Bismuth: Heavy Metal Toxicity

What is Bismuth and Where is it Found?

Image 1: A bismuth crystal and bismuth’s periodic table information.5

Bismuth (Bi) is a heavy metal with an atomic number of 83 and an atomic mass of 208.9804 atomic mass units (amu).1 Naturally occurring bismuth is very rare, found as bismuthimite and bismite ores.1 Bismuth is commercially produced as a by-product of lead, copper, tin, silver, and gold ore refining. Most bismuth is mined in Peru, Mexico, Bolivia, Japan, and Canada. Elemental bismuth is nontoxic, but bismuth salts can cause toxicity.2

Bismuth salts are relatively insoluble, so environmental and occupational exposure is low. Most toxic exposure to bismuth is from consumption, usually from medicinal use.1

Video 1: How to make bismuth crystals using a bismuth ingot. While not related to bismuth toxicity, this video is an interesting look into some of the properties of bismuth.9

What are the Medicinal Uses of Bismuth?

Bismuth salts are used for a variety of gastrointestinal disorders. Antacids, such as bismuth subnitrate, bismuth subcarbonate, and bismuth subgallate, are used for diarrhea, flatulence, intestinal cramping, constipation, and dyspepsia. Colloidal bismuth subcitrate (CBS), bismuth subsalicylate (Pepto-Bismol®), and bismuth citrate mixed with ranitidine (Tritec®) are used to treat peptic ulcers and gastritis associated with an Helicobacter pylori infection. Bismuth is also used in surgical packing and pastes used for ileostomies and colostomies.3

Table 1: Medicinal products that contain bismuth in the US.6

 

Image 2: Pepto-Bismol is a commonly used and recognized medication made with a bismuth salt.7

What are the Toxicokinetics of Bismuth?

Due to bismuth compounds being relatively insoluble, they are generally poorly absorbed, ~0.2%.1 90% of ingested bismuth is excreted in urine, so the highest concentration of bismuth is found in the kidneys. The elimination half-life is around 21 days.1

What is Bismuth’s Mechanism of Action?

The exact mechanism of action of bismuth is relatively unknown due to lack of data. Large doses of bismuth compounds lead to acute renal injury. The tubular epithelium is the primary site of toxicity, with bismuth leading to the degeneration of renal tubular cells and the production of bismuth-protein nuclear inclusion bodies.1 A large dose of CBS can cause reversible damage to the proximal tubules.1

Chronic bismuth toxicity tends to lead to more neurotoxic and behavioral effects, indicating the accumulation of bismuth in lysosomes and in the reticular, hypothalamic, oculomotor, hypoglossal, and Purkinje cells. Bismuth appears to be distributed by axonal transport.1

Is Bismuth Carcinogenic?

There is no evidence that bismuth is carcinogenic.4

What Organs are Targeted by Bismuth?1

  1. Kidneys
  2. Brain
  3. Liver
  4. Bones

What are the Signs of Bismuth Toxicity?

Bismuth toxicity has acute and chronic clinical features.1

  • Acute toxicity signs include:
    • abdominal pain
    • oliguria
    • acute tubular necrosis
    • renal failure
  • Chronic toxicity signs include:
    • progressive diffuse encephalopathy
    • behavior changes
      • apathy
      • irritability
      • poor concentration
      • poor short-term memory
      • visual hallucinations
    • movement disorders
      • myoclonus
      • ataxia
      • tremors
    • pigmentation of the skin and oral mucosa
    • seizures
    • coma
    • death

Image 3: Encephalopathy with ataxia from chronic bismuth toxicity.8

What Treatment is Available for Bismuth Toxicity?

The main treatment for bismuth toxicity is to discontinue bismuth intake. Chelation therapy can be done using dimercaprol to reduce the concentration of bismuth in the kidneys and liver and increase renal elimination of bismuth. Dimercaprol is the only chelator that can lower the levels of bismuth in brain tissue.1

Is Bismuth an Essential Nutrient? Can Humans be Deficient in Bismuth?

There is no evidence that bismuth is an essential nutrient. Since bismuth is rarely found in the environment, most people that do not take bismuth containing medications are not exposed to bismuth and suffer no negative consequences from their bismuth deficiency.4

References

  1. Tokar EJ, Boyd WA, Freedman JH, Waalkes MP. Toxic Effects of Metals. In: Klaassen CD. eds. Casarett and Doull’s Toxicology: The Basic Science of Poisons, Eighth Edition New York, NY: McGraw-Hill; 2013. http://accesspharmacy.mhmedical.com.proxy.lib.ohio-state.edu/content.aspx?bookid=958&sectionid=53483748. Accessed June 08, 2019.
  2. Bismuth (UK PID). (2019). Retrieved from http://www.inchem.org/documents/ukpids/ukpids/ukpid49.htm
  3. Reynolds, P., Abalos, K., Hopp, J., & Williams, M. (2012). Bismuth Toxicity: A Rare Cause of Neurologic Dysfunction. International Journal Of Clinical Medicine, 03(01), 46-48. doi: 10.4236/ijcm.2012.31010
  4. Gordon, M., Abrams, R., Rubin, D., Barr, W., & Correa, D. (1995). Bismuth subsalicylate toxicity as a cause of prolonged encephalopathy with myoclonus. Movement Disorders, 10(2), 220-222. doi: 10.1002/mds.870100215
  5. Pictures, stories, and facts about the element Bismuth in the Periodic Table. (2019). Retrieved from https://periodictable.com/Elements/083/index.html
  6. Bismuth toxicity. (2019). Retrieved from http://environmentalhealthrisk.blogspot.com/2010/03/bismuth-toxicity.html
  7. Pepto Bismol Chewable Tablets for Nausea, Heartburn, Indigestion, Upset Stomach, and Diarrhea Relief, Original Flavor 12 ct – Walmart.com. (2019). Retrieved from https://www.walmart.com/ip/Pepto-Bismol-Chewable-Tablets-for-Nausea-Heartburn-Indigestion-Upset-Stomach-and-Diarrhea-Relief-Original-Flavor-12-ct/17325219?athcpid=17325219&athpgid=athenaItemPage&athcgid=null&athznid=PWVUB&athieid=v0&athstid=CS020&athguid=7abbc081-359-16b3f310189f30&athena=true
  8. Siram R, Botta R, Kashikunte C, Pal PK, Yadav R. Chronic encephalopathy with ataxia, myoclonus, and auditory neuropathy: A case of bismuth poisoning. Neurol India 2017;65:186-7
  9. How to Make Bismuth Crystals. (2019). Retrieved from https://www.youtube.com/watch?v=v8KYZHMkTHw