Thallium Toxicity

Updated: Dec 12, 2021
Author: David Vearrier, MD, MPH; Chief Editor: Sage W Wiener, MD 


Practice Essentials

Thallium is a heavy metal used in the manufacture of electronic components, optical lenses, semiconductor materials, alloys, gamma radiation detection equipment, imitation jewelry, artist's paints, low temperature thermometers, and green fireworks.[1, 2, 3] Trace amounts of thallium are used as a contrast agent in the visualization of cardiac function and tumors. Thallium exposure may occur at smelters in the maintenance and cleaning of ducts and flues and through contamination of cocaine, heroin, and herbal products. Criminal and unintentional thallium poisonings are still reported, some leading to death.[4, 5]

Acute thallium poisoning is primarily characterized by gastrointestinal, neurologic, and dermatologic symptoms, while neurologic findings predominate with chronic exposure and tend to progress, even despite decreasing blood thallium levels.[6, 7] (See Presentation.)

Treatment of thallium toxicity consists of initial stabilization, prevention of absorption, enhanced elimination, and antidotal therapy.[8] (See Treatment and Medication.)

For patient education resources, see Poisoning.

See Clues on the Skin: Acute Poisonings, a Critical Images slideshow, to help diagnose patients based on their dermatologic presentations.




Thallium is a heavy metal that was serendipitously discovered by Sir William Crookes in 1861 while trying to extract selenium from the by-products of sulfuric acid production. Crookes named the new element "thallium" from the Greek thallos, meaning "green shoot or twig" after the bright green spectral emission lines that identified the element. In 1862, Claude-Auguste Lamy independently isolated thallium, studying both its chemical and physical properties.[9]

In the past, thallium was used as a therapeutic agent to treat syphilis, gonorrhea, tuberculosis, and ringworm, and it was also used as a depilatory for excess hair. In the early part of the last century, a product known as Koremlu (thallium acetate) was marketed in the United States for the treatment of ringworm as well as a depilatory agent. By 1934, 692 cases of thallium poisoning were reported with at least 31 deaths.[4, 5] Thallium was also widely used as a rodenticide. Its use as a household rodenticide was banned in the United States in 1965 after multiple unintentional poisonings.[10] Commercial use was banned a decade later. Unfortunately, unintentional poisonings are still reported in other countries where thallium is used as a rodenticide and ant killer.

Thallium is a soft and pliable metal. It melts at 303.5°C and boils at 1482°C. It is colorless, odorless, and tasteless. Thallium has a similar ionic radii to potassium (Tl 0.147 nm vs K 0.133 nm), which is one principle behind its toxicity.[9]




The biochemical research on the cellular effects of thallium is extensive, but few data exist in humans. The structural similarity of thallium to potassium results in the body treating it as such—an action that is key in poisoning.[11] Thallium demonstrates at least the following 5 major toxicologic effects[12] :

  • Disruption of potassium-dependent processes
  • Riboflavin sequestration
  • Interference with cysteine residues
  • Ribosomal inhibition
  • Myelin sheath injury

Thallium accumulates in tissues with high potassium concentrations such as muscle, heart, and central and peripheral nerve tissue. Thallium’s similar size to potassium results in early stimulation then inhibition of potassium-dependent processes. Key enzymes involved in thallium toxicity include pyruvate kinase and succinate dehydrogenase. Their inhibition leads to impaired glucose metabolism and disrupts the Krebs cycle, leading to decreased ATP production. In addition, sodium-potassium ATPase is affected, resulting in cell membrane injury. This enzymatic injury results in swelling and vacuolization of mitochondrial and cell death. Within the mitochondria, thallium also causes sequestration of riboflavin resulting in the inhibition of flavin coenzyme flavin adenine dinucleotide (FAD), impairing the electron transport chain, and further reduction of ATP.

Similar to other metals, thallium has a high affinity of disulfide bonds. This interferes with cysteine residue cross-linking reducing keratin formation. This results in alopecia and the formation of Mees lines. Decreased cysteine cross-linking also leads to decreased glutathione resulting in accumulation of lipid peroxides in the brain, which are most prominent in the cerebellum, often seen as dark pigmented lipofuscinlike areas.[13]

Thallium interferes with protein synthesis by damaging ribosomes, particularly the 60s ribosomal subunit, further leading to cellular injury and death.[14]

Although the exact mechanism of myelin injury by thallium is unknown, there are consistent findings of fragmentation and degeneration of myelin in both the central and peripheral nervous systems. A Wallerian degeneration pattern first develops in long peripheral axons (lower then upper extremities) with sensory then motor impairment.

Thallium follows a 3-phase toxicokinetics: first intravascular distribution, then CNS distribution, and finally elimination. In the first 4 hours following exposure, thallium is rapidly distributed to the blood and to well-perfused organs such as the kidney, liver, and muscle. Over the next 4-48 hours, thallium is distributed into the CNS. The elimination phase begins about 24 hours after ingestion.

Thallium is primarily eliminated through excretion in the feces (51.4%) and the urine (26.4%). The high concentrations of thallium found in the kidney (> 5.5 times more than other tissues) result from renal filtration with approximately 50% reabsorbed in the kidney tubules. Elimination is slow, with an elimination half-life of 3-30 days, varying with the dose and chronicity of the exposure. Because of this prolonged elimination phase, thallium may act as a cumulative poison.




Because it is odorless and tasteless, thallium has successfully been used worldwide as a rat poison and ant killer. It was restricted for household use in the United States in 1965 and banned commercially in 1975. Thallium is still commonly used as a rodenticide and insecticide in other countries, resulting in severe unintentional poisoning, despite the World Health Organization's recommendation against its use in 1973.[15]

Thallium has been used as a pesticide in other countries, such as in Africa, causing poisoning through contaminated foods. It has been discovered as a contaminant in some Chinese herbal medications.

Thallium is toxic by cumulative intake; it can be absorbed through the skin, respiratory, and GI tracts. Besides oral ingestion, inhalation of contaminated dust during manufacture, sniffing what was thought to be cocaine, and skin absorption through protective gloves have all been reported as causes of thallium toxicity. In addition, cases of thallium intoxication by intravenous injection of contaminated heroin have been reported. However, the vast majority of cases result from oral exposures.

Because chronic thallium exposure mimics other diseases, cases of industrial thallium exposure may go unnoticed. Accidental poisoning caused by direct contact with and careless handling of thallium-containing materials occurs more frequently.

Thallium is used most widely in the semiconductor and optical industries. In addition, it is used in some industries for the production of photoelectric cells, scintillation counters, chemical catalysts, green-emitting fireworks, cement plants, and imitation jewelry.

Trace amounts of thallium are used as a radioactive contrast agent (thallium-201) to visualize cardiac function. The amount of carrier thallium used for this purpose is 4000 times less than the dose at which some toxic effects develop in humans.



In 2019, 49 single exposures with no major outcome and no deaths were reported by the American Association of Poison Control Centers' National Poison Data System (AAPCC-NPDS). All but one exposure involved adults, and none of the exposures were intentional.[16]

Thallium toxicity is likely more common in developing countries where thallium rodenticides are still in use, but few data exist as to the incidence of thallium poisoning outside the United States.[17, 8]

No scientific data substantiate any differences in thallium toxicity that are attributable to race, sex, or age.




If recognized and treated early, thallium intoxication carries a favorable prognosis; however, the course of recovery may be lengthy.[18] Neurologic damage may persist if detoxification therapy is delayed. Patients have demonstrated persistent signs and symptoms of peripheral neuropathy at least 6 years after intoxication. Reports of persistent findings most commonly involve the feet and lower extremities.

Persistent psychiatric symptoms have been reported following thallium exposure, including the following:

  • Agitation
  • Aggression
  • Personality changes
  • Depression

The mortality rate for acute thallium toxicity has been reported as 6-15%; among survivors, 33-50% have neurologic or ocular sequelae.

The lethal dose for humans is 10-15 mg/kg (around 1 g for a 70-kg person). However, death can still occur at lower doses (minimal reported dose was 8 mg/kg). Some treated patients have survived exposure up to 28 mg/kg.




The clinical presentation of thallium toxicity can vary depending on the type, severity, and timeframe of the exposure. Acute thallium poisoning is primarily characterized by gastrointestinal, neurological, and dermatological symptoms, while neurologic findings predominate with chronic exposure and tend to progress, even despite decreasing blood thallium levels.[6]

Gastrointestinal symptoms

These symptoms predominate early, usually within the first 3-4 hours, with the most common symptoms being abdominal pain with nausea/vomiting and diarrhea or constipation.[19, 20, 21] Unlike most other metal salt exposures, gastrointestinal findings in thallium toxicity may be mild or nonexistent, especially in chronic poisoning. Rarely, the vomitus and stools are bloody.

Neurologic symptoms

These symptoms usually appear 2-5 days (though some reports are for < 24 h) postexposure and include severely painful, rapidly progressive, ascending peripheral neuropathies.[19, 20] This is generally the reason patients seek medical care. Pain and paresthesias of the hands and the lower extremities, especially the soles of the feet, are also common. Distal motor weakness may follow, with the lower limbs more affected than the upper limbs. Ataxia, tremor, athetosis, cranial nerve palsies, headache, seizures, insomnia, coma, and death may also occur.

Neuropsychological manifestations may include anxiety, confusion, delirium, hallucinations, and psychosis. Acute agitation and aggression, personality changes, depression, apathy, and confabulation have been observed in both adults and children. Psychosis and associated symptoms can occur with or without a psychiatric history.[22]

Ocular symptoms

Diplopia, abnormal color vision, and impairment of visual acuity may develop.[23] Other manifestations may include alopecia of the lateral half of the eyebrows, skin lesions on the eyelids, ptosis, seventh nerve palsy, internal and external ophthalmoplegia, and nystagmus. Noninflammatory keratitis, lens opacities, and optic atrophy due to toxic optic neuropathy also may occur.

Dermatologic symptoms

The first cutaneous signs are not specific and include scaling of the palms and soles and acneiform or pustular eruptions of the face.[24] During weeks 2-3, a sudden onset of hair loss quickly progresses to diffuse alopecia. The hair loss primarily affects the scalp, temporal parts of the eyebrows, the eyelashes, and the limbs. Less often, the axillary regions are affected. Hair discoloration may also occur. One month after the poisoning, Mees lines (transverse white lines on the nails) appear in the nail plate.[25] Other dermatologic findings include crusted eczematous lesions, hypohidrosis, anhidrosis, palmar erythema, stomatitis, and painful distal glossitis.[26]

Other symptoms

Cardiovascular symptoms include tachycardia and hypertension. Significant ongoing tachycardia may be associated with a poor prognosis.[9]

Some patients can experience pleuritic chest pain or tightness upon exposure. The mechanism for this particular symptom is unclear.



Physical Examination

Focus the physical examination primarily on the organ systems most commonly affected.

Perform careful abdominal and rectal examinations, including stool guaiac tests. Abdominal tenderness, hyperactive bowel sounds, mild guarding, and guaiac-positive stools can be found as early findings in thallium intoxication.

Perform a detailed neurologic examination, including a complete cranial nerve and visual field assessment. Findings are as follows:

  • All cranial nerves (CN) can be affected by thallium. Nystagmus (fourth and sixth CN involvement) and ptosis (third CN) may be present.

  • Decreased lower extremity strength with the lower limbs more affected than the upper limbs, hyperesthesia (especially of the soles of the feet), and decreased sensation to pinprick, touch, temperature, vibration, and proprioception in the fingers and toes may be present.

Perform a slit lamp examination and funduscopic examination, and carefully document visual acuity and color perception. Findings are as follows:

  • Decreased visual acuity with impairment of contrast sensitivity and tritanomaly (blue color vision defect) may be observed.[23]

  • In the early stages of thallium toxicity, funduscopic examination may reveal signs of an optic neuritis characterized by a red and poorly defined papilla. Continued thallium exposure causes atrophy of the optic nerve, which results in the development of a pale or white papilla.

  • Noninflammatory keratitis and lens opacities are also described.

Perform a skin and scalp examination. Findings are as follows:

  • Early skin findings include scaling of the palms and soles and acneiform lesions of the face.[24]  Scalp alopecia, which is one of the most characteristic manifestations of thallium toxicity and is related to atrophy of the hair follicles, usually occurs 10-21 days postexposure.[27]  In addition to the scalp, hair loss also occurs in the lateral eyebrows, the eyelashes, the limbs, and occasionally the axillary regions.

  • Hair roots may have dark brown or black pigmentation as a result of the accumulation of gaseous inclusions that diffract the light. With chronic exposure, these darker regions appear in bands, demonstrating multiple thallium exposures.

  • Approximately 1 month after thallium exposure, Mees lines (transverse white lines on the nails) appear in the nail plate.[25]

  • Other dermatologic findings include well-demarcated hyperkeratosis of the palms and soles, crusted eczematous lesions, hypohidrosis, anhidrosis, palmar erythema, crusted perioral dermatitis, painful distal glossitis, and stomatitis.[26]



Diagnostic Considerations

Other conditions to consider in the differential diagnosis include the following:

  • Acute intermittent porphyria
  • Diabetic polyneuritis
  • Thiamine deficiency
  • Poliomyelitis
  • Colchicine toxicity
  • Vinca alkaloids
  • Hydralazine toxicity
  • Selenium toxicity
  • Vasculitis
  • Botulism



Differential Diagnoses



Laboratory Studies

Because laboratory studies are generally nonspecific, any unexplained peripheral neuropathy, especially accompanied by alopecia, should raise clinical suspicion for thallium toxicity. In consultation with the medical toxicologist, initiate treatment of patients with high suspicion of thallium toxicity while awaiting laboratory confirmation.

The definitive clinical diagnosis of thallium poisoning can only be established by demonstrating elevated thallium levels. Thallium can be recovered in the hair, nails, feces, saliva, blood, and urine.

A 24-hour urine thallium concentration is the standard toxicologic method and is assayed by atomic absorption photospectrometry. The normal level is less than 5 mcg/L.

A urine spot test can deliver faster results. However, it often gives false-positive results, and it requires the use of 20% nitric acid, which can be dangerous and is usually not readily available.

Because thallium is rapidly distributed to the peripheral tissues, measurements of blood thallium reflect only recent exposures and may be falsely negative. Thus, they are not generally considered to be a reliable means of identifying or monitoring exposure to thallium.

A complete blood cell count (CBC) with differential can identify anemia, leukocytosis, eosinophilia, and thrombocytopenia, which have all been reported in cases of thallium exposure. However, none of these finding are sufficiently specific to make a diagnosis of thallium poisoning. 

Electrolytes, calcium, glucose, blood urea nitrogen (BUN), creatinine, and liver function tests (LFTs) should be obtained. Thallium exposure can lead to electrolyte and glucose abnormalities, hypocalcemia, and kidney and liver dysfunction.

A pregnancy test should be considered for all women of childbearing age. Thallium may cross the placental barrier and may be associated with fetal toxicity or mortality.[8]



Imaging Studies

Thallium is radiopaque; therefore, an abdominal radiograph should be obtained. This may reveal thallium metal after an acute ingestion. Radiographs of suspected exposure sources may be useful for confirming the presence of a heavy metal.

Liu et al investigated the correlation between functional imaging and long-term clinical imaging in cases of thallium toxicity. They concluded that fluorodeoxyglucose positron emission tomography (FDG/PET) imaging demonstrated the extent of brain involvement and correlated with cognitive impairment.[28]



Other Tests

Nerve conduction studies (NCS) may reveal findings consistent with an axonal sensorimotor peripheral neuropathy, with nerves innervating the feet most significantly involved. NCS may be useful in both diagnosing and monitoring patients with thallium exposure. The severity of abnormalities on NCS has been shown to correlate with the severity of other symptoms and findings.

An electroencephalogram (EEG) may show nonspecific slow-wave activity in severe cases.

Microscopic inspection of scalp hair reveals dark black and brown pigment in the hair roots in approximately 95% of poisoned patients. However, this may be difficult to visualize by the untrained observer. Darkening of the hair root can occur as early as 4 days postexposure. These dark regions are an optical phenomenon caused by the accumulation of gaseous inclusions that diffract the light, resulting in the appearance of a black band.

Electroretinographic (ERG) examination reveals a delayed visual evoked response. These ERG changes tend to occur before development of clinical symptoms in thallium intoxication. ERG may be useful when persons with known thallium exposure receive follow-up examinations.[29]

An electrocardiogram (ECG) should be obtained to identify tachycardia and cardiac arrhythmias.





Prehospital Care

The prehospital treatment should focus on the following 4 areas:

  1. Stabilizing acute life-threatening conditions
  2. Initiating supportive therapy
  3. Identifying the time and route of exposure
  4. Beginning the decontamination process

Perform the following:

  • Assess airway, breathing, and circulation (ABCs)
  • Administer oxygen as needed
  • Obtain intravenous access
  • Remove contaminated clothing as soon as possible. Avoid self-exposure and wear protective clothing that is appropriate to the type and degree of contamination; wear air-purifying or supplied-air respiratory equipment as necessary. [21]
  • Activated charcoal (0.5 - 1 g/kg) should be administered in patients with an intact or protected airway.

Emergency Department Care

The goals of treating a patient with thallium toxicity are initial stabilization, prevention of absorption, enhanced elimination, and antidotal therapy.

Following the initial assessment and stabilization of the patient, if not performed in the prehospital setting, remove contaminated clothing while avoiding self-exposure. With dermal exposure, thoroughly wash exposed skin with soap and water. For eye exposure, irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. Medical personnel should be sure to wear protective clothing appropriate to the type and degree of contamination.

Gastrointestinal decontamination, activated charcoal, and Prussian blue (potassium ferric hexacyanoferrate) are recommended in thallium ingestions.

Consider orogastric lavage in patients presenting within 1 hour postingestion if they have not vomited, or if thallium is observed in the stomach on radiographs in patients who have vomited. In addition, whole-bowel irrigation with polyethylene glycol may be useful, especially when radiopaque material is visualized on an abdominal radiograph.

Although both Prussian blue and activated charcoal adsorb thallium, Prussian blue appears to have adsorptive superiority. In addition, because it has a far better safety profile than other proposed therapies, Prussian blue should be considered the drug of choice in acute thallium poisoning. An initial dose of 3 g orally may be followed by 250 mg/kg/day divided into four doses.[30]

Prussian blue is a crystal blue lattice of potassium ferric ferrocyanide. It acts as an ion exchanger for univalent cations, with its affinity increasing as the ionic radius of the cation increases. Prussian blue exchanges potassium ions from its lattice with thallium ions in the gut lumen. Removal of thallium from the gut creates a concentration gradient causing an increase in thallium excretion into the gut lumen. This interrupts the enterohepatic recirculation of thallium and increases its elimination. Prussian blue releases a negligible amount of cyanide (< 1.6 mg; minimal lethal dose of cyanide in humans is approximately 50 mg), which does not present a safety concern.[31]

Prussian blue (Radiogardase) was approved by the US Food and Drug Administration (FDA) in 2003 but is still difficult to obtain for pharmaceutical use in the United States. However, it has been obtained from the Oak Ridge Institute for Science and Education and the Radiation Emergency Assistance Center (REAC/TS) in Oak Ridge, Tennessee. In addition, successful therapy using the laboratory reagent form of Prussian blue has been documented in the United States.[30, 32]

Multi-dose activated charcoal has been demonstrated to be effective, in animal model studies, in increasing fecal elimination of thallium. Because thallium undergoes enterohepatic and enteroenteric recirculation, repeated charcoal administration (0.25-0.5 g/kg q2-4h) may enhance fecal elimination. Multi-dose activated charcoal should be administered to patients if Prussian blue is not immediately available. 

The usefulness of hemodialysis and hemoperfusion is controversial, but they may be useful during early thallium poisoning before extensive distribution within the body tissues has occurred.[33, 34, 35]

The following are not recommended:

  • Forced diuresis with potassium loading was previously recommended to increase the renal clearance of thallium, but this may exacerbate the neurologic and cardiovascular symptoms and is no longer advised.
  • Chelating agents such as EDTA, dimercaprol, and D-penicillamine have not been shown to be effective and should be avoided.
  • N-acetylcysteine and l-cysteine have not been shown to be effective in reducing mortality in animal models.

Admit all patients with significant signs and symptoms of thallium toxicity. Initially measure thallium concentrations in the urine 3 times per week to confirm a decreasing trend. Prussian blue treatment should be continued until the 24-hour urine thallium concentration returns to the reference range (0-5 mcg/d). [32]

Thallotoxicosis also is associated with a severe form of stomatitis, so mouth hygiene should be closely monitored. Shaving the patient's head may reduce the stress induced by hair loss and improve the patient's morale. Physical therapy may be instituted to prevent development of muscle contractures. Consider transferring patients with severe signs and symptoms if a medical toxicologist is not readily available.

Patients with unintentional intoxication who are asymptomatic with a minimal increase in urine thallium level may be discharged with close follow-up care. Patients with intentional ingestions should have a psychiatric evaluation before discharge from the hospital.


Consultation with a regional poison control center or medical toxicologist may be of benefit.



Medication Summary

Institute treatment of thallium intoxication as soon as the diagnosis is suspected because tissue-bound thallium may cause prolonged neurologic damage if detoxification therapy is not commenced within 72 h of onset of acute poisoning.



GI decontaminants

Class Summary

These agents bind thallium in the GI tract and prevent enterohepatic recirculation.

Prussian blue (Antidotum Thallii-Heyl, Radiogardase-Cs)

Mixture of several ferrocyanic complexes, mainly KFe(III)Fe(II)(CN)6 (Turnbull Blue) and the reverse complex (hexacyanoferrate). Used as a pigment in paint and ink manufacturing. DOC for thallium poisoning.

Activated charcoal (Liqui-Char)

Emergency treatment in poisoning caused by drugs and chemicals; network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal; does not dissolve in water; for maximum effect, administer within 30 min of poison ingestion.