Thallium Toxicity

Thallium Toxicity

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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, neurological, and dermatological 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 (see  Treatment and Medication). [8]

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] :

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. [13]

Thallium interferes with protein synthesis by damaging ribosomes, particularly the 60s ribosome, 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 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.

 

 

United States

In 2016, 29 single exposures with one major outcome and no deaths were reported by the  American Association of Poison Control Centers’ National Poison Data System (AAPCC-NPDS). Most involved adults, and none of the exposures were intentional. [15]

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. [16, 8]

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.

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

 

 

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Wang C, Chen Y, Liu J, Wang J, Li X, Zhang Y, et al. Health risks of thallium in contaminated arable soils and food crops irrigated with wastewater from a sulfuric acid plant in western Guangdong province, China. Ecotoxicol Environ Saf. 2013 Apr. 90:76-81. [Medline].

Turner A, Furniss O. An evaluation of the toxicity and bioaccumulation of thallium in the coastal marine environment using the macroalga, Ulva lactuca. Mar Pollut Bull. 2012 Dec. 64(12):2720-4. [Medline].

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Cvjetko P, Cvjetko I, Pavlica M. Thallium toxicity in humans. Arh Hig Rada Toksikol. 2010 Mar. 61(1):111-9. [Medline].

Sharma AN, Nelson LS, Hoffman RS. Cerebrospinal fluid analysis in fatal thallium poisoning: evidence for delayed distribution into the central nervous system. Am J Forensic Med Pathol. 2004 Jun. 25(2):156-8. [Medline].

Hazardous Substances Data Bank [Internet]. Bethesda (MD): National Library of Medicine (US); [Last Revision Date 2008 Apr 25]. Thallium, Elemental; Hazardous Substances Databank Number: 4496. [Full Text].

Mercurio M, Hoffman RS. Thallium. Goldfrank’s Toxicologic Emergencies. 9th ed. 2011. 1326-33.

Rusyniak DE, Furbee RB, Kirk MA. Thallium and arsenic poisoning in a small midwestern town. Ann Emerg Med. 2002 Mar. 39(3):307-11. [Medline].

Osorio-Rico L, Santamaria A, Galván-Arzate S. Thallium Toxicity: General Issues, Neurological Symptoms, and Neurotoxic Mechanisms. Adv Neurobiol. 2017. 18:345-353. [Medline].

Galván-Arzate S, Santamaría A. Thallium toxicity. Toxicol Lett. 1998 Sep 30. 99(1):1-13. [Medline].

Hasan M, Ali SF. Effects of thallium, nickel, and cobalt administration of the lipid peroxidation in different regions of the rat brain. Toxicol Appl Pharmacol. 1981 Jan. 57(1):8-13. [Medline].

Hultin T, Näslund PH. Effects of thallium (I) on the structure and functions of mammalian ribosomes. Chem Biol Interact. 1974 May. 8(5):315-28. [Medline].

Gummin DD, Mowry JB, Spyker DA, Brooks DE, Fraser MO, Banner W. 2016 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 34th Annual Report. Clin Toxicol (Phila). 2017 Dec. 55 (10):1072-1252. [Medline]. [Full Text].

Atsmon J, Taliansky E, Landau M, et al. Thallium poisoning in Israel. Am J Med Sci. 2000 Nov. 320(5):327-30. [Medline].

Al Hammouri F, Darwazeh G, Said A, Ghosh RA. Acute thallium poisoning: series of ten cases. J Med Toxicol. 2011 Dec. 7(4):306-11. [Medline].

Li JM, Wang W, Lei S, Zhao LL, Zhou D, Xiong H. Misdiagnosis and long-term outcome of 13 patients with acute thallium poisoning in China. Clin Toxicol (Phila). 2014 Mar. 52(3):181-6. [Medline].

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Tabandeh H, Thompson GM. Visual function in thallium toxicity. BMJ. 1993 Jul 31. 307(6899):324. [Medline].

Tromme I, Van Neste D, Dobbelaere F, et al. Skin signs in the diagnosis of thallium poisoning. Br J Dermatol. 1998 Feb. 138(2):321-5. [Medline].

Saha A, Sadhu HG, Karnik AB. Erosion of nails following thallium poisoning: a case report. Occup Environ Med. 2004 Jul. 61(7):640-2. [Medline].

Lu CI, Huang CC, Chang YC, Tsai YT, Kuo HC, Chuang YH, et al. Short-term thallium intoxication: dermatological findings correlated with thallium concentration. Arch Dermatol. 2007 Jan. 143(1):93-8. [Medline].

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Shamshinova AM, Ivanina TA, Yakovlev AA, et al. Electroretinography in the diagnosis of thallium intoxication. J Hyg Epidemiol Microbiol Immunol. 1990. 34(2):113-21. [Medline].

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Misra UK, Kalita J, Yadav RK, et al. Thallium poisoning: emphasis on early diagnosis and response to haemodialysis. Postgrad Med J. 2003 Feb. 79(928):103-5. [Medline].

Huang C, Zhang X, Li G, Jiang Y, Wang Q, Tian R. A case of severe thallium poisoning successfully treated with hemoperfusion and continuous veno-venous hemofiltration. Hum Exp Toxicol. 2013 Jul 30. [Medline].

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Chip Gresham, MD, FACEM Emergency Medicine Physician, Medical Toxicologist, and Intensive Care Consultant, Department of Emergency Medicine, Clinical Director of Medication Safety, Middlemore Hospital; Consultant Toxicologist, National Poisons Centre; Director, Auckland Regional Toxicology Service; 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, Australasian College for Emergency Medicine, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

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.

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.

David Vearrier, MD, MPH Associate Professor, Medical Toxicology Fellowship Director, Department of Emergency Medicine, Drexel University College of Medicine

David Vearrier, 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 Occupational and Environmental Medicine

Disclosure: Nothing to disclose.

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.

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.

Thallium Toxicity

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