Biological toxins are defined as any toxic substances occurring in nature produced by animals, plants or microbes (pathogenic bacteria), such as bacteria, fungi, flowering plants, insects, fish, reptiles or mammals. Under the U.S. Department of Transportation/United Nations (DOT/UN) Classification system, these materials are classified as Class 6.1 Poisons.
Unlike chemical agents such as sarin, cyanide or mustard, toxins are not man made. They occur naturally, which makes them readily available for potential terrorist activities. Toxins can be produced easily and cheaply without sophisticated laboratory equipment or training. Materials used to produce toxins are so common that their purchase would likely go unnoticed.
Generally, toxins are not volatile and not considered a dermal exposure hazard (except for mycotoxins). Toxins as a family are much more toxic than any of the chemical agents, including VX and sarin. Ricin, a biological toxin produced from the castor bean plant, is 10,000 times more toxic than sarin; as little as a milligram (1/1,000th of a gram) can kill an individual. Botulinum toxin is the most toxic material known to man. One ounce of botulinum toxin (0.12 micrograms or 1,200 millionths of a gram) is enough to kill 60 million people. Mycotoxins are the least toxic of the toxins, (thousands of times less than botulism).
Exposure Routes
Routes of exposure also have a bearing on the level of toxicity. Some toxins are much more lethal when aerosolized and inhaled than when taken orally. Ricin, saxitoxin and T2 mycotoxins are examples of these types of materials. Botulism, for example, has a lower toxicity through aerosolization and inhalation than through ingestion. When ingested, however, it is so toxic overall that it is a dangerous biological warfare and terrorist agent.
Photo by Robert Burke Biological toxins are chemical poisons, much like nerve and other chemical agents, which are produced naturally, but are much more potent. Emergency responders must take precautions when responding to suspected releases of biological toxins.
Some toxins are limited in their usefulness as biological agents on a large scale because it just takes too much of the material to produce a toxic reaction. When looking at the potential toxicity of biological toxins, the lower the LD50, in micrograms per kilogram of body weight, the less agent that would be required to cover a large area. Conversely, some agents, such as ricin, would require great quantities (tons) for an aerosol attack out in the open.
Toxins can be used for their lethality or as incapacitating agents. Some toxins are incapacitating at lower doses and would cause serious illness. Because of their lack of volatility, toxins would neither be a persistent threat nor likely produce secondary or person-to-person exposures.
Bacterial toxins can be classified as membrane damaging. This group includes escherichia coli (hemolysins), aeromonas, pseudomonas and staphylococcus alpha (cytolysins and phospholipases). Toxins from this bacterium are reasonably easy to produce, but possess a varying degree of stability. Many of these toxins function by interfering with bodily functions and kill by creating pores in cell membranes. Their toxicity level is much lower than the protein toxins and are less likely as terrorist threats.
Trichothecene mycotoxins are created by numerous species of fungi. Over 40 toxins are known to be produced by fungi. T2 is a stable toxin even when heated to high temperatures. Decontamination or disinfection requires very high concentrations of sodium hydroxide and sodium hypochlorite to detoxify the material. Aerosolization would not be a likely method of dissemination because of the potential low toxicity. However, unlike other toxins, the mycotoxins are dermal active. Aerosol dissemination can cause damage by contacting skin and mucous membranes. Once absorbed into the body, the would become systemic toxins.
Plant Toxins
Plant toxins are derived from plants or plant seeds. Toxins developed from plants are easy to produce cheaply in large quantities without requiring a high level of technology.
One of the premier plant toxins is ricin, a protein taken from the castor bean. Approximately 1 million tons of castor beans are grown annually worldwide for the production of castor oil. Castor beans to grow the plants can be purchased through seed catalogs, from lawn and garden centers, and from agricultural co-ops. Waste mash resulting from the production of castor oil contains 3-5% ricin by weight.
Botulinum toxin needs to invade nerve terminals in order to block the release of neurotransmitters, which under normal conditions control muscle contraction. The symptoms from botulinum toxin develop slowly (from hours to days), but are just as lethal, causing respiratory failure. This toxin blocks biochemical action in the nerves, which activate the muscles necessary for respiration, leading to suffocation. Unlike saxitoxin, toxicity for botulinum is greater through ingestion than inhalation. Neurotoxins are effective in stopping nerve and muscle function without producing microscopic injury to the tissues, where other toxins destroy or damage tissue directly.
Microcystin is a toxin produced by blue-green algae. When it enters the body, it binds to an important enzyme inside the liver cells. No other cells in the body are affected by this toxin. If microcystin is not blocked from reaching the liver within 15 to 60 minutes of receiving a lethal dose, irreversible damage to the liver will occur.
Damage to the liver from microcystin is the same regardless of the route of exposure, but with other toxins, the damage that occurs after contact may vary greatly depending on the route of exposure, even with the same toxin family. Death occurs from ricin because it blocks protein synthesis in many different cells within the body. However, no damage occurs to the lungs unless the route of exposure is inhalation.
Lethality is not the only threat to be considered when evaluating a toxin for potential terrorist use. Terrorists may just want to put a scare into a group of people or incapacitate them for a time just to show their vulnerability. For example, the staphylococcal enterotoxins can cause illness at very low concentrations, but require very large doses to be lethal.
Trichothecene mycotoxins are the only biological toxins that are dermally active. Exposure results in skin lesions and systemic illness without the toxin being inhaled and absorbed through the respiratory system. Primary routes of exposure are through skin contact and ingestion. Because of the very low aerosol toxicity, large quantity production and aerosolization for inhalation, exposure is very unlikely.
Nanogram (one billionth of a gram) quantities per square centimeter of skin can cause irritation. One millionth of a gram quantities per square centimeter of skin can cause destruction of cells. Microgram doses to the eyes can cause irreversible damage to the cornea. Because most biological agents are not skin absorbent hazards, simple washing of contaminated skin surfaces with soap and water within one to three hours of an exposure can greatly reduce the risk of illness or injury.
Botulinum clostridium (botulism) is a deadly illness caused by any one of seven different, but related neurotoxins (A through G). All seven types have similar mechanisms of action. They all produce similar symptoms and effects when inhaled or ingested, but the length of time to development of symptoms may vary depending on the route of exposure and dose received. Botulism is not spread from person to person. Botulinum toxins as a group are among the most toxic compounds known to man. Lethal doses in research animals are 0.001 micrograms per kilogram of body weight. Botulinum toxins are 15,000 times more toxic than lethal nerve agent VX and 100,000 times more toxic than sarin. Botulism occurs naturally in improperly canned foods and infrequently in contaminated fish. Ingestion of the canned food or fish causes the illness.
Although ingestion is the primary natural route of exposure, terrorists would likely aerosolize the manufactured toxin to produce the disease through inhalation. Low-dose inhalation may not produce symptoms for several days. Inhalation or ingestion of high doses would produce symptoms much quicker. Contamination of food supplies is also a real possibility, because ingestion is a significant route of exposure. Botulism bacterium is commonly found in the soil. Two types of illness are associated with the botulinum toxin, infant and adult botulism. An adult becomes ill by eating spoiled food that contains the toxin. Infants become ill from eating the spores of the botulinum bacterium. One source of these spores comes from the ingestion of honey. Spores are not normally toxic to adults.
Botulinum toxins work by binding to the presnaptic nerve terminal at the neuromuscular junction and at cholinergic autonomic sites. They then act to stop the release of acetylchloline presynapically, thus blocking neurotransmission. This function is quite unlike the action of the nerve agents, where there is too much acetylcholine due to the inhibition of acetylcholinesterase.
What occurs with botulism is a lack of the neurotransmitter in the synapse. Therefore, using atropine as an antidote would not be helpful and could even provoke symptoms. When adults ingest contaminated food, the toxin is absorbed from the intestines and attaches to the nerves causing the signs and symptoms of botulism poisoning. Symptoms include blurred vision, dry mouth and/or sore throat, difficulty in swallowing or speaking, impairment of the gag reflex, general muscular weakness, pupils may be dilated and the victim may experience shortness of breath. Paralysis of the skeletal muscles follows with a proportional, downward and growing weakness that may result in sudden respiratory failure.
The time from the beginning of symptoms to respiratory failure can occur is as little as 24 hours when the toxin is ingested. One third of patients die within three to five days. Treatment for adults means hospitalization, usually in an intensive care unit. Individual cases could be mistaken for other neuromuscular diseases such as Guillain-Barre syndrome (muscle weakness and paralysis), myasthenia gravis or tick paralysis. Mental status changes that occur with viral encephalitis should not be present with botulinum poisoning.
Photo by Robert Burke Emergency medical personnel may be the first to respond to cases of toxin poisoning as a result of a terrorist release. Are your crews properly trained? Are your emergency vehicles adequately equipped?
Botilinum intoxication could also be confused with nerve agent or atropine poisoning. Nerve agent exposures produce copious amounts of respiratory secretions and miotic pupils, where there is a marked decrease in these fluids with exposure to botulinum. Atropine overdose produces hallucinations and delirium, which are absent from botulinum intoxication, even though the mucous membranes are dry in both cases. An antitoxin for botulism can be effective if administered quickly after the onset of symptoms. Experimental vaccines are also under development for prevention of botulinum intoxication.
Staphylococcal enterotoxin B (SEB) is a common cause of food poisoning. Cases have usually been isolated to a group of people exposed to contaminated food at some public event or through airline travel. While it can cause death, it is thought of as an incapacitating agent rather than a lethal agent. It could, however, make a large number of people ill for an extended period. The primary route of exposure is ingestion, although it can be aerosolized for inhalation exposure.
Symptoms from inhalation exposure and ingestion are completely different. Either route of exposure may produce fatalities. Symptoms appear within three to 12 hours after aerosol exposure. They include sudden onset of fever, chills, headache, myalgia and cough. Some patients may also exhibit shortness of breath and retrosternal (behind the breast bone) type of chest pain. Fevers of between 103 and 106 degrees Fahrenheit generally last for two to five days and a cough may persist for several weeks.
Ingestion produces nausea, vomiting and diarrhea. Very large doses may result in pulmonary edema, septic shock, and possibly death. No antitoxin has been developed for this illness so treatment remains supportive. No preventative vaccines are available. Diagnosis may be difficult because the symptoms are similar to a number of respiratory pathogens such as influenza, adenovirus (a group of DNA-containing viruses, 47 distinct types) and mycoplasma.
Generally, other respiratory illnesses occur over a longer period and a small number of people are involved. When illness occurs from SEB exposure, there could be a large number of victims over a 24-hour period. Naturally occurring food poisoning cases would not present with respiratory symptoms. SEB infection would have a tendency to develop quickly to a somewhat unchanging clinical condition, whereas pulmonary anthrax, tularemia pneumonia or pneumonic plague would all advance if left untreated. Tularemia, plague and Q-Fever would present with infiltrates on chest x-rays. Nerve agent exposure would bring about fasciculations (small bundle of nerves) and extensive secretions of mucus from the nose and mouth. Mustard would cause skin lesions in addition to pulmonary findings.
SEB intoxication would not present any of these symptoms. Clear signs of muscular paralysis, bulbar palsies, absence of fever and dry pulmonary tree due to cholinergic blockade would result from botulinum infection. Respiratory difficulties occur much later with SEB inhalation. Laboratory testing will provide limited data for diagnosing the disease. SEB toxin is very difficult to detect in serum when symptoms develop; however, a baseline specimen for antibody detection should be drawn anyway as early as possible after exposure. Additional specimens should be drawn during recovery. SEB can be detected in the urine and a sample should be taken and tested. High concentrations inhibit kidney function.
Ricin (ricinus communis) is a protein toxin that is produced from the castor bean and functions as a cellular poison. It is very toxic and can enter the body by ingestion, inhalation and injection. Inhalation from aerosol dispersion would produce symptoms based upon the dose that was inhaled. During the 1940s, humans were accidentally exposed to sub-lethal doses that produced fever, chest tightness, cough, dyspnea, nausea and arthralgias within four to eight hours. After several hours, profuse sweating occurred, which signaled the end of the symptomatic phase. Little data is available on human inhalation exposure, but victims would be expected to develop severe lung inflammation with a progressive cough, dyspnea, cyanosis and pulmonary edema.
When ricin enters the body through routes other than inhalation, it is not a direct lung irritant. Ingestion causes gastrointestinal hemorrhage with hepatic, splenic and renal necrosis. Intramuscular injection would cause severe localized necrosis of muscle and regional lymph nodes with moderate visceral organ involvement.
The toxicity of ricin compared to botulinum and SEB, based upon LD50 values, is much less. Natural intoxication from ricin can occur by the ingestion of the castor bean. This produces severe gastrointestinal symptoms, vascular collapse and death. When exposure to ricin occurs through inhalation of small particles, pathogenic changes can occur in as little as eight hours. This is followed by severe respiratory symptoms and acute hypoxic respiratory failure in 36 to 72 hours. Intravenous injection may result in disseminated intravascular coagulation, microcirculatory failure and multiple organ failure. Ricin is toxic to the cells in the body and acts by inhibiting protein synthesis. During tests conducted on rodents, ricin was more toxic through inhalation than ingestion. Little data is available to indicate the effects on humans.
Large numbers of victims seeking medical attention for lung injury should be an indication to medical personnel that a pulmonary irritant such as ricin may have been used as a terrorist agent. Keep in mind that other chemical and biological agents can also cause similar symptoms. These include SEB, Q-Fever, tularemia, plague and some of the chemical agents. Treatment for victims of ricin poisoning remains supportive. For gastrointestinal exposure, the stomach should be irrigated along with oral administration of superactivated charcoal, followed by use of cathartics (purging or evacuation of the bowels), such as magnesium citrate. Fluids should be administered to replace GI fluids lost. A vaccine for ricin is under development, but not currently available. A vaccine would provide the best protection against ricin poisoning.
Trichothecene mycotoxins, are toxins produced by several types of fungi (mold). They are the only group of biological agents that enter the body through skin absorption. Other routes of exposure include inhalation and ingestion. Most mycotoxins act by inhibiting protein synthesis and respiration.
Fungi toxins most likely to be used by terrorists include, diacetoxyscirpenol (DAS), Nivalenol, 4-Deoxynivalenol (DON) and T2. Of those, T2 is the most likely candidate for terrorist use because of its stability. T2 could be aerosolized or used to contaminate food supplies. It is thought that mycotoxins were aerosolized forming ("yellow rain"), producing casualties in Laos (1975-1981), Kampuchea (1979 to 1981) and Afghanistan (1979 to 1981).
Mycotoxins are fast acting and may produce symptoms within minutes of exposure. Initial symptoms include burning skin pain, redness, tenderness, blistering, and progression to skin necrosis (tissue death) with leathery blackening and sloughing of large areas of skin in lethal cases. When inhaled, the symptoms include itching and pain, sneezing, epistaxis (bleeding from the nose) and rhinorrhea. Other symptoms include pulmonary/tracheobronchial toxicity by dyspnea, wheezing, and cough. Mouth and throat exposures are characterized by pain and blood-tinged saliva and sputum. When the toxin reaches the gastrointestinal tract, anorexia, nausea, vomiting, watery or bloody diarrhea, and abdominal cramps may occur.
SEB and ricin can cause similar systemic symptoms, however, neither of them produce eye or skin symptoms. If the eyes are exposed, eye pain, tearing redness, foreign-body sensation and blurred vision may result. Irrespective of the route of exposure, when the toxin reaches the rest of the body's systems, it may cause weakness, prostration, dizziness, ataxia and loss of coordination. When victims have been exposed to lethal doses, tachycardia, hypothermia and hypotension follow. Death may occur in minutes, hours or days.
Decontamination of victims is very important to remove the mycotoxins from the skin and eyes. Clothing should be removed and disposed of prior to decontamination. Skin should be completely washed with soap and uncontaminated water. Superactive charcoal can be administered orally to absorb ingested T2, and should be administered to victims of an aerosol attack as well. Eyes should be irrigated with normal saline for at least 15 minutes. No antidotes are known for mycotoxins. Treatment is supportive and symptomatic.
Biological agents and toxins are the most likely terrorist weapons for the future. They are inexpensive, don't require a great deal of technical expertise or equipment to manufacture, and can be produced without creating a lot of attention. Biological agents have the best potential as a weapon of mass destruction.
Robert Burke, a Firehouse® contributing editor, is the fire marshal for the University of Maryland. He is a Certified Fire Protection Specialist (CFSP), Fire Inspector II, Fire Inspector III, Fire Investigator and Hazardous Materials Specialist, and has served on state and county hazardous materials response teams. Burke is a veteran of 24 years in fire and emergency services, with experience in career and volunteer departments. He has attained the rank of lieutenant, assistant chief and deputy state fire marshal. Burke is an adjunct instructor at the National Fire Academy and the Community College of Baltimore, Catonsville Campus, and the author of the textbooks Hazardous Materials Chemistry for Emergency Responders and Counter-Terrorism for Emergency Responders. He can be reached in the Internet at [email protected].