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

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

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

    Peer review group: Directors of the UK National Poisons Information


    Toxbase summary

    Type of product

    Sodium arsenite is an active ingredient in insecticides and
    acaricides.  Potassium arsenite is the active ingredient in Fowler's
    solution and is used in mirror manufacture.


    Sodium and potassium arsenite are highly soluble (trivalent) arsenic
    salts.  Substantial ingestions may be fatal (fatal dose not known).


    Systemic toxicity may follow ingestion, inhalation or topical


         -    May cause skin irritation and sensitization.  Systemic
              arsenic poisoning may occur after substantial exposure.


    Minor ingestions (small amounts of dilute solutions):
         -    Usually no serious effects.  Mild gastrointestinal upset may

    Substantial ingestions:
         -    Rapid onset (within 1-2 hours) of burning in the mouth and
              throat, hypersalivation, dysphagia, nausea, vomiting,
              abdominal pain and diarrhoea.
         -    In severe cases gastrointestinal haemorrhage, cardiovascular
              collapse, renal failure, seizures, encephalopathy and
              rhabdomyolysis may occur.

    Other features:
         -    Facial and peripheral oedema, ventricular arrhythmias
              (notably torsade de pointes), ECG abnormalities (QT interval
              prolongation, T-wave changes), muscle cramps.
         -    Investigations may show anaemia, leucopenia,
              thrombocytopenia or evidence of intravascular haemolysis.
         -    Death may occur from cardiorespiratory or hepatorenal
              failure.  The adult respiratory distress syndrome (ARDS) has
              been reported.
         -    Survivors of severe acute poisoning may develop a peripheral
              neuropathy and skin lesions typical of chronic arsenical


         -    Rhinitis, pharyngitis, laryngitis and tracheobronchitis may
              occur.  Tracheal and bronchial haemorrhage may complicate
              severe cases.

    Chronic arsenic exposure

         -    May occur following ingestion, inhalation or topical
         -    Features include weakness, lethargy, gastrointestinal upset,
              progressing to ulceration and gangrene), renal tubular or
              cortical damage and haematological abnormalities (notably



    1.   Irrigate with copious volumes of water.
    2.   Consider the possibility of systemic arsenic poisoning after
         significant exposure.


    Minor ingestions:
    1.   Gastrointestinal decontamination is unnecessary.
    2.   Symptomatic and supportive care only.

    Substantial ingestions:
    1.   Most patients will vomit spontaneously but in those who  do not,
         gastric lavage should be considered only if the patient presents
         within one hour.
    2.   Supportive measures are paramount.  Intensive resuscitation may
         be required.  Ensure adequate fluid replacement and close
         observation of vital signs including cardiac monitoring.
    3.   Diarrhoea can be controlled with loperamide.
    4.   Monitor blood urea, creatinine, electrolytes, liver function and
         full blood count.
    5.   Collect blood and urine for arsenic concentration measurements.
    6.   ECG evidence of QT prolongation may precede atypical ventricular
         arrhythmias (notably torsade de pointes). Avoid drugs which
         prolong the QT interval e.g. procainamide, quinidine or
         disopyramide.  Isoprenaline is effective with phenytoin,
         lignocaine or propranolol as alternatives.
    7.   Antidotes - chelation therapy with either dimercaprol, DMSA or
         DMPS should be considered in symptomatic patients where there is
         analytical confirmation of the diagnosis, but only after
         specialist advice from the NPIS.


    Donofrio PD, Wilbourn AJ, Albers JW, Rogers L, Salanga V, Greenberg
    Acute arsenic intoxication presenting as Guillain-Barré-like syndrome.
    Muscle Nerve 1987; 10: 114-20.

    Engel RR, Hopenhayn-Rich C, Receveur O, Smith AH.
    Vascular effects of chronic arsenic exposure: a review.
    Epidemiol Rev 1994; 16: 184-209.

    Gerhardt RE, Crecelius EA, Hudson JB.
    Moonshine-related arsenic poisoning.
    Arch Intern Med 1980; 140: 211-3.

    Goldsmith S, From AHL.
    Arsenic-induced atypical ventricular tachycardia.
    N Engl J Med 1980; 303:1096-7.

    Greenberg C, Davies S, McGowan T, Schorer A, Drage C.
    Acute respiratory failure following severe arsenic poisoning.
    Chest 1979; 76: 596-8.

    Kosnett MJ, Becker CE.
    Dimercaptosuccinic acid as a treatment for arsenic poisoning.
    Vet Hum Toxicol 1987; 29: 462.

    Massey EW, Wold D, Heyman A.
    Arsenic: Homicidal intoxication.
    South Med J 1984; 77: 848-51.

    Roses OE, García Fernández JC, Villaamil EC, Camussa N, Minetti SA,
    Martínez de Marco M, Quiroga PN, Rattay P, Sassone A, Valle Garecca
    BS, López CM, Olmos V, Pazos P, Pińeiro A, Rodriguez Lenci J.
    Mass poisoning by sodium arsenite.
    Clin Toxicol 1991; 29: 209-13

    Substance name

         Sodium arsenite

    Origin of substance

         Reaction of caustic soda with arsenious oxide
                                                 (HSDB, 1995)


         Arsenious acid, sodium salt
         Sodium arsenic oxide
         Sodium metaarsenite                     (DOSE, 1994a)

    Chemical group

         A compound of arsenic, a group VA element

    Reference number

         CAS            7784-46-5                (DOSE, 1994a)
         RTECS          CG 3675000               (HSDB, 1995)
         UN             2027 (solid)
                        1686 (aqueous solution)  (DOSE, 1994a)
         HAZCHEM        2X                       (DOSE, 1994a)

    Physicochemical properties

    Chemical structure
         NaAsO2                                  (DOSE, 1994a)

    Molecular weight
         129.91                                  (DOSE, 1994a)

    Physical state at room temperature
         Solid                                   (HSDB, 1995)

         White or greyish-white                  (HSDB, 1995)

         None                                    (CHRIS, 1995)


         Forms basic solution in water           (OHM/TADS, 1995)

         Freely soluble in water, soluble in ethanol
                                                 (DOSE, 1994a)

    Autoignition temperature

    Chemical interactions
         Arsine gas is evolved when sodium arsenite reacts with acids and
         metals.                                 (OHM/TADS, 1995)

    Major products of combustion
         Arsenic fumes and sodium oxide may be generated during a fire.
                                                 (OHM/TADS, 1995)

    Explosive limits

         Non-flammable                           (CHRIS, 1995)

    Boiling point
         Decomposes when heated                  (CHRIS, 1995)

         1.87 at 25şC                            (DOSE, 1994a)

    Vapour pressure

    Relative vapour density

    Flash Point

         Reacts with strong oxidizers            (HSDB, 1995)


         Arsenical soap manufacture              (DOSE, 1994a)

    Hazard/risk classification

    Index no.   033-002-00-5
    Risk phrases
         0.2% < conc T;  R23/25 - Toxic by inhalation and if swallowed.
         0.1% < conc < 0.2% Xn;  R20/22 - Harmful by inhalation and
         in contact with the skin.
    Safety phrases
         S (1/2)-20/21-28-45 - Keep locked up and out of the reach of
         children.  When using do not eat, drink or smoke.  After contact
         with the skin, wash immediately with plenty of ....(to be
         specified by the manufacturer).  In case of accident, or if you
         feel unwell, seek medical advice immediately (show label where
    EEC No:      NIF                             (CHIP2, 1994)

    Substance name

         Potassium arsenite

    Origin of substance

         Reaction of arsenic trioxide and potassium bicarbonate.
                                                 (HSDB, 1995)


         Arsenous acid, potassium salt
         Arsonic acid, potassium salt
         Fowler's solution
         Potassium metaarsenite                  (DOSE, 1994b)

    Chemical group

         A compound of arsenic, a group VA element

    Reference numbers

         CAS            10124-50-2               (DOSE, 1994b)
         RTECS          CG 3800000               (RTECS, 1995)
         UN             1678                     (DOSE, 1994b)
         HAZCHEM        2X                       (DOSE, 1994b)

    Physicochemical properties

    Chemical structure
         As2HKO4                                 (DOSE, 1994b)

    Molecular weight
         253.95                                  (DOSE, 1994b)

    Physical state at room temperature
         Solid                                   (HSDB, 1995)

         White                                   (HSDB, 1995)

         Odourless                               (CHRIS, 1995)


         Will form a basic solution              (OHM/TADS, 1995)

         Soluble in water                        (DOSE, 1994b)

    Autoignition temperature

    Chemical interactions
         Arsine gas is released upon contact with acid.
         Slowly converted to arsenate by atmospheric oxygen when in
         aqueous solution.                       (HAZARDTEXT, 1995)

    Major products of combustion
         Toxic fumes of arsenic and potassium oxide may be generated
         during a fire.                          (HAZARDTEXT, 1995)

    Explosive limits

         Non-flammable                           (OHM/TADS, 1995)

    Boiling point
         Decomposes at 300°C                     (HSDB, 1995)


    Vapour pressure

    Relative vapour density

    Flash Point

         Reacts with salts of iron and most heavy metals.
                                                 (HAZARDTEXT, 1995)


         In manufacture of mirrors, reducing silver salt to metallic
         Used in herbal remedies, notably Fowler's solution.
                                                 (DOSE, 1994b)

    Hazard/risk classification

    Index no.   033-002-00-5
    Risk phrases
         0.2% < conc T;  R23/25 - Toxic by inhalation and if swallowed.
         0.1% < conc < 0.2% Xn;  R20/22 - Harmful by inhalation and
         in contact with the skin.
    Safety phrases
         S (1/2)-20/21-28-45 - Keep locked up and out of the reach of
         children.  When using do not eat, drink or smoke.  After contact
         with the skin, wash immediately with plenty of ....(to be
         specified by the manufacturer).  In case of accident, or if you
         feel unwell, seek medical advice immediately (show label where
    EEC No:     NIF                              (CHIP2, 1994)


    Sodium arsenite is a trivalent arsenic salt formed from the reaction
    of arsenic trioxide with caustic soda (IPCS, 1981).

    Potassium arsenite is formed by the reaction of arsenic trioxide and
    potassium hydroxide. It has been used widely in the form of Fowler's

    Arsenite salts interact with acids and reducing metals (e.g. iron and
    zinc) or aluminium to form arsine gas, the most acutely toxic form of

    Sodium and potassium arsenite are highly soluble and represent a much
    more acute toxic hazard than less soluble trivalent arsenic compounds
    (e.g. arsenic trioxide) (Done and Peart, 1971). Interconversion of
    arsenites and arsenates may also occur readily.


    The main source of arsenic exposure in the world population is
    drinking water with an high inorganic arsenic concentration (Chiou et
    al, 1995; Das et al, 1995). Arsenic usually is found in water in the
    form of arsenite and arsenate, the proportions of each depending on
    conditions (IPCS, 1981). In 1987 an epidemic of arsenic poisoning
    occurred in Argentina when a solution of sodium arsenite was
    maliciously poured over meat in a butcher's shop. Over 700 people were
    involved but there were no fatalities (Roses et al, 1991).

    Potassium arsenite has been ingested with suicidal intent (Massey et
    al, 1984). Accidental exposure has occurred through its use in
    "traditional" ethnic remedies or other homeopathic medicines (Kerr and
    Saryan, 1986).

    Arsenic intoxication has followed the ingestion of pesticides
    containing sodium arsenite (Jenkins, 1966; Peoples et al, 1977; Vaziri
    et al, 1980), or fruit or vegetables that have been sprayed with such
    pesticides. Done and Peart (1971) found that the majority of deaths
    resulting from ingestion of arsenic-containing herbicides were
    attributable to products containing high sodium arsenite
    concentrations. Of 43 cases of human poisoning involving sodium
    arsenite or arsenate reported in the US between 1949-67, 65 per cent
    were fatal.

    Industrial arsenic exposure has occurred from accidents where arsine
    gas has been liberated from the reaction of arsenite solutions with
    hydrogen released by acids and metals such as aluminium (Levinsky et
    al, 1970; Elkins and Fahy, 1967) and zinc (Teitelbaum and Kier, 1969).


    The principle mechanism of arsenic intoxication is disruption of thiol
    proteins. For example, arsenic inactivates pyruvate dehydrogenase by
    complexing with the sulphydryl groups of a lipoic acid moiety
    (6,8-dithiooctanoic acid) of the enzyme (Jones, 1995).

    Enhanced cellular destruction of damaged thiol proteins may produce
    toxic oxygen radicals (Lee and Ho, 1994). Reduced lymphocyte
    proliferation (Gonsebatt et al, 1994) and impaired macrophage function
    also have been described (Lantz et al, 1994).

    Dong and Luo (1994) have suggested that while arsenic can directly
    damage DNA, a more important mechanism in arsenic-induced
    carcinogenicity is enhanced mutagenicity of other compounds via
    increased DNA-protein crosslinks.

    The affinity of arsenic for sulphydryl groups is utilized in chelation



    Soluble arsenic salts, such as sodium and potassium arsenite, are well
    absorbed after ingestion.

    Limited animal data suggest sodium arsenite is well absorbed through
    the lungs (Fielder et al, 1986).

    Sodium or potassium arsenite particles deposited in the upper
    respiratory tract after inhalation may be cleared via mucociliary
    transport, swallowed and then absorbed (Fielder et al, 1986).

    Direct evidence of transcutaneous arsenic absorption in man is scarce
    (Fielder et al, 1986). Robinson (1975) reported a case of systemic
    absorption in a patient whose cheek had been treated with a caustic
    arsenical paste but this involved significant arsenic uptake through
    damaged skin.


    Absorbed arsenic is distributed to all body tissues. High
    concentrations would be expected in keratin-rich tissues such as hair,
    skin and nails due to sulphydryl group binding (Fielder et al, 1986).
    Trivalent arsenic is methylated in the liver to methylarsonic acid and
    dimethylarsinic acid (IPCS, 1996). Short-term studies on humans
    indicate that daily intake in excess of 0.5 mg progressively, but not
    completely, saturates the capacity to methylate inorganic arsenic
    (IPCS, 1996).


    The half-life of arsenic in blood is about 60 hours with renal
    excretion predominantly as mono- and dimethyl- derivatives (Buchet et
    al, 1981; Waldron and Scott, 1994). The whole body half-life of
    arsenic in six human volunteers fitted a three compartment system,
    with 65.9 per cent of orally administered arsenic acid having a
    half-life of 2.1 days, 30.4 per cent a half-life of 9.5 days and 3.7
    per cent a half-life of 38.4 days (mean values) (Pomroy et al, 1980).


    Dermal exposure

    Trivalent arsenic compounds are irritating to the skin and mucous
    membranes with dermatitis the most common feature following
    occupational exposure. Erythema, burning and itching, eczematous
    eruptions and folliculitis are typical (Fielder et al, 1986).

    Robinson (1975) reported the development of a peripheral
    polyneuropathy, "generalized skin lesions" and nail thickening in a
    patient who applied a caustic arsenical paste to his cheek.

    Ocular exposure

    Sodium and potassium arsenite are eye irritants. Most injuries result
    from exposure to dusts, causing conjunctivitis, lacrimation,
    photophobia and chemosis (Grant and Schuman, 1993).


    The toxicity of ingested sodium or potassium arsenite is dependent on
    the amount and concentration of the preparation.

    Gastrointestinal toxicity

    Ingestion of a substantial quantity of sodium or potassium arsenite is
    followed, usually within two hours, by nausea and vomiting, abdominal
    pain and diarrhoea (Giberson et al, 1976; Vaziri et al, 1980; Roses et
    al, 1991). These features occurred following ingestion of 720 mg and
    400 mg sodium arsenite respectively (Vaziri et al, 1980).

    Roses et al (1991) reported a mass poisoning when sodium arsenite was
    maliciously poured over meat in a butcher's shop. Thirty five per cent
    of 85 subjects said to have urine arsenic concentrations 36 µg/L or
    less reported symptoms while gastrointestinal symptoms occurred in all
    three subjects with urine arsenic concentrations reported to be
    greater than 10000 µg/L (there were some inconsistencies in the
    publication of these concentrations). Abdominal pain and gastritis
    were the most common symptoms in subjects with lower urine arsenic
    concentrations, whilst vomiting and nausea were more common at higher
    concentrations. No subjects were symptomatic at one month follow up.

    Other features of arsenic ingestion include burning of the mouth and
    throat, dysphagia (Heyman et al, 1956; Jenkins, 1966) and

    In severe cases, gastrointestinal haemorrhage with cardiovascular
    collapse may ensue and is thought to reflect a direct toxic effect of
    arsenic on capillaries via sulphydryl-group binding (Morton and
    Dunnette, 1994).

    The mortality from substantial sodium (or potassium) arsenite
    ingestion may be high (Done and Peart, 1971).


    Acute arsenic ingestions are associated frequently with increased
    liver enzyme activities and hyperbilirubinaemia although these
    abnormalities usually resolve.


    Hypotension (Giberson et al, 1976; Vaziri et al, 1980) or
    rhabdomyolysis following substantial arsenic ingestion may precipitate
    renal failure; renal cortical necrosis has been described (Gerhardt et
    al, 1978).

    Jenkins (1966) described a 38 year-old woman who developed albuminuria
    and microscopic haematuria after ingesting an unknown amount of rat
    poison containing sodium arsenite.

    Cardiovascular toxicity

    Tachycardia is typical following arsenic ingestion (Peterson and
    Rumack, 1977; Levin-Scherz et al, 1987) and is contributed to by
    anxiety, hypovolaemia and possibly direct arsenic-induced

    Ventricular arrhythmias, notably torsade de pointes (Beckman et al,
    1991) have been observed. Other ECG abnormalities include prolongation
    of the QT interval (Goldsmith and From, 1980) and non-specific T wave
    changes. Sudden onset bradycardia, then asystole, despite vigorous
    resuscitation and no earlier arrhythmia, has also followed massive
    acute arsenic ingestion.


    Roses et al (1991) reported headache as a common feature in subjects
    who ingested sodium arsenite-contaminated meat.

    Ingestion of arsenic has resulted in muscle cramps, a sensorineural
    hearing deficit (Goldsmith and From, 1980), encephalopathy (Jenkins,
    1966) and seizures.

    A peripheral sensory and/or motor neuropathy has been described in
    survivors of severe acute arsenic poisoning although this is more
    typical following chronic exposure.

    Jenkins (1966) described a 38 year-old woman who had ingested sodium
    arsenite rat poison (amount not stated) suicidally. She developed
    "pins and needles" in her hands and feet. Physical examination showed
    distal muscle weakness in the lower limbs. There was reduced vibration
    and position sense in the toes and ankle-jerks were absent. She
    received a "full course" of dimercaprol (not specified) and no
    disability was detectable 18 months later.

    Goebel et al (1990) demonstrated acute wallerian degeneration of
    myelinated nerve fibres in a patient who developed a symmetrical
    polyneuropathy after attempting suicide by arsenic ingestion. Clinical
    improvement was associated with microscopic evidence of neurological

    Dermal toxicity

    Striate leukonychia (Mees' lines) may develop following severe
    arsenite poisoning (Jenkins, 1966; Massey, 1984), although associated
    typically with chronic exposure.

    Several weeks after attempted suicide by sodium arsenite ingestion, a
    38 year-old woman developed transverse striate leukonychia and
    desquamated skin on her palms and soles; she recovered fully (Jenkins,

    Facial and peripheral oedema have been described (Heyman et al, 1956;
    Kyle and Pease, 1965).


    In moderate or severe arsenic poisoning investigations typically show
    anaemia, leucopenia or pancytopenia (Kyle and Pease, 1965). There may
    be evidence of intravascular haemolysis and basophilic stippling has
    been reported on the blood film (Kyle and Pease, 1965).

    Multi-organ toxicity

    Severe acute arsenic poisoning may result in death from
    cardiorespiratory or hepatorenal failure (Jenkins, 1966; Armstrong et
    al, 1984; Campbell and Alvarez, 1989; Morton and Dunnette, 1994).  The
    adult respiratory distress syndrome has been described (Bolliger et
    al, 1992).


    Inhalation of arsenic compounds causes rhinitis, pharyngitis,
    laryngitis and tracheobronchitis (Morton and Dunnette, 1994).


    DiNapoli et al (1989) described a patient who injected sodium arsenite
    and potassium cyanide in a suicide attempt. He collapsed within
    minutes with probable cyanide-induced severe respiratory distress and
    coma. His condition improved following the intravenous administration
    of sodium nitrite and sodium thiosulphate although he subsequently
    experienced nausea and vomiting. The urine arsenic excretion in the
    first 12 hours following admission was 10 mg. Twenty two days later he
    complained of numbness and tingling in the upper extremities but there
    was no objective neurological abnormality. No cutaneous manifestations
    of arsenic poisoning developed.


    Dermal exposure

    Occupational cutaneous exposure may lead to chronic poisoning. Arsenic
    salts have caused skin sensitization.


    Occupational arsenical exposure may lead to chronic poisoning. Nasal
    septum perforation is also described.


    Ingestion of arsenic-contaminated drinking water (Feinglass, 1973;
    Chiou et al, 1995), illicit whisky (Moonshine) (Gerhardt et al, 1980),
    "tonics" or traditional remedies containing arsenite notably Fowler's
    solution (Nevens et al, 1990), have caused chronic arsenic poisoning.

    Systemic arsenic toxicity

    The systemic features observed are similar for each source of exposure
    and for exposure to all inorganic forms of arsenic which are
    considered together.

    General toxic effects

    Patients may present with general debility, progressive weakness
    (Feinglass, 1973; Gerhardt et al, 1980), fever and sweats (Heyman et
    al, 1956).

    Dermal toxicity

    The characteristic dermal manifestations are hyperkeratosis and
    "raindrop" pigmentation of the skin (Heyman et al, 1956; Kyle and
    Pease, 1965; Shannon and Strayer, 1989; Sass et al, 1993).

    Hyperkeratoses appear as multiple small nodules which may coalesce to
    form plaques and are found most commonly on the palms and soles. By
    contrast, hyperpigmentation is more prominent in the axilla, groin,
    areola and around the waist, typically with mucosal sparing (Shannon
    and Strayer, 1989). These changes seem to be exacerbated by poor
    nutritional status (Das et al, 1995).

    Hyperkeratotic lesions may develop into squamous cell carcinomas which
    are notable for their occurrence on non light-exposed areas of the
    upper extremities and trunk (Shannon and Strayer, 1989).

    The fingernails may become brittle with transverse white striae (Mees'
    lines) (Mees, 1919; Heyman et al, 1956; Kyle and Pease, 1965; Gerhardt
    et al, 1980; Sass et al, 1993).

    Exfoliative dermatitis (Nicolis and Helwig, 1973) and perforation of
    the nasal septum have been reported.

    Sass et al (1993) described a 42 year-old man who had been prescribed
    Fowler's solution over one year. Arsenical keratoderma was diagnosed
    but the patient was lost to follow-up for 10 years. When seen again,
    an extension of the lesions and arsenical keratoses was apparent on
    the fingers with development of squamous cell carcinoma after a
    further 12 months.

    Neuropsychological toxicity

    A symmetrical peripheral neuropathy is typical. Sensory symptoms
    predominate with paraesthesiae, numbness and pain, particularly of the
    soles of the feet, extending in a "glove and stocking" distribution
    (Jenkins, 1966; Gerhardt et al, 1980).

    Motor involvement with symmetrical distal limb weakness, muscle
    atrophy and loss of deep tendon reflexes is recognized (Heyman et al,
    1956; Gerhardt et al, 1980; Bansal et al, 1991).

    Complete respiratory muscle paralysis (Greenberg et al, 1979; Gerhardt
    et al, 1980), a phrenic neuropathy (Bansal et al, 1991) and cranial
    nerve involvement have been reported.

    The neuropathy may be confused with the Guillain-Barré syndrome (Kyle
    and Pease, 1965; Donofrio et al, 1987). Gastrointestinal symptoms and
    skin manifestations suggest arsenic poisoning, while a high CSF
    protein concentration and cranial nerve involvement are more typical
    of the Guillain-Barré syndrome.

    Electromyelography may show reduced peripheral nerve conduction
    velocities in the absence of symptoms.

    Psychological impairment is widely reported in chronic arsenical
    poisoning with defects of verbal learning ability and memory and
    personality changes.

    Gastrointestinal toxicity

    Nausea and vomiting, although more typical of acute arsenic poisoning,
    may occur also in chronic cases.


    Nevens et al (1990) reported eight cases of non-cirrhotic portal
    hypertension in patients who had received potassium arsenite in a
    herbal remedy (as Fowler's solution) for several years. All showed
    signs of hypersplenism and massive bleeding from oesophageal varices
    was reported in seven cases. Cirrhosis has also been described but may
    involve concomitant excess ethanol consumption (Morton and Dunnette,

    Narang (1987) suggested increased arsenic consumption as a
    contributing factor in the aetiology of liver disease in the Indian
    population when he found significantly increased hepatic arsenic
    concentrations at autopsy in 178 patients dying from cirrhosis, non
    cirrhotic portal fibrosis, fulminant hepatitis, Wilson's disease or
    alcoholic liver disease.


    Renal manifestations probably reflect capillary damage and include
    haematuria, proteinuria with casts and acute tubular or cortical
    necrosis (Morton and Dunnette, 1994).

    Peripheral vascular and cardiovascular toxicity

    "Black foot disease" refers to a severe form of peripheral vascular
    disease seen in Taiwan in those who drink artesian well water with an
    high arsenic concentration. Initial paraesthesiae and cold sensitivity
    progress to ulceration and gangrene (Chiou et al, 1995). It has been
    suggested that mortality due to all vascular diseases may be increased
    in these populations (Chen and Lin, 1994; Engel et al, 1994).

    Raynaud's syndrome has also been described in those chronically
    exposed to arsenic dust.

    Several authors refer to arsenic-induced myocardial toxicity
    (Schoolmeester and White, 1980; Hall and Harruff, 1989), which has
    been attributed to impaired oxidative metabolism of myocardial tissue
    plus a direct inflammatory effect. A 42 year-old agricultural worker
    presented with neuropathy and skin lesions and had a 24 hour urine
    arsenic excretion of 7000 µg (Hall and Harruff, 1989). He received a
    15 day course of dimercaprol with some improvement in motor function.
    On the 26th day of hospital admission he suddenly collapsed and died
    following a cardiac arrest. At post-mortem he had a diffuse
    interstitial myocarditis which was assumed to have triggered a fatal


    Anaemia, neutropenia (Heyman et al, 1956; Kyle and Pease, 1965),
    pancytopenia, haemolysis (Kyle and Pease, 1965), macrocytosis without
    anaemia (Heaven et al, 1994) and a myelodysplastic syndrome (Rezuke et
    al, 1991) have been reported.

    Chronic arsenic exposure complicated by aplastic anaemia may
    predispose to acute myeloid leukaemia (Kjeldsberg and Ward, 1972).
    Arsenic-induced disruption of haem metabolism with altered urinary
    porphyrin excretion is also described (Garcia-Vargas et al, 1994).

    Endocrine toxicity

    Epidemiological evidence from Taiwan (Lai et al, 1994) and
    occupational studies have associated chronic arsenic exposure with the
    development of diabetes mellitus.

    Pulmonary toxicity

    An irritating cough and haemoptysis are reported (Heyman et al, 1956).


    Dermal exposure

    Surface decontamination should be attempted where necessary. Treat
    burns conventionally. Consider the possibility of systemic arsenic
    poisoning and the need for chelation therapy (see below).

    Ocular exposure

    Irrigate the eye with copious lukewarm water. A topical anaesthetic
    may be necessary for pain relief. Seek an ophthalmic opinion if
    symptoms persist or examination is abnormal.


    Immediate management involves removal from exposure and administration
    of supplemental oxygen if necessary. Evidence of systemic arsenic
    uptake should be sought and chelation therapy considered as discussed



    After acute ingestion of a substantial quantity of sodium or potassium
    arsenite most patients will vomit spontaneously but, in those who do
    not, gastric lavage should be considered only if it is possible to
    undertake the procedure within the first hour.

    Supportive measures

    Severe acute sodium or potassium arsenite poisoning requires prompt
    intensive resuscitation with adequate fluid replacement and close
    observation of vital signs including cardiac monitoring. Diarrhoea may
    be treated symptomatically with loperamide. Chelation therapy should
    be considered in symptomatic cases. Obtain blood and urine for arsenic
    concentration determination.

    Electrocardiographic evidence of QT prolongation in arsenic poisoning
    may precede atypical ventricular arrhythmias, notably torsade de
    pointes, and in these circumstances drugs which themselves prolong the
    QT interval, such as procainamide, quinidine or disopyramide, should
    be avoided. Isoprenaline is effective; phenytoin, lignocaine or
    propranolol are alternatives (Goldsmith and From, 1980).


    Chelating agents used in the treatment of arsenic poisoning are
    dithiol compounds which can remove arsenic from endogenous sulphydryl
    groups, the targets of arsenic toxicity (Jones, 1995).

    Traditionally, dimercaprol (British anti-lewisite, BAL) has been the
    recommended chelator in arsenic intoxication (Jenkins, 1966; Greenberg
    et al, 1979; Roses et al, 1991). However, dimercaprol may produce
    unpleasant adverse effects and must be administered by deep
    intramuscular injection. There is increasing evidence that
    dimercaptosuccinic acid (DMSA, Succimer) (Aposhian et al, 1984;
    Graziano, 1986; Fournier et al, 1988; Inns et al, 1990) and
    dimercaptopropane sulphonate (DMPS, Unithiol) (Aposhian, 1983;
    Aposhian et al, 1984; Hruby and Donner, 1987; Inns et al, 1990) are
    less toxic and may be preferable. DMSA and DMPS are more effective in
    reducing the arsenic content of tissues, they increase biliary as well
    as urinary arsenic elimination and, unlike dimercaprol, do not appear
    to cause arsenic accumulation in the brain (Kreppel et al, 1990; Moore
    et al, 1994). On the other hand, arsenic mercaptide (the chelation
    complex of dimercaprol and arsenic) is dialysable and hence
    dimercaprol may be preferred in the presence of renal failure (Sheabar
    et al, 1989; Mathieu et al, 1992)

    The importance of an increased urine arsenic concentration in
    determining the need for chelation therapy is disputed. Kersjes et al
    (1987) suggested a spot urine concentration greater than 200 µg/L
    should be taken as an indication of "significant" arsenic exposure but
    Kingston et al (1993) emphasised that arsenic concentrations
    significantly higher than this (3500 µg/24 h and 5819 µg/24 h in two
    of their patients) may be observed in the acute phase following
    pentavalent arsenic ingestion without severe sequelae.

    Dimercaprol (British anti-lewisite; BAL)

    Dimercaprol was developed during the Second World War as an antidote
    for lewisite (dichloro(2-chlorovinyl) arsine) poisoning (Peters et al,
    1945). It possesses two sulphydryl groups and forms a stable
    mercaptide ring with arsenic. The alcohol group on dimercaprol confers
    some degree of water solubility, thereby enhancing excretion from the
    body. As the chelation complex tends to dissociate it is necessary to
    maintain a constant excess of dimercaprol. Unlike DMSA and DMPS,
    dimercaprol is also lipid soluble and increases the brain arsenic
    concentration in arsenic-intoxicated animals (Jones, 1995).

    Though increasingly superseded by the less toxic thiol chelating
    agents, intramuscular dimercaprol remains useful in severe arsenic
    poisoning where vomiting prevents oral antidote administration,
    supplies of DMSA or DMPS are not rapidly available (Jolliffe et al,
    1991) or renal failure requires haemodialysis; dimercaprol but not
    DMSA chelates can cross the dialysis membrane (Sheabar et al, 1989;
    Mathieu et al, 1992).

    Animal studies

    Stocken and Thompson (1946) demonstrated increased urine arsenic
    excretion (up to 33.5 per cent of the amount applied) in the 24 hours
    following cutaneous application of lewisite to rodents, when
    dimercaprol (dose not stated) was spread over the affected area up to
    one hour later. Dimercaprol also prevented arsenic-induced diarrhoea
    observed in control animals.

    Intravenous injection of dimercaprol glucoside 1.5 g/kg prevented
    death in two rabbits poisoned with cutaneous lewisite (12 mg/kg).
    Eleven control animals died, as did two treated with subcutaneous
    dimercaprol 0.07 g/kg (Danielli et al, 1947).

    A recent study has demonstrated that intramuscular dimercaprol
    protects rabbits against the lethal systemic effects of intravenously
    administered lewisite. No appreciable difference was found between the
    protective effect of dimercaprol and that of water soluble analogues
    DMPS and DMSA (Inns et al, 1990).

    Clinical studies

    In a case series, 12 men were exposed to smoke containing
    diphenylcyano-arsenic (1.6 mg/m3), "other forms of organic arsenic"
    (0.5 mg/m3) and "inorganic arsenic" (1.8 mg/m3) for six minutes. 
    They were treated with 3.5 mg/kg intramuscular dimercaprol 6.5-78
    hours post exposure. Urine arsenic excretion increased by an average
    of 40 per cent between two and four hours after the injection. The
    largest increase, both absolute and relative, was observed in those
    treated earliest (6.5 hours after exposure) (Wexler et al, 1946).

    Giberson et al (1976) described the treatment of a 44 year-old male
    who ingested 400 mg sodium arsenite. Intramuscular dimercaprol 250 mg
    was administered every four hours. Haemodialysis was initiated in
    response to renal failure with 3.3 mg arsenic removed over four hours.
    By the sixth day, when renal function had recovered, arsenic excretion
    had reached 75 mg/24h with at least 115 mg arsenic excreted between
    days two and six.

    A four year-old boy who had ingested an unknown amount of arsenic
    trioxide rat poison was treated with dimercaprol 5 mg/kg every four
    hours for 16 hours. The urine contained 2,120 µg arsenic over the
    first 12 hours. He developed an urticarial rash over the lower
    extremities which subsided with the discontinuation of dimercaprol.
    The urine arsenic concentration decreased gradually during
    d-penicillamine treatment (Peterson and Rumack, 1977).

    Schoolmeester and White (1980) reported a 16 year-old female who
    ingested 300 mg sodium arsenate in a suicide attempt. She received
    intramuscular dimercaprol 125 mg every four hours for the first 24
    hours, then twice daily for 24 hours. A 24 hour urine arsenic
    concentration (starting time not specified) was 14,200 µg/L. The
    effect of chelation therapy on arsenic excretion is not known but the
    patient fully recovered.

    Mahieu et al (1981) described a 44 year-old male who ingested an
    unknown amount of arsenic trioxide which had been mistaken for sugar.
    The dose "certainly exceeded 1000 mg". Intramuscular dimercaprol 2.5-4
    mg/kg tds was administered for 21 days. Initial arsenic excretion was
    low due to renal insufficiency but increased to 10 mg/24h from three
    to seven days post ingestion. The patient excreted a total of 129 mg
    arsenic during his 26 days in hospital. A 40 year-old woman poisoned
    at the same time and treated with the same regimen for 17 days
    excreted 16.7 mg arsenic on the first day, the amount decreasing on
    subsequent days. Seventy three milligrams arsenic were eliminated over
    three weeks.

    A 32 year-old man who ingested 900 mg sodium arsenate in a suicide
    attempt commenced treatment with intramuscular dimercaprol 5 mg/kg
    four hourly five hours later. Dimercaprol was stopped on day four.
    This patient also received oral d-penicillamine and intravenous then
    oral N-acetylcysteine between days two and 82 post ingestion. The
    urine arsenic concentration rose on the second hospital day then
    declined progressively during the next week although the data were
    incomplete and uninterpretable (Bansal et al, 1991).

    A 22 month-old female who developed diarrhoea, vomiting and lethargy
    after ingesting approximately 0.7 mg sodium arsenate was treated
    initially with one intramuscular dose of dimercaprol 3 mg/kg nine
    hours post ingestion. Three hours later the infant was asymptomatic
    and dimercaprol therapy discontinued although she subsequently
    received oral d-penicillamine then oral DMSA to treat persisting high
    urine arsenic concentrations (4880 µg/L in the first 24 hours after
    admission) (Cullen et al, 1995). On the third hospital day the urine

    arsenic concentration (from a 24 hour collection) was 1355 µg/L and
    fell progressively to 96 µg/L on day 12 . These data do not enable any
    conclusions to be drawn regarding enhanced arsenic elimination.

    No benefit from dimercaprol was reported by McCutchen and Utterback
    (1966) in the treatment of severe chronic arsenic poisoning. Other
    authors have reported disappointing results with dimercaprol in the
    management of arsenic neuropathy (Heyman et al, 1956) although Jenkins
    (1966) described "no detectable disability" 18 months after acute
    sodium arsenite ingestion in a patient who developed a peripheral
    neuropathy and received "a full course of dimercaprol" (details not

    Marcus (1987) described a 16 year-old male who survived ingestion of
    56 mg arsenic trioxide following treatment with intramuscular
    dimercaprol 4 mg/kg every four hours (duration not stated). The
    maximum urine arsenic excretion was "over 50 mg/day" falling to 20
    µg/day by day 31. At twelve month follow-up neurological effects

    Mahieu et al (1981) suggested that a high (greater than 90 per cent)
    proportion of methylated arsenic in the urine of poisoned patients
    could be used to indicate a late presentation with less likelihood of
    benefit from chelation therapy.

    Treatment protocol

    Dimercaprol must be given by deep intramuscular injection. After
    injection 90 per cent of an administered dose is absorbed and Cmax is
    attained within one hour (Peters et al, 1947). Dimercaprol is
    distributed throughout the intracellular space and metabolic
    degradation and excretion is complete in less than four hours.
    Depending on severity, 2.5-5 mg/kg should be administered four hourly
    for two days. This is to ensure that a constant excess of dimercaprol
    is always present as the chelation complex dissociates. Traditionally,
    this initial treatment is followed by 2.5 mg/kg bd intramuscularly for
    one to two weeks. However, this is an empirical recommendation and may
    be insufficient in severe cases. Dosage and duration should be
    adjusted therefore, depending on urine arsenic removal.

    Adverse effects

    The most common adverse effect of dimercaprol is dose-related
    hypertension (with an increase in systolic pressure of up to 50 mmHg)
    which usually resolves within three hours of administration (Dollery,
    1991) but may be associated with nausea, headache, sweating and
    abdominal pain. Gastrointestinal disturbance may also occur without
    hypertension. Conjunctivitis, paraesthesiae and fever have been

    Dimercaprol is contraindicated in severe liver disease since it is
    metabolized by glucuronidation with subsequent biliary excretion.


    DMSA is commercially available in some countries (though not the UK)
    mainly as meso-DMSA, although a DL-form also exists.

    Animal studies

    Aposhian et al (1984) demonstrated that DMSA was moderately more
    effective than DMPS (and substantially more effective than
    dimercaprol) in protecting mice from the lethal effects of sodium
    arsenite. DMSA mobilizes arsenic from tissues, increasing urine
    arsenic excretion without a rise in brain arsenic concentrations
    (Aposhian et al, 1984).

    Mice administered subcutaneous arsenic trioxide (5 mg/kg) followed
    immediately by intraperitoneal DMSA 100 mg/kg, showed significantly
    increased urine arsenic excretion (p<0.01) in the first 12 hours post
    chelation although the 48 hour urine arsenic elimination was not
    significantly different between DMSA-treated mice and controls
    (Maehashi and Murata, 1986).

    In animal studies DMSA protected against the embryotoxic effects of
    sodium arsenite but only when given within one hour of exposure
    (Bosque et al, 1991).

    Recent experiments suggest that oral monoester DMSA analogues may
    offer renal protection in arsenic poisoning by increasing the enteral
    arsenic content to enhance faecal rather than renal elimination
    (Hannemann et al, 1995). In other animal studies lipophilic DMSA
    analogues were inferior to the parent compound as arsenic antidotes
    (Kreppel et al, 1993).

    Clinical studies

    Lenz et al (1981) described a 46 year-old man who ingested 200 mg
    arsenic and survived following treatment with oral DMSA 300 mg qds for
    three days.

    Kosnett and Becker (1987) reported an increase in the 24 hour urine
    arsenic excretion from 26 µg to a maximum of 340 µg on the second day
    of oral DMSA treatment 660 mg tds in a patient who presented more than
    30 days after malicious acute arsenic ingestion.

    Nine days after ingesting approximately 0.7 mg of a soluble arsenic
    salt a 22 month-old female was treated with oral DMSA 30 mg/kg/day for
    at least four days (Cullen et al, 1995). The child had already
    received chelation therapy with dimercaprol and d-penicillamine, but
    further treatment was instituted because of a persistently raised
    urine arsenic concentration (650 µg/L on day five). Four days later
    the urine arsenic concentration had fallen to 96 µg/L. The authors
    reported an overall urine arsenic half-life of 2.6 days. Although the
    child initially experienced vomiting, diarrhoea and lethargy these

    features resolved within 12 hours and renal and hepatic function
    remained normal throughout (Cullen et al, 1995).

    There was no objective improvement in the neurological manifestations
    of chronic arsenic poisoning in a man poisoned by an ethnic remedy
    despite two weeks therapy with oral DMSA 400 mg tds (Kew et al, 1993).
    No urine arsenic excretion data were given.

    A 33 year-old woman with acute-on-chronic lead and arsenic poisoning
    from a herbal remedy clinically recovered following two one-week
    courses of oral DMSA 270 mg tds, though the effect of chelation
    therapy on urine arsenic excretion is difficult to interpret
    (Mitchell-Heggs et al, 1990).

    Treatment protocol

    DMSA is given orally in a dose of 30 mg/kg body weight per day; an
    intravenous preparation is available in some countries and may be
    preferable if the patient is vomiting (Hantson et al, 1995).

    Adverse effects

    Side-effects following treatment with DMSA are rare but include skin
    rashes, gastrointestinal disturbance, elevation of serum transaminase
    activities and flu-like symptoms (Reynolds, 1993). DMSA should be used
    with caution in patients with impaired renal function or a history of
    hepatic disease (Reynolds, 1993).


    Animal studies

    DMPS is commercially available as a racemic mixture of the
    dextro-rotatory and levo-rotatory forms which appear to be equally
    effective arsenic chelators (Aposhian, 1983), though animal studies
    suggest DMSA may be superior to either (Aposhian et al, 1984).

    Urine arsenic elimination of arsenic-poisoned rats in the 48 hours
    post treatment with DMPS 100 mg/kg intraperitoneally was significantly
    lower (p<0.05) than in either control (5 mg/kg subcutaneous arsenic
    trioxide only) or DMSA-treated mice (Maehashi and Murata, 1986).
    However DMPS significantly increased (p<0.01) faecal arsenic
    elimination in the 24 hours post chelation compared to control or DMSA
    treated mice, suggesting biliary excretion of the DMPS-arsenic chelate
    (Maehashi and Murata, 1986).

    Other authors have noted enhanced biliary but not faecal arsenic
    excretion following parenteral DMPS administration to arsenic-poisoned
    experimental animals. This suggests enterohepatic circulation of the
    chelate, which Reichl et al (1995) attempted to block using oral
    cholestyramine. They demonstrated enhanced faecal arsenic elimination
    (p<0.05) when intraperitoneal DMPS 0.1 mmol/kg and subcutaneous

    arsenic trioxide (0.02 mmol/kg) administration was followed by an oral
    combination of cholestyramine (0.2 g/kg) and DMPS 0.1 mmol/kg (Reichl
    et al, 1995).

    Domingo et al (1992) demonstrated a protective effect of DMPS 150-300
    mg/kg, but not dimercaprol, against experimental arsenite-induced
    embryotoxicity and teratogenicity as judged by the incidence of foetal
    malformation or death in mice administered intraperitoneal sodium
    arsenite (12 mg/kg) on day nine of gestation.

    Clinical studies

    Two men inadvertently ingested 1 g and 4 g arsenic trioxide
    respectively (Moore et al, 1994). The more severely poisoned patient
    developed acute renal failure and 26 hours post ingestion had a blood
    arsenic concentration of 400 µg/L. He received intravenous DMPS 5
    mg/kg every four hours for six days then oral DMPS 400 mg every four
    hours for one week. The other patient had a blood arsenic
    concentration of 98 µg/L, 36 hours post ingestion and received a
    shorter course of intravenous then oral DMPS. Both patients recovered
    fully but quantitative data showing the effect of chelation therapy on
    urine arsenic elimination were documented poorly.

    In another report there was no objective improvement in the
    neurological manifestations of chronic arsenic poisoning in a patient
    treated with oral DMPS 100 mg tds for three weeks (Kew et al, 1993).

    Treatment protocol

    DMPS is given orally or parenterally in a dose of 30 mg/kg body weight
    per day.

    Adverse effects

    Side effects following treatment with DMPS are infrequent but have
    included allergic skin reactions, nausea, vertigo and pruritis
    (Aposhian, 1983).


    Animal studies

    d-Penicillamine has been reported to be as effective as dimercaprol
    and NAC in prolonging the survival time of mice injected with a lethal
    dose of sodium arsenite (Shum et al, 1981). Other studies have
    disputed the validity of these results and have failed to demonstrate
    d-penicillamine as a useful chelator (Aposhian, 1982; Kreppel et al,

    Clinical studies

    Peterson and Rumack (1977) described three children who shared a
    bottle of rat poison containing arsenic trioxide 1.75 per cent. One
    died within hours following a rapidly deteriorating course of coma,
    convulsions and cardiac arrhythmias. The second, a four year-old male,
    presented with lethargy, a sinus tachycardia and tachypnoea. Oral
    d-penicillamine 25 mg/kg qds replaced dimercaprol treatment after 16
    hours when the patient developed an urticarial rash over the lower
    extremities. The first twelve-hour urine collection during dimercaprol
    treatment contained 2,120 µg arsenic with the urine arsenic
    concentration decreasing during the five days d-penicillamine therapy.
    The child made a full recovery.

    The third patient (Peterson and Rumack, 1977) had no severe features
    of toxicity at presentation. He received the same chelation therapy
    regimen as patient 2. On the second day post ingestion the 24 hour
    urine arsenic excretion was 300 µg, increasing in the next 24 hours
    (the second day of d-penicillamine therapy) to approximately 800 µg.
    This patient also recovered fully.

    A one year-old child ingested 15-20 mg sodium arsenate (as ant poison)
    and was treated within six hours with 5 mg/kg intramuscular
    dimercaprol (Peterson and Rumack, 1977). The chelating agent was then
    changed to oral d-penicillamine 100 mg/kg/day and continued for five
    days. An initial 12 hour urine collection (commenced approximately six
    hours post ingestion) contained 192 µg arsenic, increasing to 2000 µg
    arsenic in the next 24 hours before falling to approximately 200 µg/24
    h on day two. These authors advocated d-penicillamine 100 mg/kg/day as
    the treatment of choice in arsenic poisoning (where oral therapy is
    possible). They recommended d-penicillamine should be continued until
    the 24 hour urine arsenic excretion is less than 50 µg (Peterson and
    Rumack, 1977).

    A 16 month-old child was given a five day course of oral
    d-penicillamine 250 mg qds 14 hours after ingesting 9-14 mg arsenic
    trioxide. Clinical features of toxicity (diarrhoea, vomiting and
    lethargy) resolved within 24 hours and the child was discharged on day
    three. The arsenic concentration in urine collected during the first
    day of treatment was 560 µg/L. However, no earlier urine arsenic
    concentrations were measured and prior to d-penicillamine therapy the
    patient had received 185 mg dimercaprol over 18 hours (Watson et al,

    DiNapoli et al (1989) instituted d-penicillamine therapy in a patient
    unable to tolerate intramuscular dimercaprol following intravenous
    sodium arsenite injection. d-Penicillamine 500 mg tds was administered
    and after ten days a 24 hour urine arsenic excretion of 2 mg was
    reported. There were no symptoms of bone marrow depression, haemolysis
    or peripheral neuropathy. After a further ten days treatment the urine
    arsenic concentration was 20 µg/L.

    Bansal et al (1991) described a 35 year-old man with severe arsenic
    polyneuropathy involving the phrenic nerves bilaterally, who recovered
    following d-penicillamine therapy 250 mg tds for two weeks (route of
    administration not stated). However, the 24 hour urine arsenic
    excretion only rose to 82.4 µg/g creatinine in the first 72 hours of
    chelation compared to a pretreatment value of 73.5 µg/g creatinine.

    Cullen et al (1995) reported a 22 month-old child who ingested some
    0.7 mg sodium arsenate. Following a single dose of dimercaprol 3
    mg/kg, oral d-penicillamine therapy was commenced, 250 mg qds for nine
    doses. By day four the 24 hour urine arsenic concentration had dropped
    from 4880 to 682 µg/L. The child was discharged on day six on oral
    d-penicillamine therapy (dose not stated) but readmitted three days
    later due to a persistently high urine arsenic excretion (650 µg/L on
    day five). At this stage d-penicillamine was replaced by DMSA since
    the child had developed an erythematous rash.

    Oral d-penicillamine 250 mg qds for seven days failed to increase
    urinary arsenic elimination in a patient with chronic arsenic
    poisoning whose initial 24 hour urine arsenic excretion was 342 µg
    (normal <5 µg/24 h) (Heaven et al, 1994).

    In another report the urine arsenic concentration in a 67 year-old man
    with arsenic-associated aplastic anaemia had risen to 20,246 µg/L
    after four days penicillamine therapy 500 mg qds compared to a
    pretreatment concentration of 7840 µg/L (Kjeldsberg and Ward, 1972).
    The patient died from acute myeloid leukaemia some six months later.


    Animal studies

    The survival time of mice injected subcutaneously with a lethal dose
    of sodium arsenite (25 mg/kg) was increased significantly (p<0.05) if
    intraperitoneal N-acetylcysteine (NAC) 100 mg/kg was administered 30
    minutes later. There was no significant difference between this dose
    of NAC, dimercaprol 5 mg/kg and d-penicillamine 50 mg/kg as an
    antidote under these conditions (Shum et al, 1981).

    Clinical studies

    Martin et al (1990) reported "remarkable clinical improvement" in a 32
    year-old man with severe arsenic poisoning following ingestion of a
    soluble salt when he was administered intravenous NAC 70 mg/kg four
    hourly after dimercaprol had "failed to improve his condition".
    However urinary arsenic excretion data were poorly documented and
    dimercaprol was continued during treatment with NAC.

    Antidotes: Conclusions and recommendations

    There are no controlled clinical trials of chelation therapy in
    arsenic poisoning and no conclusive evidence that dithiol antidotes
    reverse arsenic-induced neurological damage. On the present evidence
    it is difficult to recommend a single preferred antidote, though in

    the absence of renal failure DMSA may offer some advantages over other
    agents; if renal failure supervenes dimercaprol and haemodialysis
    should be employed.

    Chelation therapy should be considered in symptomatic patients where
    there is analytical confirmation of the diagnosis.

    Although urine arsenic concentrations are useful to confirm the
    diagnosis of arsenic poisoning chelation therapy should not be
    instituted on the basis of an increased urine arsenic concentration


    Haemodialysis removes arsenic from the blood but achieves less
    effective arsenic clearance than chelation therapy when normal renal
    function is present. It is indicated therefore only in the presence of
    renal failure.

    Giberson et al (1976) reported an arsenic dialysis clearance of 87
    mL/min. During four hours of dialysis 3360 µg arsenic was removed in a
    patient with acute arsenic poisoning complicated by renal failure who
    was also receiving 250 mg intramuscular dimercaprol six times daily.
    The 24 hour urine arsenic excretion on the same day was 2030 µg though
    this increased to 75,000 µg/24 h on the sixth hospital day when renal
    function had recovered.

    A similar haemodialysis arsenic clearance of 76-87 mL/min was
    demonstrated in another patient with acute sodium arsenite
    intoxication complicated by acute renal failure (Vaziri et al, 1980).

    Levin-Scherz et al (1987) instituted haemodialysis promptly in a
    patient who presented 26 hours after ingesting 2 g arsenic trioxide.
    The patient also received intramuscular dimercaprol, 300 mg initially
    then 180 mg every four hours, but died within 72 hours of ingestion.
    The maximum amount of arsenic removed in the dialysate was 2.9 mg.

    Mathieu et al (1992) demonstrated a haemodialysis clearance comparable
    to some 40-77 per cent of the daily arsenic renal elimination on the
    day following diuresis recovery. In this case the total blood
    haemodialysis clearance (210 mL/min) exceeded the instantaneous plasma
    haemodialysis clearance (mean 85 mL/min), suggesting that some arsenic
    removed by haemodialysis originated in erythrocytes. These authors
    showed similar haemodialysis arsenic clearance with or without prior
    administration of intramuscular dimercaprol 250 mg, and advocated
    dimercaprol as the chelating agent of choice in arsenic poisoning
    complicated by renal failure, since it does not impair arsenic
    dialysis clearance.

    Experimental evidence in dogs (Sheabar et al, 1989) suggests
    DMSA-arsenic chelates do not pass through the dialyser membrane.


    A 37 year-old man presented within four hours of ingesting 90 mL of a
    1.5 per cent arsenic trioxide solution (Smith et al, 1981). Although
    initially only tachycardic he subsequently became hypotensive and
    oliguric. For the first 48 hours he received 200 mg intramuscular
    dimercaprol four hourly then d-penicillamine 500 mg qds. Charcoal
    haemoperfusion was instituted 11 hours after admission followed by two
    hours haemodialysis. These therapies were repeated over the next four
    days but "discontinued because of continued good renal function and
    lack of clinical response". Serum arsenic concentrations immediately
    post haemoperfusion were slightly higher than pre-haemoperfusion
    values, suggesting no benefit.


    Blood arsenic concentrations correlate poorly with exposure but may be
    useful in chronic poisoning (Morton and Dunnette, 1994).

    Arsenic concentrations in hair and nails have been used to indicate
    chronic systemic absorption, although their use as biological monitors
    of occupational exposure to airborne arsenic is limited by difficulty
    in excluding external contamination (Yamamura and Yamauchi, 1980).

    Urine arsenic concentrations are the most useful biomonitoring tool,
    ideally as a total 24 hour collection, although spot urine arsenic
    concentrations have been proposed in screening asymptomatic patients
    with a history of possible acute arsenic ingestion.

    Since certain marine organisms (especially mussels) may contain large
    amounts of organoarsenicals, it is advisable that workers refrain from
    eating seafood for at least 48 hours before urine collection (Buchet
    et al, 1994). Analytical speciation methods capable of separating
    inorganic arsenic and its methylated derivatives from dietary
    organoarsenicals partially overcome this problem (Smith et al, 1977;
    Farmer and Johnson, 1990; Buchet et al, 1994). However, Vahter (1994)
    has suggested that under certain circumstances arsenic compounds
    released from seafood can still invalidate assessment of inorganic
    arsenic exposure.

    Smith et al (1977) demonstrated a close correlation between airborne
    arsenic and urinary excretion of all arsenic species in
    arsenic-exposed workers and Farmer and Johnson (1990) found that high
    urine concentrations of inorganic arsenic plus its mono- and dimethyl
    derivatives corresponded to the possible workplace atmospheric arsenic
    concentrations for those involved in arsenic production or glass
    manufacture. Increased urine arsenic concentrations have also been
    noted in timber treatment workers using an arsenic-based wood

    Telolahy et al (1993) suggested a potential role for increased urine
    coproporphyrins as an indicator of chronic occupational arsenic
    exposure since arsenic is known to disrupt haem metabolism.

    Regular examination of the skin should be included in an occupational
    health surveillance programme. Workers with evidence of excessive
    arsenic exposure should be offered long-term monitoring for the
    development of skin, bladder or lung cancer, though in practice this
    may be difficult to execute.


    Maximum exposure limit

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



    Individuals who chronically ingest arsenic have an increased risk of
    developing skin cancer, usually squamous cell carcinoma but also basal
    cell carcinomas (Chen et al, 1988; Shannon and Strayer, 1989; Chiou et
    al, 1995). Squamous cell carcinomas may arise in areas of
    arsenic-induced Bowen's disease (Novey, 1969; Shannon and Strayer,

    Hsueh et al (1995) demonstrated a significant dose-response relation
    between skin cancer prevalence and arsenic exposure from artesian well
    water. These authors identified chronic hepatitis B carriage and
    malnutrition as risk factors for arsenic-induced dermatological

    Skin cancer has also been documented among vineyard workers and
    farmers exposed to inhaled inorganic arsenic in pesticides (Thiers et
    al 1967; Chen and Lin, 1994) although skin and gastrointestinal
    absorption probably contributed to arsenic toxicity in these cases.

    There is an association between chronic arsenic exposure and cancer of
    the urinary tract (Chen et al, 1988; Chen and Lin, 1994), lung (Chen
    and Lin, 1994; Simonato et al, 1994; Tsuda et al 1995) and liver, both
    hepatic angiosarcoma (Lander et al, 1975) and hepatocellular carcinoma
    (Chen and Lin, 1994).

    Smoking exerts a synergistic effect with ingested and inhaled arsenic
    in the development of pulmonary malignancy (Tsuda et al, 1995). There
    is limited evidence that other internal cancers, particularly of the
    gastrointestinal tract and haematological malignancies, are linked
    aetiologically to arsenic exposure (Chen and Lin, 1994).


    Animal studies suggest arsenic is embryotoxic and teratogenic but
    reliable human data are scarce (Council on Scientific Affairs, 1985).

    A woman in the third trimester of pregnancy developed acute renal
    failure after ingesting a large quantity of an arsenical rat poison.
    Her baby was delivered on the fourth day post ingestion but died
    within a few hours from hyaline membrane disease. At autopsy the
    infant showed significant arsenic accumulation in the liver, brain and
    kidneys (liver arsenic concentration 0.74 mg/100 g tissue) (Lugo et
    al, 1969).


    Sodium arsenite

     In vitro Chinese and Syrian hamster ovary cells: Induced sister
    chromatid exchanges.

    Cultured human leucocytes: Increased incidence of sister chromatid
    exchanges (DOSE, 1994a).

    Potassium arsenite

     In vitro human lymphocytes: Mitotic arrest and chromosomal
    aberrations (DOSE, 1994b).

    The lymphocytes of six patients treated with Fowler's solution showed
    an increased incidence of sister chromatid exchanges but not
    chromosomal aberrations (Burgdorf et al, 1977).

    Fish toxicity (potassium arsenite)

    Not toxic to brown trout, bluegill sunfish, yellow perch or goldfish
    at 5 ppm for 24 hours (DOSE, 1994b).

    EC Directive on Drinking Water Quality 80/778/EEC

    Maximum admissible concentration 50 µg/L, as arsenic (DOSE, 1994a).

    WHO Guidelines for Drinking Water Quality

    Guideline value 10 µg/L, as arsenic (WHO, 1993).


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

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

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

    Date of last revision


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    See Also:
       Toxicological Abbreviations
       Sodium arsenite (ICSC)