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    IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
    Health and Safety Guide No. 70

    INORGANIC ARSENIC COMPOUNDS
    OTHER THAN ARSINE
    HEALTH AND SAFETY GUIDE





    UNITED NATIONS INTERNATIONAL

    ENVIRONMENT PROGRAMME LABOUR ORGANISATION

    WORLD HEALTH ORGANIZATION




    WORLD HEALTH ORGANIZATION, GENEVA 1992

    Published by the World Health Organization for the International
    Programme on Chemical Safety (a collaborative programme of the United
    Nations Environment Programme, the International Labour Organisation,
    and the World Health Organization)

    This report contains the collective views of an international group of 
    experts and does not necessarily represent the decisions or the stated
    policy of the United Nations Environment Programme, the International
    Labour Organisation, or the World Health Organization

    WHO Library Cataloguing in Publication Data

    Inorganic arsenic compounds other than arsine: health and safety
    guide.

    (Health and safety guide ; no. 70)

    1.Arsenic - standards 2. Arsenic - toxicity
    3. Environmental exposure  I.Series

    ISBN 92 4 151070 6          (NLM Classification: QV 294)
    ISSN 0259-7268

    The World Health Organization welcomes requests for permission to
    reproduce or translate its publications, in part or in full. 
    Applications and enquiries should be addressed to the Office of
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    (c) World Health Organization 1992

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    that are not mentioned.  Errors and omissions excepted, the names of
    proprietary products are distinguished by initial capital letters.

    CONTENTS

    INTRODUCTION

    1. PRODUCT IDENTITY AND USES
         1.1. Identity
         1.2. Physical and chemical properties
         1.3. Analysis
         1.4. Composition
         1.5. Production and uses

    2. SUMMARY AND EVALUATION
         2.1. Natural occurrence and biological transformations in the
              environment
         2.2. Human exposure
         2.3. Effects on organisms in the environment
         2.4. Uptake, metabolism, and excretion
         2.5. Effects on experimental animals
         2.6. Effects on humans

    3. CONCLUSIONS AND RECOMMENDATIONS
         3.1. Conclusions
         3.2. Recommendations

    4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION
         4.1. Human health hazards, prevention and protection, first aid
              4.1.1. General population
              4.1.2. Occupationally exposed population
              4.1.3. First aid
         4.2. Advice to physicians
              4.2.1. Treatment
         4.3. Explosion and fire hazards
         4.4. Storage and transport
         4.5. Spillage
         4.6. Disposal

    5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    6. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
         6.1. Previous evaluations by international bodies
         6.2. Exposure limit values
         6.3. Specific restrictions
         6.4. Transport and labelling

    BIBLIOGRAPHY
    

    INTRODUCTION

    This Health and Safety Guide is not based on an existing Environmental
    Health Criteria document, but on critical national reviews.  The
    hazard evaluation in the Health and Safety Guide was made on the basis
    of carefully selected studies, after scrutiny of the original
    publications.

    In order to assist the peer-review process of the present Health and
    Safety Guide, a background companion document was prepared by the IPCS
    and can be obtained from the Director on request; the IPCS does not
    intend that the background document should be published.

    The first three sections of this Health and Safety Guide present
    essential technical information and the hazard evaluation.  Section 4
    includes advice on preventive and protective measures and emergency
    action; health workers should be thoroughly  familiar with the medical
    information to ensure that they can act efficiently in an emergency. 
    The section on regulatory information has been extracted from the
    legal file of the International Register of Potentially Toxic
    Chemicals (IRPTC) and from other United Nations sources.

    The target readership includes occupational health services, those in
    ministries, governmental agencies, industry, and trade unions who are
    involved in the safe use of chemicals and the avoidance of
    environmental health hazards, and those wanting more information on
    this topic.  An attempt has been made to use only terms that will be
    familiar to the intended user.  However, sections 1 and 2 inevitably
    contain some technical terms.

    Revision of the information in this Guide will take place in due
    course, and the eventual aim is to use standardized terminology. 
    Comments on any difficulties encountered in using the Guide would be
    very helpful and should be addressed to:

    The Director
    International Programme on Chemical Safety
    World Health Organization
    1211 Geneva 27
    Switzerland

    THE INFORMATION IN THIS GUIDE SHOULD BE CONSIDERED AS A STARTING POINT
    TO A COMPREHENSIVE HEALTH AND SAFETY PROGRAMME

    1.  PRODUCT IDENTITY AND USES

    1.1  Identity

    The chemical names, synonyms, trade names, chemical formulae and CAS
    numbers of some inorganic arsenic compounds are given in Table 1.

        Table 1. Chemical names, synonyms, trade names, and chemical formulae of some inorganic
    arsenic compounds

                                                                                             
    Chemical name           Formula             CAS-No.         Synonyms and trade names
                                                                                             
    Arsenic                 As                  7440-38-2       Arsen; arsenic black; grey
                                                                arsenic; metallic arsenic

    Arsenic pentoxide1      As205               1303-28-2       Arsenic acid; arsenic acid
                                                                anhydride; arsenic [V] oxide;
                                                                diarsenic pentoxide; arsenic oxide

    Arsenicsulfide          As2S3               1303-33-9       Arsenic sesquisulfide;
                                                                arsenic sulfide; arsenic
                                                                tersulphide; arsenic trisulphide;
                                                                arsenic yellow; arsenious
                                                                sulphide; arsenous sulphide;
                                                                auripigment; C.I. 77086;
                                                                C.I. pigment yellow; diarsenic
                                                                trisulphide; orpiment; King's Gold

    Arsenic                 AsCl3               7784-34-1       Arsenious chloride; arsenic
                                                                trichloride butter; arsenous
                                                                chloride;  caustic arsenic
                                                                chloride; caustic oil of arsenic;
                                                                fuming liquid arsenic

    Arsenic trioxide2       As203               1327-53-3       Arsenic[III]oxide; arsenic
                                                                sesquioxide; arsenicum album;
                                                                arsenious acid; arsenious oxide;
                                                                arsenious trioxide; arsenite;
                                                                arsenous acid; arsenous anhydride;
                                                                arsenous oxide; arsenous oxide
                                                                anhydride; crude arsenic;
                                                                diarsenic trioxide; arsenic oxide;
                                                                white arsenic; Arsenolite;
                                                                Arsodent; Claudelite

                                                                                             
    Chemical name           Formula             CAS-No.         Synonyms and trade names
                                                                                             
    Calcium arsenate        Ca3(As04)2          7778-44-1       Arsenic acid calcium salt;
                                                                calcium orthoarsenate; tricalcium
                                                                arsenate; Chipcal; Pencal; Spracal

    Cupric                  C4H6As6Cu4O16       12002-03-8      (Acetato) trimetaarsenitodicopper;
    acetoarsenite                                               bis(acetato)hexametaarseni-
                                                                totetracopper; copper acetate
                                                                arsenite; Paris green, emerald
                                                                green, French green, mineral green,
                                                                imperial green

    Gallium arsenide        AsGa                1303-00-0       Gallium monoarsenide

    Lead arsenate           PbHAs04             7784-40-9       Arsenic acid lead salt; acid lead
                                                                arsenate; acid lead ortho-arsenate;
                                                                arsenate of lead; arsinette; lead
                                                                acid arsenate; plumbous arsenate;
                                                                schultenite; standard lead
                                                                arsenate; Gypsine; Soprabel;
                                                                Talbot

    Potassium arsenate      KH2As04             7784-41-0       Arsenic acid monopotassium salt;
                                                                monopotassium arsenate;
                                                                monopotassium dihydrogen arsenate;
                                                                potassium acid arsenate; potassium
                                                                arsenate, monobasic; potassium
                                                                dihydrogen arsenate; potassium
                                                                hydrogen arsenate; Macquer's salt

    Potassium arsenite      KH(As02)2           10124-50-2      Arsenenous acid, potassium salt;
                                                                arsenious acid, potassium salt;
                                                                arsonic acid, potassium salt;
                                                                potassium metaarsenite; Fowler's
                                                                solution

    Sodium arsenate3        Na3As04             7631-89-2       Arsenic acid, sodium salt; arsenic
                                                                acid, sodium ortho-arsenate;
                                                                sodium metaarsenate

    Sodium arsenite         NaAs02              7784-46-5       Arsenenous acid, sodium salt;
                                                                arsenious acid, sodium salt;
                                                                sodium metaarsenite; sodanit;
                                                                prodalumnol 
                                                                                             
    1 The name "arsenic acid" is commonly used for the pentoxide as well as for the
      various hydrated products.
    2 Sometimes erroneously called "arsenic".
    3 The name "sodium arsenate" is applied both to the disodium and the trisodium
      salts.
    
    1.2  Physical and chemical properties

    Arsenic compounds are often unstable, and in many cases are not
    well-defined materials.  For example, the arsenites of the alkali
    metals are slowly converted in solution to arsenates, by atmospheric
    oxygen. Arsenic trisulfide reacts vigorously with oxidizing agents,
    and hydrogen sulfide is generated on contact with strong acids.
    Arsenic trichloride is highly reactive with water, strong oxidants,
    ammonia, and some alkalis; the reaction results in the generation of
    hydrogen chloride and chlorine gas.

    Inorganic arsenic compounds may generate highly toxic (and flammable)
    arsine gas when in contact with acids plus reducing metals (e.g.,zinc
    or iron), or with sodium hydroxide plus aluminium.  Some physical
    properties are summarized in Table 2.

    1.3  Analysis

    The techniques most commonly used for the determination of arsenic
    involve its transformation into arsine.  Subsequent measurements of
    arsine are carried out using spectrophotometry, flame and
    electrothermal devices for atomic absorption spectroscopy (AAS),
    atomic fluorescence (AFS), or atomic emission spectroscopy (AES).  The
    limit of detection for AAS is in the range of 2-20 ng/kg.

    1.4  Composition

    Arsenic is available as a technical grade product, usually with a
    typical purity of 99%, and as a high-purity grade for semiconductor
    use, with a purity of at least 99.999%.  Arsenic pentoxide is usually
    available as technical grade.  Arsenic sulfide is available in some
    countries as optical grade (99.999%), as well as a powder (99%
    active).  Arsenic trioxide is marketed as a 95%-pure, crude grade, and
    as a 99%-pure, refined grade, as well as a 1% solution in about 5%
    hydrochloric acid.

    Commercial calcium arsenate usually contains about 60% calcium
    arsenate and 10% calcium arsenite.  Lime and calcium carbonate are
    often also present.  Lead arsenate is available as acid lead arsenate,
    which contains 33% arsenic pentoxide.  It is sometimes available as a
    wettable powder (94-98%), as a dust or as a paste. 

    Potassium and sodium arsenates are generally available in purified as
    well as reagent grades.  Potassium arsenite is marketed by chemical
    suppliers in a purified grade.  It is also available, in some
    countries, in a 1% aqueous solution known as Fowler's solution.

    Sodium arsenite is available commercially in some countries as a pure
    grade material of 95-98% purity, and in a technical grade of 90-95%
    purity.  It was previously used as powders containing 90 or 94% of the
    chemical, and as solutions containing various concentrations (a 0.25%
    solution was available for use as a livestock dip, but most solutions
    contained 40-44% active ingredient).

        Table 2. Some physical properties of inorganic arsenic compoundsa

                                                                                                

    Compound       Vapour     Melting      Boiling       Description         Solubility
                   pressure   point        point                             (g/litre)
                   (mmHg)     (C)         (C)
                                                                                                

    Arsenic        1 at       817          615           grey, crystalline   insoluble in water;
                   372 C     (28 atm)     (sublimes)    solid with          soluble in HN03
                                                         metallic luster

    Arsenic        -          315          -             white hygroscopic   soluble in cold
    pentoxide                 (decomp.)                  powder              water (1500);
                                                                             soluble in hot
                                                                             water (767)

    Arsenic        -          300-325      707           yellow-red powder   insoluble in cold
    sulphide                                                                 water (0.0005);
                                                                             slightly soluble
                                                                             in hot water;
                                                                             soluble in
                                                                             alkali, acids,
                                                                             ethanol

    Arsenic        10 at      16           130           oily, colourless    decomposed by 
    trichloride    23.5 C                               liquid with         water; soluble 
                                                         acrid smell         in ethanol, 
                                                                             ether, conc.
                                                                             mineral acids

    Arsenic        66.1 at    312          465           white, amorphous    soluble in 
    trioxide       312 C                                or crystalline      cold water, (12);
                                                         powder              hot water (115);
                                                                             alkali and HCl

    Calcium        0          1455         decomp.       colourless,         soluble in 
    arsenate                                             amorphous powder    water (0.13); 
                                                                             soluble in dilute
                                                                             acids

    Cupric         -          n.a.         n.a.          emerald green,      insoluble in 
    acetoarsenite                                        crystalline         water, soluble 
                                                         powder              in acids

    Gallium        -          1238         n.a.          dark grey           insoluble in 
    arsenide                                             crystals            water

    Lead           -          720          decomp.       white,              slightly soluble 
    arsenate                  (decomp.)                  crystalline         in hot water; 
                                                         solid               soluble in HN03,
                                                                             caustic alkalis

                                                                                                

    Compound       Vapour     Melting      Boiling       Description         Solubility
                   pressure   point        point                             (g/litre)
                   (mmHg)     (C)         (C)
                                                                                                

    Potassium      -          288          -             white,              soluble in 
    arsenate                                             crystalline         cold water, (190);
                                                         powder              very soluble in
                                                                             hot water; soluble
                                                                             in acid, glycerol,
                                                                             ammonia

    Potassium      -          300          -             white powder        soluble in water;
    arsenite                  (decomp.)                                      slightly soluble
                                                                             in ethanol

    Sodium         -          86           -             white powder        soluble in cold
    arsenate                                                                 water, (389); 
    dodecahydrate                                                            ethanol, glycerol

    Sodium         -          n.a.         n.a.          grey-whitish        very soluble in
    arsenite                                             powder              water; slightly
                                                                             soluble in ethanol

                                                                                                
    a n.a. = not available.
      decomp. = decomposes.
    
    1.5  Production and uses

    World production of arsenic, as arsenic trioxide, has been estimated
    at around 60 000 tonnes annually;  it has been estimated that about
    one-third is used for wood preservation.  Metallic arsenic is
    currently used in alloys, in combination with lead and copper, in
    semiconductor devices, and in low-melting point glasses.  The most
    important use of arsenic(III) oxide is in the manufacture of a variety
    of insecticides, herbicides, fungicides, algicides, sheep dips, and
    pharmaceutical products (Fowler's solution).  Arsenic sulfide is used
    for dehairing skins in tanning, in the manufacture of pyrotechnics and
    semiconductors, and in the manufacture of special optical glass.

    Calcium and lead arsenates have been used as insecticides, e.g., for
    the control of boll weevil and gypsy moth, but these arsenates have
    been largely replaced for this purpose by more effective organic
    chemicals.  However, in many countries, lead arsenate is still used as
    an insecticide on fruit trees, vegetables, rubber, coffee, cacao, and
    grapefruit, and as a herbicide for the treatment of turf.  Arsenic (as
    lead or calcium arsenate) is not a normal constituent of the
    fungicidal Bordeaux mixture (calcium hydroxide and copper sulfate),
    but it has occasionally been added to widen its action to control some
    insects.  Sodium arsenite has been used in cattle and sheep dips, for
    debarking trees, and for non-selective weed control. 
    Arsenic-containing wood preservatives are widely used and usually
    consist of a chromated copper arsenate, applied under pressure.

    2.  SUMMARY AND EVALUATION

    2.1  Natural occurrence and biological transformations in the
    environment

    As a result of its natural occurrence, humans are universally exposed
    to arsenic in various forms.  The various naturally occurring
    inorganic and organic arsenic compounds are interlinked through
    complex biotic and abiotic transformations in the environment.

    Inorganic arsenic is found chiefly in the form of its compounds with
    metals (arsenides), which usually occur in isomorphous mixture with
    sulfides.  High levels of arsenic may also be present in some coals
    (up to 1500 mg/kg).  As a result of the presence of arsenic in the
    parent rock, arsenic is present naturally in soils in various
    quantities.  Soils overlying sulfide-ore deposits may contain several
    hundred mg/kg.  Arsenic is more strongly bound to soils that have a
    high clay or high organic matter content and, in these circumstances,
    is less available to plants.  Arsenic is phytotoxic.  Plants take up
    arsenic in proportion to the soil concentration, except at very high
    soil concentrations.  Plants growing on mine or smelter wastes have
    developed resistance to arsenic toxicity; such plants sometimes have
    concentrations of arsenic (6000 mg/kg has been found) that may be
    toxic to animals eating the plants.  Arsenic taken up by plants is
    distributed to all tissues.  

    Inorganic arsenic can be converted to methylated species in soil by a
    number of microorganisms under aerobic, as well as anaerobic,
    conditions.  In anoxic parts of the soil layer, arsenic can be
    immobilized as the sulfide.  Arsenic is present in water at a
    concentration that varies greatly.  Extremely high levels of inorganic
    arsenic have been found in some ground waters.   Arsenic in aquatic
    systems partitions preferentially to the sediment.

    A number of microorganisms (e.g., fungi and bacteria in soil, algae in
    water) have the capacity to methylate inorganic arsenic to the much
    less acutely toxic compounds methane-arsonic acid and dimethylarsinic
    acid (cacodylic acid);  the latter is readily converted in soil to the
    volatile methylarsines.  Algae (unicellular organisms and seaweeds)
    actively take up naturally occurring arsenate, and transform inorganic
    arsenic into a variety of organic arsenic compounds.  The
    bioconcentration of arsenic in unicellular algae has been reported to
    reach up to 3000 times the concentration in the surrounding water. 
    This is a major source of arsenic for higher organisms.  Fish and
    crustaceans accumulate arsenic compounds via the food-chain, in the
    form of arsenocholine and arsenobetaine.  Arsenobetaine is
    metabolically very stable and is bioaccumulated in the higher trophic
    levels of the aquatic food-chains.  Marine fish and crustaceans
    commonly contain 2-20 mg arsenic/kg - mainly as organic arsenic - on a
    wet weight basis, although higher values have been reported (up to
    50-100 mg/kg).

    2.2  Human exposure

    Exposure of the general population occurs mainly through arsenic
    present in food and drinking-water. In some areas, the natural high
    arsenic content of the drinking-water has caused endemic, chronic
    arsenic poisoning.  A significant portion of the population in other
    areas is exposed to arsenic levels in drinking-water that lie above
    the present WHO drinking-water guideline value for arsenic of
    50 g/litre.  In humans, the total daily intake of arsenic is greatly
    influenced by the amount of seafood in the diet, and consumers may
    reach several thousand g of total arsenic per day.  However, 85-95%
    of the arsenic present in marine products is present as the much less
    toxic, organic arsenic compounds.

    In the working environment, if precautions are not taken, high
    inhalation exposures may be associated with the smelting of
    non-ferrous sulfide ores, glass manufacturing, wood preservation
    plants, and the agricultural application of arsenic-containing
    pesticides.

    2.3  Effects on organisms in the environment

    For most aquatic animal species, the acute toxicity of inorganic
    arsenic compounds is moderate to low (LC50 10-100 mg/litre). 
    However, long-term exposure of immature fish populations to sublethal
    doses may result in toxic effects at about 4 mg/litre, and exposure of
    Daphnia may lead to slightly impaired reproduction at 0.5 mg/litre. 
    In aquatic ecosystems, algal communities seem to suffer most from
    exposure to arsenic.  The growth of some species of unicellular algae
    is inhibited at arsenate concentrations as low as 75 g/litre. 
    Communities of some species of marine macro algae (seaweed) may be
    eliminated at exposures of about 10 g/litre.  Arsenic is also toxic
    to terrestrial plants.

    2.4  Uptake, metabolism, and excretion

    Studies on experimental animals, as well as on humans, have shown that
    over 90% of an ingested dose of dissolved inorganic trivalent or
    pentavalent arsenic is absorbed from the gastrointestinal tract.  In
    the lungs, water-soluble compounds, such as oxides and arsenites, are
    rapidly absorbed, whereas there may be considerable retention of
    arsenic compounds of low solubility.  Since inorganic arsenic
    compounds are considered to be poorly absorbed through the skin
    (except for corrosive compounds like arsenic trichloride), in the work
    environment, dermal exposure is usually of less significance than
    inhalation exposure.

    Although high levels of arsenic are maintained for long periods of
    time in the bone, hair, and nails of exposed individuals, most
    inorganic arsenic is eliminated at a much higher rate with the urine,
    mainly as dimethylarsinic acid and methane-arsonic acid.  Depending on
    the administered dose, the half-life in man, after short-term
    exposure, is in the range of 1-3 days.  There is no long-term
    accumulation of arsenic in soft tissues.  Placental transfer of
    inorganic arsenic has been demonstrated in both experimental animal
    and human studies.

    With increasing arsenic intake, the proportion of arsenic detoxified
    (methylated) is reduced.  Increases in the inorganic arsenic body
    burden may be expected at daily intakes exceeding about 200 g/person. 
    The level at which overloading of the detoxification system occurs may
    be lowered by a protein-deficient diet.  In persons with a low
    (stable) dietary arsenic intake, the urinary levels may be used to
    monitor exposure to inorganic arsenic.  Since the elimination of
    arsenic takes place mainly via the kidneys, the concentration of
    arsenic in the urine is a good indication of exposure to inorganic
    arsenic. 

    2.5  Effects on experimental animals

    In general, the toxic action of arsenic in experimental animals
    resembles that seen in man.  The oral LD50 of arsenic ranges from
    15 to 293 mg/kg body weight in rats, and from 11 to 150 mg/kg body
    weight in other experimental animals.  Trivalent arsenic is, in
    general, more toxic than pentavalent arsenic.  With long-term oral
    administration, liver lesions, anaemia, and pathological skin changes
    have been produced in animal models.  Studies on experimental animals
    have demonstrated the development of tolerance towards the acute
    effects of arsenic compounds.

    There has been no consistent demonstration of carcinogenicity in tests
    with several species of animals, when various chemical forms of
    arsenic have been administered by the oral route, or to the skin.
    Teratogenic effects have been induced in pregnant golden hamsters
    given a high dose by either intravenous or intraperitoneal injection. 
    Available mutagenicity data are equivocal;  however, inorganic arsenic
    compounds have been shown to enhance the potency of other mutagenic
    agents.

    2.6  Effects on humans

    In man, the smallest recorded fatal dose is in the range of 70-180 mg,
    but recovery has been reported after much larger doses.  Acute
    symptoms develop within 30 minutes to 2 hours, in the form of a sudden
    and explosive gastroenteritis.  Common symptoms include: nausea,
    vomiting, abdominal pain, rice-water diarrhoea (which develops into
    bloody stools), progressive general weakness, and severe dehydration
    leading to collapse and heart failure.  The patient complains of a
    metallic taste, salivation, hoarse voice, constriction of the throat,

    and difficulty in swallowing.  The skin is pale and moist, and the
    stomach may be distended.  Severely poisoned patients develop shock as
    a result of increased capillary permeability and loss of fluids and
    electrolytes.  Death usually results from heart failure within 24
    hours to 4 days.  If the patient survives, hepatic and renal
    impairment and central nervous and peripheral nervous system damage
    may become evident.  The sequelae of acute poisoning include loss of
    hair (which grows back with recovery) and brittle fingernails with
    white horizontal striae ("Mees" lines).  Peripheral nervous
    disturbances, primarily of a sensory type, are frequently encountered
    in individuals surviving poisoning, and there may also be transient
    effects on the blood constituents.  Irritant and vesicant arsenic
    compounds, such as arsenic trioxide and arsenic trichloride, have been
    known to cause severe damage to the respiratory system following
    inhalation.

    Tolerance to arsenic can develop after repeated exposure.  The chronic
    signs of toxicity are insidious and may be difficult to diagnose. 
    They are chiefly related to the skin, gastrointestinal tract, and
    nervous system, but also to the mucous membranes, lungs, and liver. 
    Signs of poisoning are:  progressive general weakness, anorexia,
    nausea, vomiting, stomatitis, colitis, salivation, nose bleed and
    bleeding gums, conjunctivitis, "Mees" lines, thirst, runny nose,
    hoarseness, dermatitis, severe skin exfoliation, low-grade fever, and
    weight loss.  The following signs and symptoms might also be observed: 
    garlic odour of breath, motor paralysis, tingling of the skin of
    extremities, foot and wrist drop, tremors, severe pain and ataxia, and
    loss of hair.  Perforation of the nasal septum may be helpful in the
    diagnosis of chronic poisoning caused by inhalation of inorganic
    arsenic.  A major symptom of chronic poisoning by arsenic is a
    symmetrical hyperkeratosis of the palms and soles, as well as
    melanosis.  The skin changes may progress and cover the entire body in
    multiple forms, and eventually develop into skin cancer (mostly
    squamous cell epithelioma).  In certain populations, a vascular
    disorder resulting in gangrene of the lower extremities ("Blackfoot
    disease") has also been observed.  An allergic type of contact
    dermatitis is frequently seen among workers who are exposed to arsenic
    trioxide.  A common finding among arsenic-exposed workers is
    conjunctivitis and perforation of the nasal septum as a result of
    irritation of the upper respiratory organs by arsenic dust.

    In a number of studies of populations of smelter workers, as well as
    of pesticide applicators, a clear association between occupational
    arsenic exposure and an increased incidence of lung cancer has been
    established.  The carcinogenic effect of arsenic taken up by
    inhalation is potentiated by smoking, and possibly also by other
    agents present in these occupational environments.

    As to the chronic toxic effects caused by oral intake, it appears that
    the ingestion of 3 mg of inorganic arsenic per day, over a period of a
    few weeks, may give rise to severe poisoning in infants, and symptoms
    of toxicity in adults.  Chronic arsenic poisoning, with skin lesions,
    is often accompanied by moderate anaemia and leukopenia.  Chronic
    signs of intoxication may persist for several years after the
    cessation of exposure.

    3.  CONCLUSIONS AND RECOMMENDATIONS

    3.1  Conclusions

    Exposure of the general population to arsenic compounds occurs
    predominately via food and drinking-water.  Over-exposure in the
    working environment and during agricultural application occurs mainly
    through inhalation.

    The acute toxicity of inorganic arsenic compounds for man is very
    high.  The smallest, fatal, single dose for a human is in the range of
    70-180 mg.  With long-term exposure, significant toxic effects can be
    expected to occur above a daily oral intake of 100-200 g.

    The main chronic effects of inorganic arsenic compounds are damage to
    the nervous system and hyperkeratosis of the skin, leading to skin
    cancer.

    Inorganic arsenic is a proven human carcinogen after long-term oral
    intake, as well as after inhalation.

    Arsenic is moderately toxic for fish and aquatic invertebrates, but is
    highly toxic for some algal species.  There is field evidence of
    arsenic affecting aquatic ecosystems.

    3.2  Recommendations

    To minimize the risk to humans, the use of inorganic arsenic compounds
    as pesticides should be stopped, wherever this is feasible.

    Occupational exposure should be kept to a minimum.

    Regularly exposed workers should be kept under strict medical
    surveillance.

    A daily oral intake of 2 g of inorganic arsenic/kg body weight should
    not be exceeded.

    The medicinal use of inorganic arsenic compounds, in particular
    potassium arsenite (Fowler's solution), is to be strongly discouraged.

    4.  HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION

    4.1  Human health hazards, prevention and protection, first aid

    4.1.1  General population

    Where populations are exposed to naturally occurring arsenic in water,
    every effort should be made to provide drinking-water of better
    quality.

    4.1.2  Occupationally exposed population

    In order to interrupt the chain of generation/release/transmission of
    the hazardous agent, the main goal should be primary prevention
    through interventions in the work environment.  These should include
    such measures as exhaust ventilation, closed systems, enclosure of
    sources, and good housekeeping practices.  Local exhaust ventilation
    systems must include air cleaning devices, to prevent environmental
    pollution.

    When these measures are not technically feasible, as is the case in
    the formulation and application of pesticides, or during temporary
    operations, the use of personal protective clothing and equipment
    (e.g., disposable dust masks) is recommended.

    Respirators must be appropriately selected, used, and maintained.  In
    the case of arsenic compounds in a particulate form, a respirator for
    particles should be used;  however, when arsine is formed
    accidentally, this type of respirator is completely ineffective. 
    Routine cleaning and maintenance of respirators is  essential,
    including the renewal of filters or cartridges. This requires proper
    supervision and training of workers, and adequate facilities.  The
    exposure limits adopted should be strictly observed.

    Safe work practices are important preventive measures,  particularly 
    when the way a task is performed may influence the generation or
    release of the agent, or may influence exposure.  In the case of
    arsenic compounds, conditions that can lead to the accidental
    generation of arsine must be spelled out in the work practices, as
    well as ways of preventing such generation.

    The following precautions should be observed during handling and use:

    *    Avoid contact with the skin and eyes, by using a face-mask and
         complete protective clothing.

    *    Do not smoke, drink, or eat in the workplace.  Wash the hands and
         any exposed skin before eating, drinking, or smoking, and after
         work.

    Regular medical supervision of workers occupationally exposed to
    arsenic is recommended.  For employees exposed for 10 years or more,
    examinations should be repeated every 6 months.  Owing to its
    corrosive properties, skin contact with arsenic trichloride is
    associated with a high risk of systemic intoxication.

    Surveillance programmes should include:

    *    routine air monitoring, to ensure that air concentrations are
         below the acceptable standards;

    *    biological monitoring, by measuring arsenic concentrations in the
         urine.

    Interpretation of results must take into consideration
    non-occupational values and, therefore, pre-exposure values.

    4.1.3  First aid

    Medical attention should be obtained as soon as possible.  In the
    meantime, first aid should be commenced.  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.  If the material is in the eyes, flush with
    clean water for at least 15 minutes.  In case of ingestion, immediate
    action is imperative:  if the patient is conscious, give two glasses
    of milk (or water), or a beaten egg, induce vomiting and subsequently
    administer activated charcoal, if possible.  Transport the patient to
    a hospital.

    4.2  Advice to physicians

    Diagnosis is based on history, symptoms, signs, and laboratory
    investigations, but treatment should start on suspicion of poisoning.

    4.2.1  Treatment

    Prognosis is dependent on dose, as well as the time between ingestion
    of arsenic and first treatment.  Gastric aspiration and lavage with
    warm water followed by sodium sulfate (30 g) is indicated.  Keep
    patient warm and quiet; combat shock and dehydration.  Apply
    artificial respiration, oxygen therapy, whole blood, or fluids as
    needed.  Dimercaprol (BAL) by intra-muscular injection has been found
    to be useful in cases of intoxication.  A number of side-effects have
    been associated with BAL, and the use of this antidote for treatment
    of chronic intoxications is controversial.  D-penicillamine has also
    been used, although its efficacy has been questioned.  A water-soluble
    analogue of dimercaprol (meso-2,3-dimercaptosuccinic acid or DMSA) has
    proved to be more effective and less toxic; therefore, it is indicated
    as first choice chelator, if available.  The sodium salt of
    2,3-dimercaptopropanesulfonate (Unithiol, Dimaval, DMPS) has also been
    reported to be effective and to induce less severe side-effects, in
    comparison with dimercaprol.

    4.3  Explosion and fire hazards

    Finely divided arsenic metal may present an explosion risk.  Most
    industrially important inorganic arsenic compounds are not
    combustible, but may evolve highly toxic and flammable arsine when
    heated, or in the presence of other agents (see section 1.2).  Arsine
    may also be produced when arsenic is in contact with acids in the
    presence of some metals, e.g., zinc or iron, as a consequence of the
    liberation of hydrogen.  Arsenic sulfides are combustible and yield
    toxic and flammable hydrogen sulfide gas on contact with strong acids.

    Do not use water to extinguish fires involving arsenic trichloride;
    dry chemical or carbon dioxide extinguishers should be used.

    Water sprays should only be used to cool undamaged stock; the use of
    large amounts of water should be avoided because of the possibility of
    highly toxic run-off from the site.  Fire service personnel should be
    advised that self-contained breathing apparatus and totally
    encapsulated protective clothing are necessary.

    4.4  Storage and transport

    All products should be stored in secure buildings, kept dry and out of
    the reach of children and animals, and separated from food and animal
    feed.  Containers should be sound and adequately labelled.  Arsenic
    trichloride is highly corrosive and must not be stored in containers
    made from steel, galvanized steel, tin, or aluminium.  Suitable
    containers are high density polyethylene bottles, resin-lined metal
    drums, and glass containers.  Do not store near fertilizers, seeds,
    insecticides, or fungicides.

    These products should be transported in a separate compartment to
    prevent contamination of food or feed.

    4.5  Spillage

    Keep spectators away from any leakage.  Prevent contamination of other
    goods or cargo, nearby vegetation, and surface waters.  Absorb
    spillage of liquid products with sand or earth, sweep up and place in
    a separate container.  Empty any product remaining in damaged or
    leaking containers into a clean empty container, which should be
    suitably labelled.  Sweep up any spilt powder with damp sawdust,
    taking care not to raise a dust cloud.  Place in a separate container
    for subsequent disposal.  Contaminated absorbents, used containers,
    surplus product, etc., should not be incinerated.

    4.6  Disposal

    Arsenic-containing wastes should not be buried in landfill sites,
    except in very small quantities interspersed with large volumes of
    non-hazardous wastes.  Do not incinerate and do not discharge to
    sewers or water courses.

    Precipitation and/or solidification are preferred methods but should
    be carried out by a specialist in toxic waste disposal, because of the
    persistence and toxicity of arsenic.

    5.  HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    Inorganic arsenic compounds are moderately toxic for fish and aquatic
    invertebrates.  They are highly toxic for some algae.  Low
    concentrations have been shown to have serious effects on aquatic
    ecosystems.  Biological transformation results in the production of
    less acutely toxic organic arsenic compounds.  Inorganic arsenic in
    sediments may be released slowly over long periods.  Groundwater
    contamination has proved to be a serious problem in some areas. 
    Although persistent and taken up by plants and other organisms,
    inorganic arsenic as such is not subject to significant biological
    transfer through food-chains.

    6.  CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

    6.1  Previous evaluations by international bodies

    The Joint FAO/WHO Expert Committee on Food Additives assigned a
    provisional tolerable weekly intake (PTWI) of 0.015 mg/kg body weight
    for inorganic arsenic, but stressed that there is a narrow margin
    between the PTWI and intakes reported in epidemiological studies to
    have toxic effects.

    Arsenic trioxide has a minimum lethal dose for humans of 2 mg/kg body
    weight, and is classified in The WHO recommended classification of
    pesticides by hazard and guidelines to classification as an "extremely
    hazardous pesticide", the oral LD50 for the rat being 180 mg/kg body
    weight.

    The International Agency for Research on Cancer (IARC) evaluated
    arsenic and (inorganic) arsenic compounds and concluded that there is
    sufficient evidence of their carcinogenicity in humans, and limited
    evidence of their carcinogenicity in experimental animals (Group 1). 
    Because of the inadequacy of the data, and the concern over the
    potential carcinogenicity of arsenic, no acceptable daily intakes
    (ADI) for calcium and lead arsenate pesticides have been established
    by the Joint FAO/WHO Meeting on Pesticide Residues.

    A guideline value of 0.05 mg As(total)/litre has been recommended in
    the  WHO Guidelines for drinking-water quality.  In the  WHO Air
     quality guidelines for Europe it was concluded that, because
    inorganic arsenic is carcinogenic and there is no known safe
    threshold, no safe level for arsenic can be recommended.  At an
    arsenic air concentration of 1 g/m3, a conservative estimate of
    lifetime risk is 3  10-3.

    6.2  Exposure limit values

    The information given in this section has been extracted from the most
    recent International Register of Potentially Toxic Chemicals (IRPTC)
    legal file.  Regulatory decisions about chemicals, taken in a certain
    country, can only be fully understood in the framework of the
    legislation of that country.  The regulations and guidelines of all
    countries are subject to change and should always be verified with
    appropriate regulatory authorities before application.  Some exposure
    limit values are given in Table 3.

    6.3  Specific restrictions

    No arsenic-containing pesticides (except for wood preservatives) or
    pharmaceutical products are permitted in Sweden.  Lead arsenate has
    been prohibited from use as an insecticide in Japan since 1977.

    In Germany, emissions of arsenic are controlled.  The total
    concentration of dusts of arsenic, cobalt, nickel, selenium, and
    tellurium, including their inorganic compounds, may not exceed
    1 mg/m3 at a mass flow of 5 g/hour or more.

    In the United States of America, arsenic and compounds are classified
    as toxic pollutants, for which the US Environmental Protection Agency
    is required to set effluent limitations and pre-treatment standards
    for 21 major industries.  Permits are required for the discharge of
    arsenic into USA national waters.  Arsenic in outfalls must be
    reported.  Inspection, monitoring, and reporting requirements after
    the issue of the permit are specified.  Even if not required in the
    permit, discharge of arsenic must be reported if it exceeds the higher
    of the following levels:  (a) 100 g/litre;  (b) five times the
    maximum concentration reported in the application;  (c) the level
    established by the US EPA.

    6.4  Transport and labelling

    The United Nations Committee of Experts on the Transport of Dangerous
    Goods has classified arsenic and most inorganic arsenic compounds as
    "Poisonous (toxic) substances".  As such, strict regulations are
    applied to their transportation.  The International Maritime Dangerous
    Goods code classifies such substances as marine pollutants, which
    require appropriate warning labels.

    Within the European Economic Community, the mandatory labelling of
    arsenic,  which is classified as "Toxic", includes the "skull and
    crossbones" design.  The label should read "Toxic by inhalation and if
    swallowed", as well as:

          Keep locked up, keep out of reach of children.  When using do
          not eat, drink, or smoke. After contact with skin, wash
          immediately with plenty of .... (to be specified by the
          manufacturer). If you feel unwell, seek medical advice (show the
          label where possible).

    Within the European Economic Community legislation, arsenic trioxide
    is classified as a carcinogen
    Class 1 (known human carcinogen) requiring the label:

    FIGURE 1

     May cause cancer; very toxic if swallowed; causes burns; avoid
     exposure, obtain special instructions before use;  in case of
     accident or if you feel unwell, seek medical advice
     immediately (show label where possible).



        Table 3.  Exposure limit values

                                                                                                                                         

    Medium      Specification       Country/            Exposure limit description                      Value 
                                    organization                                                        (mg/m3)
                                                                                                                                         

    Air         Occupational        Argentina           Maximum permissible limit (MPC)
                                                        - Time-weighted average                         0.5

                                    Australia           Threshold limit value (TLV) 
                                                        -  Time-weighted average (TWA)                  0.2

                                    Belgium             Threshold limit value (TLV) 
                                                        -  Time-weighted average (TWA)                  0.2

                                    Canada              Threshold limit value (TLV)
                                                        -  Time weighted average (TWA)                  0.2

                                    Czechoslovakia      Maximum allowable concentration (MAC)
                                                         - Time-weighted average (TWA)                  0.2

                                    Finland             Maximum permissible limit (MPC)
                                                        -  Time-weighted average (TWA)                  0.01

                                    Germany             Technical guiding concentration (TRK)
                                                         - 8h - Time-weighted average (TWA)             0.1

                                    Hungary             Maximum allowable concentration (MAC)
                                                         - Time-weighted average (TWA)                  0.3

    Air         Occupational        Italy               Threshold limit value (TLV) (carcinogen)        0.25

                                    Netherlands         Maximum limit (MXL)
                                                        -  Time-weighted average (TWA)                  0.5

                                                                                                                                         

    Medium      Specification       Country/            Exposure limit description                      Value 
                                    organization                                                        (mg/m3)
                                                                                                                                         

    Air         Occupational        Poland              Maximum permissible limit (MPC) 
                                                        -  Time-weighted average (TWA)                  0.3

                                    Romania             Maximum permissible limit (MPC)
                                                        -  Time-weighted average (TWA)                  0.2

                                    Sweden              Hygienic limit value (HLV)
                                                        1 day- Time-weighted average (TWA)              0.03

                                    United Kingdom      Permissible exposure limit (PEL)
                                                        8h - Time-weighted average (TWA)                0.2

                                    USA                 Threshold limit value (TLV)
                                                        -  Time-weighted average (TWA)                  0.2

                                    USSR                Maximum allowable concentration (MAC)
                                                        -  Time-weighted average (TWA)                  0.01

                                    Yugoslavia          Maximum allowable concentration (MAC)
                                                        -  Time-weighted average (TWA)                  0.01

    Air         Ambient             Czechoslovakia      Maximum allowable concentration (MAC
                                                        - average/day                                   0.003
                                                        -  average/0.5h                                 0.01

                                    USSR                Maximum allowable concentration (MAC)
                                                        - average/day                                   0.003

    Water       Drinking-           Canada              Maximum allowable concentration (MAC)           0.05 mg/litre

                                    Czechoslovakia      Maximum allowable concentration (MAC)           0.05 mg/litre

                                    Germany             Maximum permissible limit (MPC)                 0.04 mg/litre

                                                                                                                                         

    Medium      Specification       Country/            Exposure limit description                      Value 
                                    organization                                                        (mg/m3)
                                                                                                                                         

    Water       Drinking-           Japan               Maximum permissible limit (MPC)                 0.05 mg/litre

                                    USA                 Maximum permissible limit (MPC)                 0.05 mg/litre

                                    USSR                Maximum allowable concentration (MAC)           0.05 mg/litre

                                    WHO                 Guideline level (GL)                            0.05 mg/litre

                                    EEC                 Maximum allowable concentration (MAC)           0.05 mg/litre

    Water       Surface             Czechoslovakia      Maximum allowable concentration (MAC)           0.5 mg/litre

                                    Japan               Maximum limit (MXL)                             0.05 mg/litre

                                    Mexico              Maximum permissible limit (MPC)
                                                         (depending on water use)                       0.05-5.0 mg/litre

                                    USSR                Maximum allowable concentration (MAC)           0.05 mg/litre

                                                                                                                                         
    
    BIBLIOGRAPHY

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    UNEP/IEO (1990) Storage of hazardous materials: a technical guide for
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    UNITED NATIONS (1984) Consolidated list of products whose consumption
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    UNITED NATIONS (1986) Recommendations on the transport of dangerous
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    WHO (1981) Environmental Health Criteria 18: Arsenic. Geneva, World
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    WHO (1987) Air quality guidelines for Europe. Copenhagen, WHO Regional
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    WHO (1989) Toxicological evaluation of certain food additives and
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    WHO (1992) The WHO recommended classification of pesticides by hazard
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    See Also:
       Toxicological Abbreviations