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

    International Programme on Chemical Safety
    Poisons Information Monograph 525

    1.  NAME

        1.1  Substance


        1.2  Group

             Heavy metals

        1.3  Synonyms

             Thallium Sulphate

        1.4  Identification numbers

             1.4.1  CAS number


             1.4.2  Other numbers


        1.5  Main brand names, main trade names

        1.6  Manufacturers, Importers

    2.  SUMMARY

        2.1  Main risks and target organs

             Target organs are the peripheral and central nervous
             system, the gastrointestinal tract and the skin, especially
             the hair follicles. In severe poisoning, the patient may die
             early of myocardial failure.

        2.2  Summary of clinical effects

             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.

        2.3  Diagnosis

             Diagnosis of poisoning is based on a characteristic
             clinical presentation and on laboratory confirmation of
             thallium in biological fluids.  Gastrointestinal symptoms
             appear a few hours after ingestion and constipation may
             persist. after several CNS disturbances appear (psychosis,
             polyneuritis) and after 2 weeks the typical alopecia and
             Mee's lines in the nails appear. The central and peripheral
             nervous system abnormalities may persist several months.
             The choice of an analytical method is determined by the
             nature of the sample available for analysis.  The main
             purpose of analyzing thallium in biological material is so
             that data might be obtained that are suitable for clinical
             interpretation (analysis for forensic purposes is outside the
             scope of this monograph).
             In the clinical situation, data from two biological samples,
             whole blood and urine, are necessary for interpretation (see
             Section 8.4: Interpretation).
             Two analysis methods are described in Section 8.2.2. (Tests
             for biological samples). atomic absorption spectrophotometry
             is the method of choice. The spectrophotometric method may
             yield accurate results in experienced hands but has less
             specificity.  Radiography may be useful in the diagnosis see

        2.4  First-aid measures and management principles

             Induce emesis, followed by gastric aspiration and
             Forced diuresis (8 to 12 l/24 h) until urinary thallium
             excretion is less than 1 mg/24 h (beware of heart failure due
             to impairment of the pacemaker function of the heart and
             myocardial contractility).
             Charcoal haemoperfusion has been shown to be successful if
             used within 48 hours of ingestion of thallium (and therefore
             during the distribution phase).

             Twice daily 10 g potassium ferric hexacyanoferrate (II) 
             (Prussian Blue C.I. 77510), preferably given intraduodenally
             in 100 ml 15% mannitol as a laxative, until urinary thallium
             excretion is lower than 0.5 mg/24h. Daily defaecation is


        3.1  Origin of the substance

             Natural isotopes - 203 (29.50%), 205 (70.50%) occurs in:
             crookesite (CuTlAg)2Se - found in Sweden
             lorandite TlAgS2 - found in Greece
             hutchisonite (Tl, Cu, Ag)2S.PbS.2As2S3 - found in
             occurrence in the earth's crust - 0.7 ppm (Merck, 1983)
             Thallium is present as a naturally occurring trace element in
             human tissues. The normal level in urine is 1.3  mg/l (Smith &
             Carson, 1977; Stockinger, 1981).
             Commercial sources are flue dusts, either from pyrite (FeS2)
             burners or from lead and zinc smelters and refiners and as a
             by-product of cadmium production.  In these dusts, thallium
             occurs largely as a sulphate (Stockinger, 1981).

        3.2  Chemical structure

             The chief valance is +1 (Tl+); a valence of 3+ (Tl+++)
             is known but the compounds are less numerous and less
             Thallium Sulphate: Tl2SO4

        3.3  Physical properties

             3.3.1  Colour


             3.3.2  State/Form


             3.3.3  Description

                    Thallium: Bluish-white, very soft, inelastic,
                    easily fusible, heavy metal; leaves a streak on paper. 
                    Oxidizes superficially in air forming a coating.

                    Density  11.85
                    Begins to volatilize at 174
                    Melting point  303.5°C
                    Boiling point  1457°C
                    At. Wt.  204.3%
                    Solubility:  insoluble in hot or cold water soluble in
                    nitric and sulphuric acids slightly soluble in
                    hydrochloric acid (Merck, 1983)

        3.4  Hazardous characteristics

             Thallium sulphate is odourless, colourless and


        4.1  Uses

             4.1.1  Uses

             4.1.2  Description

                    manufacture of imitation jewellery pigments.
                    manufacture of special alloy anode plates for use in
                    magnesium sea water batteries (Marcus, 1985).
                    manufacture of fireworks (green color).
                    alloyed with mercury for switches and closures which
                    operate at sub-zero temperatures.
                    in low-temperature thermometers.
                    in semiconductors.
                    in scintillation counters.
                    in optical lenses.
                    a saturated solution of thallium malonate and formate
                    is used to separate mineralogical specimens.
                    Thallium is still available in many countries as a

                    During the late 1800's, thallium sulphate was used in
                    the treatment of syphilis, gonorrhoea, gout, dysentery
                    and night sweats from tuberculosis.  Numerous side
                    effects prevented it from being accepted widely for
                    these purposes (Reed et al, 1963).  It was introduced
                    as a depilatory or for the treatment of ringworm of
                    the scalp.  However, 778 cases of thallium sulphate
                    poisoning with 46 deaths occurred;  692 of these
                    poisonings were from its clinical use as a depilatory
                    agent (Munch, 1934).  By 1940, thallium sulphate
                    depilation had generally been abandoned.
                    Thallium-201 is used widely in myocardial imaging
                    (Bulkley et al, 1975; Weich et al, 1977).

        4.2  High risk circumstance of poisoning

             Especially in countries where thallium is available as a
             rodenticide, numerous accidental (in children) and
             intentional (suicides and homicides) poisonings are

        4.3  Occupationally exposed populations

             Manufacture of rodenticide (Egen, 1955).
             Working with solutions of organic thallium compounds in the
             separation of industrial diamonds (Richeson, 1985).
             Manufacture of a special thallium - magnesium alloy (88% Mg,
             7% Tl, 5% Al) used in the anode plate of a seawater-AgCl
             battery.  Exposure is in the form of fumes from alloying in
             the furnaces, skin contact in the strip-rolling of the alloy,
             and as dust generated in the scrap-brushing of the alloy.
             In factories that manufacture various salt derivatives of
             thallium, there have been numerous reports of factory workers
             developing thallium toxicity (Prick et al, 1955; Shabalina &
             Spiridonova, 1979; Reed et al, 1963).


        5.1  Oral

             Water-soluble salts such as thallium sulphate, acetate
             and carbonate are more toxic than the less water-soluble
             forms such as thallium sulphide and iodide.

        5.2  Inhalation

             Dusts, either from pyrite (FeS2) burners or from lead
             and zinc smelters and refiners, as a by-product of cadmium
             production.  In these dusts, thallium occurs largely as a

        5.3  Dermal

             Percutaneous absorption of thallium may occur through
             rubber gloves (Reed, 1963).  The true incidence of poisoning
             may be underestimated, because chronic accumulation may occur
             from industrial exposure and as a result of the ready
             absorption of thallium through the skin.

        5.4  Eye

             No data available.

        5.5  Parenteral

             No data available.

        5.6  Others

             Three cases of thallium poisoning have been reported
             following nasal insufflation of a substance that was believed
             to be cocaine (Insley et al, 1986).

    6.  KINETICS

        6.1  Absorption by route of exposure

             The water-soluble salts of thallium (sulphate, acetate
             and carbonate) are more rapidly absorbed from the gut that
             the less water-soluble forms (sulphide and iodide). after
             ingestion of thallium sulphate, thallium can be detected in
             urine and faeces within one hour (Lund, 1956a, 1956b;
             Moeschlin, 1980).

        6.2  Distribution by route of exposure

             In animal experiments it was shown that the distribution
             of thallium can best be described by a three-compartment open
             pharmacokinetic model (Rauws, 1974)
             i)  a central compartment consisting of the blood as well as
             well-perfused peripheral organs and tissues; this is the fast
             exchange compartment.

             ii)  a compartment consisting of the brain, which can be
             considered as the target organ for the neurotoxicity of
             thallium; this is the slow exchange compartment.
             iii)  a compartment consisting of the intestine as well as
             the intestinal contents.  In this compartment, absorption of
             thallium takes place.  However, in animal experiments it was
             demonstrated that thallium is secreted into the jejunum,
             ileum and colon (Forth & Henning, 1979) and that an intensive
             entero-enteral cycle exists between absorption and secretion
             (Rauws, 1974).  Biliary excretion of thallium is of minor
             importance (Schafer & Forth, 1983).
             This three-compartment open model has been shown to be
             applicable to the toxicokinetics of thallium in man.  The
             concentration course of thallium is blood versus time shows
             three phases (Van Kesteren et al, 1980).  In the first phase
             lasting about 4 hours, thallium is distributed through the
             entire central compartment.  The second phase, from 4 - 48
             hours, involves distribution into the brain. after 24 hours
             distribution is complete and thallium is distributed
             throughout the body tissues.  The third phase, which occurs
             after 24 hours, is determined mainly by the elimination of
             thallium from the body.
             Values for the apparent volume of distribution in rats have
             been reported as 20 l/kg (Rauws, 1974) and 5 - 6 l/kg
             (Lameyer & Van Zwieten, 1977).  In rabbits, values of 6 - 14
             l/kg have been observed (. & Wellhoner, 1983).  In man,
             values of 3.6 - 5.6 l/kg were calculated after injection of
             tracer amounts of thallium-201 (Talas et al, 1983).
             The dose-dependence of thallium kinetics was studied in
             rabbits by intravenous injection, first of a 201Tl+ tracer
             dose and 2 weeks later of a 5.5  mol/kg dose. at both dose
             levels, an open three compartment model (Rauws, 1974) was
             found appropriate to describe the course of the plasma
             concentration curve.  When the dose was increased, a slight
             to moderate decrease in both the distribution volume (11.2
             l/kg versus 9.7 l/kg) and in the plasma clearance (13 ml/min
             versus 9 ml/min) was found (Talas &  Wellhoner, 1983).

        6.3  Biological half-life by route of exposure

             Due to the large volume of distribution of thallium, the
             elimination half-life is long.  Values of 3.3 days (Lie et
             al, 1960) and approximately 4 days (Rauws, 1974) were
             observed in rats.  In man, estimates of the half-life include
             1 - 3 days after low doses (Talas et al, 1983) and 1.9 days
             during intensive clinical therapy after ingestion of a
             potentially lethal dose (Hollogginitas et al, In three

             patients with acute thallium poisoning treated intensively
             with Prussian Blue, forced diuresis and haemoperfusion, the
             half-life ranged from 1 - 1.7 days (De Groot et al,

        6.4  Metabolism

             No data available.

        6.5  Elimination and excretion

             Thallium is mainly excreted in the faeces (Barclay et
             al, 1953; Lund, 1956a, 1956b) though this may be decreased
             significantly by paralysis of the small intestine, a
             characteristic feature of thallium poisoning.
             Thallium is also excreted in the urine, but about half the
             amount in the glomerular filtrate is reabsorbed in the
             tubules. The ratio of faecal to urinary elimination is
             approximately 2:1 (Rauws, 1974).
             Salivary excretion of thallium is about 15 times greater than
             urinary excretion (Richelmi et al, 1980).
             Elevated concentrations of thallium may occur in urine for
             several weeks or even months following exposure (Stockinger,
             1981).  The persistent presence of thallium has been
             explained by similarities in the properties and biological
             handling of thallium and potassium ions.  Thallium and
             potassium ions cross cell membranes in a similar way. 
             However, once inside the cell, thallium appears to be
             released less rapidly than potassium.


        7.1  Mode of Action

             The precise mode of toxicity is still unclear.  However,
             it has been postulated that thallium might interfere with
             vital potassium-dependent processes because thallium ions and
             potassium are similar in size (Cavanagh et al, 1974;  Hughes
             et al,1978).  Thallium depolarizes membranes (Mullins &
             Moore, 1960), and antagonizes the effect of calcium on the
             heart (Hughes et al, 1978).  Thallium can substitute for
             potassium in (Na+ + K+) activated ATPase; the affinity of
             thallium for this enzyme is ten times greater than that of
             potassium (Gehring & Hammond, 1967).  The toxic effects of
             thallium  could therefore be due to inhibition of

             However, this enzyme system is not believed to be significant
             in the observed selective axonal changes, because normal cord
             discharges and synchronized contraction of muscle tissue were
             maintained, conditions that would not have prevailed had
             thallium inactivated the axolemnal ATPase.  The true
             mechanism of toxicity appears to involve the ability of
             thallium to inactivate sulphydryl (SH) groups that are
             responsible for increasing the permeability of mitochondria,
             leading to water influx and swelling (Spencer et al,
             Protein synthesis, particularly incorporation of cysteine, is
             also inhibited by thallium.  This is thought to account for
             the alopecia observed in thallium poisoning because of
             prevention of keratinization (Cavanagh et al, 1974).
             Many features of thallium toxicity ar similar to those found
             in riboflavin deficiency, for example peripheral neuropathy
             and loss of hair.  The reason may be that thallium interacts
             with riboflavin to form an insoluble compound (Cavanagh &
             Gregson, 1978; Cavanagh, 1979; Kuhn et al, 1933).  Several
             energy-providing intermediates require flavine adenine
             dinucleotide in the course of their metabolism.  The toxicity
             of thallium may be caused partly by deficiency of energy
             production.  Experimental riboflavine deficiency in animals
             causes dermatitis, alopecia and neuropathy (Schoental &
             Cavanagh, 1977).

        7.2  Toxicity

             7.2.1  Human data


                             There are few estimates of the
                             minimal lethal dose and reported figures vary
                             considerably, presumably because of the
                             excessive doses taken in most cases.  Gettler
                             & Weiss (1943) suggested that 1 g thallium
                             (14 - 15 mg/kg) of soluble salts should be
                             considered as the minimum lethal dose for an
                             adult.  However, survival has been reported
                             following the ingestion of 1.3 g by adults
                             (Grunfeld & Hinostroza, 1964).


                             Single doses of as little as 4 mg/kg
                             thallium sulphate have caused toxicity in a
                             child.  Following the accidental deliberate
                             administration of 8 mg/kg thallium acetate,
                             six deaths were reported (Munch,

             7.2.2  Relevant animal data

                    The acute toxicity has been determined for 14
                    inorganic  thallium compounds in a total of five
                    animal species by oral, subcutaneous, intraperitoneal
                    and intravenous routes.  The LD50 of the 14 compounds,
                    whether soluble or insoluble, by all routes of
                    administration to all the various species fall into a
                    markedly narrow range, from 15 to 50 mg/kg thallium. 
                    There is little difference between the toxicity of Tl+
                    and Tl+++.  The rat LD50 is 16 mg/kg versus 23 mg/kg
                    for Tl+++ (Niosh, 1976).

             7.2.3  Relevant in vitro data

                    In thallium-saline perfused isolated rat
                    hearts, thallium clearly has an effect on the
                    pacemaker, with an initial stimulation followed by
                    depression (Huches et al, 1978).

             7.2.4  Workplace standards

                    A threshold limit value (TLV) of 0.1 mg/m3 of
                    thallium has been set for soluble thallium compounds
                    by the American Conference of Governmental Industrial
                    Hygienists (Stockinger, 1981).
                    Osha adopted a TLV for soluble compounds of 0.1 mg/m3
                    of thallium.
                    The Soviet Union adopted a MAK of 0.01 mg/m3 of
                    thallium for the soluble salts, the bromide and iodide
                    (1972 list).

             7.2.5  Acceptable daily intake ADI

                    No data available.

        7.3  Carcinogenicity

             No data available.

        7.4  Teratogenicity

             Embryotoxic effects of thallium have been observed in
             chicks, when thallium sulphate solutions were placed on the
             chorioallantoic membrane (Hall, 1976).  Studies in mammalian
             species, however, showed that the administration of thallium
             to pregnant mice, rabbits, and rats produced no or only a
             slight embryotoxic effect, even when amounts toxic to the
             mother were administered (Gibson and Becker, 1970).
             In a long-term study of the effects exposure to thallium in a
             population living in the vicinity of a cement plant emitting
             dust containing thallium, a significantly greater number of
             malformations than expected was noted (Dolgner et al, 1983).
             However, no specific pattern of congenital malformations was
             found in the children examined.  Moreover, there are a number
             of case reports in the literature of human thallium
             intoxication during pregnancy following which no congenital
             anomalies were observed (Sikkel et al, 1959; Van Maarseveen,
             1962; Stevens & Barbier, 1976; Erbsloh, 1960; Petersohn,
             1960).  Stevens and Barbier (1976) reported 6 cases of
             thallium poisoning in the first trimester of pregnancy in
             which no anomalies in the newborn were detected.

        7.5  Mutagenicity

             No data available.

        7.6  Interactions

             No data available.


        8.1  Material sampling plan

             8.1.1  Sampling and specimen collection

            Toxicological analyses

                             The specimens of choice are urine
                             and whole blood.  Stomach contents and
                             gastric lavage fluid are less suitable
                             because a negative result does not exclude
                             the fact that thallium may already have been
                             absorbed or entered the small intestine, and
                             a positive result is not suitable for
                             clinical interpretation; these two types of
                             specimen therefore, are only likely to be of
                             value for forensic purposes.

                             Many cases of thallium intoxication involve
                             criminal activity.  It is therefore strongly 
                             advised to take samples in duplicate, 
                             especially at the time of admission, and to 
                             store the duplicate samples until one is
                             certain  about the legal aspects of the case. 
                             Duplicate samples should be taken in the 
                             presence of a second person and all actions 
                             (from sampling to storage) should be 
                             It is advisable to collect all samples in
                             non-breakable containers and tubes.  Glass is
                             very suitable for the purposes of collection
                             but may easily break, especially during
                             transport or when stored in the freezer. 
                             All containers should be free of exogenous
                             contamination. If there is any doubt,
                             rinsing with l mmol nitric acid followed by
                             distilled water to remove traces of the
                             acid, is advisable. Commercially available
                             blood collection tubes which are evacuated,
                             sterile and pyrogen free do not need any
                             rinsing so long as the vacuum is intact. 
                             Urine collection containers should never be
                             used more than once unless it can be shown
                             that rinsing has been sufficient to exclude
                             all presence of any material from the  
                             previous collection.
                             On admission, at least 100 ml of urine should
                             be  collected.  Later on, or if the
                             analytical  result on the first specimen is
                             negative for  thallium, a 24 hour urine
                             collection is advisable.  One should keep in
                             mind that  patients treated for thallium
                             poisoning may  undergo forced diuresis,
                             leading to a daily  urinary output of 15
                             liters or even more. Collection of aliquot
                             samples is then adequate and pooled aliquots
                             should be mixed thoroughly. If the urine is
                             not analyzed correctly after collection, a
                             precipitate may form after standing for 48
                             hours or more even when stored in the
                             refrigerator.  The precipitate may include
                             considerable amounts of thallium; it's 
                             therefore advisable to add 1% of acetic acid 
                             to the collected urine to reduce the pH to 4.

                             In the case of whole blood, a 10 ml specimen 
                             should be taken in a suitable collection tube 
                             containing an anticoagulant.  Particularly in
                             the first days of intoxication, erythrocyte 
                             thallium concentrations may exceed 
                             plasma/serum values by a factor of 2 to 3.

            Biomedical analyses

            Arterial blood gas analysis

            Haematological analyses

            Other (unspecified) analyses

             8.1.2  Storage of laboratory samples and specimens

            Toxicological analyses

                             Thallium itself will only decompose
                             when exposed  to nuclear sources.  Even so,
                             inadequate  storage procedures will result in
                             samples  difficult to handle analytical
                             purposes (urine  with precipitates,
                             haemolyzed blood).  It is  therefore strongly
                             recommended that samples  should be stored in
                             a refrigerator or in a  freezer at -20°C.  In
                             the latter case,  erythrocytes may be
                             destroyed on freezing. When analysis of
                             plasma/serum and whole blood  is required,
                             separation prior to storage is  necessary to
                             avoid haemolysis on freezing.

            Biomedical analyses

            Arterial blood gas analysis

            Haematological analyses

            Other (unspecified) analyses

             8.1.3  Transport of laboratory samples and specimens

            Toxicological analyses

                             The only precaution to be taken is
                             to ensure  that no breakage and/or leakage
                             occurs during  transport.  When transport is
                             going to take a  few days cold transport
                             should be considered.  Whole blood may
                             haemolyse during transport, and prior
                             separation of blood components is  strongly
                             recommended when repeated analysis of
                             plasma/serum and whole blood is

            Biomedical analyses

            Arterial blood gas analysis

            Haematological analyses

            Other (unspecified) analyses

        8.2  Toxicological Analyses and Their Interpretation

             8.2.1  Tests on toxic ingredient(s) of material

            Simple Qualitative Test(s)

                             Thallium may be present as either a
                             thallous or  thallic compound, for example
                             thallous chloride  (TlCl) and thallic oxide
                             (Tl2O3).  The  difference in toxicity 
                             between  mono- and  trivalent thallium is
                             negligible  because in  biological systems
                             Tl+++ is reduced to Tl+.  
                             The fact that two valencies exist has 
                             implications for the so-called simple 
                             analytical tests.  For instance, Tl+ in 
                             solution precipitates on addition of 4M 
                             hydrochloric acid whereas Tl+++ does not.  
                             Furthermore, prior to the reaction taking 
                             place, the thallium salt has to be brought 
                             into solution. as thallium oxides are very 
                             insoluble in water, addition of molar 
                             sulphuric acid is necessary.

                             When potassium iodide solution (83 g/l of
                             water)  is added to a Tl+ ion-containing
                             solution, a  yellow precipitate of thallium
                             iodide is  formed.  This is almost as
                             insoluble in water as it is in cold sodium
                             thiosulfate solution (2% aqueous solution). 
                             Thallic ions give a brown-black precipitate
                             in the test.  Thallium salts also impart an
                             intense green coloration to a  Bunsen
                             When both the potassium iodide and the flame 
                             reaction are positive, the presence of a 
                             thallium salt is highly likely (Vogel,
                             However, definite proof can only be obtained
                             by aspirating a solution of the substance
                             under  investigation into the flame of an
                             atomic absorption spectrophotometer. 
                             Apparatus conditions are those for the
                             quantitative  determination.

            Advanced Qualitative Confirmation Test(s)

            Simple Quantitative Method(s)

            Advanced Quantitative Method(s)

             8.2.2  Tests for biological specimens

            Simple Qualitative Test(s)

            Advanced Qualitative Confirmation Test(s)

                             Nowadays, two main methods for
                             thallium analysis are available:
                             a)  Spectrophotometry
                             b)  Atomic absorption spectrophotometry
                                 (flame or flameless).
                             For both techniques, one method only will be
                             described. Inverse voltometry is not
                             described because the necessary
                             instrumentation is not standard in clinical

                             a)  Spectrophotometric determination with
                             Brilliant Green, according to De Wolf and
                             Lenstra (1964).
                             Sulfuric acid 96% p.a.
                             Nitric acid 65% p.a.
                             Saturated bromine water:
                             3 ml of bromine in 100 ml of distilled water
                             is shaken until saturation.  Store in the
                             dark;  when stored above bromine the solution
                             is stable for one month.
                             Toluene: p.a.
                             Saturated sulphosalicylic acid:
                             dissolve 46 g sulphosalicylic acid in 20 ml
                             of distilled water.  Store in the
                             refrigerator.  The solutionis stable for one
                             Brilliant Green solution:
                             dissolve 2 g Brilliant Green (Color Index nr.
                             42040) in 100 ml of distilled water.  Filter
                             the solution through a paper filter and
                             extract the filtrate three times with 50 ml
                             toluene.  Discard the toluene.  Prepare
                             Add to 50 ml of urine in a 100 ml 
                             Kjeldahl flask 2 ml concentrated sulphuric
                             acid and some glass beads.
                             Boil for 3 minutes and carefully add 5 ml
                             nitric acid.  Heat until destruction and add
                             an additional 5 ml nitric acid;  repeat until
                             the solution is colorless and fumes of
                             sulphur trioxide evolve.  Stop heating, cool
                             and carefully add 5 ml distilled water.  Heat
                             again until sulphur trioxide fumes evolve. 
                             Stop heating again and add water one more

                             Transfer - after cooling to room temperature
                             - the distillate into a 100 ml separating
                             funnel using 25 ml distilled water.  Now add
                             0.2 ml of the saturated bromine water
                             solution, and wait for 1 minute.  Remove the
                             bromine by addition of 0.1 ml of the
                             sulphosalicylic acid solution.
                             Add 1 ml Brilliant Green solution and shake
                             immediately with 5.0 ml of toluene.  Separate
                             both layers.  Repeat shaking with another 5.0
                             ml toluene portion.  Pool both toluene layers
                             and measure the extinction at 640 nm against
                             1.  Destruction will start when most of the
                             water has evaporated.  During destruction the
                             solution becomes darkly colored.  When
                             sulphur trioxide fumes evolve and the
                             solution is still darkly colored, destruction
                             is notcomplete and an additional 5 ml nitric
                             acid needs to be added.  The residue may be
                             yellow in the presence of iron salts.
                             2.  When destruction is complete, the end
                             volume in the Kjeldahlflasks approximates to
                             that of the volume of the concentrated
                             sulphuric acid.
                             3.  The sulphuric acid reacts violently on
                             the addition of water.  Carefully add 0.5 ml
                             portions of water to the residue.  When a
                             total of 15 ml  has been used, transfer to
                             the separating funnel.  Use the  other 10 ml
                             for rinsing.  Delay  addition of bromine
                             water until  the mixture in the funnel has 
                             returned to room temperature.
                             4.  The method has a lower limit of 
                             detection of 0.05 mg/l thallium.  The upper
                             limit is 0.15 mg/l  thallium. When lower 
                             concentrations are expected the  volume of
                             urine used should be greater.  At higher
                             concentrations, less urine should be

                             5.  Calibration graphs can be constructed by
                             adding known  amounts of thallium to blank
                             samples of urine.
                             When experience has been gained with the
                             method of destruction,  calibration graphs
                             can be  constructed by adding amounts  of
                             thallium to 25.0 ml of lM  sulphuric acid. 
                             The  destruction step then can be  omitted
                             and one can start the  method from bromine
                             water addition.
                             6.  In 20 blank urines originating from 
                             healthy people, after destruction and dilution 
                             with 25 ml of water, the molarity ranged from 
                             0.5 to 1.2 (mean 1.7).
                             7.  Extraction of the complex is 
                             quantitative within a sulphuric  acid
                             molarity range from  0.3-4.0.  This means
                             that the  ratio 2 ml sulphuric acid/25 ml 
                             water should not be altered.
                             8.  When the destruction is  finished, the
                             double addition of 5 ml water and
                             subsequently heating until sulphur trioxide 
                             fumes evolve, is essential to  decompose
                             traces of nitric and  perchloric acid.
                             9.  The thallium-brilliant green  complex in
                             the solution is  unstable.  Extraction with 
                             toluene should be undertaken  within 5
                             minutes after the  addition of the brilliant
                             green  solution.  In the toluene layer,  the
                             complex is stable for 2  hours.
                             10.  In the range 0.05-0.15 mg per  liter,
                             the recovery is 95-100%  of a spiked amount
                             in black  urine. Precision is within 5%.
                             11.  Whole blood may be processed in  the
                             same way, after dilution to  50 ml with
                             distilled water.
                             12.  Detergents interfere.  All  glassware
                             must be carefully  cleaned by rinsing with 
                             distilled water.  Lead  interferes at
                             concentrationsfrom 5  g/ml, and mercury from 
                             1  g/ml.  Using the destruction  method,
                             however, mercury is  volatilized.

                             b)  Atomic absorption spectrophotometry
                             1.  Analysis of thallium in plasma  (serum),
                             whole blood and  erythrocytes according to 
                             De Groot (1982).  2 ml of plasma (serum or
                             whole  blood) are transferred into a 12 ml
                             polyethylene test tube.
                             1 ml of water, 50  l of Sterox SE and l ml of
                             ammonium acetate buffer (0.32 M; pH=3.5) are
                             added.  The mixture is shaken vigorously for
                             15 minutes.  1 ml freshly prepared ammonium
                             pyrrolidine dithiocarbamate solution (8% in
                             water) and 1 ml of n-butyl acetate are added
                             and the mixture is shaken again for 30
                             minutes.  The phases are separated by
                             centrifugation.  The supernatant n-butyl
                             acetate is aspirated into the flame and the
                             absorbance is measured  at 276.8 nm at a
                             spectral band  pass of 0.2 nm.  The use of a 
                             denterium background corrector  is
                             Erythrocyte samples are  processed in a
                             similar manner.  The buffer solution may be 
                             omitted and 1.5 ml of n-butyl  acetate
                             instead of 1 ml is used.  Calibration
                             standards are  prepared by the addition of  1
                             ml of the respective aqueous calibration
                             standard solution to 2 ml of the blank
                             sample  under investigation.
                             The lowest quantifiable concentration is at
                             least 0.2 mg/l and depends on the atomic
                             absorption perctrophotometer used. 
                             Linearity is up to 5 mg/l.  Higher
                             concentrations can be  measured by diluting
                             the sample  under investigation with blank 
                             2.  Urine
                             Concentrations exceeding 0.5 mg/l can be
                             measured by direct aspiration into the
                             apparatus setting specified above.
                             Concentrations exceeding the  appropriate
                             concentration range  (0.5 - 10.0 mg/l) should
                             be  diluted with distilled water.

                             Standards are prepared in blank  urine and
                             processed in the same  way.  It is advisable
                             to add 2  standard drops of concentrated 
                             sulphuric acid to 10 ml of  urine; small
                             particles then  dissolve.  Concentration less 
                             than 0.5 mg/l cannot be measured  by direct
                             aspiration into the  flame and require an
                             extraction  step.  Depending on the 
                             concentration expected,  10 - 50 ml of urine
                             are used, to  which 1 - 5 ml of the ammonium 
                             acetate buffer are added.  Then  2 ml of the
                             freshly prepared  ammonium pyrrolidine 
                             dithiocarbamate solution are  added with 2 -
                             5 ml of n-butyl  acetate (concentration
                             factor  5-(10 ml solution) to  10 -(50 ml
                             solution) times).  The mixture is vigorously 
                             shaken and then processed as  described above
                             under plasma  analysis.  Standards are
                             handled  in the same way.  

            Simple Quantitative Method(s)

            Advanced Quantitative Method(s)

            Other Dedicated Method(s)

             8.2.3  Interpretation of toxicological analyses

        8.3  Biomedical investigations and their interpretation

             8.3.1  Biochemical analysis

            Blood, plasma or serum

                             Thallium is hepatotoxic and raised
                             alkaline phosphatase, aspartate transaminase
                             and alanine transaminase activities and
                             increased bromosulphthalein (BSP) retention
                             times have been reported in severe poisoning
                             (Cavanagh et al, 1974; Papp et al, 1969).
                             Renal function is impaired, with diminished
                             creatinine clearance and raised blood


                             During the acute phase the urinary
                             excretion of porphyrin and porphyrin
                             precursors may be markedly increased. 
                             Analyzing of the percentages present of the
                             individual metabolites of haem synthesis
                             revealed a preponderance of copro- and
                             uroporphyrins (the same phenomenon may be
                             found in lead poisoning).  This may be due to
                             the affinity of thallium for sulphydryl (SH)
                             groups of S-aminolevuline-dehydratase, and
                             coproporphyrin-oxidase, a ferrochelatase
                             which is inhibited by thallium.

            Other fluids

             8.3.2  Arterial blood gas analyses

                    Regular blood gas analysis may reveal
                    respiratory acidosis which may indicate the start of
                    respiratory insufficiency.

             8.3.3  Haematological analyses

                    Anaemia, leucocytosis, eosinophilia,
                    lymphopenia and thrombocytopenia have been reported in
                    the literature (Symmonds, 1953;  Reed et al, 1963; 
                    Cavanagh et al, 1974;  Saddique & Peterson, 1983; 
                    Luckit et al, 1990).

             8.3.4  Interpretation of biomedical investigations

                    Interpretation depends not only on the absolute
                    concentration measured but also on the clinical
                    picture and the time after ingestion.  When urinary
                    thallium excretion is less than 0.5 mg/24 hours,
                    treatment with Prussian Blue is only necessary when
                    neurological patterns are present.  It then may be
                    useful to maintain Prussian Blue therapy until urinary
                    excretion is less than 0.1 mg/24 hours.  In this
                    manner, the factor precipitating the symptoms may be
                    countered and the recovery time shortened.

                    When urinary thallium excretion exceeds 0.5 mg/24
                    hours, treatment with Prussian Blue should be
                    instituted, together with other therapy as
                    necessary.This should be continued until the urinary
                    24 hour thallium excretion is less than 0.5 mg/24
                    hours.  Whether the  figure of 0.5 mg or a slightly
                    lower level (e.g. 0.2 to 0.3 mg/24 hours) is employed
                    as the decision point to stop therapy will depend on
                    the clinical picture.
                    The value of additional therapy, with haemoperfusion
                    and/or haemodialysis, will depend on the time after
                    ingestion and the estimated whole blood thallium
                    concentration.  A whole blood thallium concentration
                    of around 1 mg/l within 48 hours after ingestion is an
                    indication for additional extracorporeal elimination.
                    Depending on the clinical picture, the 48 hour period
                    may be extended and the 1 mg/l level lowered,
                    especially when severe renal impairment is diagnosed.
                    Moreover, repeated extracorporeal elimination may be
                    necessary when whole blood thallium concentrations are
                    high.  Especially in severely poisoned patients with
                    marked neurological symptoms and renal impairment,
                    thallium concentrations of 0.2 - 0.3 mg/l whole blood
                    are indications to consider additional extracorporeal
                    When taking a decision about elimination therapy, the
                    clearance and half-life values mentioned in sections
                    10.6 and 11 may be helpful.

        8.4  Other biomedical (diagnostic) investigations and their

        8.5  Overall Interpretation of all toxicological analyses and
             toxicological investigations

             Sample collection
             (See 8.1 and 8.1.1)
             Biomedical analysis
             Thallium is an hepatotoxin and elevated liver enzyme activity
             is observed in severe toxicity.
             Hypokalaemia is often reported (Reed et al, 1963; Paulson et
             al, 1972).

             Renal function is often impaired:  creatinine clearances are
             diminished and there is raised blood urea and proteinuria
             (Cavanagh et al, 1974; Hollogginitas et al, 1980).
             Monitoring of respiratory insufficiency by blood gas analysis
             is recommended.
             Toxicological analysis
             (See 8.1 and 8.2)
             Other investigations
             Not relevant.

        8.6  References


        9.1  Acute poisoning

             9.1.1  Ingestion

                    The onset of toxicity is often insidious in
                    acute thallium poisoning, reaching a maximum in the
                    second or third week after exposure (Rauws, 1974; 
                    Cavanagh, 1979).
                    The initial symptoms of thallium poisoning include a
                    gradual development of gastro-intestinal disturbances;
                    hyperaesthesia (mainly in the soles of the feet);
                    polyneuritis that may lead to respiratory
                    insufficiency; and tachycardia (Prick et al, 1955; 
                    Cavanagh et al, 1974;  Grunfeld & Hinstroza, 1964; 
                    Egen, 1955; Shabalina & Spiridonova, 1979; Munch,
                    Loss of hair is the most characteristic sign of
                    thallium poisoning and usually appears after 15 days.
                    Nail changes (Mees lines) and atrophic changes of the
                    skin may be late features of toxicity. Development of
                    psychotic behavior with hallucinations and dementia
                    has also been reported (Prick et al, 1955).  Visual
                    disturbances are rare but may occur in very severe

             9.1.2  Inhalation

                    No data available.

             9.1.3  Skin exposure

                    No data available.

             9.1.4  Eye contact

                    No data available.

             9.1.5  Parenteral exposure

                    No data available.

             9.1.6  Other

                    No data available.

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    In a survey of 1265 persons living in the
                    vicinity of a cement plant emitting
                    thallium-containing dust, a mean urinary thallium
                    concentration of 2.6  g/l, ranging up to 76.5  g/l,
                    was found.  In contrast, the mean urinary thallium
                    concentrations of two reference groups were 0.2 and
                    0.4  g/l, respectively.A major cause of increased
                    intake of thallium was found to be the consumption of
                    vegetables and fruit grown in private gardens in the
                    vicinity of the cement plant.  Pulmonary and other
                    routes of uptake  did not seem to play a significant
                    role in the exposure of the  population to thallium. 
                    Polyneuritic symptoms, sleep disorders  headache,
                    fatigue and other features of asthenia were found to
                    be  the major health effects associated with increased
                    thallium levels  in urine and the prevalence of skin
                    abnormalities, hair loss or gastrointestinal
                    dysfunction (Brockhaus et al, 1981).A particular
                    feature of chronic thallium poisoning is pain,
                    especially at the onset, and it occurs particularly in
                    joints, such as the ankles, knees and in the thoracic
                    spine (Prick et al, 1955).

                    A 35-year-old man was given Celiograins on 7 to 9
                    occasions over a one year period by his mother-in-law.
                    Typical symptoms of thallium toxicity, such as pain,
                    dryness of the skin, constipation and insomnia, did
                    not occur.  The clinical picture was dominated by a
                    polyneuropathy, more pronounced in the lower
                    extremities, a lesion of the optic nerve and
                    psychiatric abnormalities.  A particular feature was
                    early loss of sensitivity of the rami anterior of the
                    intercostal nerves.  Eight years after the
                    intoxication, significant abnormalities remained,
                    including critical lability, bilateral optic atrophy
                    and peroneal palsy (Schmidbauer & Klingler,

             9.2.2  Inhalation

                    A health survey of 51 workers in the Soviet
                    Union exposed at times to levels greater than their
                    MAK of 0.01 mg/m3 thallium  revealed amongst those
                    with long-term exposure (16 - 17 years), a  functional
                    nervous syndrome of asthenia and neurosis, or asthenia
                    and autonomic dysfunction, and vascular disorders. 
                    Urinary thallium levels were greater than normal
                    (Poliakova et al, 1977, quoted by Stockinger,

             9.2.3  Skin exposure

                    Intoxication resulting solely from skin contact
                    is reported by Richeson (1958) in six men working with
                    solutions of organic thallium compounds in the
                    separation of industrial diamonds.

             9.2.4  Eye contact

                    No data available.

             9.2.5  Parenteral exposure

                    No data available.

             9.2.6  Other

                    No data available.

        9.3  Course, prognosis, cause of death

             Ingestion of the poison may sometimes give rise to
             vomiting, but typically only nausea is experienced.  This is
             followed by a latent period of 3-4 days followed by
             constipation that fails to respond to purgatives.  About 1 to
             2 weeks after ingestion, hyperaesthesia develops.  Often the
             first complaint of the patient is the sensation of walking on
             felt, followed by neuralgiform pain in the legs.  These
             disturbances in sensory nerves are soon followed by motor
             disturbances. The patient can no longer stand. The
             neuralgiform pains increase gradually until  the patient
             cannot bear even the weight of the sheets on his legs.
             Excessive thirst and sleeplessness are prominent symptoms.
             Further striking mental changes occur which often are
             interpreted as hysteria.  A characteristic early sign, often
             present in the first week of poisoning, is dark pigmentation
             round the roots of the hair.
             Tachycardia develops during the second week, usually
             associated with a moderate increase in blood pressure and a
             progressive polyneuritis becomes apparent.  Sometimes the
             arms are affected together with some of the cranial nerves. 
             Complete arreflexia of the lower limbs may ensue, and the
             initial hyperaesthesia may gradually be replaced by
             At the end of the second week, or even earlier in severe
             poisoning, the typical symptom of hair loss appears. At first
             the hair can merely be more easy plucked; later, it begins to
             fall spontaneously in tufts, and by the third week there is
             usually complete alopecia.  Axillary and pubic hair may also
             disappear.  Most textbooks state that only the lateral parts
             of the eyebrows will fall out, but this statement may have
             been copied from previous publications without
             If the patient recovers, hair will grow normally in the
             course of time.  The skin becomes dry and scaly because of
             destruction of sweat and sebaceous glands.  In the third or
             fourth week, lunular stripes across the nails (bands of Mees)
             may sometimes be seen as a sign of impaired growth for a
             certain period.
             Some months after poisoning, pronounced caries may become
             apparent and severe atrophy of the muscles develops.

             In a follow-up study of 48 children who survived the initial
             stage of poisoning (caused by accidental ingestion of
             pesticides containing thallium sulphate), they were
             specifically examined for sequelae between 6 months and 7
             years after the intoxication.  Neurological abnormalities
             were verified in 26 children.  Mental abnormalities, namely
             retardation and psychosis, were the most common finding.
             Several children were so retarded that they had to be placed
             in institutions.  Abnormal reflexes, ataxia and tremor were
             the next most common finding (Reed et al, 1963).
             In massive poisoning the prognosis is poor.  Severe poisoning
             treated with intensive care, haemoperfusion (in the first 48
             h after ingestion), forced diuresis and colloidal Prussian
             Blue, the outcome may be more favourable.
             Causes of death
             Death may be caused by pulmonary or cardiac failure.
             Paralysis of the vagal nerve was observed in two patients
             which could have been the direct cause of death on the 11th
             day after suicidal ingestion of 600 - 700 mg thallium
             sulphate (Moeschlin, 1980).
             A 26-year-old man who ingested 10 g of thallous malonate died
             of cardiac failure 48 h after ingestion.  A higher
             concentration of thallium was found in the heart that in
             other organs, suggesting that the heart is the main target in
             the early stage of acute poisoning (Aoyama et al, 1986).
             Death by ventilatory insufficiency is possible in patients
             with ascending polyneuritis if they are not artificially
             ventilated in time.

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    Effects on the heart
                    Cardiac arrhythmias may develop in severe cases as
                    early as the first week after ingestion, either due to
                    direct myocardial damage by thallium (Prick et al,
                    1955) or to a direct effect on the pacemaker (Hughes
                    et al, 1978).

                    Tachycardia may be due to the stimulating effect of
                    thallium on ATP in chromaffin cells, leading to
                    increased secretion of catecholamines (Grisham et al,
                    On the electrocardiogram, flattening of the T-waves in
                    the limb leads, and occasionally even  inversion in
                    leads II and III, was seen in 18 of 36 patients;  at
                    the same time there was flattening or inversion of the
                    T-waves in the chest leads, more often in V2 than in
                    V4 (Moeschlin, 1980).
                    Effects on vascular system:  No data available.

             9.4.2  Respiratory

                    Progressive ascending polyneuritis may cause
                    respiratory insufficiency.

             9.4.3  Neurological

            Central Nervous System (CNS)

                             Excessive thirst and intractable
                             sleeplessness appear to be due to a central
                             effect of thallium rather than being due to
                             the severe pain that patients may suffer.
                             Psychosis, hallucination and dementia may be
                             seen at the end of the first week after
                             poisoning (Prick et al, 1955; Cavanagh et al,
                             1974).  Minor psychiatric disturbances are 
                             often interpreted as hysterical behavior.
                             A severe deterioration in intellectual
                             function in a student of chemistry, seven
                             months after ingestion of thallium, was
                             reported by Thomson et al (1988).
                             In very serious cases of thallium poisoning,
                             true "pseudobulbar paralysis" may be
                             observed; this is a peripheral neuritis of
                             the cranial nerves with paralysis of the
                             bulbar muscles, ptosis, facial paralysis,
                             amblyopia and paralysis of the recurrent
                             laryngeal nerve (Moeschlin, 1980).

                             In occasional instances, the initial
                             stimulation of the ganglionic cells of the
                             brain may give rise to severe Jacksonian
                             epileptic seizures (Moeschlin,

            Peripheral nervous system

                             At the end of the first week after exposure,
                             hyperaesthesia, especially of the soles of
                             the feet, develops along with exaggerated
                             hyperreflexia (Prick et al, 1955;  Moeschlin,
                             1980).  By the second week, the picture of
                             toxic polyneuritis is complete, the initial
                             hyperreflexia vanishes and complete
                             arreflexia of the lower extremities ensues
                             (Prick et al, 1955; Moeschlin, 1980; Cavanagh
                             et al, 1974).
                             Thallium poisoning has a characteristic
                             feature:the symptoms sign and indicate that
                             the longest nerve fibers, both sensory and
                             motor, are affected first, while shorter
                             nerve fibers, such as those proximal to the
                             limbs and in the cranial nerves, may be
                             affected several days later.  Detailed
                             post-mortem studies of the nervous system
                             show that in general the abnormalities
                             observed conform  to  the clinical symptoms
                             and signs (Cavanagh et al, 1974).
                             Ultrastructural examination of nerves
                             obtained 7 and 9 days after ingestion of 5 to
                             10 g of thallium nitrate, demonstrated axonal
                             degeneration with secondary myelin loss;
                             death occurred on day 9.  Clinical signs of
                             toxicity included severe cranial and
                             peripheral neuropathy, anuria and hear
                             Severe lesions of the optic nerve may be
                             observed in acute thallium poisoning
                             (Hennekes, 1983;  Beer & Schwarz, 1982).

                             In a 4-year follow-up of 48 patients,
                             neurological abnormalities were observed in
                             26 patients, although there was insufficient
                             recorded detail to localize the lesions
                             precisely (Reed et al, 1963).
                             In very serious cases, and commonly in cases
                             of repeated administration of thallium in
                             attempted homicide, a peripheral neuritis of
                             the cranial nerves is observed with paralysis
                             of the ocular muscles, ptosis, facial
                             paralysis, amblyopia and paralysis of the
                             recurrent nerve (Moeschlin, 1980. Paralysis
                             of the vagal nerve may supervene.

            Autonomic nervous system

                             In the second week there is a
                             gradual development of tachycardia due to
                             direct vagal nerve damage along with  a
                             moderate increase in blood pressure (Paulson
                             et al, 1972).

            Skeletal and smooth muscle

                             Muscle tenderness occurs.

             9.4.4  Gastrointestinal

                    In almost all cases the patient feels some
                    nausea and vomiting initially (Prick, 1955).
                    Severe gastrointestinal bleeding is a rare sign
                    (Prick, 1955) but has been found in cases of fatal
                    poisoning (Moeschlin, 1980). Later in the course of
                    intoxication there develops a characteristic obstinate
                    constipation which fails to respond to purgatives
                    (Moeschlin, 1980).

             9.4.5  Hepatic

                    A week after exposure, evidence of liver
                    toxicity is shown by elevated SGOT, SGPT and alkaline
                    phosphatase activities. Liver cell swelling and
                    centrilobular necrosis are seen.

             9.4.6  Urinary


                             Renal involvement is rare.  In 8 of
                             70 cases, albuminuria with erythrocytes,
                             leucocytes and casts was seen (Moeschlin,


                             No data available.

             9.4.7  Endocrine and reproductive systems

                    Thallium sulphate in a single dose of 8 mg/kg
                    has been used as a depilatory agent for the treatment
                    of ringworm of the scalp (Ruschke & Peiser, 1922). 
                    Munch (1934) reported 692 cases of thallium sulphate
                    poisoning from this medical use of thallium.
                    Alopecia usually appears at the end of the second
                    week. In the third week, there is usually complete
                    alopecia, but it has been reported as early as the
                    fifth day after ingestion of 5 g thallium sulphate
                    (Grunfeld & Hinstroza, 1964).
                    In most cases, facial, pubic and axillary hair is
                    spared but they may disappear (Prick et al, 1955;
                    Cavanagh et al, 1974).
                    Many textbooks mention the fact that the inner third
                    of the eyebrows is spared, but usually this phenomenon
                    does not occur.
                    Black pigmentation of the hair roots can be seen 3 - 4
                    days after thallium exposure.  If poisoning occurred
                    by repeated doses, several zones of pigmentation may
                    be found (Moeschlin, 1980).  According to Metter &
                    Vock (1984), the black discoloration of the hair roots
                    is caused by air vesicles.
                    An explanation for the alopecia may be breakdown of
                    energy metabolism causing inhibition of hair follicle
                    mitosis (Cavanagh & Gregson, 1978).
                    Anhydrosis may occur early due to destruction of sweat
                    glands by thallium.
                    The sebaceous glands are damaged and the skin acquires
                    a dry, slightly scaly appearance.

                    Semilunar stripes across the nails (Mees-lines)
                    parallel with the growth of the nail are reported
                    (Prick et al, 1955;  Moeschlin, 1980).
                    An erythematous macular eruption may be observed
                    leading one to suspect lupus erythematosus.

             9.4.8  Dermatological

             9.4.9  Eye, ears, nose, throat: local effects

                    In a case of acute intoxication by thallium,
                    accompanied by a severe loss of visual acuity and
                    impaired visual fields, ERG changes were found even
                    though the fundus appeared to be normal. The toxic
                    action of thallium seems to occur mainly in the
                    retina, possibly resulting in an ascending (retinal)
                    atrophy of the optic nerve (Hennekes, 1983).
                    Nearly complete blindness was observed in a patient
                    with a subacute myelo-optical neuropathy following
                    suicidal thallium poisoning (Beer & Schwarz,

             9.4.10 Haematological

                    Anaemia, leucocytosis, eosinophilia,
                    lymphopenia and thrombocytopenia have been reported in
                    literature (Symmonds, 1953;  Reed et al 1963; Cavanagh
                    et al,  1974; Saddique & Peterson, 1983; Luckit et al
                    High levels of thallium have been found in the bone
                    marrow in thallium poisoning (Grunfeld & Hinostroza,

             9.4.11 Immunological

                    No data available.

             9.4.12 Metabolic

           Acid-base disturbances

                             No data available.

           Fluid and electrolyte disturbances

                             No data available.


                             No data available.

             9.4.13 Allergic reactions

                    No data available.

             9.4.14 Other clinical effects

                    Several months after thallium exposure,
                    pronounced caries of teeth may become apparent
                    (Moeschlin, 1980). The mechanism of action of thallium
                    on teeth is unknown.

             9.4.15 Special risks

                    Thallium has been shown to cross the placenta
                    the mouse and rat and in man, (Sikkel et al, 1959; Van
                    Maarseveen, 1962; Graben et al, 1980;  Ziskoven et al,

                    The thallium concentration in breast milk is 3 - 4
                    times higher than in blood (Graben et al, 1980). 
                    Following thallium poisoning after the first
                    trimester, in 5 of 15 cases the newborn had symptoms
                    compatible with thallotoxicosis, seen as alopecia (5),
                    rash (5), low birth weight (3) and premature birth
                    Serious intoxication of the mother at the end of
                    pregnancy can cause death of the newborn.  Abortion
                    failed to occur when thallium was taken for this
                    purpose (Stevens & Barbier, 1976).

        9.5  Others

             Thallium may be a cumulative poison in view of the
             fulminant lethal course observed in a patient who took a
             second overdose after a failed suicide attempt (Van Kesteren
             et al, 1990; Rasmussen, 1981).

        9.6  Summary


        10.1 General principles

             Vital functions are not usually impaired early; only in
             massive poisoning may myocardial damage due to thallium
             develop as early as in the first week.  A progressive
             polyneuritis may cause respiratory insufficiency; monitoring
             of vital functions in an intensive care department is
             therefore mandatory.

        10.2 Life supportive procedures and symptomatic treatment

             Artificial ventilation is often indicated in severe

        10.3 Decontamination

             Induce emesis, followed by gastric aspiration (for
             toxicological analysis) and lavage.
             Activated charcoal has been shown to be successful in animal
             experiments (Lund, 1956a, 1956b) and should be administered
             if the antidote Prussian Blue is not available.

        10.4 Enhanced elimination

             Forced diuresis
             Forced diuresis in thallium poisoning is important (Van Hees
             et al, 1975; Hissink Muller, 1977, Pedersen et al, 1978). 
             The mean elimination half-life of thallium with combined
             forced diuresis and charcoal perfusion was calculated as
             being 1.4 days (De Groot & Van Heijst, 1988).
             There is no good reason for alkalinization or acidification
             of the urine in thallium poisoning.
             Peritoneal dialysis and potassium chloride diuresis are
             ineffective (Koshy & Lovejoy, 1981).
             Reported experience with long-term haemodialysis
              Authors(s),       Dose      Haemodialysis    Elimination
              Year              (mg Tl)   (hours)          (mg Tl)
              Brittinger et       ?       121.5            222
              Al., 1970
              Loew et al.,        ?        72              260

              Parckow &         931.5      54              128
              Jenss, 1976
              Pedersen et       1600      120              143
              Al., 1978 
             Clearances obtained by this technique were 83 ml/min(Pedersen
             et al, 1978) and 111 ml/min (Barckow & Jenss, 1976).
             Charcoal haemoperfusion has been proved to be successful if
             used within 48 hours of ingestion of thallium, during the
             distribution phase (De Groot et al, 1985).  The average blood
             clearance at an initial blood concentration of 2 mg/l was 72
             ml/min, and 120 ml/min below this concentration.  As
             saturation of the haemoperfusion column occurs, exchange of
             the column is necessary.
             CAUTION:  Resin haemoperfusion-columns should not be used
             because the clearance is zero (De Groot et al, 1985).

        10.5 Antidote treatment

             10.5.1 Adults

                    a)  Prussian Blue can be obtained in two
                    Colloidally soluble form of K(Fe(III)Fe(II)(CN)6)2H20
                    = potassium ferric hexacyanoferrate(II).  Molecular
                    weight:  342.9 (without water 306.9).
                    It can be administered orally twice daily in a dose of
                    10 g dissolved in 100 ml 1.5% mannitol as an
                    However, because thallium may diminish gastric and
                    intestinal motility, it should preferably be
                    administered intraduodenally.
                    Administration of Prussian Blue should be continued
                    until urinary thallium excretion is less than 0.6
                    mg/24 hours.
                    Fe(III)Fe(II)(CN)63 C.I. no. 77510 = ferric
                    ferrocyanide Molecular weight:  859.29.

                    This substance has also been used in the treatment of
                    thallium poisoning and is commercially available
                    (Antidotum Thallii HeylR, synonym RadiogardaseR,
                    manufactured by the firm Heyl, Berlin, FRG). 
                    However,this salt is less effective than potassium
                    ferric hexacyanoferrate(II), as demonstrated in animal
                    experiments by Dvorak (1969, 1970) and Rauws et al,
                    In vitro, Prussin Blue has a far greater capacity to
                    absorb thallium ions than activated charcoal
                    (Kamerbeek, 1971).
                    In the gut, Prussian Blue traps thallium by exchanging
                    thallium for potassium in the molecule's lattice.
                    Neither the potassium nor the thallium Prussian Blue
                    complex are soluble or absorbable across the gut
                    Because thallium has an entero-enteric cycle (Forth &
                    Henning, 1979), thallium excreted into the intestine
                    will be trapped and redistribution of the poison
                    In vitro experiments have demonstrated that release of
                    cyanide will not occur in human conditions.  Long-term
                    administration of Prussian Blue to animals did not
                    produce any toxic effects (Dvorak et al, 1971).
                    Without treatment, the half-life of thallium is about
                    eight days (Barclay et al, 1953;  FretWurst &
                    Lochmann, 1955). With colloidally soluble potassium
                    ferric hexacyanoferrate(II) therapy the half-life is
                    reduced to 3.0 days.  When this therapy is combined
                    with forced diuresis the half-life of thallium is
                    reduced to 2.0 days.  The total clearance can thus be
                    increased from 20 to 35 to about 200 ml/min.  The
                    elimination half-life of thallium with combined
                    Prussian Blue therapy, forced diuresis and charcoal
                    haemoperfusion was calculated as being 1.4 days (De
                    Groot & Van Heijst, 1988).
                    The results of treatment with potassium ferric
                    hexacyanoferrate in patients with severe thallium
                    poisoning published in the literature have all been
                    favourable (Van Der Merwe, 1972 (2 pat.);  Barbier,
                    1974; Stevens et al, 1974 (11 pat.); Ghezzi & Bozza
                    Marubini, 1979 (5 pat.);  Van Kesteren et al, 1980 (18
                    pat.); Heath et al, 1983 (2 pat.).

                    b)  Sodium iodide
                    Administration of sodium iodide orally or
                    intragastrically has been advocated as a means of
                    immobilizing thallium as thallous iodide.  Thallous
                    iodide is one of the least soluble thallous salts, but
                    its solubility is nevertheless great enough for the
                    absorption of fatal quantities of thallium.
                    c)  Potassium chloride
                    The rate of disappearance of thallium from animals
                    increased as the level of dietary potassium
                    The increased rate of disappearance resulted primarily
                    from an increased rate of excretion of thallium in the
                    urine with no significant increase in the rate of
                    faecal excretion. In dogs, the infusion of potassium
                    increased the renal clearance of thallium and
                    increased the mobilization of thallium from tissues. 
                    A comparison of the plasma disappearance of Tl204 and
                    K42 and of the uptake of these ions by tissue suggests
                    that the ionic movements of thallium and potassium
                    ions are related. Once inside the cell, thallium is
                    less readily released than potassium.  Activation of
                    Na- and K-activated adenosine triphosphatase by the
                    substitution of thallium for potassium supports the
                    belief that the mechanism involved in the active
                    transport of potassium cannot differentiate between
                    thallium and potassium. The LD50 of thallium increased
                    when the potassium intake was increased in rats. This
                    suggests that potassium induced a translocation of
                    thallium away from the toxic receptor site (Gehring &
                    Hammond, 1967).
                    In the rat, urinary excretion increased by 47%
                    compared with activated charcoal, potassium chloride
                    thus gave slightly better protection from acute
                    intoxication in the rat (Lund, 1956b). Treatment in
                    humans increases thallium excretion.  However,
                    treatment freed intracellular stores of thallium ion
                    causing the patient to suffer increased restlessness
                    and hyperexcitability (Papp et al, 1969; Chamberlain
                    et al, 1958;  Bank et al, 1972).

                    d)  Substances with SS or SH groups
                    According to Gross et al, (1948), cystine is the agent
                    most used in this manner.  Thyresson (1951)
                    demonstrated a slight protective effect against
                    chronic thallium poisoning in rats.  An increase in
                    urinary thallium excretion of 60% was found by Lund
                    (1956b), but cystine and cysteine afforded no
                    demonstrable protection from acute thallium poisoning
                    in this experiment.  The use of these compounds has
                    been abandoned in clinical therapy.
                    The chelating agents dimercaprol (BAL), calcium
                    disodiumversenate (EDTA), and penicillamine do not
                    accelerate the excretion of thallium, nor do they
                    offer protection from thallium poisoning (Lund, 1956b;
                    Chamberlain et al, 1958;  Creteur-Dexters et al, 1960;
                    Grunfeld, 1963;  Versie et al,  1963;  Smith &
                    Doherty, 1964; Sunderman, 1967).
                    e)  Diphenylthiocarbazone (dithizone)
                    Dithizone chelates thallium in vitro at pH 9 - 10.  In
                    the rat, urinary thallium excretion was increased by
                    75% and faecal excretion of thallium by 35%, after
                    oral treatment with dithizone (Lund, 1956b).  In the
                    same investigation, considerable protection from acute
                    thallium poisoning was observeed in the rat.  However,
                    in other experiments on rats it was demonstrated that
                    although oral administration of dithizone did reduce
                    the concentration of thallium in muscle tissue, the
                    change was not significant.  No increase of thallium
                    levels in  the brain was observed, nor did dithizone
                    reduce cerebral thallium concentrations (Kamerbeek,
                    In human thallotoxicosis, clinical improvement after
                    oral administration of dithizone was reported by
                    Chamberlain et al, (1958).  However, in their report
                    one patient was treated with intravenous dithizone
                    without a favorable result.

                    f)  Dithiocarbamate (dithiocarb)
                    Dithiocarb has been reported to chelate thallium in
                    vitro at pH 7.5 - 10.  In the rat, thallium  excretion
                    in the urine increased after  administration of
                    dithiocarb (Schwetz et al, 1967).  An increase of 
                    thallium excretion in the urine in a thallium-poisoned
                    patient was  observed  following intravenous
                    administration of dithiocarb 25  mg/kg daily on four
                    consecutive days (Bass, 1963). Similar results  were
                    achieved after oral administration but the increase
                    was less  substantial (Sundermann, 1967; Moeschlin,
                    Therapy with dithiocarb was originally advocated by
                    the National Poison Information Centre of the National
                    Institute of Public Health and Environmental
                    Protection in the Netherlands to physicians attending
                    thallium poisoned patients. The fact that the
                    conditions of these patients deteriorated when
                    dithiocarb was administrated raised the suspicion that
                    dithiocarb was dangerous in thallotoxicosis. 
                    Increased excretion of thallium in urine did occur and
                    the concentration of thallium in the blood also
                    increased when dithiocarb was given.  However,
                    short-term and long-term therapy with dithiocarb
                    caused loss of consciousness for several hours and
                    electro-encephalogram disturbances persisting for days
                    and weeks.  In animals, the short-term effect of
                    dithiocarb therapy was found to be related to the
                    formation of a short-living chelate:  thallium
                    diethyldithiocarbamate. It was possible to demonstrate
                    in vitro the formation of this chelate at body pH and
                    in an experimental in-vivo model.  This chelate was
                    shown to be a lipophilic substance and to have a short
                    half-life of about 30 minutes.  It was non-toxic in
                    the rat, with an LD of 17 mg/kg.  The lipophilic
                    character of the chelate and its lack of stability
                    caused a re-distribution of thallium to the brain as
                    was demonstrated in experiments with rats.  It
                    occurred even when dithiocarb was given several days
                    after administration of thallium (Rauws et al, 1969;
                    Kamerbeek et al, 1971a).

             10.5.2 Children

        10.6 Management discussion

             Treatment with colloidal Prussian Blue C.I. 77520
             (potassium ferric hexacyanoferrate (II) has been proven to be
             very successful in the treatment of thallium poisoning (Van
             Kesteren et al, 1980).
             Prussian Blue C.I. 77510 = insoluble ferric-ferrocyane may be
             also used but it is less effective (Dvorak, 1969, 1970; Rauws
             et al, 1982).
             If Prussian Blue is not available treatment with activated
             charcoal is indicated.


        11.1 Case reports from literature

             An evaluation of different types of elimination therapy
             used in thallium  intoxication has been described by Van
             Kesteren et al, 1980.  A total of 18 patients were treated
             with colloidal Prussian Blue therapy.  In addition, forced
             diuresis therapy was employed in eight of them.  In the
             patients treated with colloidal Prussian Blue only, the mean
             elimination half-life was 3.0 days. The half-life in patients
             in which combined therapy using colloidal Prussian Blue
             administration and forced diuresis a significantly shorter
             mean half-life was found (2 days). Use of activated charcoal
             haemoperfusion therapy within 48 hours of ingestion has been
             proved to be successful.


        12.1 Specific preventive measures

             Ban the use of thallium salts as rodenticides, as is
             already the case in some countries. 

        12.2 Other

             Differential Diagnosis
             - Guillain-Barré syndrome
             Resembles the ascending paralysis of thallium poisoning in
             both time course and distribution.  However, the prominence
             of sensory involvement in thallium poisoning distinguishes it
             from Guillain-Barré.

             - Acute intermittent porphyria.
             - Systemic lupus erythematosus
             An erythematous malar eruption in thallium poisoning might
             lead to an erroneous diagnosis systemic lupus
             - Diabetic polyneuritis
             Other polyneuritis caused by toxic agents
             - ethylalcohol abuses
             - arsenic:  polyneuritic distribution is different
             - lead:  polyneuritic symptomatology, mostly unilateral
             - gold:  polyneuritic manifestations, mostly in arms
                      and legs
             - CO: chronic exposure
             - triorthocresylphosphate
             - hydrocarbons in chronic poisoning
             Because thallium is radio-opaque, poisoning by thallium-salts
             can be diagnosed radiographically.


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        Author:     A.N.P. van Heijst M.D.
                    Professor in Clinical Toxicology
                    Baarnseweg 42a,
                    3735 MJ Bosch en Duin
        Tel:        31-30-287178
        Co-author:  A. van Dijk
                    Hospital Pharmacist
                    State University Hospital
                    Heidelberglaan 100,
                    3584 CX Utrecht
        Tel:        31-30-507190 or 509111
        Reviewer:   Dr T.J. Meredith
                    Senior Medical Officer
                    Department of Health
                    Hannibal House
                    Elephant & Castle
                    London SE1 6ER
                    United Kingdom
        Tel:         44-71-9722449
        Fax:         44-71-7039565
        Peer Review: London, United Kingdom
        Date:        March 1990

    See Also:
       Toxicological Abbreviations
       Thallium (EHC 182, 1996)
       Thallium (ICSC)