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    IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
    Health and Safety Guide No. 102

    THALLIUM AND THALLIUM COMPOUNDS
    HEALTH AND SAFETY GUIDE






    UNITED NATIONS ENVIRONMENT PROGRAMME

    INTERNATIONAL LABOUR ORGANISATION

    WORLD HEALTH ORGANIZATION




    WORLD HEALTH ORGANIZATION, GENEVA 1996

    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

    Thallium and thallium compounds: health and safety guide.

    (Health and safety guide ; no. 102)

    1.Thallium - toxicity  I.Series

    ISBN 92 4 151102 8          (NLM Classification: QV 618)
    ISSN 0259-7268

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    (c) World Health Organization 1996

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    CONTENTS

    1. PRODUCT IDENTITY AND USES

         1.1. Identity
         1.2. Physical and Chemical Properties
         1.3. Analysis
         1.4. Production and Uses

    2. SUMMARY AND EVALUATION

         2.1. Environmental transport, distribution and
               transformation
         2.2. Environmental levels and human exposure
         2.3. Kinetics and metabolism in laboratory animals and humans
         2.4. Effects on laboratory mammals and  in vitro test
               systems
         2.5. Effects on humans
         2.6. Human dose-response relationship
         2.7. Effects on other organisms in the laboratory and field

    3. CONCLUSIONS AND RECOMMENDATIONS

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

         4.1. Human Health Hazards, Prevention and Protection, First
               Aid
               4.1.1. Advice to physicians
                       4.1.1.1    Signs and symptoms of exposure
                       4.1.1.2    First aid
                       4.1.1.3    Medical treatment
               4.1.2. Health surveillance advice
               4.1.3. Prevention and protection
                       4.1.3.1    General recommendations
                       4.1.3.2    Engineering control
                       4.1.3.4    Personal protective equipment and
                                  hygienic measures
         4.2. Explosion and fire hazards
         4.3. Storage
         4.4. Transport
         4.5. Spillage
         4.6. Disposal

    5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    6. SUMMARY OF CHEMICAL SAFETY INFORMATION

    7. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

         7.1. Previous Evaluations by International Bodies
         7.2. Exposure Limit Values
         7.3. Specific Restrictions
         7.4. Labelling, Packaging, and Transport
         7.5. Waste Disposal

    8. BIBLIOGRAPHY
    

    INTRODUCTION

    The Environmental Health Criteria (EHC) monographs produced by the
    International Programme on Chemical Safety include an assessment of
    the effects on the environment and on human health of exposure to a
    chemical or combination of chemicals, or physical or biological
    agents. They also provide guidelines for setting exposure limits.

    The purpose of a Health and Safety Guide is to facilitate the
    application of these guidelines in national chemical safety
    programmes. The first three sections of a Health and Safety Guide
    highlight the relevant technical information in the corresponding EHC.
    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. Within the Guide is a Summary of Chemical Safety
    Information which should be readily available, and should be clearly
    explained, to all who could come into contact with the chemical. 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. A bibliography has been included for
    readers who require further background information.

    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, chemical formula and CAS numbers of thallium
    and of some thallium compounds are given in Table 1.

    1.2  Physical and Chemical Properties

         Thallium is a soft and malleable heavy metal with a bluish-white
    colour. Its relative molecular mass is 204.283. Its most important
    compound is the colourless odourless and tasteless thallium(I)
    sulfate, previously used on a large scale as a rodenticide. 
    Monovalent (thallous) compounds behave like, and may be as, reactive
    as, alkali metals, e.g.,  potassium, whereas the trivalent (thallic)
    compounds are less basic, resembling aluminium.

         Some physical properties are summarized in Table 1.

    1.3  Analysis

         Since concentrations of thallium in environmental samples are
    normally very low, determination directly from the sample or from the
    digestion solution usually lacks sufficient accuracy.  Therefore,
    preconcentration procedures are necessary.  For the g/kg range or
    less, isotope dilution and inductively coupled plasma mass
    spectrometry coupled with electrothermal vaporization or graphite
    furnace atomic absorption spectrometry are used. Usually the limit of
    detection for the latter is in the range of 0.6-20 g/kg.

    1.4  Production and Uses

         Thallium is produced industrially only in small quantities (in
    1987 and 1988 worldwide production was about 17 tonnes; in 1991
    world-wide industrial consumption was 10 to 15 tonnes).  However, each
    year nearly 1000 tonnes of thallium are released into the environment,
    mainly from mineral smelters, coal-burning power plants, brickworks
    and cement plants.

         Thallium has a wide variety of industrial uses.  Its use as a
    depilatory for humans or as a rodenticide and insecticide has now been
    prohibited or severely reduced.  Thallium is now mainly used in the
    electrical and electronic industries and in the production of special
    glasses. Another important field of application is the use of
    radioisotopes in medicine for scintigraphy and the diagnosis of
    melanoma.

        TABLE 1  PHYSICAL AND CHEMICAL PROPERTIES OF THALLIUM AND SOME SELECTED THALLIUM COMPOUNDSa
                                                                                                                                              

    Name                     Chemical        CAS registry   Relative     Specific   Melting        Boiling        Colour         Solubility in
                             formula         number         atomic/      gravity    point          point                         water
                                                            molecular    (g/cm3)    (C)           (C)                          (g/litre)
                                                            mass
                                                                                                                                              

    Thallium                 Tl              7440-28-0      204.38       11.85      303.5          1457           bluish-white,  insoluble
                                                                                                                  metallic

    Thallium(I) acetate      TlC2H3O2        563-68-8       263.43       3.765      131            -              silky white    very
                                                                                                                                 soluble

    Thallium aluminium       TlAl(SO4)2*12   52238-56-9     639.66       2.306      91             -              colourless     117.8
     sulfate                 H2O

    Thallium(I) bromide      TlBr            7789-40-0      284.29       7.557      480            815            pale yellow    0.5
                                                                         (17.3C)                                                (25C)

    Thallium(I) carbonate    Tl2CO3          29809-42-5     468.78       7.110      273            -              white          40.3
                                                                                                                                 (15.5C)

    Thallium(I) chloride     TlCl            7791-12-0      239.84       7.004      430            720            white          2.9
                                                                         (30C)                                                  (15.5C)

    Thallium(III)            TlCl3           13453-32-2     310.74       -          25             decomposes     colourless,    very
    trichloride
                                                                                                                  hygroscopic    soluble
                             TlCl3*4H2O      13453-33-3     382.80       -          37             100 (-H2O)     colourless     862

    Thallium ethylate        TlOC2H5         20398-06-5     249.44       3.493      -3             130            colourless     -
                                                                         (20C)                    (decomposes)

    Thallium(I) fluoride     TlF             7789-27-7      223.38       8.23       327            655            colourless     786
                                                                         (4C)                                                   (15C)
                                                                                                                                              

    TABLE 1  (Con't)
                                                                                                                                              

    Name                     Chemical        CAS registry   Relative     Specific   Melting        Boiling        Colour         Solubility in
                             formula         number         atomic/      gravity    point          point                         water
                                                            molecular    (g/cm3)    (C)           (C)                          (g/litre)
                                                            mass
                                                                                                                                              

    Thallium(III)            TlF3            7783-57-5      261.38       8.36       550            -              olive          decomposes
    trifluoride                                                          (25C)     (decomposes)                  green          to TIOH

    Thallium hydroxide       TlOH            1310-83-4      221.39       -          139            -              pale           259
                                                                                    (decomposes)                  yellow

    Thallium(I)              TlI             7790-30-9      331.29       7.29       440 ()        823 ()        yellow         0.006
    iodide (alpha)                                                                                                               (20C)

    Thallium(I)              TlNO3           10102-45-1     266.39       -          206            430            white          95.5
    nitrate (alpha)                                                                                                              (20C)

    Thallium (III) nitrate   Tl(NO3)3*3H2O   13453-38-8     444.44       -          105-107        decomposes     colourless    
    decomposes
     trihydrate

    Thallium(I) oxide        Tl2O            1314-12-1      424.77       9.52       300            1080 (-O)      black          decomposes
                                                                         (16C)                                                  to TIOH

    Thallium(III) oxide      Tl2O3           1314-32-5      456.76       10.19      717  5        875 (-O2)      black          insoluble
                                                                         (22C)

    Thallium(I) sulfate      Tl2SO4          7446-18-6      504.82       6.77       632            decomposes     white          48.7
                                                                                                                                 (20C)

    Thallium(I) sulfide      Tl2S            1314-97-2      440.85       8.46       448.5          -              -              0.2
                                                                                                                                 (20C)
                                                                                                                                              

    a  From: Stokinger (1987); Budavari (1989); Lide (1990)
        2.  SUMMARY AND EVALUATION

    2.1  Environmental transport, distribution and transformation

         Near point sources such as coal-fired power-generating stations,
    some cement plants and metal smelting operations, the major source of
    thallium in air is emission of fly ash.  The results of one study
    indicate that nearly all of the thallium in fly dust from a cement
    plant was present as soluble thallium(I) chloride.

         The fate of thallium added to soil (in deposited fly ash, for
    example) depends largely on soil type.  Retention will be greatest in
    soils that contain large amounts of clay, organic matter and
    iron/manganese oxides.  Incorporation into stable complexes causes
    enhanced thallium concentrations only in the upper levels of soils. 
    The uptake of thallium by vegetation increases as soil pH decreases. 
    In some strongly acid soils significant amounts of thallium can be
    leached to local ground and surface water.

         Most dissolved thallium in freshwater is expected to be in the
    monovalent form.  However, in strongly oxidized fresh water and most
    seawater trivalent thallium may predominate.  Thallium can be removed
    from the water column and accumulate in sediment by various exchange,
    complexation or precipitation reactions.

         Although thallium can bioconcentrate, it is not likely to
    biomagnify in aquatic or terrestrial food webs.

    2.2  Environmental levels and human exposure

         In areas not contaminated by thallium, concentrations in air are
    usually < 1 ng/m3, those in water < 1 g/litre, and those in water
    sediments < 1 mg/kg.  Mean concentrations in the earth's crust range
    from 0.1 to 1.7 mg/kg, but very high concentrations are possible,
    e.g., in coal up to 1000 mg/kg, and the rarely found minerals of
    thallium consist of up to 60% of the element.  Food of plant and
    animal origin usually contains < 1 mg/kg dry weight and the human
    average dietary intake of thallium appears to be less than 5 g/day. 
    Uptake via the respiratory system is estimated to be < 0.005 g
    thallium/day.

         There are only limited data about the actual thallium content of
    workplace air.  The most recent (1980s) concentrations of thallium
    observed were < 22 g thallium/m3 (in the production of a special
    thallium alloy and in a thallium smelter). Average urinary
    concentrations were determined to be in the range of 0.3-8 g/litre
    for cement workers and 0.3-10.5 g/litre for foundry workers.

    2.3  Kinetics and metabolism in laboratory animals and humans

         Thallium is rapidly and well absorbed through the gastro-
    intestinal and respiratory tracts and is also taken up through
    the skin.  It is rapidly distributed to all organs and passes the
    placenta (as indicated by the rapid fetal uptake) and the blood-brain
    barrier.  Because of its rapid accumulation in cells, concentrations
    of thallium in whole blood do not reflect the levels in tissues.  In
    acute poisoning of experimental animals or humans, initially high
    concentrations of thallium appear in the kidney, low concentrations in
    fat tissue and brain, and intermediate concentrations in the other
    organs; later the thallium concentration of the brain also increases.

         Elimination of thallium may occur through the gastrointestinal
    tract (mainly by mechanisms independent of biliary excretion), kidney,
    hair, skin, sweat and breast milk.  Intestinal reabsorption (mainly
    from the colon) may occur with a consequent decrease in total body
    clearance.  In rats, the main routes of thallium elimination are
    gastrointestinal (about two thirds) and renal (about one third), in
    rabbits the contribution of the two routes is about equal.  Thallium
    is also secreted in saliva.

         As with many other substances, the excretion of thallium in
    humans differs from that in laboratory animals, since the rate of
    excretion is generally much lower in humans (rate constant
    = 0.023-0.069 day-1) than in laboratory animals (average rate
    constant = 0.18 day-1).  Another major difference between humans and
    animals is the relative contribution of the different routes of
    excretion.  In humans, renal excretion seems to be much more important
    than in animals, although its relative contribution to the total body
    clearance has not been definitively established, due principally to
    the lack of sufficient human data.  Moreover, exposure levels,
    duration of exposure, impairment of excretory organ function,
    potassium intake and concomitant treatment of acute poisoning may
    considerably influence the results.

         In one study renal excretion of thallium was reported to be about
    73%, whereas that through the gastrointestinal tract was about 3.7% of
    the daily excreted amount.  Excretion through hair and skin, and sweat
    has been estimated to be 19.5% and 3.7%, respectively.

         The biological half-life of thallium in laboratory animals
    generally ranges from 3 to 8 days; in humans it is about 10 days but
    values up to 30 days have been reported.

         No data on the biotransformation of thallium are available.

    2.4  Effects on laboratory mammals and in vitro test systems

         There are no striking species-specific differences in the
    toxicity of thallium(I) salts.  Usually an oral intake of 20 to 60 mg
    thallium/kg body weight is lethal within one week.  Guinea-pigs are
    slightly more sensitive than other experimental animals.  The water-
    insoluble thallium(III) oxide shows a somewhat lower acute toxicity by
    oral or parenteral administration than thallium(I) salts.  Comparison
    of acute toxicity data indicates a high degree of bioavailability from
    all exposure routes.  Most organs are affected, but the signs of
    poisoning and the sequence in which they occur reveal some intra- and
    interspecies variability.

         The symptoms of acute intoxication generally follow the following
    sequence: firstly anorexia, vomiting and depression, later diarrhoea,
    skin changes (inflammation at body orifices, skin furuncles, hair
    loss), and then dyspnoea and nervous disorders.  Finally, respiratory
    failure leads to death.

         Symptoms of chronic intoxication are similar to those of acute
    intoxication.  Loss of hair regularly occurs.

         Histological examination reveals necrosis or other cell damage. 
    Necrotic changes have been observed in the kidneys, liver, intestine,
    heart and the nervous system.  Swelling of mitochondria and loss of
    cristae, dilatations of smooth endoplasmic reticulum, increased
    numbers of autophagic vacuoles and lipofuscin granules, and loss of
    microvilli have been observed in many cells.  The thallium-induced
    alterations of functional processes may arise from physical disruption
    of the membranes of subcellular organelles.  In the heart,
    arrhythmogenic effects are restricted to the sinus node.

         Thallium intoxication causes selective impairment of certain
    behavioural elements, which are correlated with biochemical effects
    (which indicate cellular damage) in certain regions of the brain. 
    Some neurological effects seem to be caused by direct action, e.g.
    ataxia and tremor by cerebellar alterations or alterations in
    endocrine activity through changes in the hypothalamus.  The autonomic
    nervous system, mainly the adrenergic, may be activated by thallium. 
    In peripheral nerves, thallium seems to interfere presynaptically,
    with the spontaneous release of transmitter, by antagonizing these
    calcium-dependent processes.

         The exact mechanism of thallium toxicity is still unknown. 
    Several, perhaps interconnected, mechanisms have been postulated.  An
    important aspect of thallium intoxication is the significant increase
    in lipid peroxidation and in the activity of the lysosomal enzyme
    -galactosidase.  The resulting deficiency of glutathione leads to the

    accumulation of lipid peroxides in the brain and, presumably, finally
    to lipofuscin granules.  The mode of action of thallium seems to be
    mainly due to a disturbance of the function of the mitochondria.

         Sexual activity is usually reduced in chronically poisoned
    animals, and gonadotoxic effects of thallium are evident in the male
    reproductive system.  In the testes of rats given 10 mg thallium/litre
    in the drinking-water for 16 days, the Sertoli cells were most
    sensitive, and desquamation of the spermatogenic epithelium led to
    immature sperm cells in the semen.  This could explain the decreased
    survival rate of embryos or reduced life span of offspring after
    sublethal thallium-poisoning of the fathers.

         Teratogenic effects, growth inhibition and disturbances in the
    development of bones were found to occur in chicken embryos after
    injection of thallium into the egg, but such effects in mammals, even
    at maternotoxic doses, are controversial.  Although transplacental
    transfer has been demonstrated, many strains of mice and rats show no
    or only slight teratogenic effects.

         Two microbiological mutagenicity tests in  Salmonella typhimurium 
    were negative and  in vivo tests on sister chromatid exchange were
    controversial.  However, single studies report chromosomal aberrations
    or a significant increase of single-stranded DNA breaks.

         Long-term studies on the carcinogenicity of thallium are lacking.

    2.5  Effects on humans

         Since thallium salts are tasteless, odourless, colourless, highly
    toxic, were easily obtainable in the past and still are in some
    developing countries, thallium has often been used for suicide,
    homicide and attempts at illegal abortion, causing acute thallium
    poisoning.  Indeed, thallium intoxication is considered one of the
    most frequent causes, on a worldwide scale, of purposeful or
    accidental human poisoning.  Knowledge of chronic thallium
    intoxication is limited to occupational exposure, to population groups
    in contaminated areas and to cases of homicide involving multiple low
    doses.

         Symptoms of acute thallium toxicity depend on age, route of
    administration and dose.  Doses which have proved lethal vary between
    6 and 40 mg/kg, being on average 10 to 15 mg/kg.  Without therapy this
    average dose usually results in death within 10 to 12 days, but death
    occurring within 8-10 h has also been reported.

         The triad of gastroenteritis, polyneuropathy and alopecia is
    regarded as the classic syndrome of thallium poisoning, but in some
    cases gastroenteritis and alopecia were not observed.  Several other
    signs and symptoms also occur, varying in order, extent and intensity.

         Symptoms of thallium intoxication are often diffuse and initially
    include anorexia, nausea, vomiting, metallic taste, salivation,
    retrosternal and abdominal pain and occasionally gastrointestinal
    haemorrhage (blood in faeces).  Later, constipation is commonly seen
    and may be resistant to treatment, thus interfering with antidotal
    treatment.

         After 2 to 5 days some of the typical thallium disorders slowly
    develop, irrespective of the route of exposure.  Effects on the
    central and peripheral nervous system vary, but a consistent and
    characteristic feature of thallium intoxication in humans is the
    extreme sensitivity of the legs, followed by the "burning feet
    syndrome" and paraesthesia.  Involvement of the central nervous system
    (CNS) is indicated by symptoms like hallucinations, lethargy,
    delirium, convulsions and coma.  Common circulatory symptoms are
    hypertension, tachycardia and, in severe cases, cardiac failure.  Loss
    of head hair and sometimes body hair occurs after the second week of
    poisoning; dystrophy of the nails is manifested by the appearance of
    white lunular stripes (Mee's lines) 3 to 4 weeks after intoxication. 
    The black regions found in hair papillae are not caused by deposition
    of pigments or thallium but are due to small amounts of air entering
    the shaft.

         In lethal cases the time until death occurs may vary from hours
    to several weeks, but most commonly death occurs within 10 to 12 days. 
    Causes of death are mainly renal, CNS and cardiac failure.

         In sublethal poisonings, recovery often requires months. 
    Sometimes neurological and mental disturbances as well as
    electroencephalographic abnormalities and blindness can remain. 
    Additionally, intellectual functions seem to be adversely affected in
    survivors.

         In cases of chronic poisoning, symptoms are similar but in
    general milder than in cases of acute intoxication.  Sometimes
    permanent blindness occurs.  Complete recovery takes months and can be
    interrupted by relapses.

         In a well-investigated case of thallium emission around a cement
    plant in Lengerich, Germany, thallium concentrations in the hair and
    urine of exposed people did not correlate with certain features which
    are known to be usually associated with chronic thallium poisoning,
    but only with subjective neurological symptoms.

         Postmortem examinations or biopsies following thallium poisoning
    reveal damage of various organs.  For example, after ingestion of
    lethal doses, haemorrhages in the mucosa of the intestine, lung,
    endocrine glands and heart, fatty infiltrations in liver and heart
    tissue, and degenerative changes to glomeruli and renal tubules occur. 
    In the brain, fatty degeneration of ganglion cells, damage to axons
    and disintegration of myelin sheaths can be observed.

         Variations in blood pressure may be caused by direct effects of
    thallium on the autonomic nervous system.  Thallium intoxication
    causes symmetric, mixed peripheral neuropathy.  Distal nerves are
    affected more than proximal nerves, and earlier but lesser degrees of
    damage occur in nerves with shorter axons, e.g., cranial nerves. 
    Axons are swollen and contain vacuoles and distended mitochondria.  In
    lethal poisoning, severe damage of the vagus nerve, denervation of the
    carotid sinus and lesions of the sympathetic ganglia have been
    observed.  In sublethal poisoning, affected nerves may undergo axonal
    degeneration with no or only partial recovery within 2 years.

         Retrobulbar neuritis and resulting visual disorders can develop
    and persist for months after terminating treatment with thallium-
    containing depilatories, and even optic atrophy may occur.

         Limited data are available on the effects of thallium on human
    reproduction.  Menstrual cycle, libido and male potency may be
    adversely affected. Effects on sperm are known to occur following
    chronic intoxication.  As in animal studies, transplacental transfer
    occurs; this was seen following a thallium-induced abortion.  However,
    apart from a relatively low weight and alopecia of newborn babies,
    fetal development was not affected in about 20 cases of thallium
    intoxication during pregnancy.

         No reports of any carcinogenic effects or data on immunological
    effects of thallium are available.  There is no adequate evidence of
    genotoxic effects.

         Therapies of thallium intoxication combine forced diuresis, use
    of activated charcoal and prevention of re-absorption in the
    colon by administration of Prussian blue, potassium ferric
    hexacyanoferrate(II).

    2.6  Human dose-response relationship

         The mean urinary thallium concentration in unexposed populations
    is 0.3 to 0.4 g/litre.  As thallium has a short biological half-life,
    measured in days, and assuming steady-state conditions, this urinary
    concentration can be taken as an indicator of total dose following
    inhalation and dietary intake.

         The mean urinary thallium concentration in a population sample
    living near a thallium atmospheric emission source was 5.2 g/litre. 
    A clear dose-response relationship was found between urinary thallium
    concentration and the prevalence of tiredness, weakness, sleep
    disorders, headache, nervousness, paraesthesia, and muscle and joint
    pain.  A similar dose-response relationship was also reported when
    thallium in hair was used as an indicator of exposure.

         The Task Group considered that exposures causing urinary thallium
    concentrations below 5 g/litre are unlikely to cause adverse health
    effects.  In the range of 5-500 g/litre the magnitude of risk and
    severity of adverse effects are uncertain, while exposure giving
    values over 500 g/litre have been associated with clinical poisoning.

    2.7  Effects on other organisms in the laboratory and field

         Thallium affects all organisms, but species- and also strain-
    specific differences are evident.  Different inorganic thallium(I) and
    thallium(III) compounds and organothallium compounds can show
    different toxicities.

         The most important effect of thallium on microorganisms seems to
    be inhibition of nitrification by soil bacteria.  Results of one study
    suggest that microbial community structure is disturbed at soil
    concentrations in the range of 1-10 mg/kg dry weight, but the form of
    thallium used in this experiment was not identified.

         Thallium is taken up by all plant parts, but principally by the
    roots.  After uptake into the cell, it is concentrated unevenly in the
    cytosol, probably bound to a peptide.  Thallium concentrations found
    in plants depend on soil properties (especially pH, clay and organic
    matter content), as well as on the developmental stage and on the part
    of the plant.  Thallium accumulates in chlorophyll-containing regions,
    but to a lesser degree in thallium-resistant plants.  Oxygen
    production is reduced by thallium, presumably by direct action on
    electron transfer in photosystem II.  Interference with the pigments
    is indicated by the occurrence of chlorosis. In addition, impaired
    uptake of trace elements seems to be involved in the mechanism of
    toxicity.  Growth is also affected, roots reacting more sensitively
    than leaves or stems.  These effects have been reported at
    concentrations as low as 1 mg thallium/kg of dry plant tissue, after
    exposure to monovalent forms of thallium.

         Most studies of effects on aquatic organisms have used soluble
    monovalent thallium compounds.  The lowest thallium concentration
    reported to affect aquatic species is 8 g/litre, which caused a
    reduction in growth of aquatic plants.  Invertebrates are often

    affected at lower concentration than fish (96-h LC50 values are
    2.2 mg thallium/litre for daphnids and 120 mg/litre for a freshwater
    fish).  The lowest LC50 value, reported after exposure for about 40
    days, was 40 g/litre for fish.

         Many cases of thallium intoxication of wildlife have been caused
    by its large scale application as a rodenticide.  In seed-eating
    animals and predators the CNS and/or the gastrointestinal tract are
    most severely affected.  These effects can also be observed in farm
    animals.  In addition, thallium causes a loss of dorsal feathers in
    ducks, salivation from the nose and mouth of cattle, and reduced
    growth in broilers, laying hens, sheep and steers.

    3.  CONCLUSIONS AND RECOMMENDATIONS

         Thallium is currently produced and used industrially in only
    small quantities.  However, metal mixing and smelting operations, as
    well as cement plants using thallium-containing pyrite, can release
    significant amounts of thallium.  Stack gases and wastewater should be
    monitored and, if necessary, controlled.  Measures should be taken to
    reduce occupational exposure (e.g., protective clothing should be
    worn, dust scattering should be avoided).

         Environmental exposure to thallium does not pose a health threat
    for the general population.  The total intake has been estimated to be
    less than 5 g/day, the vast majority coming from food.  Drinking-
    water and air generally contribute only very small amounts of
    thallium.

         Exposures should be kept to levels that lead to urinary
    concentrations of less than 5 g/litre, which corresponds to a daily
    oral intake of approximately 10 g thallium.

         Where thallium is still available for use as a rodenticide, the
    potential for poisoning remains a significant concern.  Thallium
    should no longer be used for this purpose, particularly as less
    hazardous methods of rodent control are available.

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

    4.1  Human Health Hazards, Prevention and Protection, First Aid

         Since all thallium compounds are toxic and since thallium is
    rapidly absorbed through all exposed epithelia, it is essential that
    the correct precautions should be observed during handling and use.

    4.1.1  Advice to physicians

    4.1.1.1  Signs and symptoms of exposure

         In acute thallium poisoning the onset of symptoms is often
    insidious, reaching a maximum in the second or third week after
    exposure.  The initial clinical features include a gradual development
    of gastrointestinal disturbance (severe constipation), hyperaesthesia,
    paraesthesia, hyperalgesia of the lower limbs (affecting especially
    the soles of the foot), followed by motor weakness of the lower limbs
    and foot drop.  Encephalopathy and retrobulbar neuritis occur in
    severe poisoning.  At the end of the second week, the characteristic
    symptom of hair loss appears.  Development of psychiatric disturbances
    ranging from hysterical behaviour to complete psychosis may be
    observed.  In severe poisoning the patient may die early of myocardial
    failure.

    4.1.1.2  First aid

         Medical care and hospital treatment is necessary as soon as
    possible. Contaminated skin should be flushed with water and washed
    with soap and water. If the eyes are splashed with thallium-containing
    liquids they should be flushed immediately with clean water for at
    least 15 min. In the event of ingestion, vomiting should be induced in
    conscious patients and followed by gastric aspiration and lavage. 
    Charcoal haemoperfusion has been shown to be successful if used within
    48 h of thallium ingestion but this should be restricted to
    intoxications with high doses of thallium.

    4.1.1.3  Medical treatment

         Forced diuresis (8-12 litres/day) may be used until the urinary
    excretion rate is < 1 mg thallium/24 h (beware of heart failure due
    to impairment of the pacemaker function of the heart and myocardial
    contractility).

         A very effective oral antidote is Prussian Blue, potassium ferric
    hexacyanoferrate(II), an inorganic pigment which is not absorbed by
    the gut. Potassium ions in the molecule are exchanged for thallium
    ions. Thus, absorption in the intestine is prevented and the thallium-
    loaded molecule is excreted with the faeces. This therapy results in
    faecal elimination greatly exceeding urinary elimination.

         Two 10 g doses of Prussian Blue should be given daily (preferably
    intraduodenally in 100 mg 15% mannitol as a laxative) until urinary
    thallium excretion is < 0.5 mg/24 h.  Daily defecation is necessary.

    4.1.2  Health surveillance advice

         People suffering from renal or hepatic disease, anaemia, blood
    dyscrasias, hypertension, alcoholism, chronic infections or endocrine
    gland dysfunction should be excluded from working with thallium.

         The urinary thallium concentration of people exposed
    occupationally should be  determined periodically in a programme of
    biological monitoring.  The intervals between monitoring should depend
    on the degree of exposure.  Periodic examinations should pay
    particular attention to the typical effects of thallium, e.g., kidney
    and eye function, the presence of pain in the limbs and hair loss.

    4.1.3  Prevention and protection

         Recommendations for the protection of employees in industrial
    plants using thallium fall under three headings:

    4.1.3.1  General recommendations

         Access to rooms in which thallium is used should be restricted to
    a limited number of employees.  Employees should be repeatedly
    informed about risk and industrial hygiene, as applies to employees
    working with radioisotopes. They should be instructed to report any
    unusual health symptoms.  Employees should be encouraged to eat
    potassium-rich food, e.g., bananas.

    4.1.3.2  Engineering control

         Dust scattering should be avoided and handling of thallium should
    be carried out under a hood.  Dust should be controlled within the
    recommended threshold limit value of 0.1 mg/m3. Floors and tables
    should be wet-mopped.  Dust samplers should be installed for the
    determination of thallium concentrations in the air.

    4.1.3.4  Personal protective equipment and hygienic measures

         Employees should be required to use protective workclothes,
    including gloves. The complete set of personal work clothes should be
    kept separate from normal clothes.  They should be washed at least
    once a week.  Clothes should be changed before eating, drinking or
    smoking, which should all be prohibited at the working place.  Washing
    and showering facilities should be provided and their use encouraged. 
    Individual respirators should be worn in all operations producing dust
    or fumes.

    4.2  Explosion and Fire Hazards

         Finely dispersed thallium particles can form explosive mixtures
    in air.  However, thallium compounds do not present an explosion risk,
    nor are they flammable.  Only thallium(III) nitrate trihydrate
    (Tl(NO3)3.3H2O) is classified as a fire supporting agent and so
    contact with flammable compounds should be avoided.

    4.3  Storage

         All products should be stored in secure buildings, kept dry and
    out of the reach of children and animals, and separated from food,
    drinks and animal feed.

         Thallium should be stored in a fireproof location, separate from
    strong oxidants, strong acids, fluorine and oxygen, and kept under
    vasoline oil.

    4.4  Transport

         For transport unbreakable packaging should be used or breakable
    packaging should be put into unbreakable containers. Transporters
    should comply with national and international requirements regarding
    the transport of hazardous materials.

    4.5  Spillage

         The danger area should be evacuated and an expert be consulted. 
    The spilled substance should be swept up and placed into containers.
    Extra personal protection is required, i.e. complete protective
    clothing including a self-contained breathing apparatus.

    4.6  Disposal

         Thallium(III) oxide can be precipitated with sodium hydroxide
    from aqueous solutions of thallium compounds.

    5.  HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

         Thallium is not used on a large scale in industry, but emissions
    can pollute the environment around mineral smelters, coal-burning
    power plants, brickworks and cement plants using thallium-enriched
    pyrite. The emissions can be reduced by the use of raw material with
    low concentrations of thallium and by the exclusion of enrichment
    procedures. Waste slags should be marked and sealed to avoid leaching
    into soil and pollution from dust. The discharge of thallium from
    tailing ponds and emissions into the atmosphere should be reduced by
    adequate procedures.

         Since thallium is incorporated into stable humus complexes, it
    remains for a long time in the upper layer of the soil. In regions
    with contaminated agricultural or garden soil, the thallium
    concentrations in the upper layer should be reduced by deep ploughing
    or by the addition of uncontaminated soil.

         Thallium is toxic to aquatic organisms but effects are likely to
    be limited to sites adjacent to point sources.  Although it can
    bioconcentrate, thallium is unlikely to biomagnify in aquatic or
    terrestrial food webs.

         The use of thallium as a rodenticide has resulted in poisoning of
    non-target organisms, including foxes, badgers, martens, partridges,
    pheasants and eagles.  Poisoning of domestic animals, such as dogs,
    cats, ducks and pigeons, has also been widely reported.  Less
    hazardous methods or rodent control should be used.

    6.  SUMMARY OF CHEMICAL SAFETY INFORMATION

         This summary should be easily available to all health workers
    concerned with, and users of, thallium.  It should be displayed at, or
    near, entrances to areas where there is potential exposure to thallium
    and on processing equipment and containers.  The summary should be
    translated into the appropriate language(s).  All persons potentially
    exposed to the chemical should also have the instructions in the
    summary clearly explained.

         Space is available for insertion of the National Occupational
    Exposure Limit, the address and telephone number of the National
    Poison Control Centre, and local trade names.

        SUMMARY OF CHEMICAL SAFETY INFORMATION
                                                                                                                                              

    PHYSICAL PROPERTIES                   THALLIUM METAL   THALLOUS       OTHER CHARACTERISTICS
                                                           SULFATE
                                                                                                                                              

    Relative atomic/molecular mass        204.4            504.8          Thallium

    Melting point (C)                    304              632            Soft malleable heavy metal with bluish-white colour; reacts with
                                                                          halogens at room temperature; incompatible with strong acids,
    Boiling point (C)                    1457             decomposes     strong oxidants and oxygen; forms toxic compounds on contact with
                                                                          moisture; finely dispersed thallium particles can form explosive
    Water solubility (g/litre at 20C)    insoluble        48.7           mixtures in air; thallium may be absorbed into the body by
                                                                          inhalation, through the skin or by ingestion; dust formation can lead
    Relative density (water = 1)          11.9             6.77           to harmful concentration of airborne particles.

    CAS No. 7440-28-0                     7446-18-6

                                                                          Thallous sulfate

                                                                          White crystals; decomposes on heating emitting very toxic fumes
                                                                          of thallium and sulfur oxides; not combustible, not explosive; may be
                                                                          absorbed into the body by inhalation of its aerosol, through the skin
                                                                          and by ingestion.
                                                                                                                                              

    SUMMARY OF CHEMICALS SAFETY INFORMATION (continued)
                                                                                                                                              

    HAZARD/SYMPTOM                               PREVENTION AND PROTECTION                         FIRST AID
                                                                                                                                              

    GENERAL:  Short-term exposure may result     Prevent any spillage dispersion of dust; avoid
    in effects on the nervous system and in      inhalation of dust or skin contact; pregnant
    death; effects may be delayed; long-term     women should avoid exposure
    exposure may cause hair loss and have
    effects on vision, the liver, lungs,
    nervous system and kidneys; may cause
    birth defects, specifically skeletal
    deformation, low birth weight, and
    premature birth; danger of cumulative
    effects

    INHALATION:  Nausea, vomiting, loss of       Apply ventilation, local exhaust or breathing     Remove victim to fresh air and keep warm;
    hair, abdominal colic, pain in legs and      protection                                        if breathing has stopped, apply artificial
    chest, nervousness, irritability                                                               respiration; obtain medical attention
                                                                                                   immediately

    SKIN:  May be absorbed, resulting in the     Avoid skin contact; wear clean, impervious        Remove contaminated clothes and shoes
    same symptoms as following inhalation        clothing, gloves and shoes                        immediately; rinse and then wash skin with
                                                                                                   plenty of water and soap; obtain medical
                                                                                                   attention immediately

    EYES:  May be absorbed; redness, pain,       Wear safety goggles or eye protection             First rinse with plenty of water for at
    blurred vision (after exposure to thallium                                                     least 15 min. (remove contact lenses if
    sulfate)                                                                                       possible), then obtain medical attention

    INGESTION:  Abdominal pain, constipation,    Do not eat, drink, chew, or smoke during work;    Rinse mouth; in conscious patients vomiting
    diarrhoea, headache, nausea, vomiting,       do not keep food in areas with potential          can be induced (e.g. by giving two glasses
    loss of vision, loss of hair, nervousness,   exposure; change clothes before eating,           of milk); subsequently give a slurry of
    irritability, tremor, delirium,              drinking or smoking                               activated charcoal in water to drink;
    convulsions, paralysis, coma (in the case                                                      obtain medical attention
    of thallous sulfate)
                                                                                                                                              

    SUMMARY OF CHEMICALS SAFETY INFORMATION (continued)
                                                                                                                                              

    HAZARD/SYMPTOM                               PREVENTION AND PROTECTION                         FIRST AID
                                                                                                                                              

    ENVIRONMENT:  May be hazardous to aquatic    Contamination of water, soil and atmosphere
    and terrestrial organisms and to the soil    should be avoided by proper methods of
    microflora                                   storage, transport, and waste disposal
                                                                                                                                              

    SPILLAGE                                     STORAGE                                           FIRE AND EXPLOSION
                                                                                                                                              

    Evacuate the area and consult an expert;     Store away from foodstuffs and separate from      Thallium
    sweep up spilled substance and place into    strong oxidants, strong acids, fluorine and       Combustible, explosive, when in contact
    containers; remove to safe place (extra      oxygen; keep under vasoline oil in a dry,         with fire or flame; finely dispersed
    personal protection required: complete       fire-proof and well-labelled room                 particles form explosive mixtures in air;
    protective clothing including                                                                  NO open flames prevent deposition of dust;
    self-contained breathing apparatus)                                                            use in closed system with dust
                                                                                                   explosion-proof electrical equipment and
                                                                                                   lighting; extinguish fires with foam,
                                                                                                   carbon dioxide, water spray, or powder;
                                                                                                   provision to contain effluent from fire
                                                                                                   extinguishing

                                                                                                   Thallous sulfate
                                                                                                   Not combustible or explosive; avoid contact
                                                                                                   with hot surfaces; in case of fire
                                                                                                   extinguish with water in large amounts,
                                                                                                   foam, carbon dioxide, or powder; provision
                                                                                                   to contain effluent from fire extinguishing
                                                                                                                                              

    SUMMARY OF CHEMICALS SAFETY INFORMATION (continued)
                                                                                                                                              

    WASTE DISPOSAL                               NATIONAL INFORMATION
                                                                                                                                              

    Dilute thallium solutions may be buried in   National occupational exposure limit:
    an approved dump or landfill where there
    is no risk of contamination of surface or
    groundwater; when possible, thallium
    should be recovered and returned to the
    suppliers; comply with any local
    legislation regarding disposal of toxic
    wastes                                       National Poison Control Centre:
                                                                                                                                              
        7.  CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

         Most of the information given in this section has been extracted
    from the International Register of Potentially Toxic Chemicals (IRPTC)
    legal file.  A full reference to the original national document from
    which the information was extracted can be obtained from IRPTC.

         The reader should be aware that regulatory decisions about
    chemicals, taken in a certain country, can only be fully understood in
    the framework of the legislation of that country.  Furthermore, the
    regulations and guidelines of all countries are subject to change and
    should always be verified with appropriate regulatory authorities
    before application.

    7.1  Previous Evaluations by International Bodies

         A  Poisons Information Monograph for thallium has been issued
    (IPCS, 1992).

         On the basis of an acute oral LD50 of 11 mg/kg, thallium sulfate
    has been classified in the  WHO Recommended Classification of Pesticides
     by Hazard as "highly hazardous" (Class Ib).

         International Chemical Safety Cards have been issued for thallium
    metal (no. 77) and for thallous sulfate (no. 336) (CEC/IPCS, 1990,
    1991).

    7.2  Exposure Limit Values

         Some exposure limit values are given in the Current Regulations,
    Guidelines and Standards table

    7.3  Specific restrictions

         In the Czech Republic the presence of thallium or its compounds
    in cosmetics is prohibited.  In the European Economic Community
    countries, no detectable quantities of thallium may be contained in
    colouring matter authorized for use in foodstuffs intended for human
    consumption.

         The use of thallium as a rodenticide has been prohibited in many
    countries.

        CURRENT REGULATIONS, GUIDELINES AND STANDARDS
                                                                                                                                    

    Exposure Limit Values
                                                                                                                                    

    Medium   Specification  Country            Exposure limit description                         Value              Effective date
                                                                                                                                    

    AIR      Occupational    Argentina          Maximum permissible concentration (MAC)
                                                -  Time-weighted average (TWA)                     0.1 mg/m3              1991

                             Canada             Threshold limit value (TLV)
                                                -  Time-weighted average (TWA)                     0.1 mg/m3              1991

                             Germany            Maximum worksite concentration (MAK)
                                                -  Time-weighted average (TWA)                     0.1 mg/m3
                                                -  Short-term exposure limit (STEL) (30 min)       1.0 mg/m3              1992

                             Mexico             Maximum limit (MXL)
                                                -  Time-weighted average (TWA)                     0.1 mg/m3              1991

                             United Kingdom     Occupational exposure standard (OES)
                                                -  Time-weighted average (TWA)                     0.1 mg/m3              1992

                             USA (ACGIH)        Threshold limit value (TLV)
                                                -  Time-weighted average (TWA)                     0.1 mg/m3              1991

    WATER    surface         Russian            Maximum allowable concentration (MAC)              0.0001 mg/litre        1990
                             Federation
                                                                                                                                    
        7.4  Labelling, Packaging and Transport

         The United Nations Committee of Experts on the Transport of
    Dangerous Goods and the International Maritime Organization classify
    thallium compounds as poisonous substances (Hazard Class 6.1) and,
    with regard to packing, as substances presenting medium danger
    (Packing Group II).

         European Economic Community legislation requires labelling as a
    very toxic substance, using the symbol T+ and the following pictogram:

    FIGURE 1

         The following label statements are required for thallium

    R 26/28   Very toxic by inhalation and if swallowed
    R 33      Danger of cumulative effects
    S 2       Keep out of reach of children
    S 13      Keep away from food, drink and animal feeding stuffs
    S 28      After contact with skin, wash immediately with plenty of
              soap and water
    S 45      In case of accident or if you feel unwell, seek medical
              advice immediately (show label where possible)


         For thallium sulfate the following label statements are required:

    R 28      Very toxic if swallowed
    R 38      Irritating to skin
    R 48/25   Toxic: danger of serious damage to health by prolonged
              exposure if swallowed
    S 13      Keep away from food, drink and animal feeding stuffs
    S 36/37   Wear suitable protective clothing and gloves
    S 45      In case of accident or if you feel unwell, seek medical
              advice immediately (show the label where possible)

    7.5  Waste Disposal

         When possible, thallium should be recovered and returned to the
    suppliers.  Dilute thallium solutions may be buried in an approved
    dump or landfill where there is no risk of contamination of surface or
    groundwater.  Local legislation regarding disposal of toxic wastes
    must be complied with.

    8.  BIBLIOGRAPHY

    Aderjan R, von Clarmann M, Daldrup T, Geldmacher-von Mallinckrodt M,
    van Heijst ANP, Machbert G, Schtz H, & Stppler (in Press) [Thallium
    - clinical toxicological analysis after acute intoxications. 
    Communications of the Senate Committee on clinical and toxicological
    analysis.]   German Research Council (in German).

    ATSDR (1992) Toxicological profile for thallium. Atlanta, Georgia,
    Agency for Toxic Substances and Disease Registry, pp. 1-90
    (ATSDR/TP-91/26).

    Barlow SM & Sullivan FM (1982) Reproductive hazards of industrial
    chemicals. An evalution of animal and human data. Chapter 41: Thallium
    and its compounds. New York, Academic Press 530-537.

    Bowen HJM (1979) Environmental chemistry of the elements. New York,
    London, Academic Press.

    Cavanagh JB (1979) Metallic toxicity and the nervous system. In: Smith
    WT & Cavanagh JB ed. Recent advances in neuropathology. Edinburgh,
    Churchill Livingstone, pp. 247-275.

    CEC/IPCS (1990)  International Chemical Safety Card 77:  Thallium
    metal.  Luxemburg, Commission of the European Communities.

    CEC/IPCS (1991)  International Chemical Safety Card 336:  Thallous
    sulfate.  Luxembourg, Commission of the European Communities.

    DFG (German Research Council) (1990) [Maximal concentrations at the
    work place and biological tolerance values of chemicals in the work
    area.]  Weinheim, Verlag Chemie (in German).

    IPCS (1992) Poisons information monograph:  Thallium.  Geneva, World
    Health Organization (IPCS/INTOX/PIM/525).

    Kemper FH & Bertram HP (1991) Thallium. In: Merian E ed. Metals and
    their compounds in the environment. Weinheim, Verlag Chemie,
    1227-1241.

    LIS (Land Institute of Protection against Emissions) (1980)
    [Environmental burden by thallium. Investigations in the neighbourhood
    of the Dyckerhoff-cement plant AG in Lengerich and other thallium-
    emitting plants in the country NW.] Bonn, Bonner Universittsdruckerei
    (in German).

    Oehme FW ed. Toxicity of heavy metals in the environment. New York,
    Marcel Dekker Inc, vol. 1.

    Schoer J (1984) Thallium. In: Hutzinger O ed. The handbook of
    environmental chemistry.  Volume 3: Anthropogenic compounds, Part C. 
    Berlin, Springer Verlag, 143-214.

    Sessions HK & Goren S (1947) Report of investigation of health hazards
    in connection with the industrial handling of thallium.  US Navy Med
    Bull, 47: 545-550.

    Smith IC & Carson BL (1977) Trace metals in the environment. Volume 1:
    Thallium. Ann Arbor, Ann Arbor Science.  Publishers.

    US EPA (US Environmental Protection Agency) (1980) Ambient water
    quality criteria for thallium.  Springfield, Virginia, US
    Department of Commerce, National Technical Information Service
    (EPA 440/5-80-074).

    Zitko V (1975) Chemistry, applications, toxicity, and pollution
    potential of thallium. Department of Environment, Fisheries and Marine
    Services, Research and Development Directorate (Technical Report 
    No. 518).
    


    See Also:
       Toxicological Abbreviations