"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 (1).
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 U.S. 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.
(See also Overview of Incidents Involving Mass-Casualty Weapons.)
General reference
1. Madsen JM. Toxins as weapons of mass destruction. A comparison and contrast with biological-warfare and chemical-warfare agents. Clin Lab Med. 2001;21(3):593-605.
Botulinum Toxin as Mass-Casualty Weapon
Botulinum toxin, or botulinum neurotoxin, refers to any of 8 known types of neurotoxins produced by Clostridium botulinum, of which 5 affect humans. It is one of the most concentrated poisons, with an LD50 (the dose that would cause death in half of an exposed group) of from 1000 ng/kg orally to as little as 10 ng/kg via inhalation and 1 ng/kg IM or IV. Even the oral toxicity is far greater than that of most poisons commonly encountered.
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 botulinum toxin could occur from widespread contamination of food or water or from inhalation of aerosolized botulinum toxin (1).
Botulinum toxin blocks the action of acetylcholine at muscarinic receptors in smooth muscle and exocrine glands but does not penetrate the blood-brain barrier to gain entry to the central nervous system. 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 hours (range 2 hours to 8 days) after exposure. Sensation and mentation are not affected.
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 antitoxin diluted 1:10 in 0.9% saline solution is given slowly IV. The antitoxin binds only to circulating toxin and thus does not alleviate existing manifestations caused by toxin already attached to receptors.
Botulinum toxin reference
1. Arnon SS, Schechter R, Inglesby TV, et al. Botulinum toxin as a biological weapon: medical and public health management [published correction appears in JAMA 2001 Apr 25;285(16):2081]. JAMA. 2001;285(8):1059-1070. doi:10.1001/jama.285.8.1059
Ricin and Abrin as Mass-Casualty Weapons
Ricin (from beans of the castor plant) and abrin (from jequirity, or rosary pea) both inactivate ribosomes catalytically; 1 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 (1).
The clinical manifestations of ricin intoxication vary by route of exposure. Following inhalation, there is a latent period of 4 to 8 hours followed by cough, respiratory distress, and fever. Multiple organ systems are progressively affected over the next 12 to 24 hours, culminating in respiratory failure. Diagnosis is by clinical suspicion, no specific antidote or antitoxin is available, and treatment is supportive.
Ricin and abrin reference
1. Chen HY, Foo LY, Loke WK. Ricin and abrin: A comprehensive review of their toxicity, diagnosis, and treatment. Toxinology. 2014:1-20. doi: 10.1007/978-94-007-6645-7_1-1
Staphylococcal Enterotoxin B (SEB) as Mass-Casualty Weapon
Staphylococcal enterotoxin B (SEB) is 1 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 (1).
The latent period is typically 1 to 12 hours after ingestion and 2 to 12 hours (with a range of 1.5 to 24 hours) 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 weeks. Specialized toxin assays may help confirm the diagnosis. Treatment is supportive.
Staphylococcal enterotoxin B reference
1. Ahanotu EN, Alvelo-Ceron D, Ravita TD, Gaunt EE. Staphylococcal Enterotoxin B as a Biological Weapon: Recognition, Management, and Surveillance of Staphylococcal Enterotoxin. Applied Biosafety, 11, 120 - 126, 2006.
