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Thallium Toxicity

  • Author: Chip Gresham, MD, FACEM; Chief Editor: Asim Tarabar, MD  more...
 
Updated: Apr 23, 2014
 

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.[1]

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.[2, 3] 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.[4] 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.

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

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.[5, 6, 7] 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.[2, 3]

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.[1]

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Pathophysiology

The biochemical research on the cellular effects of thallium is extensive, but little data exist in humans. Its structural similarity to potassium results in the body treating it as such—an action that is key in poisoning. Thallium demonstrates at least the following 5 major toxicologic effects[8] :

  • 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 Kreb’s 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.[9]

Thallium interferes with protein synthesis by damaging ribosomes, particularly the 60s ribosome, further leading to cellular injury and death.[10]

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 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.

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Epidemiology

Frequency

United States

In 2012, 23 exposures and no deaths were reported by the American Association of Poison Centers. 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.[11]

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.[12, 11]

Mortality/Morbidity

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.

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.

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Contributor Information and Disclosures
Author

Chip Gresham, MD, FACEM Emergency Medicine Physician and Medical Toxicologist, Department of Emergency Medicine, Clinical Director of Medication Safety, Middlemore Hospital; Senior Lecturer, Auckland University Medical School, New Zealand

Chip Gresham, MD, FACEM is a member of the following medical societies: American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine, Emergency Medicine Residents' Association

Disclosure: Nothing to disclose.

Coauthor(s)

Emma A Lawrey, MBChB, Dip Paeds, PG Cert ClinEd, FACEM Emergency Medicine Consultant and Clinical Toxicology Fellow, Department of Emergency Medicine, Middlemore Hospital, New Zealand

Emma A Lawrey, MBChB, Dip Paeds, PG Cert ClinEd, FACEM is a member of the following medical societies: Australasian College for Emergency Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

John G Benitez, MD, MPH Associate Professor, Department of Medicine, Medical Toxicology, Vanderbilt University Medical Center; Managing Director, Tennessee Poison Center

John G Benitez, MD, MPH is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Medical Toxicology, American College of Preventive Medicine, Undersea and Hyperbaric Medical Society, Wilderness Medical Society, American College of Occupational and Environmental Medicine

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Additional Contributors

William K Chiang, MD Associate Professor, Department of Emergency Medicine, New York University School of Medicine; Chief of Service, Department of Emergency Medicine, Bellevue Hospital Center

William K Chiang, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Mary L Arvanitis, DO, FACOEP Clinical Assistant Professor, Department of Emergency Medicine, Michigan State University, College of Human Medicine; Consulting Staff, Department of Emergency Medicine, Covenant Hospital; Director, Osteopathic Medical Education, Synergy Medical Education Alliance

Disclosure: Nothing to disclose.

Igor Boyarsky, DO Emergency Room Physician, Kaiser Permanente Southern California

Igor Boyarsky, DO is a member of the following medical societies: American Academy of Anti-Aging Medicine, American Academy of Emergency Medicine, American College of Emergency Physicians, and American Osteopathic Assocation

Disclosure: Nothing to disclose.

Adrian D Crisan, MD Staff Physician, Department of Emergency Medicine, Martin Luther King Jr/Drew Medical Center

Disclosure: Nothing to disclose.

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

G Patrick Daubert, MD is a member of the following medical societies: American College of Emergency Physicians, American College of Medical Toxicology, American Medical Association, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Wendy R Regal, MD Clinical Instructor, Department of Emergency Medicine, Synergy Medical Education Alliance, Michigan State University

Disclosure: Nothing to disclose.

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