    effects on the lipid profile (Hooper et al, 1980). This may be a
    further effect of deranged copper metabolism (Fosmire, 1990).

    In a review of the effects of zinc supplements on serum lipid
    concentrations the Agency for Toxic Substances and Disease Registry
    (1997) reported mixed results with limited and inconsistent evidence
    of zinc-associated reduced serum HDL cholesterol concentrations and/or
    raised serum LDL cholesterol in those taking 1.5-4.3 mg zinc/kg body
    weight daily for five to 12 weeks.


    Dermal exposure

    Decontamination with soap and water is likely to be all that is
    required. Chronic skin contact should be avoided.

    Ocular exposure

    Irrigate with copious amounts of lukewarm water for at least ten
    minutes. A topical anaesthetic may be required 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. Specialist ophthalmological advice should
    be sought if any significant abnormality is detected on examination
    and in those whose symptoms do not resolve rapidly.


    Symptomatic and supportive measures are the priority. Symptomatic
    patients and those with abnormal respiratory signs should have a chest
    X-ray, receive supplemental oxygen and bronchodilators if necessary
    and be observed until symptoms resolve.


    Zinc sulphate is a fairly potent emetic and spontaneous vomiting is
    likely to occur following significant ingestion. Gastric lavage has no
    role. Supportive measures are the mainstay of management. It is
    reasonable, though of unproven benefit, to attempt dilution by the
    oral administration of milk or water. Burkhart et al (1990) advocated
    whole-bowel irrigation as an effective gut decontamination method
    following zinc sulphate ingestion but there are no controlled data to
    support this view. Patients in whom significant gastrointestinal
    corrosive damage is suspected should be considered for early upper
    gastrointestinal endoscopy and managed as for other acid ingestions
    (see, for example, zinc chloride monograph).


    Animal studies

    Domingo et al (1988) investigated the antidotal potential of DTPA
    (trisodium calcium diethylene triamine-pentaacetate), CDTA
    (cyclohexane diamine tetraacetate), d-penicillamine, sodium
    calciumedetate, DMSA (dimercapto-succinic acid) and the sodium salt of
    DMPS (dimercaptopropanesulphonate) on reducing mortality in rodents
    poisoned with intraperitoneal zinc acetate 66-330 mg/kg. This dose
    range was selected to span the previously calculated intraperitoneal
    LD50 (108 mg/kg) and LD99 (216 mg/kg) for this zinc salt.

    Chelation therapy (or 0.9 per cent saline as control) was administered
    intraperitoneally to ten mice ten minutes after dosing with zinc.
    Antidote doses and outcome (measured as survival at 14 days) are
    summarized in Table 1.

    The very high antidote doses employed in this study necessitate
    caution in interpreting the results with regard to potential clinical
    value. Nevertheless at a zinc acetate dose in excess of the LD99
    there was 100 per cent survival following treatment with DTPA,
    d-penicillamine and DMPS. DMSA was not an impressive antidote under
    these conditions.

    The same research group (Llobet et al, 1988) undertook a similar
    study. Intraperitoneal zinc acetate 0.49 mmol/kg (a dose approximately
    equivalent to its LD50) and 1.15 mmol/kg (approximately the LD99)
    was administered immediately before antidote administration to ten
    mice. Outcome was measured as survival ratio. Sodium calciumedetate
    (2152 mg/kg), DTPA (2262 mg/kg) and d-penicillamine (857 mg/kg),
    completely protected against mortality at the LD99 for zinc acetate.

    Under exactly the same conditions (each chelating agent at a dose of
    5.75 mmol/kg) the survival ratios for CDTA, DMPS and DMSA were 80, 50
    and 70 per cent respectively.

    Table 1. Survival (%) following parenteral chelation therapy in mice
    after a single zinc acetate injection (after Domingo et al, 1988)


    Chelating agent     Antidote dose     Zinc acetate dose
                           (mg/kg)             (mg/kg)
                                           66    153     241

    Control             -                  40     20       0
    Na2CaCDTA           1360              100     90      90
    Na2CaEDTA           1644              100     90      90
    Na2CaDTPA           1569              100    100     100
    d-Penicillamine      857              100    100     100
    DMSA                 619               80     30      10
    DMPS                 273              100    100     100

    Several antidotes have been investigated for their potential to
    enhance zinc elimination. Domingo et al (1988) measured 24 hour faecal
    and urinary zinc excretion in mice administered 88 mg/kg
    intraperitoneal zinc acetate followed ten minutes later by an
    intraperitoneal dose of chelating agent (or saline in the control
    group). The same chelating agents and doses were used as in Table 1,
    again with ten mice in each treatment group. In the control group
    urine zinc elimination was less than half faecal excretion. CDTA
    enhanced urine zinc excretion some six fold and DTPA, DMSA and DMPS
    each some four fold. d-Penicillamine enhanced 48 hour urine zinc
    elimination by some 80 per cent. Sodium calciumedetate did not enhance
    urine zinc excretion but was the only antidote to increase 24 hour
    faecal zinc elimination (by some 20 per cent).

    The effect of increasing the time delay between zinc dosing and DTPA
    or CDTA administration was investigated by Llobet et al (1989).
    Intraperitoneal zinc acetate 0.4 mmol/kg (LD50 0.49 mmol/kg) was
    followed 0-24 hours later by a single intraperitoneal dose of
    chelating agent to give a chelating agent: zinc acetate molar ratio of
    approximately 10:1.

    Urine and faecal zinc elimination were monitored for 48 hours with
    five mice in each treatment group. Urine and faecal zinc elimination
    were increased significantly (p < 0.05) by both chelating agents when
    administered up to two hours after poisoning but only DTPA
    significantly enhanced the 48 hour urine and faecal zinc excretion
    when the antidotes were given 12 hours after zinc dosing.

    When there was a 24 hour delay between zinc acetate injection and
    antidote administration, DTPA significantly (p < 0.05) enhanced urine
    but not faecal 48 hour zinc elimination (CDTA was not effective).

    In summary, animal studies suggest DTPA is the most effective zinc
    antidote as judged by improved survival (100 per cent following a zinc
    acetate dose in excess of the LD99) and increased zinc elimination.
    CDTA produced 90 per cent survival and increased urine zinc excretion
    some six fold. d-Penicillamine also gave excellent results in
    mortality studies, with 100 per cent survival following administration
    of zinc acetate at a dose exceeding the LD99. However,
    d-penicillamine did not enhance zinc elimination significantly. Sodium
    calciumedetate improved survival (90-100 per cent) and in one study
    (Domingo et al, 1988) was the only chelating agent to increase faecal
    zinc elimination. DMPS 273 mg/kg completely protected mice against the
    lethal effects of zinc acetate at a dose in excess of the LD99 and
    the same antidote dose enhanced urine zinc excretion some four fold
    following administration of 88 mg/kg zinc acetate. By contrast DMSA
    619 mg/kg resulted in only 10 per cent survival following 241 mg/kg
    zinc acetate.

    Clinical studies

    Although increased renal zinc excretion has been noted during
    chelation therapy instituted to enhance elimination of other toxic
    heavy metals, there is no convincing evidence of benefit in human zinc
    poisoning. In health, most zinc is eliminated via the gastrointestinal
    tract with only a small contribution made by renal excretion. No data
    have been found regarding the effect of chelation therapy on biliary
    zinc excretion in man.


    McKinney et al (1994) reported improved mental status in a patient
    with severe zinc chloride poisoning (by ingestion) following
    administration of intramuscular dimercaprol 12 mg/kg/day for 24 hours
    and intravenous sodium calciumedetate 1 g/m2 for five days. This
    treatment was instituted 74 hours post ingestion. Chelation therapy
    was not associated with increased urine zinc elimination.

    Intramuscular dimercaprol 4 mg/kg qds was instituted less than four
    hours after the ingestion of 3 g each of zinc sulphate and copper
    sulphate by an 86 year-old woman. This patient also received oral
    d-penicillamine (see below) but both antidotes were discontinued after
    48 hours due to deteriorating renal function. The patient made a full
    recovery over 20 days.

    A 16 year-old who ingested 12 g elemental zinc was treated some nine
    days later with intramuscular dimercaprol 2.3-9.2 mg/kg daily.
    Chelation was associated with clinical improvement and a reduction in
    the blood zinc concentration but urine zinc concentrations were not
    measured (Murphy, 1970).

    Sodium calciumedetate

    A 24 year-old man who developed erosive pharyngitis and oesophagitis,
    hyperamylasaemia, microscopic haematuria and a serum zinc
    concentration of 1.46 mg/L (normal range 0.5-0.9 mg/L) after ingesting
    liquid zinc chloride, made an uneventful recovery following supportive
    care and intravenous sodium calciumedetate 45 mg/kg in divided doses
    over 36 hours. No zinc excretion data were given (Chobanian, 1981).

    Potter (1981) utilized intravenous sodium calciumedetate 150 mg in the
    management of a 28 month-old child who had ingested a zinc chloride
    solution; no urine zinc excretion data were given.

    The patient reported by McKinney et al (1994) who was severely
    poisoned after ingesting one tablespoon of a zinc chloride-containing
    soldering flux was treated with intravenous sodium calciumedetate 1
    g/m2 for five days. The urine zinc excretion in the eight hours
    preceding chelation was 950 µg. Urine zinc excretion was not increased
    by sodium calciumedetate with only 1000 µg/24 h removed on the fourth
    day of treatment (no interim data were given).


    In response to a rising serum zinc concentration, a soldier who
    developed adult respiratory distress syndrome following two minutes
    inhalation of zinc chloride smoke was administered intravenous (140
    mg/kg/day for three days) and nebulized (100 mg qds for 13 days)
    N-acetylcysteine between days 19 and 32 in an attempt to enhance zinc
    elimination. The urine zinc excretion increased from some 125 µmol/24h
    on day 20 to 260 µmol/24h on day 22 (coinciding with intravenous
    N-acetylcysteine administration) then rose to nearly 300 µmol/day (the
    maximum observed zinc excretion) on day 24. Unfortunately no
    pre-chelation zinc excretion measurements were made. There was no
    clinical improvement with therapy and the patient died in respiratory
    and renal failure on day 32.


    An 86 year-old woman who developed chemical pneumonitis, gastritis,
    cardiac and renal failure following the ingestion (and partial
    aspiration) of 3 g each of zinc and copper sulphate, received 250 mg
    oral d-penicillamine qds (in addition to intramuscular dimercaprol 4
    mg/kg qds) commenced less than four hours after zinc ingestion
    (Hantson et al, 1996). Unfortunately there were no pre-chelation urine
    zinc excretion data and treatment was discontinued after 48 hours due
    to deteriorating renal function. The maximum 24 hour urine zinc
    excretion, achieved on the first day of chelation therapy was some
    6000 µg.

    Another patient with zinc chloride poisoning by inhalation survived
    following treatment with oral penicillamine 125 mg twice daily (Allen
    et al, 1992). No blood or urine zinc concentrations were measured.

    Antidotes: Conclusions and recommendations

    1.   There are no controlled clinical data of chelation therapy in
         zinc poisoning and animal studies must be interpreted with
         caution in view of the extremely high antidote doses employed.
         Nevertheless, animal studies suggest that of the antidotes
         readily available for clinical use, sodium calciumedetate is the
         preferred agent with d-penicillamine or DMPS potential
    2.   Although case reports claim clinical benefit following parenteral
         administration of dimercaprol, sodium calciumedetate and
         d-penicillamine, urine and/or faecal zinc excretion data to
         support these claims are lacking.
    3.   Chelation therapy cannot be advocated routinely in the management
         of zinc poisoning; symptomatic cases should be discussed with the


    Patients with haemochromatosis are at greater risk of zinc toxicity
    due to the iron-induced increased metallothionein concentrations since
    metallothionein concentrations since metallothionein was a greater
    affinity for zinc than iron.


    Serum zinc concentrations are increased in acute zinc poisoning. The
    24 hour urine zinc excretion is useful when monitoring chronic
    exposure although there is no well established relationship between
    the extent of exposure and urine zinc concentration. Hair zinc
    concentrations are not useful (Agency for Toxic Substances and Disease
    Registry, 1997).

    Normal zinc concentrations in biological fluids

    Plasma and serum: 1.1-1.3 mg/L (IPCS, 1996).
    Whole blood: 6.8-10.8 mg/L (IPCS, 1996).
    24 hour urine excretion: less than 500 µg (IPCS, 1996).


    Occupational exposure standard




    There is no conclusive evidence that zinc is a human carcinogen
    (Léonard and Gerber, 1989) and the Environmental Protection Agency has
    concluded zinc is not classifiable in this regard (Agency for Toxic
    Substances and Disease Registry, 1997).


    There is no conclusive evidence regarding the reprotoxicity of zinc in
    humans (Reprotext, 1996). There were no adverse effects following the
    administration of oral zinc sulphide (providing 20 mg elemental zinc
    daily) to 494 women during the last two trimesters of pregnancy
    (Mahomed et al, 1989).

    A relationship between high amniotic fluid or maternal serum zinc
    concentrations and foetal neural tube defects has been proposed, but
    evidence for this is inconsistent (Reprotext, 1996; Reprotox, 1996).
    There was no association between serum zinc concentrations and the
    incidence of neural tube defects in 82 affected pregnancies compared
    to 85 controls (Hambidge et al, 1993).

    Pre-eclampsia, abnormal deliveries, anencephaly, and an increased
    incidence of stillbirths have been associated with low maternal serum
    zinc concentrations. Zinc deficiency also has been associated with
    delayed sexual maturity.

    Low seminal fluid zinc concentrations have been implicated in male
    infertility but the use of zinc supplements to treat this condition
    remains controversial (Reprotext, 1996; Reprotox, 1996).


     In vitro human lymphocytes, unscheduled DNA synthesis positive
    (DOSE, 1994).

    Fish toxicity

    Lethal in fathead minnow at < 10 mg/L as zinc (exposure unspecified).

    LC50 (96 hr) cichlid 13 ppm (DOSE, 1994).

    EC Directive on Drinking Water Quality 80/778/EEC

    Zinc: Guide level 100 µg/L at supply works, 5000 µg/L after 12 hour
    contact with consumers pipework; Sulphates: Guideline level 25 mg/L
    (DOSE, 1994).

    WHO Guidelines for Drinking Water Quality



    SM Bradberry BSc MB MRCP

    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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