Thallium

Thallium is a soft, heavy, inelastic metal that has not been produced in the United States since 1984 due to its deleterious effects following accidental exposure.

It is still imported for use in the manufacturing of electronics, low temperature thermometers, optical lenses, and imitation jewels.

Thallium is tasteless, odorless, and water soluble with a diagnosis that relies on close observation of clinical signs, making it a highly effective poison in its unsuspecting victims.

Source 1

• Not found free in nature
• Discovered independently in 1861 by Chemists William Crookes (England) and Claude-Auguste Lamy (France) in sulfuric acid production residue via flame spectroscopy

Biotransformation 1

• Thallium is structurally similar to potassium and is treated as such at the cellular level

Toxicokinetics 1, 2

• Thallium is rapidly absorbed through the skin, mucous membranes, and gastrointestinal (GI) tract, with the majority being absorbed through the GI tract
• There are three phases to the toxicokinetics:
  1. Intravascular distribution phase: During the first 4 hours post-exposure, thallium is distributed to organs via the blood
  2. CNS distribution phase: During the next 4 to 48 hours, thallium reaches the central nervous system
  3. Elimination phase: This phase begins around 24 hours post-exposure and is mainly achieved through renal excretion and feces
     • This is a slow phase and may take up to 30 days

Carcinogenicity

• There is not published information that indicates thallium has carcinogenic properties in human or animals

Mechanism of Action 3

• Thallium has a very well known mechanism of action
• The key MOA’s are:
  • Interference with potassium dependent processes
  • Substitution of potassium in (Na+/K+)-ATPase
  • High affinity for sulfhydryl groups from proteins and other biomolecules
    • Thallium combines with the sulfhydryl groups of mitochondria, interfering with oxidative phosphorylation, which may lead to the generation of reactive oxygen species

Target organs

• Nervous System
• Integumentary System
• Reproductive Systems
  • Male and Female

Signs and Symptoms of Toxicity 1,4

• Within 3-4 hours (up to 14 hours)
  • Gastrointestinal Signs
    • Hemorrhage into the GI Tract
    • Nausea
    • Vomiting
    • Diarrhea or Constipation
    • Abdominal Pain
• 2-5 Days Post Ingestion
  • Neurologic Signs
    • Ascending Peripheral Neuropathies
    • Distal Motor Weakness
    • Ataxia
    • Tremors
    • Cranial Nerve Palsies
    • Headache
    • Seizures
    • Insomnia
    • Coma
• 2-3 Weeks Post Ingestion
  • Dermatologic Signs
    • Alopecia
    • Hypohidrosis
    • Anhydrosis
    • Painful Glossitis
    • Mees Lines on Nails
• Other symptoms
  • Tachycardia
  • Arrhythmia
  • Diplopia
  • Nystagmus
  • Hypertension

                

Mees Lines                                   Alopecia                   Peripheral Neuropathy

Genetic Susceptibility

• There is no genetic predisposition to thallium toxicity

Treatment 5

• Initial Care
  • Initial care begins with stabilization of the patient via establishment of an airway and circulation
  • For dermal exposures, contaminated clothing will be removed and skin will be washed
  • For ocular exposures, eyes will be irrigated with room temperature water
• Medications
  • Prussian blue
    • The most commonly prescribed antidote
    • It interrupts the re-adsorption of thallium in the GI tract and enhances elimination from the body
    • It has limited availability in many regions
  • Activated charcoal
    • Activated charcoal may be administered to patients that have ingested Thallium within one hour

Biomarkers 6

• Thallium levels in urine, blood, and hair have been used as indications of exposure to thallium
• Urine is the most widely used of the three
  • Blood clearance of thallium is too rapid to be reliable
  • Hair testing can pose issues due to the inability to differentiate between thallium incorporation into the hair follicle via the body (internally) or the environment (externally)

Essentiality and deficiency

• Thallium is not normally found within the body (unlike Copper and Zinc), which makes it non-essential to the human body

For a summary on Thallium, please watch this video:

References

1. Kemnic TR, Coleman M. Thallium Toxicity. [Updated 2020 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513240/
2. Léonard A, Gerber GB. Mutagenicity, carcinogenicity and teratogenicity of thallium compounds. Mutat Res. 1997 Aug;387(1):47-53. doi: 10.1016/s1383-5742(97)00022-7. PMID: 9254892.
3. Tyagi R, Rana P, Khan AR, Bhatnagar D, Devi MM, Chaturvedi S, Tripathi RP, Khushu S. Study of acute biochemical effects of thallium toxicity in mouse urine by NMR spectroscopy. J Appl Toxicol. 2011 Oct;31(7):663-70. doi: 10.1002/jat.1617. Epub 2011 Jan 7. PMID: 21218500.
4. Borges, T., & Daugherty, M. L. (1994, December). The Risk Assessment Information System. The Risk Assessment Information System. https://rais.ornl.gov/tox/profiles/thallium_f_V1.html
5. Lin, Guodong PhD^a; Yuan, Luo PhD^b; Peng, Xiaobo Dr^a; Long, Jianhai PhD^b; Wang, Chunyan PhD^a; Bai, Lili Dr^a; Lu, Xiaoxia PhD^a; Dong, Jianguang Dr^a; Liu, Yanqing Dr^a; Wang, Yongan PhD^b,∗; Qiu, Zewu PhD^a,∗ Clinical characteristics and treatment of thallium poisoning in patients with delayed admission in China, Medicine: July 2019 – Volume 98 – Issue 29 – p e16471 doi: 10.1097/MD.0000000000016471
6. “Toxicological Profile for Thallium.” Agency for Toxic Substances and Disease Registry U.S. Public Health Service, 19992, www.atsdr.cdc.gov/toxprofiles/tp54.pdf.
7. https://www.cdc.gov/niosh/ershdb/emergencyresponsecard_29750026.html