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    UKPID MONOGRAPH




    ANTIMONY POTASSIUM TARTRATE




    WN Harrison PhD CChem MRSC
    SM Bradberry BSc MB MRCP
    JA Vale MD FRCP FRCPE FRCPG FFOM

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


    ANTIMONY POTASSIUM TARTRATE

    Toxbase summary

    Type of product

    Industrial chemical and pesticide. Has been used as an anti-parasitic
    drug.

    Toxicity

    The most toxic trivalent antimony compound. A potent emetic. Ingestion
    of 0.2 g has been reported to be fatal (Miller, 1982) although a child
    has survived the ingestion of 2.3 g (Iffland and Bosche, 1987).

    Features

    Topical

         -    Irritant to the skin and eyes.
         -    "Antimony spots" (papules and pustules around sweat and
              sebaceous glands) may develop after repeated exposure,
              particularly in warm conditions.

    Inhalation

         -    Irritant to the respiratory tract and mucous membranes
              causing conjunctivitis, laryngitis, pharyngitis, tracheitis,
              rhinitis bronchitis and rarely non-cardiogenic pulmonary
              oedema.
         -    There may be radiological evidence of pneumonitis.
         -    Chronic occupational inhalation may cause pneumoconiosis
              with cough, wheeze and diffuse, punctate opacities in the
              middle and lower zones.

    Ingestion

    Moderate ingestions:
         -    Features usually start within 30 minutes to two hours with
              nausea, vomiting, abdominal pain and diarrhoea. A garlic
              odour on the breath has been described following ingestion
              of antimony salts.

    Substantial ingestions:
         -    Severe vomiting and diarrhoea (which may contain blood) and
              haemorrhagic gastritis may ensue. Myocardial depression,
              vasodilation and fluid loss may cause shock with
              hypotension, electrolyte disturbances and acute renal
              failure. Cerebral oedema, coma and convulsions are possible.
              Fatalities have occurred (Miller, 1982).

    Injection

         -    The treatment of leishmaniasis and schistosomiasis has been
              associated with anorexia, nausea, vomiting, abdominal pain,
              a metallic taste, diarrhoea, pancreatitis, reversible
              elevation of liver enzyme activities, myalgia, arthralgia,
              proteinuria, ECG changes (T wave inversion, Q-T interval
              prolongation, S-T segment abnormalities), phlebitis,
              uveitis, optic atrophy and rarely anaphylactic shock, acute
              renal failure, hepatic necrosis and bone marrow hypoplasia.


    Management

    Dermal

    1.   If possible the patient should remove soiled clothing and wash
         him/herself.
    2.   Wash contaminated hair and skin with soap and copious amounts of
         water.
    3.   Pay special attention to skin folds, fingernails and ears.
    4.   A physician may need to examine the area if irritation or pain
         persists after washing.
    5.   Steroids may be used to treat areas of contact dermatitis.

    Ocular

    1.   Immediately irrigate the affected eye thoroughly with tepid water
         or 0.9 per cent saline for at least 10-15 minutes.
    2.   Any particles lodged in the conjunctival recesses should be
         removed.
    3.   Continue irrigation with saline infusion using drip tubing.
    4.   Repeated instillation of local anaesthetic (eg amethocaine) may
         reduce discomfort and help more thorough decontamination.
    5.   Corneal damage may be detected by instillation of fluorescein.
    6.   Patients with corneal damage and those whose symptoms do not
         resolve rapidly should be referred for ophthalmological
         assessment.

    Ingestion

    Minor ingestions (very mild or no symptoms):
    1.   Gastrointestinal decontamination is unnecessary.
    2.   Symptomatic and supportive measures only.

    Moderate/substantial ingestions:
    1.   Gastric lavage should be considered only if the patient presents
         within one hour; its value is unproven.
    2.   Symptomatic and supportive measures as dictated by the patient's
         condition.
    3.   Monitor the ECG, biochemical and haematological profiles.

    4.   Collect urine and blood for antimony concentration measurements
         to confirm diagnosis although these assays are not widely
         available. Check with NPIS.
    5.   Chelation therapy with dimercaprol, DMSA or DMPS may be
         considered; seek specialist advice from an NPIS physician.

    Inhalation

    Acute exposure
    1.   Remove from exposure.
    2.   Secure cardiorespiratory stability.
    3.   Perform a chest X-ray in symptomatic patients.
    4.   Treat symptomatically.
    5.   If significant respiratory symptoms occur investigate for
         systemic toxicity: ECG, biochemical and haematological profiles
         and blood and urine samples for antimony concentration
         determination.

    Chronic exposure
    1.   Investigate as for other causes of pneumoconiosis.
    2.   Obtain blood and urine for antimony concentration measurements to
         confirm diagnosis. However, these assays are not widely
         available. Check with NPIS.
    3.   Consider the possibility of systemic toxicity.

    Injection

         -    Discontinue therapy if adverse effects occur and monitor as
              above.

    References

    Bailly R, Lauwerys R, Buchet JP, Mahieu P, Konings J.
    Experimental and human studies on antimony metabolism: their relevance
    for the biological monitoring of workers exposed to inorganic
    antimony.
    Br J Ind Med 1991;48: 93-7.

    Hepburn NC, Nolan J, Fenn L, Herd RM, Neilson JM, Sutherland GR,
    Fox KA.
    Cardiac effects of sodium stibogluconate: myocardial,
    electrophysiological and biochemical studies.
    QJM 1994; 87: 465-72.

    Iffland R, Bosche G.
    [Therapy and clinicotoxicologic follow-up of tartar emetic poisoning
    caused by an ant insecticide in a small child].
    Monatsschrift Kinderheilkunde 1987; 135: 227-30.

    Lauwers LF, Roelants A, Rosseel M, Heyndrickx B, Baute L.
    Oral antimony intoxications in man.
    Crit Care Med 1990; 18: 324-6.

    Miller JM.
    Poisoning by antimony: a case report.
    South Med J 1982; 75: 592.

    Renes LE.
    Antimony poisoning in industry.
    Arch Ind Hyg Occup Med 1953; 7: 99-108.

    White Jr GP, Mathias CGT, Davin JS.
    Dermatitis in workers exposed to antimony in a melting process.
    J Occup Med 1993; 35: 392-5.

    Winship KA.
    Toxicity of antimony and its compounds.
    Adverse Drug React Acute Poisoning Rev 1987; 2: 67-90.

    Substance name

         Antimony potassium tartrate

    Origin of substance

         Manufactured from potassium bitartrate and metallic antimony in
         the presence of nitric acid or solid antimony oxide.
                                                 (MERCK, 1996).

    Synonyms

         Antimonate (2)-, bis(mu-tartrato (4-)) di-, dipotassium,
         trihydrate
         Antimonyl potassium tartrate
         ENT 50,434
         Potassium antimony tartrate
         Potassium antimonyl tartrate
         Potassium antimonyl d-tartrate
         Tartaric acid, antimony potassium salt
         Tartar emetic
         Tartarized antimony
         Tartrated antimony
         Tartox                                  (RTECS, 1997)

    Chemical group

         A compound of antimony, a group V A element.

    Reference numbers

         CAS            28300-74-5               (DOSE, 1992)
         RTECS          CC6825000                (RTECS, 1997)
         UN             1551                     (DOSE, 1992)
         HAZCHEM        2X                       (DOSE, 1992)

    Physicochemical properties

    Chemical structure
         K2 (Sb2 (C4H4O6)2)3H2O
                                                 (DOSE, 1992)

    Molecular weight
         667.86                                  (DOSE, 1992)

    Physical state at room temperature
         Solid                                   (CHRIS, 1997)

    Colour
         White                                   (CHRIS, 1997)

    Odour
         Odourless                               (HSDB, 1997)

    Viscosity
         NIF

    pH
         Aqueous solution is slightly acidic.    (MERCK, 1996)

    Solubility
         Water: 83 g/L.                          (MERCK, 1996)
         Soluble in glycerol.                    (DOSE, 1992)
         Insoluble in alcohol.                   (MERCK, 1996)

    Autoignition temperature
         NIF

    Chemical interactions
         Trivalent antimony compounds tend to form explosive mixtures with
         hot perchloric acid.                    (HSDB, 1997)

    Major products of combustion
         Antimony and potassium oxide.           (SAX'S, 1996)

    Explosive limits
         NA

    Flammability
         Not flammable                           (CHRIS, 1997)

    Boiling point
         NIF

    Density
         2.6 at 20C                             (CHRIS, 1997)

    Vapour pressure
         NIF

    Relative vapour density
         NIF

    Flash point
         NA

    Reactivity
         NIF

    Uses

         As a mordant in the leather and textile industry.
         In treatment of infections caused by  Schistosoma japonicum.
         As a spray on gladiolus and citrus for control of thrips.
         An ingredient in liquid baits used to attract and kill wasps,
         moths and yellow jackets.
         Pesticide.
         Used as a parasiticide, ruminatoric and an expectorant in
         animals.
                                                 (MERCK, 1996; HSDB, 1997)

    Hazard/risk classification

    Index no. (Antimony compounds) 051-003-009
    Risk phases
         Xn; R20/22 - Harmful by inhalation and if swallowed.
    Safety phrases
         S(2-) S22 - Keep out of reach of children. Do not breathe dust
         (if appropriate).
    EEC No.  NIF                                 (CHIP2, 1994)

    INTRODUCTION AND EPIDEMIOLOGY

    Antimony potassium tartrate is a trivalent antimony compound commonly
    known as tartar emetic. It is used mainly as an industrial chemical
    and as a pesticide.

    Historically, the systemic administration of antimony compounds has
    been used in the treatment of many conditions including syphilis,
    whooping cough and gout and topical antimony compounds were believed
    to improve herpetic lesions, leprosy, mania and epilepsy. Antimony has
    been used also as an emetic, a decongestant and a sedative and still
    has a role in the treatment of tropical infections. However, trivalent
    antimony therapy has generally been superseded by less toxic
    treatment.

    Antimony potassium tartrate is the most potent and most toxic of the
    trivalent antimony compounds. Adverse effects are associated with
    therapeutic use and the accidental ingestion of pesticides.

    MECHANISM OF TOXICITY

    The mechanism of toxicity of antimony compounds is unclear but may
    involve disruption of thiol proteins via binding to sulphydryl groups
    (de Wolff, 1995).

    TOXICOKINETICS

    Absorption

    Antimony compounds may be absorbed by inhalation and ingestion, though
    gastrointestinal absorption in man is poor necessitating parenteral
    administration of antimony pharmaceuticals.

    Distribution

    Absorbed trivalent antimony readily enters red blood cells and
    accumulates primarily in the spleen, liver and bone (IPCS, 1996).

    Lauwers et al (1990) estimated that the total body antimony pool in a
    patient who died following accidental antimony potassium tartrate
    ingestion was only five per cent of the ingested dose with high
    antimony concentrations in the liver, gall bladder and
    gastrointestinal mucosa. This is consistent with antimony undergoing
    enterohepatic circulation (see below).

    Excretion

    Antimony compounds are eliminated mainly in the urine, with small
    amounts appearing in faeces via bile after conjugation with
    glutathione. A significant amount of antimony excreted in bile
    undergoes enterohepatic circulation (Bailly et al, 1991). Rees et al
    (1980) demonstrated that some 80-90 per cent of an intramuscular dose
    of sodium stibogluconate was recovered in the urine within six hours
    of administration. However, even some 6-24 months after parenteral
    antimony therapy, Mansour et al (1967) reported increased urine
    antimony concentrations (range 5.8-145.3 g/L) compared to untreated
    controls (range 2.9-9.1 g/L).

    Gerhardsson et al (1982) reported significantly higher lung antimony
    (p<0.001) concentrations in 40 deceased smelter and refinery workers
    who had been exposed to antimony for some 30 years, compared to 11
    unexposed controls. The time from last exposure to death varied from
    0-23 years. The antimony concentration in liver and kidney was not
    significantly different between the two groups, suggesting that
    following occupational inhalation antimony may be retained in the lung
    for several years without significant systemic distribution.

    Kentner et al (1995) estimated a renal elimination half-life of four
    days following occupational inhalation of antimony trioxide and
    stibine in 21 employees of a starter battery manufacturing plant.

    CLINICAL FEATURES: ACUTE EXPOSURE

    Dermal exposure

    Antimony and its compounds are skin irritants although antimony
    dermatitis typically occurs during chronic occupational exposure (see
    below) (Poisindex, 1997).

    Ocular exposure

    Exposure to high concentrations may produce severe eye irritation.

    Ingestion

    Gastrointestinal toxicity

    In 1982 Miller recounted the case of the author Oliver Goldsmith who
    died after ingesting a mixture of antimony trioxide and antimony
    potassium tartrate. The estimated dose was 132-198 mg antimony. He
    succumbed after 18 hours severe vomiting and diarrhoea.

    More recently, Lauwers et al (1990) reported four adults who presented
    with abdominal pain, nausea, vomiting and diarrhoea having mistaken
    "tartar emetic" (antimony potassium tartrate) for "cream of tartar".
    Three of them made an uneventful recovery but the fourth died from
    haemorrhagic gastritis complicated by cardiorespiratory failure.

    A report in the German literature has described a three year-old child
    who survived ingestion of 50 mL of a liquid ant killer containing 2.3
    g antimony potassium tartrate. However, the features, treatment and
    antimony concentrations were not given in the English abstract
    (Iffland and Bosche, 1987).

    Cardiovascular and peripheral vascular toxicity

    Electrocardiographic abnormalities are associated typically with
    chronic antimony exposure. Following acute antimony ingestion two
    patients had "moderate bradyrhythmic dysfunctions" at presentation
    (Lauwers et al, 1990).

    Phlebitis occurred in four patients who accidentally ingested antimony
    potassium tartrate (Lauwers et al, 1990).

    Inhalation

    Pulmonary toxicity

    Dusts and fumes of antimony and its compounds are irritant to the
    respiratory tract and mucous membranes and inhalation causes
    conjunctivitis, laryngitis, pharyngitis, tracheitis, rhinitis and
    bronchitis (Renes, 1953; Taylor, 1966). Metal fume fever has been
    described (Anonymous, 1984) though less frequently than following
    exposure to zinc oxide.

    There may be radiological evidence of pneumonitis which resolves upon
    removal from exposure (Renes, 1953).

    Injection

    Hepatotoxicity

    A 27 year-old woman with cutaneous leishmaniasis developed a transient
    rise in alanine aminotransferase activity (to 2.4 times the upper
    limit of normal) when she was inadvertently given ten times the
    intended dose of parenteral pentavalent sodium stibogluconate
    (Herwaldt et al, 1992). However, hepatotoxicity is observed more
    typically during prolonged therapy with antimony pharmaceuticals.

    Cardiovascular toxicity

    No cardiovascular complications arose in a patient who accidentally
    was given ten times the intended intravenous dose of sodium
    stibogluconate (Herwaldt et al, 1992).

    CLINICAL FEATURES: CHRONIC EXPOSURE

    Dermal exposure

    Dermatitis following contact with antimony compounds is well described
    (McCallum, 1989).

    Typical lesions arise on the arms, legs and in the flexures, sparing
    the face, hands and feet (Renes, 1953; McCallum, 1989).

    Papules and pustules predominate around sweat and sebaceous glands
    with areas of eczema and lichenification. These so-called "antimony
    spots" occur mainly in the summer (McCallum, 1989).

    White et al (1993) described three cases of occupational antimony
    dermatitis following several months exposure to antimony dust and
    antimony trioxide fumes. Two of these patients also experienced
    frequent nose bleeds. Both problems resolved when exposure ceased. In
    one patient patch testing for antimony was negative and in another the
    urine antimony concentration was 53.2 g/L ('normal' < 1.0 g/L).
    Positive patch testing to antimony trioxide has been noted in
    enamellers and decorators in the ceramics industry (Motolese et al,
    1993).

    Inhalation

    Pulmonary toxicity

    Chronic occupational exposure to antimony and its compounds may cause
    "antimony pneumoconiosis" (McCallum, 1989). Typical radiological
    findings include diffuse, dense, punctate non-confluent opacities
    predominately in the middle and lower lung fields, sometimes
    associated with pleural adhesions (Potkonjak and Pavlovich, 1983).

    These changes developed after at least ten years working in an
    antimony smelting plant where the dust contained nearly 90 per cent
    antimony trioxide with some antimony pentoxide and small amounts (up
    to five per cent) of silica (Potkonjak and Pavlovich, 1983). Cough (in
    31 of 51 subjects) and exertional breathlessness (in 26 cases) were
    the symptoms most frequently reported with wheeze, chest pain,
    generalized weakness or conjunctivitis in a minority. Nine workers had
    obstructive lung function defects with a combined
    restrictive/obstructive picture in five cases but no isolated
    restrictive defects or radiological evidence of diffuse fibrosis.

    Perforation of the nasal septum has been described in antimony workers
    but these cases probably have involved concomitant exposure to arsenic
    (McCallum, 1989). There were no cases of nasal perforation in 51
    workers employed at an antimony smelter for 9-31 years (mean 17.9
    years) (Potkonjak and Pavlovich, 1983).

    Brieger et al (1954) attributed ECG T-wave changes and sudden deaths
    to antimony-induced cardiotoxicity following occupational exposure to
    antimony trisulphide although the reliability of this study has been
    criticized (McCallum, 1989).

    Injection

    Dermal toxicity

    Davis (1968) reported antimony dermatitis in some four per cent of 160
    patients treated with antimony-containing drugs.

    Gastrointestinal toxicity

    Patients treated for some one to two weeks with parenteral antimony
    compounds frequently reported anorexia, nausea and vomiting with some
    complaints of abdominal pain, a metallic taste and diarrhoea (Davis,
    1968).

    Pancreatitis also has been reported as a complication of parenteral
    therapy with stibogluconate or meglumine antimonate (McCarthy et al,
    1993; de Lalla et al, 1993; Gasser et al, 1994).

    Hepatotoxicity

    Parenteral treatment with antimony compounds has caused hepatic
    necrosis although reversible elevations of liver enzyme activities are
    more typical (Winship, 1987; Saenz et al, 1991; Hepburn et al, 1993).

    Nephrotoxicity

    Parenteral antimony therapy has caused acute tubular necrosis (Balzan
    and Fenech, 1992; Rai et al, 1994a; Rai et al, 1994b).

    Renal tubular acidosis has also been described (Horber et al, 1991).

    In a review of 92 patients with visceral leishmaniasis (kala-azar)
    treated with sodium stibogluconate, two showed evidence of renal
    toxicity with casts and proteinuria although these patients also were
    receiving intramuscular pentamidine, another recognized renal toxin
    (Chunge et al, 1984).

    Cardiovascular and peripheral vascular toxicity

    ECG changes following exposure to antimony compounds are seen
    typically in patients with leishmaniasis or schistosomiasis who have
    been treated with parenteral antimony compounds. Typical features
    include T wave inversion or amplitude reduction, Q-T interval
    prolongation and S-T segment abnormalities (Davis, 1968; Chulay et al,
    1985; Henderson and Jolliffe, 1985). These effects usually reverse
    when treatment is discontinued.

    In 12 soldiers with cutaneous leishmaniasis treated with sodium
    stibogluconate Hepburn et al (1994) found that although a reversible
    decrease in T-wave amplitude occurred during treatment there were no
    significant changes in echocardiographic indices of left ventricular
    function, arrhythmia frequency or heart-rate variability. The authors
    concluded that 20 mg/kg/day sodium stibogluconate for 20 days had no
    cardiac side-effects in most fit, young patients.

    Gupta (1990) similarly noted that T-wave changes induced by antimony
    therapy were not associated with a deterioration in cardiac function.

    In a review of 160 patients with schistosomiasis treated with
    antimony-containing drugs (Davis, 1968) retrosternal chest pain was
    reported by 27 individuals. In three cases this was associated with
    acute vascular collapse immediately after intravenous drug
    administration (after the first dose in one case) suggesting an
    anaphylactic-type response.

    Phlebitis occurred in 31 patients receiving intravenous sodium
    stibogluconate in the treatment of visceral leishmaniasis (Chunge et
    al, 1984) and in one patient administered antimony sodium tartrate in
    the treatment of urinary schistosomiasis (Davis, 1968).

    Neurotoxicity

    Acute hydrocephalus in association with significant ocular toxicity
    (see below) occurred in a child following 23 antimony potassium
    tartrate injections (Grant and Schuman, 1993).

    Rai et al (1994b) described combined ninth and tenth cranial nerve
    palsies in a patient with kala-azar treated with parenteral
    stibogluconate. There was significant improvement within two weeks of
    cessation of treatment.

    Reversible peripheral neuropathy associated with sodium stibogluconate
    therapy has been reported also (Brummitt et al, 1996).

    Haemotoxicity

    Mallick (1990) described bone marrow hypoplasia as a complication of
    sodium stibogluconate administration. Haematological indices improved
    significantly following treatment withdrawal and steroid therapy.
    Other authors have described leucopenia (Hisnmez et al, 1988; Saenz
    et al, 1991) or recurrent episodes of thrombocytopenia (Braconier and
    Mirner, 1993) during parenteral antimonial therapy though no bone
    marrow biopsies were performed.

    Chunge et al (1984) reported epistaxis in 13 patients receiving
    parenteral antimony-containing drugs, in three cases associated with
    pancytopenia.

    Musculoskeletal toxicity

    Myalgia and arthralgia are reported frequently by patients with
    leishmaniasis or schistosomiasis treated with parenteral antimony
    compounds (Davis, 1968; Winship, 1987; Castro et al, 1990; Saenz et
    al, 1991).

    Ocular toxicity

    In an early case report cited by Grant and Schuman (1993) a child
    developed acute onset bilateral blindness with fixed dilated pupils
    following 23 antimony tartrate injections. There was clinical evidence
    of optic neuritis with papilloedema and subsequent permanent optic
    atrophy.

    Forsyth (1958) reported one patient who developed transient retinal
    haemorrhages and exudates and another in whom the fundus was described
    as 'granular' following parenteral sodium antimony tartrate therapy
    for schistosomiasis. Visual acuity was diminished in both cases but
    returned to normal within six months.

    Three children who received repeated courses of parenteral tartar
    emetic in the treatment of schistosomiasis developed optic atrophy
    (Kassem et al, 1976).

    In a review of 92 patients with visceral leishmaniasis treated with
    parenteral stibogluconate, six developed uveitis and two retinal
    haemorrhages after completion of treatment and apparent cure (Chunge
    et al, 1984).

    MANAGEMENT

    Dermal exposure

    Ensure adequate self protection before attempting treatment. If
    possible the patient should remove any contaminated clothing
    him/herself. Affected areas of skin should be washed with copious
    quantities of water. Pay special attention to skin folds, fingernails
    and ears. The most effective treatment for irritant antimony
    dermatitis is removal from exposure.

    Ocular exposure

    Irrigate immediately with lukewarm water or preferably saline for at
    least 10-15 minutes. A local anaesthetic may be indicated for pain
    relief and to overcome blepharospasm. The use 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.

    Ingestion

    Following substantial ingestion of an antimony compound spontaneous
    vomiting is likely but if this does not occur gastric lavage may be
    considered if presentation is within the first hour. There are no data
    to confirm that charcoal adsorbs antimony. Other symptomatic and
    supportive measures should be dictated by the patient's condition. An
    ECG should be performed and biochemical and haematological profiles
    monitored. Blood and urine antimony concentrations are not widely
    available but may be of interest retrospectively to confirm systemic
    uptake.

    Inhalation

    Removal from exposure and measures to secure cardiorespiratory
    stability are the priority following acute inhalation of antimony
    compounds. An ECG should be performed. Respiratory symptoms in those
    with possible chronic antimony toxicity should be investigated as for
    other cases of pneumoconiosis. Urine antimony concentrations may be
    useful to monitor the initial extent of and subsequent reduction in
    exposure but these assays are not widely available.

    Antidotes

    Dimercaprol (British anti-lewisite, BAL) (Braun et al, 1946; Thompson
    and Whittaker, 1947), dimercaptosuccinic acid (DMSA, Succimer)
    (Basinger and Jones, 1981) and dimercaptopropane sulphonate (DMPS,
    Unithiol) (Basinger and Jones, 1981; Hruby and Donner, 1987) have
    antidotal activity in experimental systemic antimony poisoning (see
    below). These findings have not been confirmed in controlled studies
    in man.

    Dimercaprol

     In vitro studies

    Using the pyruvate oxidase system of pigeon brains as a test model,
    dimercaprol in a molar ratio of 6:1 dimercaprol: antimony was able to
    protect the enzyme system from inhibition by several antimony salts
    (Thompson and Whittaker, 1947).

    Animal studies

    The LD50 of intramuscular antimony tartrate administered to rabbits
    was raised from 90 mg Sb/kg in controls to 160 mg Sb/kg in animals
    treated with intramuscular dimercaprol (30 mg/kg one hour after
    intoxication followed by 15 mg/kg at six, 24 and 48 hours) (Braun et
    al, 1946). A total of 45 controls received 50-200 mg/kg antimony
    tartrate with 56 treated animals receiving 125-200 mg/kg.

    Clinical studies

    Four adults with antimony poisoning following the inadvertent
    consumption of antimony potassium tartrate were treated with
    intramuscular dimercaprol 200-600 mg daily. Three patients made an
    uneventful recovery but the fourth, who had a history of
    cardiorespiratory disease, died on day three. There were no
    pre-chelation antimony excretion data but in two survivors maximum
    antimony urine concentrations of 1000 g/L and 1500 g/L were reported
    some 36 and 72 hours after poisoning respectively. Urine volumes were
    not stated (Lauwers et al, 1990).

    Bailly et al (1991) reported a 24 year-old woman who made an
    uneventful recovery after ingesting an undetermined amount of antimony
    trisulphide. She was treated with dimercaprol 200 mg tds for five days
    but there was no evidence of enhanced urinary antimony elimination
    with therapy.

    DMSA

    Animal studies

    DMSA was given intraperitoneally to mice at a molar ratio of 10:1
    DMSA: antimony twenty minutes after administration of potassium
    antimonyl tartrate (120 mg/kg; twice the LD50). The survival ratio
    was 28/30 (Basinger and Jones, 1981).

    Clinical studies

    There are no human data.

    DMPS

    Animal studies

    DMPS has been shown to be an effective chelating agent in mice
    following intraperitoneal administration of potassium antimonyl
    tartrate (120 mg/kg; twice the LD50). The survival rate was 19/30
    when intraperitoneal DMPS was given twenty minutes after intoxication
    at a molar ratio of 10:1 DMPS: antimony. However, DMSA was
    significantly more effective under these conditions (see above)
    (Basinger and Jones, 1981).

    Clinical studies

    There are no human data.

    Antidotes: Conclusions and recommendations

    1.   Clinical data regarding antimony chelation are scarce.

    2.   Dimercaprol effectively chelates antimony but has been superseded
         by the less toxic thiol antidotes DMPS and DMSA.

    3.   In limited animal studies DMSA is a more effective antimony
         chelator than DMPS.

    4.   Parenteral or oral DMSA therapy may be considered in antimony
         potassium tartrate poisoning. The discussion of individual cases
         with a NPIS physician is recommended.

    MEDICAL SURVEILLANCE

    Improved occupational health measures have reduced industrial airborne
    antimony concentrations significantly but monitoring of ambient air
    antimony concentrations remains important in some industries (Bailly
    et al, 1991; Kentner et al, 1995).

    Routine examination of the skin for "antimony spots" and chest
    radiography for evidence of pneumoconiosis may also be useful. The
    potential risk of pulmonary carcinogenicity should be remembered (see
    below).

    Although Bailly et al (1991) found that urine antimony excretion among
    workers exposed to airborne antimony pentoxide and sodium antimoniate
    correlated to the intensity of exposure, a recent publication from the
    European Commission concluded "no indicator of effect is available"
    for biological monitoring of antimony (Apostoli et al, 1994).

    Normal concentrations in biological fluids

    "Normal" serum and urine antimony concentrations are quoted as
    approximately 3 g/L and 0.8 g/L respectively (Poisindex, 1997).

    OCCUPATIONAL DATA

    Maximum exposure limit

    Antimony and compounds: Long-term exposure limit (8 hour TWA reference
    period) 0.5 mg/m3 (Health and Safety Executive, 1997).

    OTHER TOXICOLOGICAL DATA

    Carcinogenicity

    There is some evidence that occupational antimony exposure is
    associated with an increased risk of lung cancer although frequent
    concomitant exposure to arsenic and other heavy metals precludes a
    definitive conclusion about its carcinogenic potential (Gerhardsson et
    al, 1982; McCallum, 1989; Gerhardsson and Nordberg, 1993; Jones 1994;
    Schnorr et al, 1995).

    Antimony also has been implicated in the aetiology of bladder tumours
    in patients with schistosomiasis who have been treated with antimony
    compounds (Winship, 1987).

    Reprotoxicity

    In the Russian literature women occupationally exposed to antimony
    aerosols were reported to have a higher incidence of spontaneous
    abortion, premature births and menstrual disorders. Antimony was
    present in the blood, urine, placentae, amniotic fluid and breast milk
    of these women. Further details were not available in the English
    abstract (Belyaeva, 1967).

    Genotoxicity

    NIF

    Fish toxicity

    NIF

    EEC Directive on Drinking Water Quality 80/778/EEC

    Maximum admissible concentration 10 g/L, as antimony (DOSE, 1992).

    WHO Guidelines for Drinking Water Quality

    Provisional guideline value 5 g/L, as antimony (WHO, 1993).

    AUTHORS

    WN Harrison PhD CChem MRSC
    SM Bradberry BSc MB MRCP
    JA Vale MD FRCP FRCPE FRCPG FFOM

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

    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
    28/1/98

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    See Also:
       Toxicological Abbreviations