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 entry

    Type of product

    Used in wood preservatives and insecticides. In water arsenic acid
    forms the arsenate ion.


    Small ingestions of dilute (<3%) arsenate solutions usually are
    without serious adverse effects. A patient has survived the deliberate
    ingestion of 10 g arsenate (Mathieu et al, 1992).


    Systemic toxicity may follow arsenic acid ingestion, inhalation or
    topical exposure.


         -    Causes skin burns. Systemic arsenic poisoning may occur
              after substantial exposure.


    Minor ingestions (small amounts of dilute (<3%) solutions):
         -    Usually no serious effects. Mild gastrointestinal upset may

    Substantial ingestions:
         -    Rapid onset (within 1-2 hours) of burning of 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 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
              exposure. Features include weakness, lethargy,
              gastrointestinal upset, dermal manifestations
              (hyperkeratosis and "raindrop" pigmentation of the skin), a
              peripheral (motor and sensory) neuropathy and psychological

         -    Also reported: peripheral vascular disease (cold sensitivity
              progressing to ulceration and gangrene), renal tubular or
              cortical damage and haematological abnormalities (notably



    1.   Irrigate with copious volumes of water.
    2.   Treat burns conventionally.
    3.   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.


    Armstrong CW, Stroube RB, Rubio T, Siudyla EA, Miller GB.
    Outbreak of fatal arsenic poisoning caused by contaminated drinking
    Arch Environ Health 1984; 39: 276-9.

    Donofrio PD, Wilbourn AJ, Albers JW, Rogers L, Salanga V, Greenberg
    Acute arsenic intoxication presenting as Guillain-Barr-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.

    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.

    Kersjes MP, Maurer JR, Trestrail JH, McCoy DJ.
    An analysis of arsenic exposures referred to the Blodgett Regional
    Poison Center.
    Vet Hum Toxicol 1987; 29: 75-8.

    Kingston RL, Hall S, Sioris L.
    Clinical observations and medical outcome in 149 cases of arsenate ant
    killer ingestion.
    Clin Toxicol 1993; 31: 581-91.

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

    Mathieu D, Mathieu-Nolf M, Germain-Alonso M, Neviere R, Furon D,
    Wattel F.
    Massive arsenic poisoning - effect of hemodialysis and dimercaprol on
    arsenic kinetics.
    Intensive Care Med 1992; 18: 47-50.

    McWilliams ME.
    Accidental acute poisoning by a concentrated solution of arsenic acid
    from percutaneous absorption: a case report.
    Vet Hum Toxicol 1989; 31: 354.

    Peterson RG, Rumack BH.
    D-penicillamine therapy of acute arsenic poisoning.
    J Pediatr 1977; 91: 661-6.

    Substance name

         Arsenic acid

    Origin of substance

         Reaction of arsenic trioxide with nitric acid
                                                 (HSDB, 1995)


         Orthoarsenic acid                       (DOSE, 1992)

    Chemical group

         A compound of arsenic, a group VA element

    Reference numbers

         CAS            7778-39-4                (DOSE, 1992)
         RTECS          CG0700000                (RTECS, 1995)
         UN             1554 (solid) 1553 (liquid)    (DOSE, 1992)
         HAZCHEM        2X                       (DOSE, 1992)

    Physicochemical properties

    Chemical structure
         H3AsO4                                  (DOSE, 1992)

    Molecular weight
         141.94                                  (DOSE, 1992)

    Physical state at room temperature
         Solid                                   (HSDB, 1995)

         White                                   (HSDB, 1995)



         Weakly acidic                           (HSDB, 1995)

         3020 g/L in water at 12.5C             (HSDB, 1995)

    Autoignition temperature

    Chemical interactions
         Aqueous solutions emit arsine gas when in contact with active
         metals such as arsenic, iron, aluminium and zinc.
                                                 (HSDB, 1995)

    Major products of combustion
         Produces arsine gas                     (HSDB, 1995)

    Explosive limits

         Not flammable                           (HSDB, 1995)

    Boiling point

         2.2 at 20C                             (HSDB, 1995)

    Vapour pressure

    Relative vapour density

    Flash Point

         Arsenic acid is a strong oxidizer.      (HSDB, 1995)


         Preparation of arsenate salts
         Manufacture of pesticides               (DOSE, 1992)

    Hazard/risk classification

    Index no. 033-005-00-1
    Risk phrases
         Carc. Cat. 1; R45 - May cause cancer
         T: R23/25 - Also toxic by inhalation and if swallowed
    Safety phrases
         S53-45 - Avoid exposure-obtain special instructions before use.
         In case of accident or if you feel unwell seek medical advice
         immediately (show label where possible).
    EEC No:  NIF                                 (CHIP2, 1994)


    Arsenic acid is one of the most commercially important pentavalent
    compounds of arsenic. It is formed from the treatment of arsenic
    trioxide with nitric acid and used in the manufacture of arsenate
    salts and pesticides. It is also formed by the slow reaction of
    arsenic pentoxide in water (Fielder et al, 1986).

    Aqueous solutions of arsenic acid can liberate arsine gas, the most
    acutely toxic form of arsenic, when in contact with active metals
    (HSDB, 1995).

    It has been suggested that soluble arsenic compounds such as arsenic
    acid represent a much more acute toxic hazard than insoluble, poorly
    absorbed forms (Done and Peart, 1971).


    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). In water arsenic acid forms the arsenate
    ion. Arsenate is the most thermodynamically stable oxide of arsenic in
    water and as such is believed to be the predominant species,
    especially under aerobic conditions (IPCS, 1981).

    Arsenic acid and its salts have been used widely in industry (Fielder
    et al, 1986; McWilliams 1989) and in pesticide formulations (Done and
    Peart, 1971; Miller et al, 1980) where they have been the source of
    acute and chronic, accidental and deliberate intoxication.


    Once absorbed pentavalent arsenic is reduced  in vivo to trivalent
    arsenic. The principle mechanism of arsenic intoxication is disruption
    of thiol proteins. For example, trivalent 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. Arsenic-induced 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 arsenical compounds such as arsenic acid are well absorbed
    after ingestion, when absorption is almost complete. Following
    inhalation there is significant mucociliary clearance and
    gastrointestinal absorption of respired particles (Fielder et al,

    From very limited animal data arsenic acid appears to be well absorbed
    through the lungs (Fielder et al, 1986).

    Although direct evidence of transcutaneous arsenic absorption in man
    is scarce (Fielder et al, 1986) there are reports of systemic arsenic
    toxicity following presumed dermal exposure (Garb and Hine, 1977;
    McWilliams, 1989).


    Absorbed arsenic is distributed to all body tissues (Fielder et al,
    1986). Once absorbed pentavalent arsenic is reduced  in vivo to
    trivalent arsenic. 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 (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

    Severe foot burns occurred in a patient exposed to concentrated
    arsenic acid-saturated clothing for eight hours (McWilliams, 1989).
    Soft tissue deposits believed to be metallic arsenic were noted on
    X-ray. The patient was transiently encephalopathic and developed a
    chronic painful foot motor neuropathy. Twenty four hour urine arsenic
    elimination ranged from 2500 mg falling to 160 mg during an eight week
    course of penicillamine.

    Garb and Hine (1977) reported a worker splashed down the left side of
    his body with arsenic acid in an industrial accident. He immediately
    removed a contaminated glove and washed his hands but did not notice
    arsenic acid in his left shoe for some ten minutes. After washing the
    affected leg and removing a soiled sock he continued to work for a
    further four hours by which time he had sustained second degree burns
    in the acid-exposed areas. Eleven hours after the incident he
    developed pain and swelling at the contact sites plus nausea,
    vomiting, diarrhoea and abdominal pain necessitating hospital
    admission. During the next three days his vision became "foggy" and he
    complained of a sore tongue and "aching teeth". After seven days he
    developed a burning sensation in the unexposed foot accompanied by
    paraesthesiae in all extremities. He became progressively weaker and
    was confined to a wheelchair. Two years after the accident diminished
    touch sensation and tendon reflexes persisted and he could walk only
    with a left leg brace and crutches. Chelation therapy was not employed
    at any time.

    Ocular exposure

    Arsenic acid is an eye irritant and may cause burns. Most injuries
    result from exposure to dusts, causing conjunctivitis, lacrimation,
    photophobia and chemosis (Grant and Schuman, 1993).


    The oral toxicity of arsenic acid is dependent on the amount ingested
    and the concentration of the preparation. Tallis (1989) noted that
    arsenate salts can react with hydrochloric acid in the stomach to
    liberate arsenic acid and the corresponding metal chloride. In this
    way poorly soluble salts such as lead arsenate can be a source of
    arsenic acid which is soluble and well absorbed.

    Although pentavalent arsenic is reduced  in vivo to the generally
    more toxic trivalent arsenic (Waldron and Scott, 1994) ingestion of
    dilute arsenic acid salt solutions (less than three per cent) usually
    are without serious adverse effects (Kingston et al, 1993). In 149
    such cases involving sodium arsenate (2.28 per cent) ant killer, 97
    per cent of patients were asymptomatic and only one required hospital
    admission (Kingston et al , 1993).

    Gastrointestinal toxicity

    Of 57 cases of ant killer ingestion involving arsenic acid salts
    (maximum arsenate concentration three per cent) only seven patients
    were symptomatic. All these vomited, with abdominal pain, diarrhoea
    and nausea also reported (Kersjes et al 1987).

    Armstrong et al (1984) reported eight family members (two of whom
    died) poisoned by well-water which contained arsenic 108 mg/L (form
    unknown). All had gastrointestinal symptoms including dry mouth,
    vomiting, dysphagia and/or diarrhoea. Urine arsenic concentrations
    were directly related to the amount of water consumed. The estimated

    daily dose of arsenic ingested by the surviving family members ranged
    from 26-127 mg. An 11 year-old girl and a 27 year-old man died after
    ingesting approximately 77 mg and 166 mg arsenic daily respectively
    (duration unknown). Autopsy of the most severely poisoned patient
    showed diffuse gastrointestinal tract inflammation.

    A 32 year-old man ingested 900 mg of an arsenic acid salt, vomited
    within one hour and developed diarrhoea three hours later. His
    clinical course was complicated by hypotension and renal failure but
    after 82 days chelation therapy with N-acetylcysteine he fully
    recovered (Martin et al, 1990).

    Another patient survived the deliberate ingestion of 10 g of an
    arsenic acid salt (Mathieu et al, 1992). Severe nausea, vomiting and
    abdominal tenderness developed within three hours with cardiovascular
    collapse and subsequent acute renal failure requiring haemodialysis.
    The patient made a full recovery over three months.

    Other gastrointestinal features of arsenic poisoning include burning
    of the mouth and throat with dysphagia (Heyman et al, 1956) and
    hypersalivation (Schoolmeester and White, 1980).


    Armstrong et al (1984) reported a 27 year-old man poisoned by well
    water containing 108 mg/L arsenic. He presented after feeling unwell
    for six days and on examination was jaundiced with a bilirubin
    concentration of 120 mol/L. He collapsed and died later that day and
    autopsy showed a liver arsenic concentration of 86 mg/kg. He had
    ingested an estimated 166 mg arsenic daily (duration unknown) and had
    a urine arsenic concentration of 1.6 mg/L at post mortem. Seven other
    members of his family with lower arsenic exposure showed transiently
    elevated serum hepatic transaminase activities and total bilirubin
    concentrations (values not given).

    Schoolmeester and White (1980) reported a 16 year-old female who
    ingested 300 mg sodium arsenate in a suicide attempt. She developed
    severe abdominal pain and vomiting within 30 minutes. A 24 hour urine
    collection had an arsenic concentration of 14.2 mg/L (time of
    collection not stated). Forty-eight hours later serum liver
    transaminase and alkaline phosphatase activities were elevated (values
    not given) but these abnormalities resolved within six months.


    Hypotension (Martin et al, 1990; Mathieu et al, 1992) or
    rhabdomyolysis following substantial arsenic acid ingestion may
    precipitate renal failure. Renal cortical necrosis has been described
    (Gerhardt et al, 1978). Haematuria was reported in one patient in a
    series of 57 cases of sodium arsenate ingestion (Kersjes et al, 1987).

    Pyuria, proteinuria and elevated serum creatinine concentrations were
    reported in members of a family poisoned with arsenic-contaminated
    well-water (Armstrong et al, 1984). The most severely poisoned
    patient, who died after a six day illness, developed gross haematuria,
    a serum creatinine concentration of 390 mol/L and heavy proteinuria.
    He had consumed an estimated 166 mg arsenic daily (duration unknown)
    and had a urine arsenic concentration at post mortem of 1.6 mg/L. No
    chelation therapy was given. The other family members were treated
    with dimercaprol and penicillamine. Six eventually recovered.

    Cardiovascular toxicity

    Tachycardia is reported frequently following ingestion of arsenic acid
    salts and is contributed to by anxiety, intravascular fluid depletion
    and possibly direct arsenic-induced cardiotoxicity (Le Quesne and
    McCleod, 1977; Martin et al, 1990; Cullen et al, 1995).

    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; Schoolmeester and White,
    1980), idioventricular rhythm (Armstrong et al, 1984) and non-specific
    T wave changes. Sudden onset bradycardia then asystole has been
    reported following massive acute arsenic ingestion despite vigorous
    resuscitation and no earlier arrhythmia.

    Armstrong et al (1984) reported a 27 year-old man who had consumed an
    unstated quantity of well-water containing 108 mg/L arsenic. After a
    six day illness (diagnosed as an upper respiratory tract infection) he
    collapsed and sustained a respiratory arrest and seizures. An
    idioventricular rhythm was noted. He was resuscitated but remained
    comatose and died a few hours later.

    Pericardial effusion with tamponade was reported in another member of
    the same family who had also drunk arsenic-contaminated water; the
    outcome in this case was not stated (Armstrong et al, 1984).


    In 57 sodium arsenate ingestions involving solutions containing
    1.5-3.0 per cent arsenate, headache, dizziness, lethargy and
    somnolence were each reported in 2 per cent of cases; 88 per cent of
    patients were asymptomatic (Kersjes et al 1987).

    More substantial arsenic ingestions have caused 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.

    Armstrong et al (1984) reported eight family members poisoned with
    well-water containing 108 mg/L arsenic. All developed gastrointestinal
    symptoms with "altered mental status" and seizures noted in four. Coma
    developed in three patients and a peripheral neuropathy in two.

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

    A 46 year-old man developed feet numbness ten days after drinking a
    solution of sodium arsenate (concentration unknown) in attempted
    suicide. Two months after ingestion neurological examination
    demonstrated distal muscle weakness bilaterally, absent knee and ankle
    reflexes and reduced position and vibration sense with a high-stepping
    gait. Sixteen months later there was improvement in both sensory and
    motor deficits although residual disability was evident at eight year
    follow-up (Le Quesne and McCleod, 1977).

    Dermal toxicity

    Le Quesne and McCleod (1977) described a patient who developed a
    papular erythematous rash and generalized epidermal desquamation one
    week after drinking 10 mL of an arsenate solution (concentration

    Striate leukonychia (Mees' lines) and hyperkeratotic or hyperpigmented
    skin lesions are characteristic of chronic arsenic intoxication but
    have been described also following substantial acute ingestion (Heyman
    et al, 1956; Kyle and Pease, 1965; Jenkins, 1966).

    Facial and peripheral oedema have also been reported following arsenic
    ingestion (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; Armstrong
    et al, 1984). There may be evidence of intravascular haemolysis and
    the blood film often shows basophilic stippling (Kyle and Pease,

    Mathieu et al (1992) described a 30-year-old male who ingested 10 g
    sodium arsenate with suicidal intent. He developed severe
    gastrointestinal features of arsenic poisoning within hours and
    required haemodialysis for management of acute renal failure. Five
    days after ingestion he developed thrombocytopenia and anaemia. Bone
    marrow examination showed maturation arrest but recovery ensued over
    10 days.

    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 (ARDS) has been described
    (Bolliger et al, 1992).


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


    Dermal exposure

    Occupational exposure may lead to chronic arsenical toxicity.

    Contact dermatitis has been reported in workers exposed to arsenic
    acid salts used in crystal manufacture (Barbaud et al, 1995).


    Ingestion of arsenic-contaminated drinking water (Feinglass, 1973;
    Chiou et al, 1995), illicit whisky (Moonshine) (Gerhardt et al, 1980)
    "tonics" or traditional remedies have caused chronic arsenical


    Occupational exposure may lead to chronic arsenical poisoning.
    Perforation of the nasal septum has been reported.

    Systemic arsenic acid toxicity

    The systemic features observed are similar for each source of exposure
    which are considered together.

    General toxic effects

    Patients with chronic arsenic acid poisoning 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). 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).

    Exfoliative dermatitis (Nicolis and Helwig, 1973) has been reported.

    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 (Schoolmeester and White, 1980) have been reported.
    The neuropathy may be confused with the Guillain-Barr 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-Barr 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 (Heyman et al, 1956; Schoolmeester and White,

    Hutton et al (1982) described a case of chronic self-intoxication with
    sodium arsenate ant poison. The patient was initially admitted with
    gastrointestinal symptoms and pancytopenia. He subsequently developed
    severe peripheral neuropathy and myelopathy. Urinalysis revealed an
    arsenic concentration of 3600 mg/L. The patient eventually admitted
    self-administering arsenic in order to secure early retirement on
    medical grounds.

    Gastrointestinal toxicity

    Nausea is common in chronic arsenical poisoning. In the German
    literature Reinl (1970) reported a 53 year-old man who had been
    exposed to arsenic acid used as an oxidizing agent in chemical
    manufacture. During his ten year employment he developed symptoms
    including diarrhoea and vomiting. He died of lung cancer believed to
    be related to arsenic exposure.


    Abnormal liver enzyme activities (Schoolmeester and White, 1980) have
    been observed in chronic arsenic poisoning.

    Arsenic-induced cirrhosis has been described but may be explained by
    concomitant excess ethanol consumption (Morton and Dunnette, 1994).

    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.

    In the German literature cirrhosis and splenomegaly were reported at
    autopsy of a 53 year-old man occupationally exposed to arsenic acid
    for ten years. Dermal and gastrointestinal symptoms occurred during
    his employment and arsenic induced lung cancer was cited as the cause
    of death (Reinl, 1970).


    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 the myocardial toxicity of arsenic
    (Schoolmeester and White, 1980; Hall and Harruff, 1989) which has been
    attributed to impaired oxidative metabolism of myocardial tissue plus
    a direct arsenic-induced inflammatory process. A 42 year-old
    agricultural worker presented with systemic features of chronic

    arsenic poisoning (neuropathy and skin lesions) and had a 24 hour
    urine arsenic excretion of 7000 g (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


    Pancytopenia has been reported in cases of chronic intoxication by
    arsenic acid salts (Schoolmeester and White, 1980; Hutton et al,
    1982). Anaemia, neutropenia (Heyman et al, 1956; Kyle and Pease,
    1965), or evidence of haemolysis (Kyle and Pease, 1965) have also been
    reported as have macrocytosis without anaemia (Heaven et al, 1994) and
    a myelodysplastic syndrome (Rezuke et al, 1991).

    Chronic arsenic exposure complicated by aplastic anaemia may
    predispose to acute myeloid leukaemia (Kjeldsberg and Ward, 1972).

    Disrupted haem metabolism with altered urinary porphyrin excretion
    (Garcia-Vargas et al, 1994) has been reported.

    Pulmonary toxicity

    An irritating cough and haemoptysis have been reported in chronic
    arsenic intoxication (Heyman et al, 1956).

    Endocrine toxicity

    Epidemiological evidence from Taiwan (Lai et al, 1994) has recently
    associated chronic arsenic exposure with the development of diabetes


    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.



    After acute ingestion of a substantial quantity of arsenic acid 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 arsenic acid 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).


    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


    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 g/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 g/24 h and 5819 g/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 g 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 g/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 (Bansal et al, 1991). 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.

    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 (Cullen et al, 1995). 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 g/L in the first
    24 hours after admission). On the third hospital day the urine arsenic
    concentration (from a 24 hour collection) was 1355 g/L and fell
    progressively to 96 g/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
    g/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 g to a maximum of 340 g on the second day
    of oral DMSA 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 g/L on day five). Four days later
    the urine arsenic concentration had fallen to 96 g/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 g/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 g/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 g 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 g, increasing in the next 24 hours
    (the second day of d-penicillamine therapy) to approximately 800 g.
    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 g arsenic, increasing to 2000 g
    arsenic in the next 24 hours before falling to approximately 200 g/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 g (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 (Watson et al, 1981). 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 g/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, 1981).

    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 g/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 was not stated). However, the 24 hour urine arsenic
    excretion only rose to 82.4 g/g creatinine in the first 72 hours of
    chelation compared to a pretreatment value of 73.5 g/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 g/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 g/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 g
    (normal <5 g/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 g/L
    after four days penicillamine therapy 500 mg qds compared to a
    pretreatment concentration of 7840 g/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

    1.   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.

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

    3.   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 alone.


    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 g 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 g though
    this increased to 75,000 g/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 24 hour urine arsenic excretion collection, although spot
    urine arsenic concentrations have been proposed in screening
    asymptomatic patients with a history of possible acute arsenic
    ingestion (Grande et al, 1987).

    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 (Farmer and Johnson,
    1990; Buchet et al, 1994). However, Vahter (1994) has suggested that

    under certain circumstances these compounds are released from seafood
    which can invalidate assessment of inorganic arsenic exposure.

    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 preservative (Gollop and Glass,

    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 practise 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 (Schoolmeester and White, 1980; 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
    (Shannon and Strayer, 1989).

    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 (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) and liver, both hepatic angiosarcoma and hepatocellular
    carcinoma (Chen and Lin, 1994).

    Reinl (1970) reported the death of a 53 year-old man who had been
    exposed to arsenic acid for ten years. The compound had been used an
    as oxidizing agent in a chemical manufacturing process. He suffered
    gastrointestinal and dermal symptoms of arsenic toxicity during his
    employment and at autopsy arsenic induced metastatic bronchial
    carcinoma was diagnosed as the cause of death.

    Smoking exerts a synergistic effect with ingested and inhaled arsenic
    in the development of pulmonary malignancy. 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).

    Daya et al (1989) reported a 22 year-old female who ingested 340 mg
    sodium arsenate while 20 weeks pregnant. Treatment with dimercaprol
    150 mg four hourly was commenced two hours post ingestion, the maximum
    24 hour urine arsenic excretion was 3030 g/L and a healthy infant was
    delivered at 36 weeks.

    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).

    Genotoxicity (sodium arsenate)

    Cultured human peripheral lymphocytes: Induced chromosomal aberrations
    and sister chromatid exchanges.

    Syrian hamster cells and human lymphocytes: Induced sister chromatid
    exchanges and chromosomal aberrations.

    Chinese hamster ovary cells: Induced chromosomal aberrations.

     Drosophilia melanogaster: Wing spot test negative (sodium arsenate
    is highly toxic to  Drosophilia and hence could only be tested at
    very low concentrations) (DOSE, 1994).

    Fish toxicity (arsenic)

    EC50 (96 hr) fathead minnow 141-144 mg/L.

    LC50 96 hr) knifefish 31 mg/L.

    Oral administration (0.52 mg/kg/day for 24 weeks) to rainbow trout
    caused chronic inflammatory changes in subepithelial tissues of the
    gall bladder wall in 71 per cent of the group.

    LC50 (96 hr) striped base 30 mg (DOSE, 1992).

    EC Directive on Drinking Water Quality 80/778/EEC

    Maximum admissible concentration 50 g/L, as arsenic (DOSE, 1992).

    WHO Guidelines for Drinking Water Quality

    Guideline value 10 g/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