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Toxicity, Thallium

Author: G Patrick Daubert, MD, Assistant Professor, Assistant Medical Director, Sacramento Division, California Poison Control System; Director of Clinical and Medical Toxicology Education, Department of Emergency Medicine, University of California, Davis Medical Center
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Updated: Aug 6, 2008

Introduction

Background

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.

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 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. 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. 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.

Currently, thallium is 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. 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.

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.

Pathophysiology

The biochemical research on the cellular effects of thallium is extensive, but little data exist in humans. Thallium demonstrates at least 5 major toxicologic effects:

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

The lethal dose of thallium is approximately 15-20 mg/kg; however, significant toxicity and death may occur with smaller amounts. Severe poisoning is expected with oral exposures greater than 200 mg. Thallium poisoning more commonly occurs after oral ingestion. Thallium is rapidly distributed intracellularly throughout all body tissues. Little information is known about the volume of distribution in humans but is estimated to be 3.6-5.6 L/kg.

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 into 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.

Frequency

United States

Between 2003 and 2006, 82 cases if thallium exposures were reported to poison centers. No deaths were reported, and only one major outcome was reported. There is likely an overlap of reports from patients with concerns of the radioactive contrast agent (thallium-201) following noninvasive cardiac studies rather than true thallium poisonings. Although several deaths have been reported in the literature following suicidal or homicidal poisonings over the past few years, few data exist related to actual thallium intoxication cases in the United States.

International

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.

Mortality/Morbidity

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

Thallium is lethal to humans. The lethal dose for humans is 15-20 mg/kg (around 1 g for a 70-kg person). Nonfatal effects occur below this dose. However, it is conceivable that even smaller doses can still cause fatality (minimal reported dose was 8 mg/kg). In addition, some treated patients have survived exposure up to 28 mg/kg.

Race

No scientific data substantiate any differences in thallium toxicity that are attributable to race.

Sex

No scientific data substantiate any differences in thallium toxicity that are attributable to sex.

Age

No scientific data substantiate any differences in thallium toxicity that are attributable to age.

Clinical

History

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 symptoms, while neurologic findings predominate with chronic exposure. The neurologic manifestations tend to progress, even despite decreasing blood thallium levels. Thallium toxicity is characterized by a painful ascending peripheral neuropathy and alopecia; this clinical manifestation presents 2-3 weeks after an acute poisoning.

• Gastrointestinal symptoms: These symptoms predominate early, usually within the first 3-4 hours, and the most common symptom is severe, paroxysmal abdominal pain. It is important to remember that, unlike most other metal salts exposures, gastrointestinal findings in thallium toxicity may be mild or nonexistent, especially in chronic poisoning. Nausea, vomiting, constipation, and diarrhea are reported. Somewhat characteristic for thallium exposure, patients report abdominal pain, mild diarrhea, followed by constipation. The vomitus and stools are often bloody.
• Neurologic symptoms: These symptoms usually appear 2-5 days postexposure and include severely painful, rapidly progressive, ascending peripheral neuropathies. Pain and paresthesias of the hands and the lower extremities, especially the soles of the feet, also predominate. Distal motor weakness occurs, 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.
• Ocular symptoms: Diplopia, abnormal color vision, and impairment of visual acuity may develop. Other manifestations may include loss of the lateral half of the eyebrows, skin lesions on the lids, 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. 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. Other dermatologic findings include crusted eczematous lesions, hypohidrosis, anhidrosis, palmar erythema, stomatitis, and painful glossitis with redness of the tip of the tongue. 
• Pulmonary symptoms: Some patients can experience pleuritic chest pain or tightness upon exposure. The mechanism for this particular symptom is unclear.

Physical

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.
  • All cranial nerves 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.
  • Decreased visual acuity with impairment of contrast sensitivity and tritanomaly (blue color vision defect) may be observed.
  • 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.
  • Early skin findings include scaling of the palms and soles and acneiform lesions of the face. 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. 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.
  • Other dermatologic findings include well-demarcated hyperkeratosis of the palms and soles, crusted eczematous lesions, hypohidrosis, anhidrosis, palmar erythema, crusted perioral dermatitis, painful glossitis with redness of the tip of the tongue, stomatitis, and hair discoloration.

Causes

• 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. This is despite the World Health Organization recommendation against its use in 1973.
• Thallium has been used as a pesticide in other countries, such as Africa, causing poisoning through contaminated foods. It has been discovered as a contaminant in some Chinese herbal medications.
• In review of the American Association of Poison Control Centers Annual Report for toxic exposures from 2003-2006, unintentional thallium poisoning accounts for the majority of reported cases. There is likely an overlap of reports from patients with concerns of the radioactive contrast agent (thallium-201) following noninvasive cardiac studies. However, homicide and suicide represent a significant percentage of cases in the United States.
• Thallium is toxic by cumulative intake; it can be absorbed through the skin, respiratory, and GI tracts. Therefore, 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 disease, many cases of industrial thallium exposure most likely go unnoticed. On the other hand, accidental poisoning caused by direct contact with and careless handling of thallium-containing materials occurs more frequently.
• Thallium is used most often 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 first appear in humans.

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