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    ANTIMONY TRIOXIDE




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

    Toxbase summary

    Type of product

    Used mainly as a fire retardant in plastics, rubbers, textiles, paper
    and paints.

    Toxicity

    Acute antimony trioxide poisoning is rare. Exposure may occur in
    industry. Fatal dose not known.

    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.

    Ingestion

    Moderate ingestions:
         -    Features usually occur within two hours with nausea,
              vomiting, abdominal pain and diarrhoea. A garlic odour on
              the breath has been described following ingestion of other
              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.
              A fatality occurred following ingestion of a soluble
              antimony trioxide derivative (Miller, 1982).

    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.

    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.

    Ocular

    1.   Immediately irrigate the affected eye thoroughly with tepid water
         or 0.9% 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 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.

    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.

    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.

    Werrin M.
    Chemical food poisoning.
    Q Bull Assoc Food Drug Offic 1963; 27: 38-45.

    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 trioxide

    Origin of substance

         Minerals such as senarmontite and valentinite.
                                                 (MERCK, 1996)
         Manufactured by roasting antimony trisulphide ores.
                                                 (IARC, 1989)

    Synonyms

         Diantimony trioxide
         Antimony white
         Exitelite
         Flowers of antimony
         Valentinite                             (DOSE, 1992)

    Chemical group

         A compound of antimony, a group VA element

    Reference numbers

         CAS            1309-64-4                (DOSE, 1992)
                        1327-33-9                (CSDS, 1989)
         RTECS          CC 5650000               (CSDS, 1989)
         UN             1549                     (CSDS, 1989)
         HAZCHEM        NIF

    Physicochemical properties

    Chemical structure
         Sb2O3                                   (DOSE, 1992)

    Molecular weight
         291.5                                   (DOSE, 1992)

    Physical state at room temperature
         Crystalline solid                       (CSDS, 1989)

    Colour
         White                                   (CSDS, 1989)

    Odour
         None                                    (CHRIS, 1997)

    Viscosity
         NA

    pH
         NIF

    Solubility
         Slightly soluble in water. Soluble in potassium hydroxide,
         hydrochloric acid. Insoluble in organic solvents.
                                                 (CSDS, 1989)

    Autoignition temperature
         NA

    Chemical interactions
         Reacts with organic acids, alcohols, glycols, alpha-hydroxy
         acids, o-dihydric phenols, sugar alcohols and other polyhydroxy
         compounds.                              (OHM/TADS, 1997)

    Major products of combustion
         When heated to combustion emits toxic antimony fumes.
                                                 (HAZARDTEXT, 1997)

    Explosive limits
         NIF

    Flammability
         Ignites on heating in air.              (CSDS, 1989)

    Boiling point
         1550°C                                  (DOSE, 1992)

    Density
         5.2                                     (DOSE, 1992)

    Vapour pressure
         NA

    Relative vapour density
         NA

    Flash Point
         NA

    Reactivity
         Reacts explosively with chlorinated rubber.
         Forms explosive mixtures with perchloric acid when hot.
                                                 (CSDS, 1989)

    Uses

         Fire retardant in plastics, rubbers, textiles, paper and paints.
                                                 (IARC, 1989)
         In enamels and glass.
         Tartar emetic (antimony potassium tartrate) manufacture.
                                                 (DOSE, 1992)

    Hazard/risk classification

    Index no. 051-005-00-X
    Risk phases
         Carc. Cat. 3; R40 - Possible risk of irreversible effects.
         Xn; R40 - Harmful, possible risk of irreversible effects.
         S(2-)22-36 - Keep out of reach of children. Do not breathe dust.
         Wear suitable protective clothing.
    EEC No.  215-175-0                           (CHIP2, 1994)

    INTRODUCTION

    Antimony trioxide is a trivalent antimony compound which occurs
    naturally as the ores valentinite and senarmontite. It is produced
    commercially by the vapour phase reaction of antimony trisulphide and
    oxygen.

    It is used as a fire retardant and as an additive in enamel and glass
    manufacture.

    EPIDEMIOLOGY

    The main route of antimony trioxide exposure is occupational
    inhalation of dusts. Workers have been exposed in the production of
    antimony trioxide (Renes, 1953; Schnorr et al, 1995) and from its
    formation as a by-product of metal smelting (Gerhardsson et al, 1982;
    Potkonjak and Pavlovich, 1983; Jones, 1994; Schnorr et al, 1995).

    Other occupational exposure has occurred in the manufacture of
    ceramics (Motolese et al, 1993), batteries (Kentner et al, 1995) and
    alloys (White et al, 1993).

    Accidental intoxication has been reported after leaching of antimony
    from agate and ceramic containers into acidic beverages (Dunn, 1928;
    Monier-Williams, 1934; Werrin, 1963).

    It has been suggested that stibine generated from microbial growth on
    cot mattresses containing antimony trioxide is a contributing factor
    in sudden infant death syndrome (SIDS). Although there is some
    evidence consistent with undue antimony exposure in infants who died
    of SIDS (Taylor, 1996) other evidence disagrees such that it is most
    unlikely stibine is the only cause of the syndrome (de Wolff, 1995). A
    provisional comment by the Chair of the UK Expert Group on Cot Death
    Theories states so far "there is no evidence of risk to babies" from
    cot mattress PVC (Bradbury, 1997).

    Historically, intoxication has resulted from the medical use of
    antimony trioxide and potassium tartrate as tartar emetic in the
    treatment of a variety of conditions including malaise, fever,
    whooping cough and syphilis (Miller, 1982).

    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 trioxide may be absorbed by inhalation and ingestion, though
    gastrointestinal absorption in man is poor.

    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). Some 6-24
    months after parenteral antimony therapy, Mansour et al (1967)
    reported increased urine antimony concentrations (range 5.8-145.3
    µg/L) compared to untreated controls (range 2.9-9.1 µg/L).

    Gerhardsson et al (1982) reported significantly (p<0.001) higher
    antimony concentrations in the lung tissue of 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 trioxide is an irritant although antimony dermatitis
    typically occurs during chronic occupational exposure.

    Ocular exposure

    Antimony trioxide is an eye irritant. Conjunctivitis and blurred
    vision were reported in workers exposed to antimony trioxide fumes in
    a smelter plant (Renes, 1953).

    Ingestion

    Acute poisoning is rare. Antimony trioxide is poorly soluble and is
    not readily absorbed from the gastrointestinal tract. Cases have been
    reported only when the compound has been leached into acidic beverages
    or has been converted into a more soluble form.


    Gastrointestinal toxicity

    Ingestion of a substantial quantity of antimony trioxide may result in
    nausea, vomiting and diarrhoea.

    Over fifty people were "very sick" and treated in hospital after
    drinking lemonade contaminated with 13 mg/L antimony. Antimony
    trioxide had leached from an enamel container in which the drinks were
    stored overnight. All the patients recovered completely within several
    days (Dunn, 1928).

    Similarly, antimony trioxide leached from enamel or ceramic glaze into
    acidic beverages caused "a burning sensation in the stomach", colic,
    nausea, vomiting and "collapse" (Monier-Williams, 1934).

    One hundred and fifty children developed nausea, vomiting, abdominal
    pain and diarrhoea some 15 minutes after drinking
    antimony-contaminated lemonade. The lemonade had a pH of 2.5-3.1 and
    leached an estimated 30 mg/L antimony into solution from an agate pot
    in which it was stored for 20-22 hours. Most of the affected children
    recovered within a few hours, the remainder recovering within a few
    days (Werrin, 1963).

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

    Cardiovascular and peripheral vascular toxicity

    Electrocardiographic abnormalities are associated typically with
    chronic antimony exposure although have not been associated with
    exposure to antimony trioxide alone.

    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 trioxide are irritant to the respiratory
    tract and mucous membranes and inhalation causes laryngitis (ranging

    from hoarseness to aphonia), pharyngitis, tracheitis, rhinitis,
    epistaxis, and bronchitis (Renes, 1953). Metal fume fever has been
    described (Anonymous, 1984) though less frequently than following
    exposure to zinc oxide.

    Radiological evidence of pneumonitis was found in six workers exposed
    to antimony smelter fumes for 2-12 hours. Inflammatory changes were
    characteristically peri-hilar with no evidence of peripheral
    parenchymal damage. Symptoms were alleviated by removal from exposure
    (and treatment with penicillin aerosols). The average airborne
    antimony concentration was 10-12 mg/m3 with a maximum measured
    breathing zone concentration of 70.7 mg/m3 (Renes, 1953).

    Gastrointestinal toxicity

    Workers heavily exposed (not specified) to antimony trioxide in a
    smelter plant developed "gastritis", abdominal pain, diarrhoea and
    vomiting. Urine antimony concentrations ranged from a trace up to an
    "exceptionally high" 600 mg/L (Renes, 1953).

    Neurotoxicity

    "Neuritis", dizziness and headache were reported amongst workers
    exposed to antimony trioxide fumes at an antimony smelting plant
    (Renes, 1953).

    Nephrotoxicity

    Albuminuria was reported in a "severely ill" worker with a urine
    antimony concentration of 600 mg/L after exposure to antimony trioxide
    in a smelting plant (Renes, 1953). Removal from exposure and
    symptomatic treatment for several days "provided relief".

    CLINICAL FEATURES: CHRONIC EXPOSURE

    The major source of antimony trioxide exposure is as a by-product in
    the smelting of metal ores (which may also contain arsenic) and in
    industries such as ceramic, glass and alloy manufacture. Inhalation
    and dermal contact are the most common routes of exposure.

    Dermal exposure

    Dermatitis following contact with antimony trioxide is well described
    (Oliver, 1933; 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 (Paschoud, 1962). These so-
    called "antimony spots" occur mainly in the summer (McCallum, 1989).

    Skin lesions developed in 23 men employed at an antimony trioxide
    production plant. Most of those affected were furnace workers with
    lesions typically appearing within two weeks of exposure. Itching,
    erythematous papules and pustular eruptions were characteristic,
    usually on dust laden sweaty areas of skin. The lesions usually
    resolved over two weeks in individuals removed to cooler parts of the
    factory. Histological examination showed epidermal cellular necrosis
    associated with an acute dermal inflammatory reaction. Antimony
    trioxide patch testing was negative whilst injection of methacholine
    into the affected areas caused enlargement of the lesions. The author
    concluded that antimony trioxide dust initiated an irritant reaction
    when it penetrated sweat ducts (Stevenson, 1965).

    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 µg/L ("normal" < 1.0 µg/L).

    Positive patch testing to antimony trioxide has been noted in
    enamellers and decorators in the ceramics industry (Motolese et al,
    1993).

    Ocular exposure

    Antimony trioxide is an irritant. Conjunctivitis was reported in 14 of
    51 workers exposed to antimony trioxide dust in a smelting plant
    (Potkonjak and Pavlovich, 1983).

    Inhalation

    Pulmonary toxicity

    Chronic occupational antimony trioxide exposure may cause "antimony
    pneumoconiosis" (Cooper et al, 1968; 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 or
    generalized weakness 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.

    Pneumoconiosis was reported also in workers at an antimony oxide
    production plant. Lung biopsies from two affected individuals revealed
    antimony concentrations of 600-3000 µg/g (Le Bouffant et al, 1987)

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

    Cardiovascular toxicity

    Although ECG changes have been reported in patients treated with
    antimony drugs there are no reports following exposure to antimony
    trioxide alone.

    In the Czechoslovakian literature Klucik and Ulrich (1960) reported
    subjective cardiac complaints and ECG changes (not specified in
    English abstract) in 14 workers occupationally exposed to antimony
    trioxide dust. However, significant antimony trisulphide exposure also
    occurred.

    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).

    An epidemiological study of workers at an antimony processing plant
    showed no excess deaths from ischaemic heart disease in workers
    exposed to antimony trioxide compared with other employees at the same
    site (McCallum, 1989).

    Ingestion

    Chronic ingestion is not a recognized toxicological hazard.

    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 gastric lavage
    may be considered if presentation is within the first hour. There are
    no data to confirm that charcoal adsorbs antimony but the
    administration to a co-operative patient of 50 g activated charcoal
    within the first hour following a suspected substantial ingestion is
    reasonable. 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) (Thompson and Whittaker,
    1947; Braun et al, 1946), 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 µg/L and 1500 µg/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
         trioxide poisoning. The discussion of individual cases with an
         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 µg/L and 0.8 µg/L respectively (Poisindex, 1997).

    OCCUPATIONAL DATA

    Maximum exposure limit

    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).

    The International Agency for Research on Cancer has concluded antimony
    trioxide is "possibly carcinogenic to humans" (IARC, 1989).

    Reprotoxicity

    In the Russian literature women occupational 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 but further details were not available in the English
    abstract (Belyaeva, 1967).

    Genotoxicity

     Bacillus subtilis: produced gene conversion and mitotic
    recombination (DOSE, 1992).

    Fish toxicity

    LC50 (96 hr) bluegill sunfish, fathead minnow 530-833 mg/L (DOSE,
    1992).

    EEC Directive on Drinking Water Quality 80/778/EEC

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

    WHO Guidelines for Drinking Water Quality

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

    AUTHORS

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

    REFERENCES

    Apostoli P, Porru S, Alessio L.
    Antimony. In: Alessio L, Berlin A. Roi R, van der Venne MT, eds.
    Biological indicators for the assessment of human exposure to
    industrial chemicals.
    Luxembourg: Office for Official Publications of the European
    Communities, 1994.

    Anonymous.
    Metals and the lung.
    Lancet 1984; 2: 903-4.

    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.

    Basinger MA, Jones MM.
    Structural requirements for chelate antidotal efficacy in acute
    antimony(III) intoxication.
    Res Commun Chem Pathol Pharmacol 1981; 32: 355-63.

    Belyaeva AP.
    [The effect produced by antimony on the generative function.]
    Gig Tr Prof Zabol 1967; 11: 32-7.

    Bradbury J.
    Cot death debate becomes heated after publication of new research.
    Lancet 1997; 349: 625.

    Braun HA, Lusky LM, Calvery HO.
    The efficacy of 2,3-dimercaptopropanol (BAL) in the therapy of
    poisoning by compounds of antimony, bismuth, chromium, mercury and
    nickel.
    J Pharmacol Exp Ther 1946; 87: 119-25.

    Brieger H, Semisch CW, Stasney J, Piatnek DA.
    Industrial antimony poisoning.
    Ind Med Surg 1954; 23: 521-3.

    CHIP2/Chemicals (Hazard Information and Packaging for Supply).
    Regulations 1994.
    Health and Safety Commission.
    Sudbury: Heath and Safety Executive, 1994.

    CHRIS/Chemical Hazard Response Information System.
    In: Tomes plus. Environmental Health and Safety Series 1. Vol 33.
    United States Coast Guard, 1997.

    Cooper DA, Pendergrass EP, Vorwald AJ, Maycock RL, Brieger H.
    Pneumoconiosis among workers in an antimony industry.
    Am J Roentgenol 1968; 103: 495-508.

    CSDS/Chemical Safety Data Sheets. Vol 2.
    Cambridge: Royal Society of Chemistry, 1989.

    DOSE/Dictionary of substances and their effects. Vol 1.
    Cambridge: Royal Society of Chemistry, 1992.

    de Wolff FA.
    Antimony and health. Incriminating stibine in the sudden infant death
    syndrome is difficult on current evidence.
    Br Med J 1995; 310: 1216-7.

    Dunn JT.
    A curious case of antimony poisoning.
    Analyst 1928; 53: 532-3.

    Gerhardsson L, Brune D, Nordberg GF, Wester PO.
    Antimony in lung, liver and kidney tissue from deceased smelter
    workers.
    Scand J Work Environ Health 1982; 8: 201-8.

    Gerhardsson L, Nordberg GF.
    Lung cancer in smelter workers - interactions of metals as indicated
    by tissue levels.
    Scand J Work Environ Health 1993; 19: 90-4.

    Hazardtext.
    In: Tomes plus. Environmental Health and Safety Series 1. Vol 33.
    Colorado: Micromedex, Inc., 1997.

    Health and Safety Executive.
    EH40/97. Occupational exposure limits 1997.
    Sudbury: Health and Safety Executive, 1997.

    Hruby K, Donner A.
    2,3-dimercapto-1-propanesulphonate in heavy metal poisoning.
    Med Toxicol 1987; 2: 317-23.

    IARC/International Agency for Research on Cancer.
    Antimony trioxide and antimony trisulfide.
    IARC Monographs on the Evaluation of Carcinogenic Risk of Humans 1989;
    47; 291-305.

    IPCS/International Programme on Chemical Safety.
    Guidelines for drinking-water quality. 2nd ed. Vol 2. Health criteria
    and other supporting information.
    Geneva: World Health Organization, 1996.

    Jones RD.
    Survey of antimony workers: mortality 1961-1992.
    Occup Environ Med 1994; 51: 772-6.

    Kentner M, Leinemann M, Schaller KH, Weltle D, Lehnert G.
    External and internal antimony exposure in starter battery production.
    Int Arch Occup Environ Health 1995; 67: 119-23.

    Klucik I, Ulrich L.
    [Electrocardiographic examinations of workers in an antimony
    metallurgical plant].
    Pracovni Lekarstvi 1960; 5: 236-43.

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

    Le Bouffant L, Giroulle H, Guerrin F, Normand C, Cornu L, Tichoux G.
    Pneumoconiose a l'antimoine. Etude anatomo-physique.
    [Pneumoconiosis due to antimony]
    Inst Natl Sante Rech Med 1987; 155: 447-55.

    Mansour MM, Rassoul AAA, Schulert AR.
    Anti-bilharzial antimony drugs.
    Nature 1967; 214: 819-20.

    McCallum RI.
    The industrial toxicology of antimony. The Ernestine Henry lecture
    1987.
    J R Coll Physicians Lond 1989; 23: 28-32.

    MERCK/The Merck Index.
    Antimony trioxide. In: Budavari S, ed. An encyclopedia of chemicals,
    drugs, and biologicals. 12th ed.
    New Jersey: Merck and Co., Inc., 1996; 120.

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

    Monier-Williams GW.
    Reports on public health and medical subjects. No 73. Antimony in
    enamelled hollow-ware.
    London: HMSO, 1934.

    Motolese A, Truzzi M, Giannini A, Seidenari S.
    Contact dermatitis and contact sensitization among enamellers and
    decorators in the ceramics industry.
    Contact Dermatitis 1993; 28: 59-62.

    OHM/TADS-Oil and Hazardous Materials/Technical Assistance Data System.
    In: Tomes plus. Environmental Health and Safety Series 1. Vol 33.
    United States Environmental Protection Agency, 1997.

    Oliver T.
    The health of antimony oxide workers.
    Br Med J 1933; 1: 1094-5.

    Paschoud J-M.
    Deux cas d'eczéma de contact lichénoid rappelant des très près lichen
    plan.
    [Two cases of lichenoid contact eczema which closely resemble lichen
    planus]
    Dermatologica 1963; 127: 99-107.

    Poisindex.
    In: Micromedex International Healthcare Series. Vol 92.
    Colorado: Micromedex, Inc., 1997.

    Potkonjak V, Pavlovich M.
    Antimoniosis: a particular form of pneumoconiosis. I. Etiology,
    clinical and X-ray findings.
    Int Arch Occup Environ Health 1983; 51: 199-207.

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

    Schnorr TM, Steenland K, Thun MJ, Rinsky RA.
    Mortality in a cohort of antimony smelter workers.
    Am J Ind Med 1995; 27: 759-70.

    Stevenson CJ.
    Antimony spots.
    Trans St. Johns Hospital Dermatol Soc 1965; 51: 40-5.

    Taylor A.
    Antimony, cot mattress, and SIDS.
    Lancet 1996; 347: 616.

    Thompson RHS, Whittaker VP.
    Antidotal activity of British Anti-Lewisite against compounds of
    antimony, gold and mercury.
    Biochem J 1947; 41: 342-6.

    Werrin M.
    Chemical food poisoning.
    Q Bull Assoc Food Drug Offic 1963; 27: 38-45.

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

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

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


    See Also:
       Toxicological Abbreviations
       Antimony trioxide (ICSC)