1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Main brand names, main trade names
   1.6 Main manufactures, main importers
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First-aid measures and management principles
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Colour
      3.3.2 State/Form
      3.3.3 Description
   3.4 Hazardous characteristics
   4.1 Uses
      4.1.1 Uses
      4.1.2 Description
   4.2 High risk circumstance of poisoning
   4.3 Occupationally exposed populations
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Others
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination by route of exposure
   7.1 Mode of action
   7.2 Toxicity
      7.2.1 Human data Adults Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
      7.2.4 Workplace standards
      7.2.5 Acceptable daily intake (ADI) and other guideline levels
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection Toxicological analyses Biomedical analyses Arterial blood gas analysis Haematological analyses Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens Toxicological analyses Biomedical analyses Arterial blood gas analysis Haematological analyses Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens Toxicological analyses Biomedical analyses Arterial blood gas analysis Haematological analyses Other (unspecified) analyses
   8.2 Toxicological analyses and their interpretation
      8.2.1 Tests on toxic ingredient(s) of material Simple qualitative test(s) Advanced qualitative confirmation test(s) Simple quantitative method(s) Advanced quantitative method(s)
      8.2.2 Tests for biological specimens Simple qualitative test(s) Advanced qualitative confirmation test(s) Simple quantitative method(s) Advanced quantitative method(s) Other dedicated method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis Blood, plasma or serum Urine Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical (diagnostic) investigations and their interpretation
   8.5 Overall interpretation of all toxicological analyses and toxicological investigations
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological Central Nervous System (CNS) Peripheral nervous system Autonomic nervous system Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary Renal Other
      9.4.7 Endocrine and reproductive systems Endocrine system Reproductive system
      9.4.8 Dermatological
      9.4.9 Eye, ears, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.2.12 Metabolic Acid-base disturbances Fluid and electrolyte disturbances Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Others
   9.6 Summary
   10.1 General principles
   10.2 Life supportive procedures and symptomatic treatment
   10.3 Decontamination
   10.4 Enhanced elimination
   10.5 Antidote treatment
      10.5.1 Adults
      10.5.2 Children
   10.6 Management discussion
   11.1 Case reports from literature
   12.1 Specific preventive measures
   12.2 Other

    International Programme on Chemical Safety
    Poisons Information Monograph 042

    1.  NAME

         1.1  Substance

              Arsenic, inorganic

         1.2  Group

         1.3  Synonyms
        Table 1 Arsenic and salts: synonyms, structure and identification
    numbers   (IPCS, 1992)

    Chemical             Relative    Structural          Identification numbers
    name                 molecular   formula
                         mass                       CAS              RTECS          UN


    Arsenic sulfide      246,02      As2S3        1303-33-9       CG2638000        1557

    and trade

    * Arsenic
    * Arsenic
    * Arsenic
    * Arsenic
    * Arsenious
    * Arsenous
    * Auripigment
    * C.I. 77086
    * C.I. pigment
    * Diarsenic
    * Kings Gold
    * Orpiment

    Chemical             Relative    Structural          Identification numbers
    name                 molecular   formula
                         mass                       CAS              RTECS          UN

    Arsenic              181,27      AsCl3        7784-34-1       CG1750000        1560

    and trade

    * Arsenic
    * Arsenious
    * Arsenous
    * Caustic
    * Caustic
    oil of
    * Fuming

    Arsenic              197,82      As2O3        1327-53-3       CG3325000        1561

    and trade

    * Arsenic
    * Arsenic
    * Arsenic
    sesqui oxide
    * Arsenicum
    * Arsenious
    * Arsenious
    * Arsenious
    * Arsenite
    * Arsenolite
    * Arsenous

    * Arsenous
    * Arsenous
    * Arsenous
    * Arsodent
    * Claudelite
    * Crude
    * Diarsenic
    * White

    Chemical             Relative    Structural          Identification numbers
    name                 molecular   formula
                         mass                       CAS              RTECS          UN

    Cupric               187,46      CuHAsO3      10290-12-7      CG3385000        1586

    and trade

    * Schelle's

    Gallium              144,64      AsGa         1303-00-0       LW8800000        n.a.

    and trade

    * Gallium

    Potassium            399,65      KH(AsO2)2    10124-50-2      38000000         1678

    and trade

    * Arsenenous
    * Arsenious

    * Arsonic
    * Fowlers
    * Potassium

    Chemical             Relative    Structural          Identification numbers
    name                 molecular   formula
                         mass                       CAS              RTECS          UN

    Sodium               129,9       NaAsO2       7784-46-5       CG367500         1686
    arsenite                                                                       2027

    and trade

    * Arsenenous
    * Arsenious
    * Prodalumnol
    * Sodanit
    * Sodium


    pentoxide            229,84      As2O5        1303-28-2       GC2275000        1559

    and trade

    * Arsenic
    * Arsenic
    * Arsenic
    * Arsenic (V)

    * Diarsenic

    Chemical             Relative    Structural          Identification numbers
    name                 molecular   formula
                         mass                       CAS              RTECS          UN

    Calcium              398,06      Ca3(AsO4)2   7778-44-1       CG0830000        1573

    and trade

    * Arsenic
    * Calcium
    * Chipcal
    * Pencal
    * Spracal
    * Tricalcium

    Lead                 347,12      PbHAsO4      7784-40-9       CG0980000        1617

    and trade

    * Acid
    * Acid
    * Arsenate
    of lead
    * Arsenic
    lead salt
    * Arsinette
    * Gypsine
    * Lead acid
    * Plumbous
    * Schultenite
    * Soprabel

    * Standard
    * Talbot

    Chemical             Relative    Structural          Identification numbers
    name                 molecular   formula
                         mass                       CAS              RTECS          UN

    *Potassium           180,04      KH2AsO4      7784-41-0       CG1100000        1677

    and trade

    * Arsenic
    * Macquers
    * Monopotassium
    * Monopotassium
    * Potassium
    * Potassium
    * Potassium
    * Potassium

    Sodium               302,88      Na3AsO4      7631-89-2       CG1225000        1685

    and trade

    * Arsenic

    * Arsenic
    * Sodium

    * n.a.: not available
            1.4  Identification numbers

             1.4.1  CAS number

                    See table 1.3

             1.4.2  Other numbers

                    See table 1.3

        1.5  Main brand names, main trade names

        1.6  Main manufactures, main importers

    2.  SUMMARY

        2.1  Main risks and target organs

             After absorption, arsenic may cause multi-organ failure.
             The primary target organs initially are gastrointestinal
             tract, the heart, brain and kidneys. The skin, bone marrow
             and peripheral nervous system may be affected.
             In severe poisoning, the patient may die early of
             cardiovascular disturbances, mainly intravascular volume
             depletion and severe shock.

        2.2  Summary of clinical effects

             In acute poisoning, symptoms begin usually within the
             first hours following ingestion. Garlic-like odour of breath,
             gastric content and faeces may be indicative.
             Gastrointestinal disturbances (vomiting, gastrointestinal
             pain, diarrhoea) are the main clinical effects.
             After an apparent remission (1 to 2 days), several organs are
             affected by the systemic action of inorganic arsenic
             (cardiovascular, renal, hepatic and cutaneous
             manifestations).  This will produce hypotension, tachycardia,
             ECG modifications of QT and T wave, airway irritation,
             pulmonary oedema, haematuria, acute renal failure, acute
             haemolysis, altered mental status, confusion, delirium,
             convulsions, encephalopathy.
             If the patient survives the cardiovascular failure, and after
             a long convalescence, sequelae are observed, mainly
             peripheral neuropathy and Mee's lines on nails.

        2.3  Diagnosis

             Diagnosis is based on history, symptoms, signs and
             laboratory investigations, but treatment should start on
             suspicion of poisoning.  The diagnosis may be confirmed by
             quantification of arsenic in urine in acute cases and hair in
             chronic exposure.
             In acute, massive arsenic ingestion, barium-like opacities on
             abdominal X-ray may be demonstrated.

        2.4  First-aid measures and management principles

             Due to the toxic action of inorganic arsenic on the
             gastrointestinal tract in acute poisoning, and the subsequent
             liquid losses, special care to the fluid-electrolyte balance
             is required to prevent cardiovascular toxicity. Hypovolemia,
             cardiac arrhythmias and cardiovascular failure are the main
             cause of early death.
             Transport of the patient to an hospital and monitoring of
             vital functions in an intensive care department is therefore
             Gastric decontamination using gastric lavage and activated
             charcoal is highly recommended. Whole bowel irrigation should
             be considered if the presence of arsenic in the lower
             gastro-intestinal tract is observed by X-ray. Maintain high
             urine output with an alkaline pH. Chelation therapy using BAL
             or DMSA or DMSP should be rapidly envisaged.
             In the meantime, first aid should be commenced.


        3.1  Origin of the substance

             Arsenic is an ubiquitous element mainly present in the
             lithosphere as arsenic minerals or arsenic impurities in
             minerals or as arsenic in various rock types and fossil fuels
             (NRCC, 1978). In soils, arsenic is present as arsenite
             (As(III)) and arsenate (As(V)) and in an organic form.
             Industrial and agricultural sources of arsenic may enhance,
             sometimes in a dramatic way, the natural levels of arsenic:
             mining activities, smelters, coal and coal combustion
             by-products, withdrawal sludges, pesticides (Bhumbla, 1994;
             NRCC, 1978).

        3.2  Chemical structure

             Chemical name                  : See table 1.3
             Relative molecular mass        : See table 1.3
             Structural formula             : See table 1.3
        Table 2 Arsenic and salts: physico-chemical properties 
    (IPCS, 1992)
    Arsenic      Normal state     Colour           Odour    Soluble         Insoluble
    compound     (at room                                   (g/litre)
    * Arsenic    * Powder         * Yellow-red     n.a.     * Hot water     * Water
    sulphide                                                (slightly)      (cold)
                                                            * Alkali
                                                            * Acids
                                                            * Ethanol
    * Arsenic    * Liquid         * Colourless     Acrid    * Ethanol       * (decomposed
    trichloride    (oily)                          smell    * Ether         by water)
                                                            * Concentrated
                                                            mineral acids
    * Arsenic    * Powder         * White          Odour    * Water         * Alcohol
    trioxide     (amorphous or                     less     - cold (12)     * Chloroform
                 crystalline)                               - 20EC (37)     * Ether
                                                            - hot (115)
                                                            * Alkali
                                                            * HCl

    Arsenic      Normal state     Colour           Odour    Soluble         Insoluble
    compound     (at room                                   (g/litre)
    * Cupric     * Powder         * Yellowish-     n.a.     * Acids         * Water
    arsenite                      green                     * Ammonia       * Alcohol
    * Gallium    * Solid          * Dark grey      n.a.     n.a.            * Water
    arsenide     (cubic           with
                 crystals)        metallic
    * Potassium  * Powder         * White          n.a.     * Water         n.a.
    arsenite                                                * Ethanol
    * Sodium     * Powder         * White          n.a.     * Water         n.a.
    arsenite                      or greyish-               (very)
                                  white                     * Ethyl
    * Arsenic    Powder           * White          n.a.     * Cold          n.a.
    pentoxide    (hygroscopic)                              water (1500)
                                                            * Hot
                                                            water (767)
    * Calcium    Powder           * Colourless     Odour-   * Water         n.a.
    arsenate     (amorphous)                       less     (slightly)
                                                            * Dilute
    * Lead       * Powder         * White          n.a.     * Hot water
    arsenate     or solid                                   (slightly)      n.a.
                 (crystalline)                              * Dilute
                                                            nitric acid
                                                            * Caustic
    * Potassium  * Powder         * White          n.a.     * Cold          n.a.
    arsenate     (crystalline)                              water (190)
                                                            * Hot
                                                            water (very)
                                                            * Acid
                                                            * Glycerol
                                                            * Ammonia

    Arsenic      Normal state     Colour           Odour    Soluble         Insoluble
    compound     (at room                                   (g/litre)
    * Sodium     * Powder         * Clear          Odour    * Water (very)  * Ether
    arsenate                      colourless       less     * Alcohol
    Arsenic compound     Boiling point (EC)    Melting point (EC)    Sublimation (EC)
    * Arsenic            707                   300 -325             n.a.
    * Arsenic            130                   16                   n.a.

    * Arsenic            465                   n.a.                 315
    * Cupric             n.a.                  Decomposes           n.a.
    * Gallium            n.a.                  1238                 n.a.
    * Potassium          n.a.                  300 (decomposes)     n.a.
    * Sodium             n.a.                  n.a.                 n.a.
    * Arsenic            n.a.                  315 (decomposes)     n.a.
    * Calcium            Decomposes            1455                 n.a.
    * Lead               Decomposes            720 (decomposes)     n.a.
    * Potassium          n.a.                  288                  n.a.
    * Sodium             180                   n.a.                 n.a.
    *  n.a.: not available
            3.3  Physical properties

             3.3.1  Colour

                    See Table 2

             3.3.2  State/Form

                    See Table 2

             3.3.3  Description

                    See Table 2

        3.4  Hazardous characteristics

             See table 2

    4.  USES

        4.1  Uses

             4.1.1  Uses

             4.1.2  Description

                    Arsenic salts are used as pesticides, wood
                    preservative, for glass manufacturing, in alloys,
                    electronics, paint pigment and in the manufacture of
                    Arsenic preparations are no longer recommended and are
                    rarely used for medical purpose. Some homeopathic
                    preparations (arsenicum album: As2O3) (Kerr &
                    Saryan, 1986) or "natural" remedies or preparations
                    (Asian herbal remedies: e.g. herbal tea for example)
                    (Gorby, 1988) may contain different arsenic compounds.

        4.2  High risk circumstance of poisoning

             The main sources of human exposure to arsenic are:
             -   Ingestion of contaminated water and /or food, mainly in
                 environmentally exposed populations. Many outbreaks of
                 arsenic poisoning are related to ingestion of water
                 obtained from contaminated wells.
             -   Ingestion of medicinal/homeopathic preparations
                 containing arsenic.
             -   Malicious or criminal activity, or for suicidal attempts.

        4.3  Occupationally exposed populations

             Inhalation of arsenic containing dusts or volatile
             arsenicals during industrial or agricultural exposures.
             Absorption through skin and mucous membranes during the
             handling of arsenicals or through prolonged therapeutic usage
             of arsenical preparations.
             Main occupational exposures are the following:
             -   Workers (mainly roaster workers) engaged in the smelting
                 industries: copper, gold, lead, silver and zinc ores,
                 where arsenic is present as a contaminant or 
             -   Workers engaged in the manufacturing of pesticides,
                 herbicides and other agricultural products using arsenic
                 preparations and industrial or agricultural workers using

             -   Arsenic in wood processing plants.
             -   Arsenic as desiccant or defoliant for the preparation of
                 cotton fields for harvesting.
             -   Various metallurgical or industrial activities like the
                 electrolysis of copper, or cadmium, with arsenic as a


        5.1  Oral

             Oral absorption of arsenic is the main route of exposure
             for the general population and may be accidental (ingestion
             of arsenical pesticides by children) or, more rarely,
             voluntary or criminal. During occupational exposure,
             ingestion of inhaled arsenic dusts or direct contamination
             through lack of occupational hygiene.

        5.2  Inhalation

             Inhalation exposure to dusts or aerosols containing
             arsenic occurs mainly in industry (smelting of ores) or
             agriculture (mixing and/or spraying pesticides) and can
             produce toxic effects on the respiratory tract along with
             systemic effects.

        5.3  Dermal

             Dermal absorption can result from topical application of
             arsenical agents or from accidental contact with arsenicals
             (eg. arsenic acid: Garb & Hine, 1977) and may result in
             systemic toxicity.

        5.4  Eye

             Ocular contact with dusts or accidental splashing has
             occurred in industry (Grant, 1986), resulting in local toxic

        5.5  Parenteral

             No data available.

        5.6  Others

             No data available.

    6.  KINETICS

        6.1  Absorption by route of exposure

             Oral absorption
             Pentavalent arsenic compounds are almost totally absorbed
             (till 90%) in most species. The absorption of trivalent
             arsenic is limited, although the toxicity is greater because
             of the high lipid solubility (Mahieu et al., 1981;
             Schoolmeester & White, 1980).
             Absorption by inhalation
             Animals studies indicate a wide range of absorption according
             to species, chemical form and particle size of arsenicals;
             the clearance half-life from the lungs being from 30 minutes
             to several days.
             Several studies, involving workers exposed to inorganic
             arsenic, indicate a rather good relationship between airborne
             concentrations of inorganic arsenic and urinary excretion of
             arsenic and its metabolites.
             Skin absorption
             Systemic poisoning involving prolonged cutaneous application
             of arsenical agents (Robinson, 1975) or splashing on the skin
             of arsenic acid (Garb & Hine, 1977) indicate an absorption of
             inorganic arsenic through the skin.

        6.2  Distribution by route of exposure

             Once absorbed, arsenic is bound to haemoglobin,
             leucocytes, and plasma proteins. It is cleared from the
             intravascular space within 24 hours, and distributed in most
             tissues (Jolliffee, 1991; Schoolmeester & White, 1980).
             The ratio between red cell and plasma arsenic concentrations
             increases with the level of exposure: from 1/1 for low
             exposures to 3/1 for high environmental exposures (Vahter,
             Soluble inorganic compounds, well absorbed by
             gastro-intestinal tract or by lungs, are rapidly distributed
             to organs or tissues rich in proteins containing sulfhydryl
             groups, and accumulate mainly in liver, kidneys, spleen and
             adrenal gland (Quatrehomme, 1992).

             In humans, not exposed occupationally or environmentally to
             arsenic compounds, arsenic binds to the sulfhydryl groups in
             keratin and can be detected in hair, nails, and skin 2 to 4
             weeks after exposure.  After 4 weeks, arsenic localizes in
             bone, coinciding with decreasing levels in the liver and
             kidneys (Jolliffe et al., 1991; Schoolmeester & White, 1980;
             Winship, 1984).
             Arsenic compounds can cross the placental barrier (Lugo,

        6.3  Biological half-life by route of exposure

             Blood clearance of arsenic occurs in three phases. In
             phase 1, a rapid decline occurs within 2 to 3 hours; some
             estimate that greater than 90% of arsenic clears from the
             blood, with a half-life of 1 to 2 hours (Vahter, 1980;
             McKinney, 1992). For the remaining arsenic, a more gradual
             decline occurs in phase 2, from 3 hours to 7 days (estimated
             half-life is 30 hours), followed by phase 3, a slower
             elimination phase with an estimated half-life of 200 hours
             (Vahter, 1980; Mealey, 1959)

        6.4  Metabolism

             After absorption inorganic arsenic is biotransformed
             into two organic methylated derivatives:
             -  Monomethylarsenic (MMA) and
             -  Dimethylarsenic acid (DMA)
             DMA seems to be produced by a subsequent methylation of the
             MMA precursor (Buchet et al., 1981;  Buchet & Lauwerys,
             The methylation process is dose dependent and as the dose of
             arsenic increases, a reduction of the percentage of DMA is
             observed in urine while retention of arsenic is higher (EPA,
             1984; Vahter, 1983).
             Unusual metabolic processes have been reported in literature:
             -  Case of methylenetetrahydrofolate reductase deficiency,
                with increased neurotoxicity of arsenic, in a 16-year-old
                girl, exposed to arsenic from CCA, in Suriname (Brouwer et
                al., 1992).

             -  Very little excretion of arsenic in urine, as MMA (about
                2%), in native Andean women exposed to high levels of
                arsenic in water (Vahter et al., 1995).  In this case, a
                genetic polymorphism in the control of the
                methyltransferase activity has been postulated.

             Compared with inorganic As, the methylated metabolites are
             less reactive with tissue constituents, less acutely toxic,
             less cytotoxic, and more readily excreted in the urine
             (ATSDR, 1998).

        6.5  Elimination by route of exposure

             Inorganic arsenic compounds are mainly excreted via the
             kidneys but the rate of urinary arsenic excretion depends
             upon the chemical form of the compound ingested, the route of
             exposure and the dose level (Vahter, 1983).  Other secondary
             routes of elimination are hair, nails, sweat and faeces.
             Urinary excretion
             Following absorption of inorganic arsenic, arsenic is
             excreted in the urine as DMA (60%) MMA (20%) and inorganic
             arsenic (20%) (Crecelius, 1977; Tam et al., 1979).
             One day after an ingestion of an oral dose (10 µg of arsenic
             as main pentavalent compound, i.e. arsenic acid 90%), 22.4%
             is recovered in urine; 57.9% after 5 days (Tam et al.,
             In the presence of insoluble inorganic compounds like arsenic
             selenite, there is no urinary excretion (Mappes, 1977).
             When multiple doses are administered, at steady state, 60% of
             the dose is excreted in urine (Buchet et al., 1981).
             It has been estimated that the daily excretion of arsenic
             metabolites is 30 - 60% of the inhaled amount (ATSDR,
             Other routes of excretion
             -  Faecal/biliary excretion
             Only a few percent is excreted in faeces (Ishinishi et al.,
             1986). This small faecal excretion (< 10%) is probably
             related to a reabsorption by intestines of arsenic eliminated
             by the bile.
             -  Sweat
             Sweat in a hot, humid environment can eliminate 2 µg of As
             per hour (Vahter, 1983).
             -  Skin
             Desquamation of skin can contribute to an elimination of 0,1
             to 0,2 µg of As per day (Molin, 1976).

             -  Hair and nails
             Inorganic arsenic is incorporated to hairs or nails (Winship,


        7.1  Mode of action

             The toxicity of arsenic compounds is generally linked to
             the soluble inorganic trivalent forms. The toxicity of
             pentavalent inorganic compounds seems related to the in vivo
             reduction of As(V) to As(III) (Harvey, 1970).
             Inorganic arsenic compounds react with sulfhydryl (-SH)
             groups of cellular proteins, thereby inhibiting cellular
             oxidative processes (pyruvate and succinate oxidative
             pathways) (Arena & Drew, 1986; Harvey, 1970; Schoolmeester &
             White, 1980).
             Competition with phosphorus in the oxidative phosphorylation
             process is caused by inorganic compounds (Dickerson, 1994),
             mainly in the pentavalent form (Harvey, 1970).
             The diffuse toxic process of arsenic poisoning causes
             widespread endothelial cellular toxicity, resulting in
             capillary damage and tissue hypoxia precipitating generalized
             vasodilatation and transudation of plasma. Gastrointestinal,
             cardiac, renal, bone marrow, central nervous system, and
             hepatic damage may be noted at different stages of arsenic
             poisoning (Donofrio et al., 1987; Fincher & Koeker, 1987;
             Jolliffe et al., 1991; Schoolmeester & White, 1980; Winship,

        7.2  Toxicity

             7.2.1  Human data


                             A certain tolerance is believed to
                             develop upon repeated long term exposure with
                             low doses as seen in arsenic-eaters in
                             Austria and Styria, in last century (Tardieu,
                             1867).  Though not well documented in the
                             scientific literature, that tolerance could
                             be seen against acute poisoning (Foa,
                             In adults, the estimated lethal dose varies
                             from 50 to 300 mg of inorganic compounds
                             (Armstrong et al., 1984; Hindmarsh, 1986;
                             Vallee, 1960; Zaloga et al., 1985).

                             For As2O3, the lowest reported lethal
                             dose is about 120 mg (Arena, 1967). The fatal
                             dose of ingested arsenic trioxide has also
                             been reported to lie between 70 and 180 mg
                             (Vallee, 1960).
                             Severe toxicity has been reported with the
                             ingestion of as little as 1 mg As203, but
                             as little as 20 mg can be life threatening
                             (Schoolmeester et al., 1980; Winship,


                             Subchronic oral exposure to only 3
                             mg/day was fatal in a number of children
                             exposed to arsenic via contaminated milk
                             (Hamamoto, 1955).

             7.2.2  Relevant animal data

                    Experimental data suggest that animals are not
                    as sensitive to inorganic arsenic compounds as humans,
                    and that this difference is not due entirely to
                    differences in gastro-intestinal absorption  (ATSDR,

             7.2.3  Relevant in vitro data

                    No relevant data.

             7.2.4  Workplace standards

                    American conference of Governmental Industrial
                    Hygienists (ACGIH)
                    -   ACGIH (1995) consider arsenic, elemental
                        (7440-38-2) and inorganic arsenic compounds
                        (except arsine) as a confirmed human carcinogen,
                        and has set up the standard for arsenic at 0,01
                        mg/m3 (TLV-TWA: Threshold Limit Value - Time -
                        Weighted Average).
                    -   ACGIH (1995) has adopted also a Biological
                        Exposure Indice (BEI) for arsenic and soluble
                        compounds including arsine (7784-42-1) of 50 µg/g
                        creatinine (inorganic arsenic metabolites in
                        urine), for a sampling time at the end of the

             7.2.5  Acceptable daily intake (ADI) and other guideline

                    International standards

                    -  Provisional tolerable weekly intake (PTWI)

                    0.015 mg/kg/body weight for inorganic arsenic. There
                    is a narrow margin between the PTWI and intakes
                    reported in epidemiological studies to have toxic
                    effects (FAO/WHO, 1989).

                    -  Reference dose (RfD)

                    0.0003 mg/kg/day is the oral reference dose
                    established by the EPA for inorganic arsenic (IRIS,

                    -  Drinking water guidelines

                    0.01 mg/As (total)/L is the provisional guideline
                    value recommended by the World Health Organization
                    (WHO, 1996).

                    -  Air quality guidelines

                    No safe level for arsenic can be recommended, because
                    there is no known safe threshold (WHO, 1987).

        7.3  Carcinogenicity

             American Conference of Governmental Industrial
             Hygienists (ACGIH)
             ACGIH (1995) consider As elemental (7440-38-2) and inorganic
             compounds (except arsine) as confirmed human carcinogen.
             Environmental Protection Agency (EPA)
             Inorganic arsenic is classified by EPA as a group A
             carcinogen (a known human carcinogen), under the EPA
             classification (ATSDR, 1989)
             International Agency for Research on Cancer (IARC)
             In humans, exposure to inorganic arsenic via drinking water
             (contaminated wells), drugs (Fowler's solution) and
             pesticides can lead to skin cancers.
             Respiratory cancers have been observed in workers
             manufacturing arsenical pesticides and among copper smelter
             workers, exposed to inorganic arsenic, but also to other
             toxic substances (IARC, 1990).

             There is inadequate evidence for the carcinogenicity of
             arsenic compounds in animals (IARC, 1990).
             There is sufficient evidence that inorganic arsenic compounds
             are skin and lung carcinogens in humans. The data suggesting
             an increased risk for cancer at other sites are inadequate
             for evaluation (IARC, 1990).
             Arsenic and arsenic compounds are classified by IARC in the
             group 1:  "The agent is carcinogenic to humans".

        7.4  Teratogenicity

             In animals, inorganic arsenic compounds are embryo
             lethal or teratogenic (Barlow & Sullivan, 1982):
             -  sodium arsenate: hamster, mouse, rat
             -  sodium arsenite: mouse
             Although sodium arsenate has been shown to be teratogenic and
             embryo toxic in several experimental animals, intravenous and
             intra peritoneal doses to produce this effect are greater
             than or equal to 20 mg/kg (Beaudouin, 1974; Ferm et al.,
             1971; Ferm & Carpenter, 1968).
             In humans, arsenic can cross the placental barrier. Some
             studies indicate an accumulation of arsenic in infant tissues
             with age and a more sensitivity of infants to arsenic, with
             long term brain damage (Barlow & Sullivan, 1982). There is
             however, little evidence concerning effects of arsenic in
             pregnancy (Barlow & Sullivan, 1982). Spontaneous abortions
             and low weight babies reported in people working or living
             close to a smelter can be linked to arsenic but also to many
             other toxic compounds (Nordström, 1979). In many experimental
             studies on reproductive effects of inorganic arsenical
             compounds, maternal and developmental toxicity occur at the
             same dose administered. But various evidence from the basic
             science literature indicates that developmental toxicity is
             not secondary to maternal toxicity (Golub, 1994).

        7.5  Mutagenicity

             There is limited evidence that arsenic may be mutagenic
             in people exposed to inorganic arsenic compounds (drugs,
             occupational exposure) with effects persisting for many years
             (Barlow & Sullivan, 1982).
             Inorganic arsenic compounds can produce detectable
             cytogenetic changes, in vivo, in human somatic cells (Hantson
             et al., 1996); but theses changes, seen with sister chromatid
             exchanges (SCEs), occur at very high doses.

        7.6  Interactions

             Phosphorus (P)
             Arsenic can compete with phosphorus in the oxidative
             phosphorylation process and this can lead to the replacement
             of phosphorus in the bone, where it may remain for many years
             (Arena & Drew, 1986; Ellenhorn & Barceloux, 1988).
             Selenium (Se)
             It has been suggested that arsenic could form complexes with
             GSH-peroxidase, Se-dependent enzyme, thereby depleting body
             stores of enzymatically active selenium.


        8.1  Material sampling plan

             8.1.1  Sampling and specimen collection

            Toxicological analyses

            Biomedical analyses

            Arterial blood gas analysis

            Haematological analyses

            Other (unspecified) analyses

             8.1.2  Storage of laboratory samples and specimens

            Toxicological analyses

            Biomedical analyses

            Arterial blood gas analysis

            Haematological analyses

            Other (unspecified) analyses

             8.1.3  Transport of laboratory samples and specimens

            Toxicological analyses

            Biomedical analyses

            Arterial blood gas analysis

            Haematological analyses

            Other (unspecified) analyses

        8.2  Toxicological analyses and their interpretation

             8.2.1  Tests on toxic ingredient(s) of material

            Simple qualitative test(s)

            Advanced qualitative confirmation test(s)

            Simple quantitative method(s)

            Advanced quantitative method(s)

             8.2.2  Tests for biological specimens

            Simple qualitative test(s)

            Advanced qualitative confirmation test(s)

            Simple quantitative method(s)

            Advanced quantitative method(s)

            Other dedicated method(s)

             8.2.3  Interpretation of toxicological analyses

        8.3  Biomedical investigations and their interpretation

             8.3.1  Biochemical analysis

            Blood, plasma or serum


            Other fluids

             8.3.2  Arterial blood gas analyses

             8.3.3  Haematological analyses

             8.3.4  Interpretation of biomedical investigations

        8.4  Other biomedical (diagnostic) investigations and their

             In acute, massive ingestions, barium like opacities may
             be demonstrated by abdominal X-ray (Adelson et al., 1961;
             Gousios & Adelson, 1959; Gray et al., 1989; Hilfer & Mandel,
             1962; Levin-Scherz et al., 1987; Lee et al., 1995).

        8.5  Overall interpretation of all toxicological analyses and
             toxicological investigations

             Interpretation: The use of urinary arsenic excretion as
             the sole determinant for chelation therapy may lead to
             inaccurate assessment of tissue burden and over estimate the
             risk of toxicity. Less toxic, water soluble forms of arsenic
             such as organoarsenicals or sodium arsenate are excreted
             rapidly after acute exposure and urinary arsenic levels
             obtained shortly after exposure may not accurately reflect
             tissue or target organ levels (Hayes, 1982; Monier-Williams,
             1949; Schoolmeester & White, 1980; Schroeder & Balassa,

             Recent ingestion of seafood rich in organic arsenic may lead
             to false positive diagnosis of arsenic poisoning, especially
             if no speciation is done of the type of arsenic measured in
             Biomedical analysis
             A slightly increased liver enzymatic activity is observed in
             severe acute poisoning.
             Fluid losses are often accompanied by electrolyte
             Acid-base disturbances may occur.
             Oliguria, anuria are observed in severe cases.  Monitor renal
             functions (serum creatinine).
             Other investigations
             As inorganic arsenic compounds are radio-opaque, an X-ray of
             the abdomen will be useful, in all cases of acute inorganic
             arsenic ingestion.


        9.1  Acute poisoning

             9.1.1  Ingestion

                    Symptoms begin usually within the first hour
                    following ingestion.
                    Gastrointestinal disturbances are the main clinical
                    effects: vomiting, oesophageal and abdominal pain,
                    bloody rice water diarrhoea (Quatrehomme, 1992).
                    Metallic taste and garlic odour of breath or faeces
                    can be noted (Lee, 1995).
                    After an apparent remission (1 to 2 days), several
                    organs are affected by the systemic action of
                    inorganic arsenic, resulting in the following delayed
                    Cardiovascular: hypotension, tachycardia,
                    dysrrhythmia, prolonged QT interval, torsades de
                    pointes, myocarditis, cardiovascular failure and coma;
                    Renal: albuminuria, haematuria, oliguria, anuria,
                    renal failure; Hepatic: toxic hepatitis; Cutaneous:
                    various eruptions; Neurological: hyperpyrexia, toxic
                    delirium, convulsions, tremor, coma; Respiratory:
                    pulmonary oedema, ARDS, respiratory failure.
                    If patient survives the cardiovascular failure,
                    hepatic and renal impairment and central and
                    peripheral nervous system damage may develop
                    (Armstrong, 1984; Goldsmith, 1980; Bolliger et
                    al.,1992; Greenberg et al., 1979; Ellenhorn,
                    After a long convalescence, sequelae may be
                    Sensorimotor polyneuropathy, usually symmetrical, may
                    occur one to three weeks after the beginning of the
                    intoxication (Campbell, 1989; Donofrio, 1987; Bansal,
                    1991; Wesbey, 1981).
                    The encephalopathy may be stated (Fincher & Koerker,
                    Mee's lines i.e. transverse white striae on the nails
                    appear several weeks after absorption (Aldrich, 1904;
                    Mees, 1919; Sass, 1993).

             9.1.2  Inhalation

                    Irritation of the respiratory tract: dyspnoea,
                    accompanied by cough, thoracic pain during inspiration
                    (Hathaway et al., 1991).

             9.1.3  Skin exposure

                    Following accidental splashing of an arsenic
                    acid solution, local effects (pain and swelling at the
                    site of contact) were noted, followed several hours
                    later by gastrointestinal disturbances: nausea,
                    vomiting, diarrhoea, stomach pains. In the next days,
                    neurological effects and peripheral neuropathy were reported (Garb &
                    Hine, 1977).

             9.1.4  Eye contact

                    Ocular irritation: eyelids dermatitis,
                    conjunctivitis. Corneal necrosis has been observed
                    with exposition to arsenic trichloride: AsCl3 (Grant,

             9.1.5  Parenteral exposure

                    No data available.

             9.1.6  Other

                    No data available.

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    During chronic ingestion of inorganic arsenic
                    compounds, the following effects are noted:
                    gastrointestinal disturbances: nausea, vomiting,
                    diarrhoea, metallic taste;
                    Sensorimotor symmetrical polyneuropathy, polyneuritis,
                    psychiatric disturbances are the more frequent
                    Haematological effects: anaemia; aplastic anaemia was
                    reported in one case (Kjeldsberg & Ward, 1972). More
                    rarely, cardiovascular, renal, hepatic problems
                    Cutaneous signs: hyperkeratosis, melanosis, Mee's

             9.2.2  Inhalation

                    Local effects on mucous membranes  -
                    irritation, perforation of the nasal septum are noted.
                    Systemic effects are rarely observed.

             9.2.3  Skin exposure

                    Local irritation signs are observed with
                    chronic cutaneous contact: ulcerations, vesiculation
                    (Zaloga et al., 1985).
                    Inorganic arsenic compounds may act as contact
                    allergens (ATSDR, 1989).

             9.2.4  Eye contact

                    Dermatitis of the eyelids and conjunctivitis
                    have been reported in the literature.

             9.2.5  Parenteral exposure

                    No data available.

             9.2.6  Other

                    No data available.

        9.3  Course, prognosis, cause of death

             After absorption, arsenic may cause multi-organ failure.
             The primary target organs initially are gastrointestinal
             tract, the heart, brain and kidneys. The skin, bone marrow
             and peripheral nervous system may be affected.
             In case of severe acute poisoning by ingestion,
             gastrointestinal disturbances begin within the first 20 to 30
             minutes and are marked: diffuse capillary damage results in
             haemorrhagic gastroenteritis. Nausea, vomiting abdominal pain
             and watery, profuse diarrhoea is noted; sometimes the term
             "arsenical cholera" has been used. Intense thirst,
             retrosternal pain, dysphagia, marked dyspnea, fluid-
             electrolyte disturbances, oligo-anuria, delirium are
             observed. In severe cases, extensive tissue third spacing of
             fluids combined with fluid loss from gastroenteritis may lead
             to hypotension, cardiovascular failure and death. If prompt
             treatment is not initiated, death may occur within 12 to 24
             hours and the mortality rate is high, 50 to 75% (Evreux et
             al., 1968, Gosselin et al., 1984)
             Survivors of severe poisoning (after a vigorous fluid
             replacement therapy) may develop a peripheral neuropathy and
             skin lesions, which were only seen formerly in chronic
             poisoning (Gosselin et al., 1984). Recovery from arsenical
             neuropathy is generally poor, even after treatment with
             chelating agents (Kew et al., 1993; Murphy et al., 1981).

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    Cardiac effects
                    Acute poisoning:
                    Cardiotoxicity may manifest itself as non-specific ECG
                    changes: QT prolongation, ST depression, or T wave
                    inversion. Minor ECG changes may remain for as long as
                    6 to 8 weeks. Cases of torsade de pointes, ventricular
                    tachycardia, ventricular fibrillation, asystole have
                    been reported by Beckman et al., 1991; Campbell &
                    Alvarez, 1989; Goldsmith, 1980; 1990; Levin-Scherz et
                    al., 1987; Poklis & Saady, 1990, Schoolmeester &
                    White, 1980; St-Petery et al., 1970; Wang & Mazzia,
                    1969). Death may occur secondary to dysrrhythmias.
                    Chronic poisoning:
                    An increase of the frequency of mortality by
                    cardiovascular diseases has been observed in workers
                    exposed to As2O3 in a copper smelter (Axelson et
                    al., 1978). Myocardial infarction and arterial
                    thickening has been observed in children exposed to
                    inorganic arsenic via drinking water (Rosenberg, 1974;
                    Zaldivar, 1974). Toxic myocardial action of inorganic
                    arsenic was reported in vineyard workers, exposed
                    chronically to arsenic pesticides with
                    electrocardiographic abnormalities: QT prolongation, T
                    wave depression or inversion (Haguenoer & Furon,
                    1982). Interstial myocarditis resulting in fatal
                    ventricular arrhythmias has been reported after
                    chronic exposure to arsenic (Hall & Robertson,
                    Vascular effects
                    Acute poisoning
                    The toxic action of arsenic on blood vessels result in
                    fluid leakage into the intestinal space with
                    subsequent intravascular volume depletion and severe
                    hypotension (Hall & Robertson, 1990).
                    Chronic exposure
                    Raynaud's syndrome was observed in Chile, infants and
                    children showing more severe symptoms than adults
                    (Rosenberg, 1974; Zaldivar, 1980) exposed to high
                    inorganic arsenic concentrations in drinking

                    In vineyard workers, peripheral vascular disturbances
                    have been reported: endoangiitis, gangrene of the
                    extremities, atrophic acrodermatitis, peripheral
                    circulatory troubles (Ishinishi et al., 1986; Grobe,
                    Black-foot disease, as described in Taiwan, is a
                    gangrene of the extremities, due to peripheral
                    vascular disorders (Tseng, 1977), prevalence of the
                    disease being 8.9 per 1000.
                    Hypertension has been linked to long-term arsenic
                    exposure (Chen et al., 1995) and increased prevalence
                    of cerebrovascular disease, particularly cerebral
                    infarction was observed

             9.4.2  Respiratory

                    Local effects in acute poisoning by inhalation
                    are irritation of the respiratory tract: rhinitis,
                    pharyngitis, laryngitis and tracheobronchitis, with
                    cough, pain during inspiration and dyspnoea (Hathaway,
                    Massive inhalation and swallowing of substantial
                    amounts of crude arsenic dust (more than 80%
                    As2O3) has been responsible for the death, within
                    several hours, of a worker. At autopsy, trachea and
                    main bronchi showed widespread mucosal and submucosal
                    haemorrhages and there was intense visceral congestion
                    (Gerhardsson et al., 1988).
                    Acute respiratory failure occurs infrequently in acute
                    arsenic poisoning and is usually due to the muscle
                    weakness. Pulmonary oedema, either noncardiogenic from
                    capillary leaking, or cardiogenic from myocardial
                    depression may occur. Adult respiratory distress
                    syndrome (ARDS) has been reported (Bolliger, 1992;
                    Greenberg, 1979; Schoolmeester & White, 1980; Zaloga 
                    et al., 1985).

             9.4.3  Neurological

            Central Nervous System (CNS)

                             Neurological symptoms range from
                             vertigo or altered mental status to seizures
                             or toxic encephalopathy (Campbell & Alvarez,
                             1989; Poklis & Saady, 1990; Schoolmeester &
                             White, 1980).
                             Encephalopathy has been observed in acute or
                             subacute poisoning by ingestion contaminated
                             drinking water from well (Armstrong, 1984)
                             and deliberated ingestion of arsenic trioxide
                             (Danan et al., 1985).

                             In chronic poisoning encephalopathy was
                             observed after ingestion (Freeman & Couch,
                             1978), inhalation of fumes during a smelting
                             process of antimony ore (Beckett et al.,
                             1986) or from wood treated with ammoniated
                             copper arsenate (Morton & Caron, 1989).

            Peripheral nervous system

                             The most common long-term sequela
                             associated with arsenic poisoning, occurring
                             usually 7 to 14 days after ingestion, is a
                             polyneuropathy, which is the result of a
                             direct toxic effect leading to damage of the
                             peripheral nerve bodies (Bansal et al., 1991;
                             Campbell & Alvarez, 1989; Donofrio et al.,
                             1978; Wesbey & Kunis, 1981).
                             Peripheral neuropathy occur in acute or in
                             chronic poisonings. It is frequently a
                             progressive ascending and painful
                             polyneuritis, involving both sensory and
                             motor neurons.  It is due to a
                             demyelimination of axons.
                             Paresthesias, numbness, tingling sensations,
                             pain in extremities.  Muscular weakness is
                             commonly observed.
                             Electromyographic disturbances are observed
                             (Hindmarsh et al., 1977) and the reduction of
                             nerve conduction velocity, without symptoms,
                             has been noted (Feldman et al., 1979).
                             In severe poisoning, motor palsy may

            Autonomic nervous system

                             No data available.

            Skeletal and smooth muscle

                             In a case of acute massive arsenic
                             poisoning a severe rhabdomyolysis was observed
                             (Fernandez-Sola et al., 1991).

             9.4.4  Gastrointestinal

                    Gastrointestinal disturbances, such as severe
                    gastritis or gastroenteritis are the first and
                    prominent manifestations of acute toxicity by
                    ingestion.  These gastrointestinal effects can lead to
                    a choleriform syndrome ("arsenical cholera").

                    Digestive lesions are not due to a corrosive effect on
                    the gastrointestinal mucosa, but are the consequence
                    of vascular damage of the mucosa with subsequent fluid
                    loss. Thus, the first symptoms may be delayed for
                    several hours. Symptoms are the following: nausea,
                    vomiting, severe gastroenteric pain, sensation of
                    burning in the mouth and thorax, profuse and sometimes
                    bloody diarrhoea, dehydration.
                    If fluid losses are important, the clinical course may
                    be cardiovascular collapse, shock and death.
                    (Quatrehomme, 1992, Moore, 1994)
                    Stools and emesis may have a garlic like odour.
                    In cases of poisoning by inhalation, these
                    gastrointestinal effects are delayed later and less
                    prominent than after ingestion.
                    During chronic occupational exposure, gastrointestinal
                    disturbances are not common.

             9.4.5  Hepatic

                    Patients may develop hepatomegaly, jaundice,
                    portal hypertension or pancreatitis caused by the
                    direct effect of arsenic. However, Labadie et al.
                    (1990) suggested that arsenic induced hepatic injury
                    is caused by vascular and not hepatocellular
                    In chronic occupational exposures, hepatomegaly with
                    jaundice may be observed, evolving in some cases
                    toward cirrhosis, as seen in vineyard workers
                    (Haguenoer & Furon, 1982) or in copper smelter workers
                    (Axelson et al., 1978).
                    Jaundice, with sometimes ascites, has been described
                    after prolonged arsenical medication (Haguenoer &
                    Furon, 1982; Ishinishi et al., 1986).
                    Non-cirrhotic portal hypertension has been observed in
                    chronic arsenic intake (Guha Mazumdar & Das Gupta,
                    1991; Nevens et al., 1990).
                    Hepatic angiosarcoma and hepatocellular carcinomata
                    have been reported (Lander et al., 1975; Regelson et
                    al., 1968; Roth, 1957).

             9.4.6  Urinary


                             Renal failure is caused by
                             vasodilatation leading to increased
                             glomerular filtration and capillary
                             permeability. The resulting protein leakage
                             may cause acute tubular necrosis or diffuse
                             interstitial fibrosis (Cullen et al.,
                             Acute renal tubular necrosis and also
                             cortical necrosis (Gerhardt et al., 1978)
                             have been reported in severe acute poisoning
                             (ATSDR, 1989).
                             Tubulo-interstitial nephritis has been
                             reported in chronic poisoning (Prasad &
                             Rossi, 1995).


                             No data available.

             9.4.7  Endocrine and reproductive systems

            Endocrine system

                             Chronic oral exposure to inorganic
                             arsenic has been linked to the induction of
                             diabetes mellitus (Lai et al., 1994).

            Reproductive system

                             See 7.4 Teratogenicity

             9.4.8  Dermatological

                    In acute poisoning, melanosis, hyperpigmentation 
                    and exfoliative dermatitis have been described, 
                    but dermatologic effects are mainly seen after 
                    chronic ingestion or inhalation exposure 
                    (Zaloga et al, 1985; Schoolmeester & White, 1980;)
                    Chronic local effects include local irritation
                    - erythema, painful ulcerations, dermatitis (neck,
                    face, eyelids, forearms, hands), vesiculation (Zaloga
                    et al., 1985).
                    Skin lesions, occurring in environmentally, medically
                    or occupationally exposed populations are frequently

                        melanosis, generally seen on eyelids, temples,
                    neck, nipples, axillae and, in severe cases, on chest,
                    back and abdomen (Ishinishi et al., 1986; ATSDR,
                    1989); sometimes accompanied by punctiform leucoderma
                    ("raindrop" pigmentation).
                        hyperkeratosis, commonly seen on the palms and
                    soles, either as warts or diffuse plaque and
                    characterised by thickening of corneal layer (Sass et
                    al., 1993).
                        other skin lesions may evolve to a Bowen's disease
                    (Haguenoer & Furon, 1982). 
                    Skin lesions are now rare in industry: only one case
                    of hyperkeratosis was described during the last
                    decades (Frost, 1967).
                    However, skin alterations, skin malignant tumors and
                    Bowen's disease have been found frequent among wine
                    growers, during the 1960-1977 period (Lüchtrath,

             9.4.9  Eye, ears, nose, throat: local effects

                    Dermatitis of the eyelids and conjunctivitis
                    characterised by redness, swelling and pain is seen in
                    acute or chronic exposure by inhalation.  No valid
                    evidence of injury of the optic nerve by inorganic
                    arsenic can be found in the literature (Grant,
                    Irritation of the nose and pharynx, causing acute or
                    chronic rhino-pharyngo-tracheo-bronchitis has been
                    observed (Buchanan, 1962).
                    Perforation of the nasal septum has been observed in
                    arsenic-exposed workers (Ishinishi et al.,

             9.4.10 Haematological

                    Bone marrow depression/failure and haemolysis
                    may develop.
                    The peripheral haematologic abnormalities associated
                    with arsenic intoxication include leucopenia, anemia
                    and thrombocytopenia (Kyle & Pease, 1965; Lerman et
                    al., 1980;  Selzer & Ancel, 1983; Rezuke et al., 1991;
                    Terada et al., 1962; Van Tongeren et al., 1965;
                    Westhoff et al., 1975).
                    The anemia, usually associated with arsenic, has
                    normocytic indices (Kyle & Pease, 1965; Terada et al.,
                    1962).  Megaloblastic anaemia has been reported rarely
                    (Lerman et al., 1980; Westhoff et al., 1975).

                    Macrocytosis without anaemia has been reported by
                    Heaven et al., 1994.
                    Severe dyserythropoiesis has been reported after
                    ingestion of kelp supplements (Pye et al., 1992).

             9.4.11 Immunological

                    An immunosuppressive effect has been elicited
                    on mice exposed to sodium arsenite at doses of 0,5 ppm
                    to 10 ppm via drinking water (Blakely, 1980).
                    No data available in humans.

             9.2.12 Metabolic

           Acid-base disturbances

                             No data available.

           Fluid and electrolyte disturbances

                             In acute poisoning by ingestion, fluid 
                             losses are severe and are followed by
                             electrolyte disturbances.


                             Hyperthermia can be seen in the
                             acute phase of the intoxication.

             9.4.13 Allergic reactions

                    Contact dermatitis have been observed in
                    workers exposed to As2O3 (Ishinishi et al.,
                    Positive dermal patch tests have been observed in
                    workers (ATSDR, 1989; Haguenoer & Furon, 1982).

             9.4.14 Other clinical effects

                    In chronic exposure, the presence of white
                    striae in fingernails, i.e. Mee's lines is frequently
                    Cases of alopecia would have been observed (Haguenoer
                    & Furon, 1982).
                    Breath, perspiration, and stools of poisoned patients
                    intoxicated may have a garlic like odour.

             9.4.15 Special risks

                    Inorganic arsenic crosses the placental barrier. A
                    case of neonatal death has been reported, following
                    acute maternal intoxication (Lugo et al., 1969).
                    Arsenic can be present in human milk (WHO, 1989).

        9.5  Others

             No data available.

        9.6  Summary


        10.1 General principles

             After ingestion, aggressive decontamination by gastric
             lavage is recommended. Activated charcoal should be left in
             the stomach.
             Due to the toxic action of inorganic arsenic on the
             gastrointestinal tract in acute poisoning, and the subsequent
             fluid losses, special care to the fluid-electrolyte balance
             is required to prevent cardiovascular toxicity (hypovolemia,
             arrhythmias, cardiogenic shock).
             Admission of the patient into the intensive care unit of the
             hospital is therefore mandatory in order to allow close
             monitoring of vital signs. Antidote treatment with BAL or
             DMSA or DMSP should be initiated as soon as the diagnosis is
             reasonably established.

        10.2 Life supportive procedures and symptomatic treatment
             In case of hypotension, place patient in Trendelenburg
             position and administer IV fluids. If the response is
             inadequate, administer dopamine or norepinephrine
             (levarterenol) at the dosage required (See
             IPCS-INTOX Treatment Guide on shock and hypotension).
             If gastrointestinal hemorrhage occurs, blood products may be
             Arrhythmias, may be controlled by standard measures.
             Morphine may be necessary to control abdominal pain.

        10.3 Decontamination

             Aggressive decontamination with gastric lavage is
             recommended. Prior control of convulsions and protection of
             airway is required.
             Activated charcoal, has been suggested, although its efficacy
             has not been proven.
             Cathartics do not seem useful.
             Whole bowel irrigation may be useful if arsenic is visible
             using abdominal X-ray (Mahieu et al., 1987; Lee et al.,

             If material has been spilled on the skin, immediately remove
             the patient from the source of contamination, remove all
             contaminated clothing, and wash affected areas with soap and
             water (IPCS, 1992).
             If the material is in the eyes, flush with clean water for at
             least 15 minutes (IPCS, 1992).

        10.4 Enhanced elimination

             Haemodialysis may enhance elimination of free inorganic
             arsenic or arsenic-BAL chelate  (Mahieu et al., 1987;
             Winchester, 1977). Especially in cases of early anuria,
             haemodialysis is an effective arsenic elimination method
             (Mathieu et al., 1992). If a combination with chelator
             therapy is chosen, then BAL should be used because it has
             been shown that arsenic-BAL complexe cross dialyser membranes
             (Varizi et al., 1980), while for instance arsenic-DMSA
             complexes do not pass the dialyser membrane (Sheabar et al.,
             But its use has been recommended essentially in situations of
             concomitant renal failure (Vaziri, 1980).

        10.5 Antidote treatment

             10.5.1 Adults

                    Dimercaprol (BAL):
                    3 to 5 mg/kg intramuscularly every 4 hours for 2 days,
                    then every 12 hours for 7 to 10 days until recovery or
                    until oral therapy can be started (Gorby, 1988).
                    Caution must be taken to avoid decreased urine pH,
                    which may result in dissociation of the BAL-arsenic
                    complex, increasing the risk of renal failure (Poklis
                    & Sandy, 1990; Reynolds, 1996). Urine alkalization
                    reduces the risk of renal failure and also promotes
                    the excretion of the BAL-arsenic complex (Reynolds,

                    BAL has many side effects a.o. painful injection,
                    nausea, vomiting, chest- and abdominal pain,
                    headaches, fever, hypertension, central nervous system
                    depression, and seizures. Peak side effects are noted
                    10 to 30 minutes after injection and usually subside
                    in 30 to 50 minutes. It is contraindicated in patients
                    with renal or hepatic impairment, pregnant patients,
                    and in patients with glucose-6-phosphate dehydrogenase
                    (G6PD) deficiency (Schoolmeester & White, 1980).
                    Besides its many side effects, it has been suggested
                    that the lipophilic BAL could serve as a carrier for
                    arsenic across the blood-brain barrier. Some authors
                    indeed found in the brain of the rabbits treated with
                    BAL higher arsenic concentrations than in the control
                    animals (Aposhian, 1984; Kreppel et al., 1990). 
                    However Tsutsumi et al., (1983) found the arsenic
                    content in the brain following BAL treatment
                    unchanged, while Graziano et al. (1978) found the
                    arsenic concentration in the brain even decreased,
                    compared to controls.
                    25 mg/kg four times per day for a total of 5 days with
                    a maximum of 2 g/day. Although it has been advocated
                    for the treatment of As, based on anecdotal case
                    reports, Kreppel et al. (1989, 1990) using a
                    controlled experimental model, demonstrated that it
                    was ineffective in preventing the lethal action of
                    arsenic. The findings of Aposhian et al. (1983)
                    confirmed this experiment.
                    Also many side effects are reported: Hypersensitivity
                    reactions, leucopenia, eosinophilia, thrombocytopenia,
                    optic neuritis, and nephrotoxicity.
                    Dimercaptosuccinic acid (DMSA): 
                    10 mg/kg every 8 hours for 5 days.
                    Side effects are rare, but include reversible
                    elevation in serum transaminases, gastrointestinal
                    symptoms, leucopenia, and hypersensitivity. DMSA is 20
                    to 30 times less toxic than BAL and can be given to
                    patients with G6PD deficiency without causing
                    2,3-dimercaptopropanesulphonate (DMPS):
                    5 mg/kg every 4 hours intravenously for 24 hours with
                    transfer to oral DMPS 400 mg every four hours.

                    It has been reported to be effective in a severe acute
                    arsenic poisoning (Moore et al., 1994).
                    Because of its relatively few side-effects and proven
                    efficacy in the treatment of arsenic poisoning in
                    animal studies, DMPS may be the preferred agent as an
                    oral chelator for arsenic poisoning (Cullen et al.,
                    Regardless of the chelator that is chosen, therapy can
                    be terminated if the arsenic level is < 5 µg/L after
                    5 days (Kreppel et al., 1990).
                    Drastic antidote therapy, for instance by BAL, could
                    be limited by measuring the extent of methylation of
                    arsenic (the natural detoxifying mechanism). This can
                    be performed by the determination of monomethylarsenic
                    acid (MMA) and dimethylarsenic acid (DMA) in urine
                    (Mahieu et al., 1981).

             10.5.2 Children

                    3 mg/kg intramuscularly every 4 hours for 2 days, then
                    every 12 hours for 7 to 10 days until recovery or
                    until oral therapy can be started.
                    25 mg/kg four times per day for a total of 5 days with
                    a maximum of 1 g/day.
                    10 mg/kg or 350 mg/m2 every 8 hours for 5 days. 
                    Because of its relatively low in side-effects and
                    proven effective in the treatment of arsenic poisoning
                    in animal studies, DMSA may be the preferred agent as
                    an oral chelator for arsenic poisoning. (Cullen et
                    al., 1995).
                    Regardless of the chelator that is chosen, therapy can
                    be terminated if the arsenic level is < 5 µg/L after
                    5 days (Kreppel et al., 1990).

        10.6 Management discussion

             BAL (re)distribution of arsenic to the brain has to be
             evaluated. In the mean time the use of the water-soluble
             dithiols, like DMSA or DMPS, should be preferred as antidotes
             for arsenic when available. Another advantage of these two
             drugs is the fact that they cause fewer side-effects.


        11.1 Case reports from literature

             Beer epidemic of 1900
             A large outbreak of poisoning by inorganic arsenic, among
             beer drinkers, was detected in the north of England by the
             mid of 1900. Among the sources of arsenic contributing to the
             contamination of beer, we can note (Abbot, 1984):
             *  Sulfuric acid, used to produce glucose for fermentation
                from various starches and produced from purification of
                Spanish pyrites, with a high white arsenic (As2O3)
             *  Malt, dried or kilned over local gas coke. Recording of
                deaths among beer-drinkers occurred at mid 1900.  Deaths
                were ascribed to alcoholism and nervous system
                disturbances (peripheral or multiple neuritis). Inorganic
                arsenic (contaminated sulfuric acid) as a cause of death
                was pointed out several months later and the amount of
                arsenic used in the preparation of beer was estimated to
                several tons.  The total number of cases, recorded in
                several locations, was estimated to about 6000 and the
                number of death to about 70.
             Until the discovery of the other source of arsenic
             (contaminated malt), once again the diagnosis of arsenic
             poisoning was difficult to establish based on the symptoms
             only and was ascribed to alcoholic neuritis.
             Mass poisoning by sodium arsenite
             This episode of criminal mass poisoning by inorganic arsenic
             occurred in Argentina in 1987 (Roses et al., 1991).  An
             acaricide containing an aqueous solution of 45% weight volume
             of sodium arsenite was intentionally poured over meat, in a
             butcher's shop. Of the 718 subjects who had purchased
             contaminated meat, 207 were tested for urine arsenic i.e.
             symptomatic patients and non symptomatic individuals
             requesting to have an urinary analysis. No treatment was
             given to patients having urine arsenic concentration below 75
             µg/dL.  Patients of other groups (As urine: 76-500 µg/dL and
             As urine > 500 µg/dL) were treated with BAL. Symptomatology
             occurred at all levels and abdominal pain was recorded at the
             lowest urine arsenic levels while vomiting, nausea and
             systemic symptoms tended to increase at higher levels. Follow
             up of treated patients showed that all were asymptomatic one
             month after treatment and subsequently an early detection was

             Acute oral arsenic trioxide intoxication (Mahieu et al.,
             Thirty minutes after having voluntarily ingested ten small
             bags of 1 g of arsenic trioxide (for veterinary purpose) a 27
             years old woman was presenting gastrointestinal disturbances:
             epigastric pain, nausea, vomiting, dysphagia, metallic taste. 
             Three hours later, she was admitted to a local hospital where
             gastric lavage and intestinal washout (Mannitol 20%) were
             done.  Diuresis (Mannitol 20%) was initiated.  BAL (250 mg
             IM) was administered. Thirteen hours post-ingestion, she was
             transferred, somnolent, to an university hospital (BP:90/60
             mng/Hg) hypovolemia, oliguria).  Opacities in digestive bowel
             were detected with an abdominal X-ray. 
             Main therapeutic measures were the following:
             *  Volume replacement, under the control of a central venous
                catheter (albumin, plasma)
             *  Large osmotic diuresis (mannitol 20%)
             *  "Intestinal washout" with Mannitol 20% and enema
             *  Duodenal probe, under gastroscopy (aspiration of duodenal
                content and bile)
             *  Extra-corporeal dialysis (haemodialysis with
                hemoperfusion): two periods (4 h) at the first and the
                second day of hospitalization.
             *  BAL treatment, until the 8th day.
             *  Sulfo-adenosyl-L-methionine (Samyr 7), a methyl group
                donor, given after 48 h by IV, IM and introduodenal
                routes, with simultaneous administration of vitamin B12
                for the last two routes.
             Evolution of the patient was favourable.
             *  Digestive symptomatology has persisted during 3 days.
             *  At day 3, a diffuse cutaneous erythema was noticed, with a
                more or less pronounced swelling of the face.
             *  At day 4, hepatalgia with a light cytolysis was noticed.
             Patient was discharged from the intensive care at day 10.
             Subacute arsenic poisoning (Kew et al., 1993)
             A 35-year-old Asian man presented with a three month history
             of progressive weakness of his hands and legs associated with
             distal sensory disturbances. The patient had become aware of
             the symptom six weeks after an Indian ethnic practitioner had
             started treating him for atopic eczema. On examination Mees
             lines were present in the finger nails and there was
             hyperkeratosis of the soles of the feet. Symmetrical wasting
             and weakness was present in the upper and lower limbs and all
             tendon reflexes were absent. Cutaneous sensation was impaired
             in a glove and stocking distribution.  He could not stand
             from a sitting position without using his arms and walked

             with difficulty unsupported. Electromyography suggested a
             peripheral sensoria-motor neuropathy. The presence of an
             increased urinary concentration of inorganic arsenic (63
             µg/L; normal < 2 µg/L) and a hair arsenic concentration of
             20 µg/g on x-ray fluorescence spectrometry (normal < 1 µg/g)
             confirmed arsenic intoxication. Chelation therapy with DMPS
             100 mg daily for three weeks and later DMSA 400 mg three
             times daily for two weeks was given without objective
             improvement in muscle strength. Two years after the onset of
             symptoms the patient was still unable to return to


        12.1 Specific preventive measures

             No relevant information.

        12.2 Other

             Other useful references:
             Environmental Protection Agency (EPA), Jacobson-Kram D,
             Mushak P, Piscator M, Sivulka DJ, Chu M, Gibb HJ, Thorslund
             TW, Crump KS (1984) Health assessment document for inorganic
             arsenic. Final report EPA 600/8-83-021F. Environmental
             Protection Agency, Research Triangle Park.


        Abbott H (1984)  Fool's gold and the arsenic in beer epidemic
        of 1900.  Chem Ind 13:481-484.
        Adelson L, Georg R, Mandel A (1961) Acute arsenic intoxication
        shown by roentgenograms. Arch. Intern Med 107:401-404.
        Agency for Toxic Substances and Disease Registry (ATSDR) (1998)
        Toxicological profile for arsenic. ATSDR, Atlanta, Georgia, 349
        Agency for Toxic Substances and Disease Registry (ATSDR) (1989)
        Toxicological profile for arsenic. ATSDR, Atlanta, Georgia, 125
        Aldrich CJ (1904) Leuconychia striata arsenicalis transversus:
        with report of three cases. Am J Med Sci 127:702-709.
        American Conference of Govermental Industrial Hygienists (ACGIH)
        (1995) 1995-1996 Threshold Limit Values (TLVsTM) for Chemical
        Substances and Physical Agents and Biological Exposure Indices
        (BEIsTM). Second printing. American Conference of Governmental
        Industrial Hygienists, Cincinnati, OH, 139 pp.
        Aposhian HV (1983) DMSA and DMPS-water soluble antidotes for heavy
        metal poisonings. Ann Rev Pharmacol Toxicol 23:193-215.
        Arena JM, Drew RH, Eds (1986) Poisoning. Fifth edition. Charles C
        Thomas, Springfield, 1128 pp.
        Armstrong CW, Stroube RB, Rubio T, Siudyla EA, Miller GB Jr (1984)
        Outbreak of fatal arsenic poisoning caused by contaminated
        drinking water. Arch Environ Health 39(4):276-279.
        Axelson O, Dahlgren E, Jansson CD, Rehnlund SO (1978)  Arsenic
        exposure and mortality: a case-referent study from a Swedish
        copper smelter. Br J Ind Med 35(1):8-15.
        Bansal SK, Haldar N, Dhang UK (1991) Phrenic neuropathy in arsenic
        poisoning. Int J Dermatol 30:304-306.
        Barlow SM, Sullivan FM (1982) Arsenic and its compounds in
        reproductive hazards of industrial chemicals. Academic Press,
        London pp. 62-82.
        Beaudouin AR (1974) Teratogenicity of sodium arsenate in rats. 
        Teratology 10(2):153-158.
        Beckett WS, Moore JL, Keogh JP, Bleecker ML (1986) Acute
        encephalopathy due to occupational exposure to arsenic. Br J Ind
        Med 43(1):66-67.

        Beckman KJ, Bauman JL, Pimental PA, Garrard C, Hariman RJ (1991)
        Arsenic-induced torsade de pointes.  Critical Care Med
        Bhumbla DK, Keefer RF (1994) Arsenic mobilization and
        bioavailability in soils.  Adv. Env. Sci Technol 26:51-82.
        Blakely BR, Sisodia CS, Mukkur TK  (1980) The effect of
        methylmercury, tetraethyl lead and sodium arsenite on the humoral
        immune response in mice.  Toxicol Appl Pharmacol 52:245-254.
        Bolliger CT, van Zijl P, Louw JA (1992) Multiple organ failure
        with the adult respiratory distress syndrome in homicidal arsenic
        poisoning.  Respiration 59(1):57-61.
        Brouwer OF, Onkenhout W, Edelbrock PM, de Kom JFM, de Wolff FA,
        Peters ACB (1992) Increased neurotoxicity of arsenic in
        methylenetetrahydrofolate reductase deficiency. Clin Neurol
        Neurosurg 94(4):307-310.
        Buchanan WD (1962) Toxicity of arsenic compounds. Elsevier
        Publishing Co, New York,
        Buchet JP, Lauwerys R (1985)  Study of inorganic arsenic
        methylation by rat liver in vitro: relevance for the
        interpretation of observations in man. Arch Toxicol
        Buchet JP, Lauwerys R, Roels H (1981) Urinary excretion of
        inorganic arsenic and its metabolites after repeated ingestion of
        sodium metaarsenite by volunteers. Int Arch Occup Environ Health
        Campbell JP, Alvarez JA (1989) Acute arsenic intoxication. Am Fam
        Physician 40(6):93-97.
        Chen CJ, Hsueh YM, Lai MS, Shyu MP, Chen SY, Wu MM, Kuo TL, Tai TY
        (1995) Increased prevalence of hypertension and long-term arsenic
        exposure. Hypertension 25(1):53-60.
        Crecelius EA (1977) Changes in the chemical speciation of arsenic
        following ingestion by man. Environ Health Perspect
        Cullen NM, Wolf LR, St. Clair D (1995) Pediatric arsenic
        ingestion. Am J Emerg Med 13(4):432-435.
        Danan M, Conso F, Dally S, Bertaux L, Chouraki L, Balme R (1985) 
        Intoxication par l'anhydride arsénieux. Neuropathie périphérique
        et altération des fonctions cognitives. Ann Med Int (Paris)

        Dickerson OB (1994) Antimony, arsenic and their compounds In Zenz
        C, Dickerson OB, Horwath EP Jr (Editors) Occupational medicine. 
        Third edition. Mosby-Year Book, Inc. St-Louis, pp. 468-473.
        Donofrio PD, Wilbourn AJ, Albers JW, Rogers L, Salanga V,
        Greenberg HS (1987) Acute arsenic intoxication presenting as
        Guillain-Barré-like syndrome.  Muscle Nerve 10(2):114-120.
        Ellenhorn MJ (1997)  Arsenic In Medical toxicology.  Diagnosis and
        treatment of human poisoning.  2nd Ed Elsevier, Baltimore,

        Ellenhorn MJ, Barceloux DG (1988) Arsenic In Medical toxicology. 
        Diagnosis and treatment of human poisoning.  Elsevier, New York,
        Evreux JC, Motin J, Roche L, Vincent V (1968) Arsenic et dérivés,
        In Précis de toxicologie clinique. Masson et Cie (Editeurs),
        Paris, pp. 249-252.
        FAO/WHO (1989) Toxicological evaluation of certain food additives
        and contaminants. Food and Agricultural Organization/World Health
        Organization Food additive Series 24, Geneva, pp. 155-162.
        Feldman RG, Niles CA, Kelly-Hayes M, Sax DS, Dixon WJ, Thompson
        DJ, Landau E (1979)  Peripheral neuropathy in arsenic smelter
        workers.  Neurology 29(7):939-944.
        Ferm VH, Carpenter SJ (1968) Malformations produced by sodium
        arsenate. J Reprod Fertil 17:199-201.
        Ferm VH, Saxon A, Smith BM (1971) The teratogenic profile of
        sodium arsenate in the golden hamster. Arch Environ Health
        Fernandez-Sola J, Nogue S, Grau JM, Casademont J, Munne P (1991)
        Acute arsenical myopathy: morphological description.  Clin Toxicol
        Fincher RM, Koerker RM (1987) Long-term survival in acute arsenic
        encephalopathy.  Follow-up using newer measures of
        electrophysiologic parameters.  Am J Med 82(3):549-553.
        Foa V, Colombi A, Maroni M, Buratti M (1987) Arsenic In Alessio L,
        Berlin A, Boni M, Roi R (Editors) Biologic indicators for the
        assessment of human exposure to industrial chemicals. Commission
        of the European Communities, Luxembourg, pp. 22-41.
        Freeman JW, Couch JR (1978)  Prolonged encephalopathy with arsenic
        poisoning.  Neurology 28(8):853-855.

        Frost DV (1967)  Arsenicals in biology retrospect and prospect. 
        Federation Proceedings 26(1):194-208.
        Garb LG, Hine CH (1977)  Arsenical neuropathy: residual effects
        following acute industrial exposure.  J.O.M. 19(8):567-568.
        Gerhardsson L, Dahlgren E, Ericksson A (1988) Fatal arsenic
        poisoning - A case report.  Scand J Work Environ Health
        Gerhardt R, Hudson J, Rao R, Sobel R (1978)  Chronic renal
        insufficiency from cortical necrosis induced by arsenic poisoning. 
        Arch Intern Med 138:1267-1269.
        Goldsmith S (1980)  Arsenic induced atypical ventricular
        tachycardia.  N Engl J Med 303:1096-1098.
        Golub MS (1994) Maternal toxicity and the identification of
        inorganic arsenic as a developmental toxicant.  Reprod Toxicol
        Gorby MS (1988) Arsenic poisoning-Clinical conference.  West J Med

        Gosselin RE, Smith RP, Hodge HC (1984)  Arsenic In Clinical
        toxicology of commercial products, 5th edition.  Williams and
        Wilkins, Baltimore, pp.11142-11147.
        Gousios AG, Adelson L (1959) Electrocardiographic and radiographic
        findings in acute arsenic poisoning.  Am J Med 27:659-663.
        Grant WM (1986)  Toxicology of the eye. 3rd edition.  Charles C
        Thomas, Springfield, 1083 pp.
        Gray JR, Khalil A, Prior JC (1989) Acute arsenic toxicity.  An
        opaque poisoning.  J Can Assoc Radiol 40(4):226-227.
        Graziano JH, Cuccia D, Friedheim E (1978) The pharmacology of
        2,3-dimercaptosuccinic acid and its potential use in arsenic
        poisoning. J Pharmacol Exp Ther 207(3):1051-1055.
        Greenberg C, Davies S, McGowan T, Schorer A, Drage C (1979) Acute
        respiratory failure following severe arsenic poisoning. Chest
        Grobe JW (1976) Peripheral circulation disorders and acrocyanosis
        in arsenic-injured viticulturists.  Berufs-Dermatogen
        Guha Mazumdar DN, Das Gupta J (1991) Arsenic and non-cirrhotic
        portal hypertension [letter; comment]. J Hepat 13(3):376.

        Haguenoer JM, Furon D (1982)  Arsenic In Toxicologie et hygiène
        industrielles Tome 2.  Les dérivés minéraux, 2ème partie. 
        Technique et documentation, Paris, pp. 183-236.
        Hall AH, Robertson WO (1990)  Arsenic and other heavy metals In 
        Haddad LM, Winchester JF  Clinical management of poisoning and
        drug overdose. Second edition, WB Saunders Company, Philadelphia,
        pp. 1024-1034.
        Hamamoto E (1955) [Infant arsenic poisoning by powdered milk]. 
        Jap Med J 1649:2-12.
        Hantson P, Verellen-Dumoulin C, Libouton JM, Leonard A, Leonard
        ED, Mahieu P (1996) Sister chromatid exchanges in human peripheral
        blood lymphocytes after ingestion of high doses of arsenicals. 
        Int Arch Occup Environ Health 68(5):342-344.
        Harvey SC (1970)  Heavy metals In Goodman LS, Gilman A (Editors) 
        The pharmacological basis of therapeutics.  Collier - Macmillan,
        Toronto, pp. 958-965.
        Hathaway GJ, Proctor NH, Hughes JP et al (1991) Chemical Hazards
        of the Workplace. 3rd ed. Van Nostrand Reinhold Company, New
        York, NY.
        Hayes WJ (1982) Arsenic In Hayes WJ (Editor) Pesticides studied in
        man.  Williams and Wilkins, Baltimore, pp. 41-50.
        Hazardous Substances Data Bank (HSDB) Arsenic In Tomes Plus7
        Databases.  Micromedex, Inc., Emglewood, Colorado (Edition expires
        Heaven R, Duncan M, Vukelja SJ (1994) Arsenic intoxication
        presenting with macrocytosis and peripheral neuropathy, without
        anemia.  Acta Haematol 92(3):142-143.
        Hilfer RJ, Mandel A (1962) Acute arsenic intoxication diagnosed by
        roentgenograms.  Report of a case with survival.  N Engl J Med
        Hindmarsch JT, McCurdy RF (1986)  Clinical and environmental
        aspects of arsenic toxicity.  Crit Rev Clin Lab Sci
        Hindmarsh JT, McLetchie OR, Heffernan LPM, Hayne OA, Ellenberger
        HA, McCurdy RF, Thiebaux HJ (1977)  Electromyographic
        abnormalities in chronic environmental arsenicalism. J Anal
        Toxicol 1(6):270-276.
        Integrated Risk Information System (IRIS) Arsenic, inorganic In
        Tomes Plus7 Databases. Micromedex, Inc., Emglewood, Colorado
        (Edition expires 31-01-97).

        International Agency for Research on Cancer (IARC) (1990)  Arsenic
        and arsenic compounds In IARC Monographs on the evaluation of the
        carcinogenic risk of chemicals to humans.  Volume 23, Some metals
        and metallic compounds.  World Health Organization, Geneva, pp.
        International Programme on Chemical Safety (IPCS) (1992) Health
        and Safety Guide NE70:  Inorganic arsenic compounds other than
        arsine.  World Health Organization, Geneva,  31 pp.
        Ishinishi N, Tsuchiya K, Vahter M, Fowler BA (1986)  Arsenic In
        Friberg L, Nordberg GE, Vouk VB (Editors).  Handbook on the
        toxicology of metals. Second edition.  Volume II: Specific metals. 
        Elsevier, Amsterdam, pp. 43-83.
        Jolliffe DM, Budd AJ, Gwilt DJ (1991) Massive acute arsenic
        poisoning.  Anaesthesia 46(4):288-290.
        Kerr HD, Saryan LA (1986) Arsenic content of homeopathic
        medicines.  Clin Toxicol 24(4):451-459.
        Kew J, Morris C, Aihie A, Fysh R, Jones S, Brooks D (1993) Arsenic
        and mercury intoxication due to Indian ethnic remedies.  Br Med J
        Kjeldsberg CR, Ward HP (1972)  Leukemia in arsenic poisoning.  Ann
        Intern Med 77(6):935-937.
        Kreppel H, Reichl FX, Forth W, Fichtl B (1989)  Lack of
        effectiveness of D-penicillamine in experimental arsenic
        poisoning.  Vet Hum Tox 31(1):1-5.
        Kreppel H, Reichl FX, Szinicz L, Fichtl B, Forth W  (1990)
        Efficacy of various dithiols compounds in acute As2O3 poisoning
        in mice.  Arch Toxicol 64(5):387-392.
        Kyle RA, Pease GL (1965) Hematologic aspect aspects of arsenic
        intoxication.  N Eng J Med 273(1):18-23.
        Labadie H, Stoessel P, Callard P, Beaugrand M (1990) Hepatic
        venooclusive disease and perisinusoidal fibrosis secondary to
        arsenic poisoning.  Gastroenterology 99(4):1140-1143.
        Lai MS, Hsueh YM, Chen CJ, Shyu MP, Chen SY, Kuo TL, Wu MM, Tai TY
        (1994) Ingested inorganic arsenic and prevalence of diabetes
        mellitus.  Ann J Epidem 139(5):484-492.
        Lander JJ, Stanley RJ, Sumner HW, Boswell DC, Aach RD (1975)
        Angiosarcoma of the liver associated with Fowler's solution
        (potassium arsenite).  Gastroenterology 68(6):1582-1586.

        Lee DC, Roberts JR, Kelly JJ, Fishman SM (1995) Whole-bowel
        irrigation as an adjunct in the treatment of radiopaque arsenic. 
        Am J Emerg Med 13(2):244-245.
        Lerman BB, Ali N, Green D (1980) Megaloblastic dyserythropoietic
        anemia following arsenic ingestion.  Ann Clin Lab Sci
        Levin-Scherz JK, Patrick JD, Weber FH, Garabedian C Jr  (1987)
        Acute arsenic ingestion. Ann Emerg Med 16(6):702-704.
        Lüchtrath H (1983) The consequences of chronic arsenic poisoning
        among Moselle wine growers.  Pathoanatomical investigations of
        post-mortem examinations performed between 1960 and 1977.  J
        Cancer Res Clin Oncol 105(2):173-182.
        Lugo G, Cassady G, Palmisano P (1969)  Acute maternal arsenic
        intoxication with neonatal death. Am J Dis Child
        Mahieu P, Buchet JP, Lauwerys R (1987)  Evolution clinique et
        biologique d'une intoxication orale aiguë par l'anhydride
        arsénieux et considérations sur l'attitude thérapeutique.  J Tox
        Clin Exp.   7(4):273-278.
        Mahieu P, Buchet JP, Roels HA, Lauwerys R (1981)  The metabolism
        of arsenic in humans acutely intoxicated by As2O3. Its
        significance for the duration of BAL therapy. Clin Toxicol
        Mappes R (1977)  Versuche Zur Ausscheidung Von Arsen in Urine. 
        Int Arch Occup Environ Health  40(4):267-272.
        Mathieu D, Mathieu-Nolf M, Germain-Alonso M, Neviere R, Furon D,
        Wattel F (1992) Massive arsenic poisoning-effect of hemodialysis
        and dimercaprol on arsenic kinetics.  Intensive Care Med
        McKinney JD (1992) Metabolism and disposition of inorganic arsenic
        in laboratory animals and humans. Environ Geochem Health 14:
        Mealey J, Brownell GL, Sweet WH (1959) Radioarsenic in plasma,
        urine, normal tissues, and intracranial neoplasms. Arch Neurol
        Psychiatr 8: 310-320.
        Mees RA (1919) Nails with arsenical polyneuritis. Nederl T Geneesk
        Molin L, Wester PO (1976) The estimated daily loss of trace
        elements from normal skin by desquamation.  Scand J Clin Lab
        Invest 36:679-682.

        Monier-Williams GW (1949) Arsenic In Trace elements in Foods. John
        Wiley & Sons Inc, New York, pp. 162-206.
        Moore DF, O'Callaghan CA, Berlyne G, Ogg CS, Davies HA, House IM,
        Henry JA (1994) Acute arsenic poisoning: absence of neuropathy
        after treatment with 2,3-dimercaptopropanesulphonate (DMPS).  J
        Neurol Neurosurg Psychiat 57:1133-1135.
        Morton WE, Caron GA (1989)  Encephalopathy: an uncommon
        manifestation of workplace arsenic poisoning?  Am J Ind Med
        Murphy MJ, Lyon LW, Taylor JW (1981) Subacute arsenic neuropathy: 
        Clinical and electrophysiological observations.  J Neurol
        Neurosurg Psychiat 44(10):896-900.
        National Research Council of Canada (NRCC) (1978)  Associated
        committee on scientific criteria for environmental quality
        subcommittee on heavy metals and other compounds.  Effects of
        arsenic in the Canadian environment.  NRCC, Ottawa, 349 pp.
        Nevens F, Fevery J, Van Steenbergen W, Sciot R, Desmet V, De
        Groote J (1990) Arsenic and non-cirrhotic portal hypertension.  A
        report of eight cases.  J Hepatol 11:80-85.
        Nordström (1979) S, Beckman L, Nordenson I (1979) Occupational and
        environmental risks in and around a smelter in northern Sweden. V.
        Spontaneous abortion among female employees and decreased birth
        weight in their offspring.  Hereditas 90 ( ):291-296.
        Poklis A, Saady JJ (1990) Arsenic poisoning: acute or chronic?
        Suicide or murder? Am J Forensic Med Pathol 11(3):226-232.
        Prasad GVR, Rossi NF (1995) Arsenic intoxication associated with
        tubulointerstitial nephritis.  Am J Kidney Diseases
        Pye KG, Kelsey SM, House IM, Newland AC (1992) Severe
        dyserythropoiesis and autoimmune thrombocytopenia associated with
        ingestion of kelp supplements.  Lancet 339(8808):1540.
        Quatrehomme G, Ricq O, Lapalus P, Jacomet Y, Ollier A (1992) 
        Acute arsenic intoxication: forensic and toxicologic aspects (an
        observation)  J Forensic Sci 37(4):1163-1171.
        Regelson W, Kim U, Ospina J (1968) Hemangioendothelial sarcoma of
        liver from chronic arsenic intoxication by Fowler's solution. 
        Cancer 21:514-522.
        Reynolds JEF (Editor) (1996) Martindale.  The Extra Pharmacoepia. 
        Thirty-first edition.  Royal Pharmaceutical Society, London, pp.

        Rezuke WN, Anderson C, Pastuszak WT, Conway SR, Firshein SI (1991)
        Arsenic intoxication presenting as a myelodysplastic syndrome: a
        case report.  Am J Hematol 36(4):291-293.
        Robinson TJ (1975) Arsenical polyneuropathy due to caustic
        arsenical paste. Br Med J 19;3(5976):139
        Rosenberg HG (1974) Systemic arterial disease and chronic
        arsenicism in infants.  Arch Pathol 97:360.
        Roses OE, Garcia Fernandez JC, Villaamil EC (1991)  Mass poisoning
        by sodium arsenite.  J Toxicol Clin Toxicol 29(2):209-213.
        Roth F (1957) Tumoren (hemangiendothelioma).  Z Krebsforsch
        Sass U, Grosshans E, Simonart JM (1993) Chronic arsenicism:
        criminal poisoning or drug-intoxication?  Report of two cases. 
        Dermatology 186(14):303-305.
        Schoolmeester WL, White DR (1980) Arsenic poisoning. Review
        article. Southern Med J 73(2):198-208.
        Schroeder HA, Balassa JJ (1966) Abnormal trace elements in man:
        arsenic. J Chron Dis 19:85-78.
        Selzer PM, Ancel MA (1983) Chronic arsenic poisoning masquerading
        as pernicious anemia.  West J Med 139:219-220.
        Sheabar FZ, Yannai S, Taitelman U (1989) Efficiency of arsenic
        clearance from human blood in-vitro and from dogs in-vivo by
        extracorporeal complexing hemodialysis. Pharmacol Toxicol
        St-Petery J, Gross, C, Victoria BE (1970) Ventricular fibrillation
        caused by arsenic poisoning. Am J Dis Child 120:367-371.
        Tam GKH, Charbonneau SM, Bryce F, Pomroy C, Sandi E  (1979) 
        Metabolism of inorganic arsenic (74As) in humans following oral
        ingestion. Toxicol Appl Pharmacol 50:319-322.
        Tardieu A, avec la collaboration de Roussin Z (1867) 
        Empoisonnement par l'arsenic In Étude médico-légale et clinique
        sur l'empoisonnement. Baillière JB et Fils, Paris, pp.
        Terada H, Sasagawa T, Saito H, Shirata H, Sekiya T (1962) Chronic
        arsenical poisoning and hematopoietic organs.  Acta Med Biol

        Tseng WP (1977)  Effects and dose-response relationships of skin
        cancer and Blackfoot disease with arsenic. Environ Health Perspect
        Tsutsumi S, Kawaguchi M, Ishii Y, Matsumoto Y (1983) Effects of
        dimercaprol or thioctic acid on the distribution and excretion of
        Na374AsO3 injected subcutaneously in rats. J Toxicol    Sci
        Vahter M, Concha G, Nermell B, Nillsson R, Dulout F, Natarajan AT
        (1995) A unique metabolism of inorganic asenic in native Andean
        women.  Eur J Pharmacol Environ Toxicol Pharmacol Section
        Vahter M (1983)  Metabolism of arsenic In Fowler BA (Editor)
        Biological and Environmental effects of arsenic. Elsevier,
        Amsterdam, pp. 171-198.
        Vallee BL, Ulmer DD, Wacker WEC (1960)  Arsenic toxicology and
        biochemistry. A.M.A. Arch. Ind. Health 21:132-151.
        Van Tongeren JHM, Kunst A, Majoor CLH, Schillings PHM (1965)
        Folic-acid deficiency in chronic poisoning. Lancet 1:784:786.
        Vaziri ND, Upham T, Barton CH (1980)  Haemodialysis clearance of
        arsenic. Clin Toxicol 17(3):451-456.
        Wang BC, Mazzia VDB (1969)  Arsenic poisoning as an anaesthetic
        risk. NY State J Med 69:2911-2912.
        Wesbey G, Kunis A (1981) Arsenical neuropathy. Ill Med J
        Westhoff DD, Samaha RJ, Barnes A Jr (1975) Arsenic intoxication as
        a cause of megaloblastic anemia.  Blood 45(2):241-246.
        Winship KA (1984)  Toxicity of inorganic arsenic salts. Adverse
        Drug React Acute Poisoning Rev 3(3):129-160.
        World Health Organization (WHO) (1996) Guidelines for drinking
        water quality. Vol 2: Health criteria and other supporting
        information, Second edition, Geneva, 973 pp.
        World Health Organization (WHO) (1989) Environmental Health
        Criteria 18 - Arsenic. World Health Organization, Geneva, 174
        World Health Organization (WHO) (1987) Air quality guidelines for
        Europe. European Series No 23, Copenhagen, WHO Regional Office for
        Europe, pp. 171-181.

        Zaldivar R, Ghai GL (1980) Clinical epidemiological studies on
        endemic chronic arsenic poisoning in children and adults,
        including observations on children with high-intake and low-intake
        of dietary arsenic.  Zentrabl Baktoriol 170(5):409-421.
        Zaldivar R (1974)  Arsenic contamination of drinking water and
        foodstuffs causing endemic chronic poisoning.  Beitr Path
        Zaloga GP, Deal J, Spurling T, Richter J, Chernow B (1985)  Case
        report: unusual manifestations of arsenic intoxication.  Am J Med
        Sci 289(5):210-214.


        Author:     Jean-Louis Benedetti, M.D.
                    Centre de Toxicologie du Québec
                    Centre Hospitalier Universitaire de Québec (CHUQ)
                    Pavillon Centre Hospitalier de l'Université Laval
                    2705 Boulevard Laurier
                    Sainte-Foy, Québec
                    Canada, G1V 4G2
                    Tel:     1-418-6542254
                    Fax:     1-418-6542148
                    E-mail:  ctqdoc@riq.qc.ca
        Reviewer:   Prof. Dr. A.N.P. van Heijst
                    Baarnseweg 42A
                    3735 MJ Bosch en Duin
                    Tel:     31-30-2287178
        Date:       July 1996
        Peer Reviewed,  Sao Paulo INTOX-11, October 21, 1999.
        (Drs W. Temple, New Zealand- co-ordinator; B. Groszek, Poland; J.
        de Kom, Surinam;
        J.C. Rios Bustamante, Chile; J.C. Piola, Argentina).


    See Also:
       Toxicological Abbreviations
       Arsenic (EHC 18, 1981)
       Arsenic (ICSC)
       Arsenic (WHO Food Additives Series 18)
       Arsenic (WHO Food Additives Series 24)
       ARSENIC (JECFA Evaluation)