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Bismuth Toxicity, Often Mild, Can Result in Severe Poisonings

DiPalma, Joseph R. MD

Laboratory Rounds

Dr. DiPalma is an emeritus professor of pharmacology at MCP/Hahnemann University and a consultant at National Medical Services, Inc., an independent bioanalytical toxicology testing facility in Willow Grove, PA whose medical director is G. John DiGregorio, MD, the editor of Laboratory Rounds. For more information about NMS, contact Dr. DiGregorio at (215)784–9294 or g.j.digregorio@nmslab.com.

Diagnosis of bismuth intoxication is usually made easily from a history of ingestion of a bismuth-containing oral preparation or the use of a cosmetic compound

Of the heavy metals including lead, mercury, arsenic, and bismuth, it is the latter whose salts are relatively the least toxic. This is probably because of the great insolubility of many bismuth salts that prevents their absorption. They also have physical qualities that are demulcent and protective of mucous membranes and skin.

Bismuth salts likewise have modest antibiotic properties, which may be useful in surface inflammation and for deodorizing fecal material. It is no wonder that bismuth salts have been widely used since antiquity, and still hold a secure place in medicinal therapy today.

In industry, bismuth metal is used to manufacture alloys, catalysts, ceramics, cosmetics, magnets, paints, pharmaceuticals, semiconductors, and x-ray contrast media. Poisonings from this source are seldom reported. In contrast, toxicity from the medicinal use is not uncommon, and may even occur in epidemic form. In the U.S., Pepto-Bismol (and many imitators) contains bismuth subsalicylate, 262 or 524 mg/ml, widely used and available without prescription for dyspepsia, nausea, stomach ulcer, and diarrhea.

Bismuth subgallate, Devrom 200 mg tablets, also is available over-the-counter for controlling the fecal odor in colostomy patients. Heliac, a prescription medication composed of bismuth subsalicylate 250 mg, tetracycline 500 mg, and metroniadazole 200 mg is used for Heliobactor pylori infections. These are the only bismuth-containing preparations in the U.S. that are FDA approved. The many other products containing bismuth as an active ingredient are now available from other countries or underground sources (Federal Register 1992;57:165). A classical example is Balmex ointment, widely sold for more than 30 years for diaper rash. A zinc oxide ointment, it also contained bismuth subnitrate as an active ingredient. The FDA forced the manufacturer to remove the bismuth salt from the preparation because it could not be proven safe and effective.

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Cosmetic Preparations

In the 1970s and 1980s there was an epidemic of bismuth poisoning mostly confined to France and Australia. This was generally attributed to sales promotion of cosmetic preparations containing bismuth salts. Another factor was the increased use of bismuth to treat the increasing number of colostomy patients. Naturally such therapy is long-term, and this greatly increases the chance of bismuth intoxication.

Table

Table

Before 1950, syphilis and other parasitic diseases were treated with soluble salts of bismuth by a parenteral route. Naturally this led to severe toxicity, and the therapy could be given only by using rest periods between courses. This experience emphasizes the importance of solubility of the bismuth salts in relation to toxicity. The table has a useful classification of commonly used salts of bismuth and their toxicity potential. An important additional factor is that some salts of bismuth have the additional toxicity potential of the anion apart from the metal component. The average dose of bismuth subsalicylate contained in Pepto-Bismol has a dose of salicylate almost equal to that of an aspirin once the compound dissociates in the stomach. Those allergic to aspirin may suffer as will children susceptible to Reye's syndrome. With prolonged dosage, actual salicylism has occurred. Likewise, preparations containing bismuth subnitrate taken orally may cause nitrite poisoning.

Bismuth toxicity like that of other heavy metals is attributable to its predilection to combine with sulhydril groups. Because sulhydril groups are components of many vital enzymes, the effect of bismuth is to denature and destroy the function of these enzymes. Bismuth is toxic to all living organisms who depend on these enzymes. There is little selective toxicity for a particular cell type and the degree of injury depends upon the concentration that develops in a particular organ. Renal toxicity in acute poisoning is evident early because bismuth is excreted mainly by this route, only 10 percent appearing in the feces after an oral dose. In chronic poisoning, all organs are affected. In the skin a lichen planus-like rash, in the mouth stomatitis with a blue black gum line. Inflammation and inclusion bodies in the liver, kidney, and bone are characteristic. In the brain, the lesions will cause encephalitis.

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Diagnosing Bismuth

Diagnosis of bismuth intoxification is usually made easily from a history of ingestion of a bismuth-containing oral preparation or the use of a cosmetic compound. Colostomy patients are obviously suspect. Physical signs in chronic poisoning include poor oral hygiene with a blue-black gum line, lichen planus-like skin rashes, weight loss, gastrointestinal symptoms, signs of encephalopathy including confusion, disorientation and rarely seizures, and black stools. Specific diagnosis by blood levels is difficult because of the extremely low blood levels found in normal patients as well as those who have been poisoned. The normal blood level is on average less than 1 ug/dl while poisoned subjects average 3 ug/dl. Much more reliable is the urine level which averages 0–20 mmol/L in normal patients and as high as 400mmol/L or more in poisonings. In appropriate cases, a simple flat plate of the abdomen will reveal the bismuth in the intestine because it is almost as dense as lead.

A simple, reliable, and fast bedside test is the modified Reinsch's test. It can identify mercury, arsenic, antimony, and bismuth. Use 10 to 15 g of gastric contents or tissue homogenate. Add 3 ml of concentrated hydrochloric and insert a copper wire spiral. Heat gently for two hours. A silvery deposit is mercury; shiny black is bismuth; dull black is arsenic; and purple is antimony. Confirmatory tests such as the Gutzeit test can confirm each deposit, and they can even be quantified. (For details, see Kaye S. Handbook of Emergency Toxicology, Charles C. Thomas, Springfield, IL. 1980, pp. 55, 84.)

Prevention of bismuth toxicity can be achieved easily by avoiding bismuth medications and cosmetics. Pepto-Bismol and preparations of those types have been popularized for use in traveler's diarrhea, where they enjoy a good reputation. As long as therapy is not continued beyond three or four days, there is little danger of poisoning. Therapy of colostomy patients with bismuth preparations is more apt to lead to poisoning because treatment is often prolonged for months or years.

For severe acute and chronic poisoning, chelation therapy with BAL is often recommended. Many experts prefer to treat conservatively and expectantly, allowing the bismuth to be excreted gradually. In support of this view, there is evidence that chelation therapy that solubilizes the bismuth leads to an increased concentration in the brain so some harm can be done by attempting to rapidly excrete bismuth. Other authorities feel that penicillamine is a safer chelator for bismuth. It is practical to conclude that only life-threatening cases of bismuth poisoning should receive chelation therapy.

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Suggested Readings

1. DiPalma JR. Bismuth toxicity. Am Fam Phys 1988;36:244.
2. Haddad LM, Shannon MW, Winchester JF. Clinical Managing of Poisoning and Drug Overdose. 3rd Edition, W.B. Saunders Company, Philadephia,1998.
    Bradley B, Singleton M, Li Wan Po A. Bismuth toxicity: A reassesment. J Clin Pharm 1989;14:424.
      © 2001 Lippincott Williams & Wilkins, Inc.