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Toxins as Mass-Casualty Weapons

By James Madsen, MD, MPH, Adjunct Associate Professor of Preventive Medicine and Biometrics; Chief, Consultant Branch, Chemical Casualty Care Division, Uniformed Services University of the Health Sciences; US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground South, MD

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"Toxin" is often loosely used to refer to any poison, but technically refers only to a poisonous chemical produced by an organism (although some toxins can now also be produced synthetically). Because toxins used as mass casualty weapons do not include the infectious agents from which they are derived, they do not replicate in the body and are not transmissible from person to person (see Table: CDC High-Priority Biological Agents and Toxins). Thus, toxins are more like chemical agents than biological agents; they cause poisoning rather than infection.

Hundreds of toxins are known. However, because of difficulties in isolating sufficient quantities, and problems with dissemination or environmental fragility, most toxins are more suited to assassination than to production of mass casualties. Only 4 toxins are considered high-threat agents by the US Centers for Disease Control and Prevention (CDC):

  • Botulinum toxin

  • Epsilon toxin from Clostridium perfringens

  • Ricin toxin

  • Staphylococcal enterotoxin B

Of these, only botulinum toxin is classified among the highest priority agents. Epsilon toxin from C. perfringens is mainly of historical interest as an agent reportedly developed by Iraq in the 1980s; its main action is to increase capillary permeability, especially in the intestine.

Botulinum Toxin

Botulinum toxin, or botulinum neurotoxin (BoNT), refers to any of 7 known types of neurotoxins produced by Clostridium botulinum. Botulism is the poisoning produced by exposure to botulinum toxin; infection with C. botulinum is not required. Food-borne, wound, and infant botulism are described elsewhere (see Botulism). Mass casualties from BoNT could occur from widespread contamination of food or water or from inhalation of aerosolized BoNT.

BoNT blocks the action of acetylcholine (ACh) at muscarinic receptors in smooth muscle and exocrine glands but does not penetrate the blood-brain barrier to gain entry to the CNS. As with wound botulism, neurologic symptoms (typically bilaterally symmetrical descending paralysis with mydriasis) without nausea, vomiting, cramping, or diarrhea would be expected 12 to 36 h (range 2 h to 8 days) after exposure. Sensation and mentation are intact.

Clinical diagnosis is sufficient to make the decision to administer antitoxin, which becomes progressively less effective as symptoms and signs develop. One vial of equine heptavalent botulism immune globulin diluted 1:10 in 0.9% saline solution is given slowly IV.

Ricin and Abrin

Ricin (from beans of the castor plant) and abrin (from jequirity, or rosary pea) both inactivate ribosomes catalytically; one molecule of either toxin is capable of poisoning all of the ribosomes in a cell. Although ricin has been injected in assassination attempts, mass casualties would probably involve inhalation of aerosolized toxin.

The clinical manifestations of ricin intoxication vary by route of exposure. Following inhalation, there is a latent period of 4 to 8 h followed by cough, respiratory distress, and fever. Multiple organ systems are progressively affected over the next 12 to 24 h, culminating in respiratory failure. Diagnosis is by clinical suspicion, no specific antidote or antitoxin is available, and treatment is supportive.

Staphylococcal Enterotoxin B (SEB)

Staphylococcal enterotoxin B (SEB) is one of 7 enterotoxins (toxins acting in the intestine) produced by Staphylococcus aureus. SEB is responsible for staphylococcal food poisoning when ingested. Mass casualties could result from food adulteration but also from inhalation of aerosolized toxin; SEB was developed for use as an aerosol to cause incapacitation in military personnel.

The latent period is typically 1 to 12 h after ingestion and 2 to 12 h (with a range of 1.5 to 24 h) after inhalation. After initial influenza-like symptoms of fever, chills, headache, and myalgias, subsequent symptoms and signs depend on the route of exposure. Ingestion causes nausea, vomiting, and diarrhea for 1 to 2 days. Inhalation causes nonproductive cough, retrosternal chest pain, and often nasal irritation and congestion. Conjunctivitis can result from contact of aerosol with the eyes. Although SEB was intended to be an incapacitating agent, inhalation can cause death due to pulmonary edema and circulatory collapse. In survivors, fever may persist up to 5 days and cough for 4 wk. Specialized toxin assays may help confirm the diagnosis. Treatment is supportive.

The views expressed in this article are those of the author and do not reflect the official policy of the Department of Army, Department of Defense, or the US Government.