| 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. PHYSICO-CHEMICAL PROPERTIES|
| 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. USES/CIRCUMSTANCES OF POISONING|
| 4.1 Uses|
| 4.1.1 Uses|
| 4.1.2 Description|
| 4.2 High risk circumstance of poisoning|
| 4.3 Occupationally exposed populations|
|5. ROUTES OF EXPOSURE|
| 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|
| 18.104.22.168 Adults|
| 22.214.171.124 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. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS|
| 8.1 Material sampling plan|
| 8.1.1 Sampling and specimen collection|
| 126.96.36.199 Toxicological analyses|
| 188.8.131.52 Biomedical analyses|
| 184.108.40.206 Arterial blood gas analysis|
| 220.127.116.11 Haematological analyses|
| 18.104.22.168 Other (unspecified) analyses|
| 8.1.2 Storage of laboratory samples and specimens|
| 22.214.171.124 Toxicological analyses|
| 126.96.36.199 Biomedical analyses|
| 188.8.131.52 Arterial blood gas analysis|
| 184.108.40.206 Haematological analyses|
| 220.127.116.11 Other (unspecified) analyses|
| 8.1.3 Transport of laboratory samples and specimens|
| 18.104.22.168 Toxicological analyses|
| 22.214.171.124 Biomedical analyses|
| 126.96.36.199 Arterial blood gas analysis|
| 188.8.131.52 Haematological analyses|
| 184.108.40.206 Other (unspecified) analyses|
| 8.2 Toxicological Analyses and Their Interpretation|
| 8.2.1 Tests on toxic ingredient(s) of material|
| 220.127.116.11 Simple Qualitative Test(s)|
| 18.104.22.168 Advanced Qualitative Confirmation Test(s)|
| 22.214.171.124 Simple Quantitative Method(s)|
| 126.96.36.199 Advanced Quantitative Method(s)|
| 8.2.2 Tests for biological specimens|
| 188.8.131.52 Simple Qualitative Test(s)|
| 184.108.40.206 Advanced Qualitative Confirmation Test(s)|
| 220.127.116.11 Simple Quantitative Method(s)|
| 18.104.22.168 Advanced Quantitative Method(s)|
| 22.214.171.124 Other Dedicated Method(s)|
| 8.2.3 Interpretation of toxicological analyses|
| 8.3 Biomedical investigations and their interpretation|
| 8.3.1 Biochemical analysis|
| 126.96.36.199 Blood, plasma or serum|
| 188.8.131.52 Urine|
| 184.108.40.206 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. CLINICAL EFFECTS|
| 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|
| 220.127.116.11 Central Nervous System (CNS)|
| 18.104.22.168 Peripheral nervous system|
| 22.214.171.124 Autonomic nervous system|
| 126.96.36.199 Skeletal and smooth muscle|
| 9.4.4 Gastrointestinal|
| 9.4.5 Hepatic|
| 9.4.6 Urinary|
| 188.8.131.52 Renal|
| 184.108.40.206 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|
| 220.127.116.11 Acid-base disturbances|
| 18.104.22.168 Fluid and electrolyte disturbances|
| 22.214.171.124 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. ILLUSTRATIVE CASES|
| 11.1 Case reports from literature|
|12. ADDITIONAL INFORMATION|
| 12.1 Specific preventive measures|
| 12.2 Other|
|14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)|
International Programme on Chemical Safety
Poisons Information Monograph 525
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
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.
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
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. PHYSICO-CHEMICAL PROPERTIES
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
Thallium: Bluish-white, very soft, inelastic,
easily fusible, heavy metal; leaves a streak on paper.
Oxidizes superficially in air forming a coating.
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. USES/CIRCUMSTANCES OF POISONING
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 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. ROUTES OF EXPOSURE
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.
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
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.
No data available.
No data available.
Three cases of thallium poisoning have been reported
following nasal insufflation of a substance that was believed
to be cocaine (Insley et al, 1986).
6.1 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;
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
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,
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 &
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
The Soviet Union adopted a MAK of 0.01 mg/m3 of
thallium for the soluble salts, the bromide and iodide
7.2.5 Acceptable daily intake ADI
No data available.
No data available.
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.
No data available.
No data available.
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
126.96.36.199 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
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.
188.8.131.52 Biomedical analyses
184.108.40.206 Arterial blood gas analysis
220.127.116.11 Haematological analyses
18.104.22.168 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
22.214.171.124 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.
126.96.36.199 Biomedical analyses
188.8.131.52 Arterial blood gas analysis
184.108.40.206 Haematological analyses
220.127.116.11 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
18.104.22.168 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
22.214.171.124 Biomedical analyses
126.96.36.199 Arterial blood gas analysis
188.8.131.52 Haematological analyses
184.108.40.206 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
220.127.116.11 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
18.104.22.168 Advanced Qualitative Confirmation Test(s)
22.214.171.124 Simple Quantitative Method(s)
126.96.36.199 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
188.8.131.52 Simple Qualitative Test(s)
184.108.40.206 Advanced Qualitative Confirmation Test(s)
Nowadays, two main methods for
thallium analysis are available:
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
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.
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
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
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
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
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.
220.127.116.11 Simple Quantitative Method(s)
18.104.22.168 Advanced Quantitative Method(s)
22.214.171.124 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
126.96.36.199 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.
188.8.131.52 Other fluids
8.3.2 Arterial blood gas analyses
Regular blood gas analysis may reveal
respiratory acidosis which may indicate the start of
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
(See 8.1 and 8.1.1)
Thallium is an hepatotoxin and elevated liver enzyme activity
is observed in severe toxicity.
Hypokalaemia is often reported (Reed et al, 1963; Paulson et
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
(See 8.1 and 8.2)
9. CLINICAL EFFECTS
9.1 Acute poisoning
The onset of toxicity is often insidious in
acute thallium poisoning, reaching a maximum in the
second or third week after exposure (Rauws, 1974;
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
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.
No data available.
9.2 Chronic poisoning
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,
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.
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
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
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.
Progressive ascending polyneuritis may cause
184.108.40.206 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,
220.127.116.11 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.
18.104.22.168 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).
22.214.171.124 Skeletal and smooth muscle
Muscle tenderness occurs.
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
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.
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.
9.4.9 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,
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,
No data available.
126.96.36.199 Acid-base disturbances
No data available.
188.8.131.52 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).
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).
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
10.2 Life supportive procedures and symptomatic treatment
Artificial ventilation is often indicated in severe
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 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
Loew et al., ? 72 260
Parckow & 931.5 54 128
Pedersen et 1600 120 143
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
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
Administration of Prussian Blue should be continued
until urinary thallium excretion is less than 0.6
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
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 &
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).
10.6 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. ILLUSTRATIVE CASES
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. ADDITIONAL INFORMATION
12.1 Specific preventive measures
Ban the use of thallium salts as rodenticides, as is
already the case in some countries.
- 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
- 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
- CO: chronic exposure
- hydrocarbons in chronic poisoning
Because thallium is radio-opaque, poisoning by thallium-salts
can be diagnosed radiographically.
Aoyama H, Yoshida M, Yamamura Y (1986). Acute poisoning by
intentional ingestion of thallous malonate. Human Toxicol
Bank WJ, Pleasure DE, Susuki J, Nigro M, Katz R (1972). Thallium
poisoning. Arch Neurol 26:456.
Barbier F (1974). Treatment of thallium poisoning. Lancet
Barckow J. Jenss H (1976). Thalliumvergiftung
Kombinationsbenhandlung mit Hämodialyse, forcierte Diurese und
Antidot. Med Klin 71:1377-82.
Barclay RK, Peacok WC, Karnovsky DA (1953). Ditribution and
excretion of radioactive thallium in the chick embryo, rat, and
man. J Pharm Pharmacol 107:178.87.
Bass M (1963). Thallium poisoning. A preliminary report. J Am
Osteopath Ass 63:229.
Beer G, Schwartz RB (1982). Subacute Myelo-Optiko-Neuropathic
(SMON) bei Thalliumintoxikation. Der Nervenartzt 53:451-5.
Brittinger WD, Strauch M, Schwarzbeck A, Huber RW, Von Henning GE,
Wilk G, Haag T (1970). Erfolgreiche Hämodialyse behandlung einer
schweren Thalliumintoxikation. Therapie Woche 7:228.
Brockhaus A, Dolgner R, Ewers U, Krämer U, Soddeman H, Wiegand H
(1981). Intake and health effects of thallium among a population
living in the vicinity of a cement plant emitting thallium
containing dust. Int Arch Occ Environ Health 48:375-89.
Bulkley BH, Rouleau J, Strauss HW, Pitt B (1975). Idiopathic
hypertrophic subaortic stenosis. Detection by thallium 201
myocardial perfusion imaging. New Eng J Med 293:1113-6.
Cavanagh JB, Fuller NH, Johnson NAM, Rudge P (1974). The effects
of thallium salts, with particular reference to the nervous system
changes. Quart J Med J 43:293.
Cavanagh JB, Gregson L (1978). Some effects of thallium salt on
the proliferation of hair follicle cells. J Pathol 125:179.
Cavanagh JB (1979). Metallic toxicity and the nervous system.
Recent advances in Neuropathology 1:247-75.
Chamberlain PH, Stavinoha WB, Davis H, Kniker WT, Panos TC (1958).
Thallium poisoning. Pediatrics 22:1170-82.
Creteur-Dexters J, Versie R, Lambrechts A (1960). Un cas
d'intoxication par le thallium chez l'enfant. Rev Méd Liège
Dolgner R, Brockhaus A, Ewers U, Wiegand H, Majewski F, Soddemann
H (1983). Repeated surveillance of exposure to thallium in a
population living in the vicinity of a cement plant emitting dust
containing thallium. Int Arch Occ Environ Health 52:79-94.
Dvorak P (1969). Kolloidale Hexacyanoferrate(II) als Antidote bei
der Thallium-intoxikation. Z ges exp Med 151:89-92.
Dvorak P (1970). Hexacyanoferrate(II) als Thallium-Antidote.
Herstellung und Eigenschaften. Arzneim Forsch 20:1886-8.
Dvorak P, Günther M, Zorn U, Catsch A (1971). Metabolisches
Verhalten von kolloidalem Ferrihexacyanoferrate(II).
Naunyn-Schmiedeberg's Arch Pharmak 269:48-56.
Egen B (1955). Thalliumvergiftung. Zbl Arbeitsmed und
Erbslöh J (1960). Thallium-Vergiftungen in der Zweiten
Schwangerschaftshälfte. Arch Toxicol 18:156-9.
Forth W, Henning CH (1979). Thallium-Vergiftung und ihre
Behandlung. Dtsch Artzeblatt 43:2803-7.
Fretwurst F, Lochmann FW (1955). Akute Thalliumvergiftung. Arch
Gehring P, Hammond T (1967). The inter-relationship between
thallium and potassium in animals. Pharmacol Exp ther
Gettler AO, Weiss L (1943). Thallium poisoning. III Clinical
toxicology of thallium. Am J Clin Pathol 13:422-9
Ghezzi R, Bozza-Marrubini M (1979). Prussian Blue in the
treatment of thallium intoxication. Vet Hum Toxicol 21:64-6.
Gibson JE, Becker BA (1970). Placental transfer, embryotoxicity,
and teratogenicity of thallium sulphate in normal and
potassium-deficient rats. Toxicol Appl Pharmacol 16:120-32.
Graben N, Klöppel HA, Heidemann H, Weiler G (1980). Zur
Behandlung der Thalliumvergiftung unter besonderer
Berüchsichtigung von Schwangerschaft und Laktation. Med Welt
Grisham CM, Cupta RK, Barnett RE, Mildvan AS (1974). Thallium-205
nuclear relation and kinetic studies of sodium and potassium
ion-activated adenosine triphosphatase. J Biol Chem
Groot de G (1982). Haemoperfusion in clinical toxicology. Ph.D.
thesis, State University of Utrecht, The Netherlands.
Groot de G, van Heijst ANP, van Kesteren RG, Maes RAA (1985). An
evaluation of the efficacy of charcoal haemoperfusion in the
treatment of three cases of acute thallium poisoning. Arch
Groot de G, van Heijst ANP (1988). Toxicokinetic aspects of
thallium poisoning, methods of treatment by toxin elimination.
The Science of Total Environment 71:411-8.
Gross P, Kunne E, Wilson JW (1948). Studies on the effect of
thallium poisoning of the rat. The influence of cystine and
methionine on alopecia and survival periods. J Invest Dermatol
Grunfeld O (1963). Thallium poisoning treated with BAl. New Eng
J Med 269:1138-40.
Grunfeld O, Hinostroza G (1964). Thallium poisoning. Arch Intern
Hall BK (1976). Thallium-induced achondroplasia in chicken
embryos and the concept of critical periods during development.
Hasan M, Chandra S, Dua PR, Raghubir R, Ali SF (1977).
Biochemical and electrophysiological effects of thallium poisoning
on the rat corpus striatum. Toxicol Appl Pharmacol 41:353-9.
Heath A, Ahlmen J, Branegard B, Lindstedt S, Wickstrom I, Andersen
O (1983). Thallium poisoning. Toxin elimination and therapy in
these cases. J Toxicol Clin Toxicol 20:451-63.
Hees van PAM, Jansen AP, Fennis JFM, van 't Laar (1975). Forced
diuresis in thallium intoxication. Neth J Med 18:125-8.
Hennekes R (1983). Netzhautfunktions schädigung bei akuter
Thalliumintoxikation. Klin Mbl Augenheilk 182:334-6
Hissink Muller W (1977). Een patient die een ernstige
thallium-intoxicatie overleefde. Ned Tijdischr Geneeskd
Hollogginitas C, Ullicci P, Dricoll J, Gauerholz J, Martin H
(1980). Thallium elimination kinetics in acute thallotoxicosis.
JAnalytical Toxicol 4:68-73.
Hughes MN, Man WK, Whaler BC (1978). The toxicity of thallium(I)
to cardiac and skeletal muscle. Chem Biol Interact 28:85-97.
Insley BM, Grufferman S, Ayliffe (1986). Thallium poisoning in
cocaine abusers. Am J Emerg Med 4:545-8.
Kamerbeek HH (1971). Therapeutic problems in thallium poisoning.
Thesis ed Gianotten-Tilburg.
Kamerbeek HH, Rauws AG, ten Ham M, van Heijst ANP (1971).
Prussian Blue in therapy of thallotoxicosis. Acta Med Scand
Kamerbeek HH, Rauws AG, ten Ham M, van Heijst ANP (1971).
Dangerous redistribution of thallium by treatment with sodium
dithiocarbamate. Acta Med Scand 189:149-54.
Kesteren van RG, Rauws AG, de Groot G, van Heijst ANP (1980).
Thallium intoxication. An evaluation of therapy. Intensive Med
Koshy KM, Lovejoy FH (1981). Thallium ingestion with survival
ineffectiveness of peritoneal dialysis and potassium chloride
diuresis. Clin Toxicol 18:521-5.
Kuhn R, Rudy H, Wagner-Jauregg T (1933). Uber Lactoflavin
(Vit.B2). Berichte der Deutschen Chemischen Gessellschaft
Lameyer A, van Zwieten PA (1977). Kinetic behaviour of thallium in
the rat. Accelerated elimination owing to treatment with potent
diuretic agents. Arch Toxicol 37:265-73.
Lie R, Thomas RG, Scott JK (1960). The distribution and excretion
of thallium-240 in the rat, with suggested MCP's and a bio-essay
procedure. Health Physics 2:334-40.
Loew H, Tillmann P, Winter R, Wiessmann B, Koch R, Schiller M
(1972). Thallium-Elimination durch der Hämodialyse im Vergleich
zur grossen Diurese bei einer schweren Thallium Intoxikation. Med
Luckit J, Mir N, Hargraves M, Costello C, Gazzard B (1990).
Thrombocytopenia associated with thallium poisoning. Human Exp
Lund A (1956a). Distribution of thallium in the organs and its
elimination. Acta Pharmacol Toxicol 12:251-9.
Lund A (1956b). The effect of various substances on the excretion
and toxicity of thallium in the rat. Acta Pharmacol Toxicol
Maarseveen van DA (1962). Een geval van thallium-intoxicatie
tijdens de zwangerschap. Ned Tijdschr Geneeskd 106:1765-6.
Marcus RL (1985). Investigation of a working population exposed
to thallium. J Soc Occup Med 35:4-9
Merck Index 1983. 10th ed. Merck & Co, Inc Rahway, NY USA.
Merwe van der CF (1972). The treatment of thallium poisoning. S
Afr Med J 46:960-1.
Metter D, Vock R (1984). Haarbefunde bei einer Serie von secks
Thalliumvergiftungen. Beitr Gerichtl Med 42:379-85.
Moeschlin S (1967). Exogene und endogene Vergiftungen. Helv Med
Acta suppl 47,;34:75-100.
Moeschlin S (1980). Thallium poisoning. Clin Toxicol
Mullins LJ, Moore RD (1960). The movement of thallium ions in
muscle. J Gen Physiol 43:759-73.
Munch JC (1934). Human thallotoxicosis. J Am Med Assoc
NIOSH (1976). Registry of Toxic Effects of Chemical Substances,
Papp JP, Gay PC, Dodson VN, Pollard HM (1969). Potassium chloride
in the treatment of thallotoxicosis. Ann Intern Med
Paulson G, Vergara G, Young J, Bird M (1972). Thallium
intoxication treated with dithizone and hemodialysis. Arch Intern
Pedersen RS, Olesen AS, Freund LG, Solgaard P, Larsen E (1978).
Thallium intoxication treated with long-term hemodialysis, forced
diuresis and Prussian Blue. Acta Med Scand 204:429-32.
Petersohn KL (1960). Thallium-Vergiftungen in der
Schwangerschaft. Arch Toxicol 18:160-4.
Poliakova MM et al (1977). Quoted by Stockinger 1981. Gig Tr
Prof Zabol 2:14.
Prick JJG, Sillevis Smitt WG, Muller L (1955). Thallium
poisoning. Elsevier Publishing Co, Amsterdam.
Rasmussen OV (1981). Thallium poisoning; an aspect of human
cruelty. Lancet 1:1164.
Rauws AG, ten Ham M, Kamerbeek HH (1969). Influence of the
antidote dithiocarb on distribution and toxicity of thallium in
the rat. Arch Intern Pharmacodyn 182:425-6.
Rauws AG (1974). Thallium pharmacokinetics and its modification by
Prussian Blue. Naunyn-Schmiedeberg's Arch Pharmacol
Rauws AG, de Groot G, van Heijst ANP (1982). Quality control of
the thallium antidote Prussian Blue. Comparison of binding in
vitro and effect in vivo. Report of the Nat. Inst. Publ. Health,
The Netherlands nr.328001001.
Reed D, Crawley J, Faro S, Pieper S, Kurland L (1963).
Thallotoxicosis, acute manifestations and sequelae. J Am Med
Richelmi P, Bono F, Guarda L, Ferrini B, Manzo L (1980). Salivary
levels of thallium in acute human poisoning. Arch Toxicol
Richeson EM (1958). Industrial thallium intoxication. Ind Med
Ruschke A, Peiser B (1922). Die Wirkung des Thallium auf das
Endokrine System. Klin Wschr 1:995.
Saddique A, Peterson CD (1983). Thallium poisoning. A review.Vet
Hum Toxicol 25:16-22.
Schafer SG, Forth W (1983). Excretion of metals into the rat
intestine. Biol Trace Elem Res 5:205-17.
Schmidbauer H, Klingler D (1979). Chronische Thalliumvergiftung.
Wien Med Wschr 129:334-6.
Schoental R, Cavanagh JB (1977). Mechanism involved in the "dying
back" process - an hypothesis involving co-factor. Neuropathol
appl Neurobiol 3:145.
Schwetz BA, O'Neill PV, Voelker FA, Jacobs DW (1967). Effects of
diphenylthiocarbazone and diethyldithiocarbamate on the excretion
of thallium by rats. Toxicol Appl Pharmacol 10:79-88.
Shabalina LP, Spiridonova VS (1979). Thallium as an industrial
poison (Review of literature). J Hyg Epid Microbiol Immun
Sikkel A, Posthumes Meyes FE, Zondag HA (1959). Een geval van
thallium vergiftiging in de zwangerschap. Ned Tijdschr Geneeskd
Smith DH, Doherty RA (1964). Thallotoxicosis. Report of three
cases in Massachusetts. Pediatrics 34:480.
Smith IC, Carson BL (1977). Vol I Thallium, Trace metals in the
environment. Ann Harbor, Ann Harbor Science.
Spencer PS, Peterson ER, Ricardo MA, Raine CS (1973). Effects of
thallium salts on neuronal mitochondria in organotypic
cord-ganglia-muscle combination cultures. J Cell Biol
Stevens W, van Peteghem C, Heyndrickx A, Barbier F (1974).
Eleven cases of thallium intoxication treated with Prussian Blue.
Int J Clin Pharmacol 10:1-22.
Stevens WJ, Barbier F (1976). Thallium intoxicatie gedurende
zwangerschap. Act Clin Belg 31:188-93.
Stockinger HE (1981). The Metals. Patty's Industrial Hygiene 3rd
Ed New York, Wiley, Clayton GT & Clayton FE (ed):1914-31.
Sunderman FW Jr (1967). Diethyldithiocarbamate therapy of
thallotoxicosis. Am J Med Sci 253:209-20.
Symmonds WJC (1953). Alopecia, optic atrophy and peripheral
neuritis of probably toxic origin. Lancet 11:1338-9.
Talas A, Pretschner DP, Wellh ner HH. Pharmacokinetic parameters
for thallium(I) ions in man. Arch Toxicol 1983;53:1-7.
Talas A, Wellh ner HH (1983). Dose-dependency of Tl+ kinetics as
studied in rabbits. Arch Toxicol 53:9-16.
Thomson C, Dent J, Saxby P (1988). Effects of thallium poisoning
on intellectual function. Br J Psychiatry 153:396-9.
Thyresson N (1951). Experimental investigation on thallium
poisoning. Effect of thallium on the growth and differentiation
of hairs and epidermis, studied in young rats and in tissue
cultures of embryonic rat skin. Acta Derm-Venereol
Versie R, Deleixhe A, Lapiere ChM (1963). Deux cas simultanés
d'intoxication par le thallium. Act Clin Belg 18:511-8.
Vogel AI (1954). A textbook of macro- and semimicro qualitative
inorganic analysis, 4th Ed. Longmans, London.
Weich HF, Strauss H, Pitt B (1977). The extraction of thallium
201 by the myocardium. Circulation 56:188-91.
Wolf de JNM, Lenstra JB (1964). De bepaling van thallium in
urine. Pharm Weekbl 99:377-82.
Ziskoven R, Achenbach C, Bahr U, Schulten HR (1980). Quantitative
investigations on the diaplacental transfer of thallium by field
desorption mass spectrometry. Z Naturf 35c:902-6.
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
Author: A.N.P. van Heijst M.D.
Professor in Clinical Toxicology
3735 MJ Bosch en Duin
Co-author: A. van Dijk
State University Hospital
3584 CX Utrecht
Tel: 31-30-507190 or 509111
Reviewer: Dr T.J. Meredith
Senior Medical Officer
Department of Health
Elephant & Castle
London SE1 6ER
Peer Review: London, United Kingdom
Date: March 1990