Toxins are poisons produced by living organisms. In general, toxins are extremely poisonous; they have a toxicity several orders of magnitude greater than the nerve agents.

Toxins can be classified by the mechanism of toxicity:

• Cytotoxins cause cellular destruction; ricin is an example.
  • Enterotoxins affect the digestive tract; Staphylococcal enterotoxin B is an example.
  • Hemorrhagic toxins cause bleeding; mycotoxin T-2 is an example.
  • Hepatotoxins cause liver damage.
  • Nephrotoxins cause kidney damage.
  • Others that inflame skin and mucous membranes
• Neurotoxins affect the central nervous system.
  • Presynaptic and postsynaptic neurotoxins; Botulinum toxin and saxitoxin are examples.
  • Ion-channel and sodium-ion binding toxins; tetrodotoxin is an example of an ion-channel neurotoxin.
  • Ionophores

Mixed toxins are toxins showing multiple mechanisms from different categories above.

Ricin

Chemical Abstracts Service registry no.	9009-86-3
Source	Produced by the castor bean plant, ricinus communis, of the family Euphorbiaceae
Structure	Ricin has a molecular weight of 64,000. It consists of two peptide chains linked by a disulfide bond; each chain has a molecular weight of approximately 32 kD. The three-dimensional x-ray crystallographic structure of ricin has been published by the Robertus group at the University of Texas.
LD 50	Estimated on the order of 3 mg/kg; ingestion of two castor beans has been fatal for humans
Symptoms	The onset of symptoms after inhaling ricin may vary from minutes up to 6 hour, depending on the dose. Symptoms include a drop in body temperature, drop in blood pressure, edema of the lungs (also stomach and intestines if ingested), mild degeneration of the intestinal epithelium, necrosis of the liver, hemorrhage
Mechanism	The toxin B chain binds to cell surface receptors. The toxin-receptor complex enters the cell where the A chain has endonuclease activity. Extremely low concentrations will inhibit protein synthesis.
Properties	Water-soluble, heat coagulable globulin protein from the castor bean, remains in castor bean press cake after oil has been pressed from the bean.
Routes	Inhalation, ingestion, injection

Ricin was once referred to as Agent W. The most notorious uses of ricin have been as assassination weapons:

• On 7 September 1978, Georgi Markov, a Bulgarian exile journalist and writer, was jabbed in the thigh with an umbrella as he mounted the steps at the BBC in London. That evening, he developed a fever, and his blood pressure began to drop; two days later he succumbed to cardiac arrest. His wife had the police conduct an autopsy, during which a small platinum-iridium ball with four holes drilled into it was removed.
• A friend of Markov's read about his death and recalled that he too had been jabbed with an umbrella on the Paris Metro. He had also developed a fever, but had recovered after four days. The second man went to the French police, who has a platinum-iridium pellet removed from his back. The pellet had lodged in fatty tissue and the wax sealing the holes in the pellet had failed to melt, leaving some of the agent in the ball; analysis showed it to be ricin.

Crude castor bean extracts also contain ricinine (1,2-dihydro-4-methoxy-1-methyl-2-oxo-3-pyridinenitrile), CAS reg. no. [524-40-3], mp 201.5ƒ C. Ricinine is sparingly soluble in water, and is also toxic. However, it has somewhat different symptoms from ricin poisoning and is less toxic than the ricin protein. Some sources incorrectly attribute the toxicity of ricin to ricinine.

References

• Compton, J. A. F., Military Chemical and Biological Agents, Telford Press: Caldwell, NJ, 1988, pp. 345-347.
• Lin, T. T.; Li, S. S., Eur. J. Biochem., 1980, 105, 453.
• The Merck Index, 11 ed., Budavari, S.; O'Niel, M. J.; Smith, A.; Heckelmanm, P. E., Eds., Merck & Co.: Rahway, 1989, compound no. 8211, p. 1307.
• Montfort, W.; Villafranca, J. E.; Monzingo, A. F.; Ernst, S. R.; Katzin, B.; Rutenber, E.; Xuong, N. H.; Hamlin, R.; Robertus, J. D., J. Biol. Chem., 1987, 262, 5398-5403
• Rutenber, E.; Katzin, B. J.; Ernst, S.; Collins, E. J.; Mlsna, D.; Ready, M. P.; Robertus, J. D., Proteins, 1991, 10, 240-250.

Botulinum Toxin

Chemical Abstracts Service registry no.	—
Source	from anaerobic bacillus Clostridium botulinum
Structure	Seven related protein toxins, known as A through G with approximately 150 kD molecular weight are produced by different strains of the bacillus. Botulinum toxin type A is the most toxic for humans, and has a 97 kD chain and a 53 kD chain linked by at least one disulfide bond.
LD 50	0.001 mg/kg for type A
Symptoms	The onset of symptoms after inhaling botulinum toxin may vary from 24 to 36 hours. Initial symptoms include headache, queasiness, increased flow of saliva, vomiting, dizziness, acute pain in the limbs, involuntary defecation. Effects on the central nervous system result in blurred vision, mouth dryness, paralysis, respiratory paralysis and death.
Mechanism	Neurotropic poison, inhibits formation of acetylcholine and thus blocks neurotransmission, paralyzing the voluntary musculature.
Properties	—
Routes	Ingestion, inhalation

Botulinum toxin is the cause of botulism , which results from C. botulinum growth in spoiled canned food or poorly smoked, insufficiently salted meats. Crystalline botulinum toxin type A was licensed in December 1989 by the Food and Drug Administration for treatment of certain spasmodic muscle disorders.

The use of botulinum toxin as a military weapon was studied by the Imperial Japanese Army in the 1930s. It is thought by some to have been the weapon provided by MI6 to the Czech partisans who assassinated Reinhard Heyrich in 1942. The toxin was part of the US stockpile prior to its destruction in 1972. More recently, Iraq admitted to a United Nations inspection team in August of 1991 that it had done research on the offensive use of botulinum toxin prior to the Gulf War. Further information given to the UN in 1995 after the defection of a leading Iraqi official revealed that Iraq had filled and deployed over 100 munitions with botulinum toxin.

Botulinum toxin poisoning has the opposite mechanism from nerve agent poisoning. Nerve agents inhibit acetylcholinesterase, leading to a buildup of too much acetylcholine, whereas the mechanism in botulism is lack of the neurotransmitter in the synapse. Thus, antidotes such as atropine are not helpful in botulism and could make the symptoms worse.

References

• Compton, J. A. F., Military Chemical and Biological Agents, Telford Press: Caldwell, NJ, 1988, pp. 345-347.
• Antharavally, B. S.; DasGupta, B. R., Covalent structure of botulinum neurotoxin type B; location of sulfhydryl groups and disulfide bridge and identification of C-termini of light and heavy chains, J. Protein Chem., 1998, 17, 417-428.
• Antharavally, B. S.; DasGupta, B. R., Covalent structure of botulinum neurotoxin type E: location of sulfhydryl groups, and disulfide bridges and identification of C-termini of light and heavy chains, J. Protein Chem., 1997, 16, 787-799.
• Sathyamoorthy, V.; DasGupta, B. R.; Foley, J.; Niece, R. L., Botulinum neurotoxin type A: cleavage of the heavy chain into two halves and their partial sequences, Arch. Biochem. Biophys., 1988, 266, 142-151.

Staphylococcal Enterotoxin B

Chemical Abstracts Service registry no.	—
Source	Produced by certain Staphylococcus aureus strains
Structure	Staphylococcal enterotoxin B (SEB) has a molecular weight of 28 kD. SEB is one of at least five antigenically distinct enterotoxin proteins which have been identified (SEA, SEB, SEC, SEE, TSS T-1).
LD 50	1.7 mg/person by inhalation (27 ng/kg)
Symptoms	The onset of symptoms after inhaling SEB may vary from 1 to 6 hours. Symptoms of ingested SEB include vomiting and diarrhea. Initial symptoms of inhaled SEB are headache, fever, and chills. Inhalation of SEB can induce extensive pathophysiological changes including shock.
Mechanism	Many of the effects of staphylococcal enterotoxins are mediated by stimulation of T lymphocytes of the host's own immune system.
Properties	These toxins are heat stable. The incapacitating dose is 30 ng/person by inhalation.
Routes	Ingestion, inhalation

SEB has caused many cases of food poisoning in humans after the toxin is produced in improperly handled foodstuffs that are subsequently ingested. Typically, these cases form clusters due to a common source in a setting such as a church picnic or passengers on an airliner eating the same contaminated food.

The toxin was part of the  US stockpile prior to its destruction in 1972.

References

• Papageorgiou, A. C.; Tranter, H. S.; Acharya, K. R., Crystal structure of microbial superantigen staphylococcal enterotoxin B at 1.5 A resolution: implications for superantigen recognition by MHC class II molecules and T-cell receptors, J. Mol. Biol., 1998, 277, 61-79.
• Swaminathan, S.; Furey, W.; Pletcher, J.; Sax, M., Crystal structure of staphylococcal enterotoxin B, a superantigen, Nature, 1992, 359, 801-806.

Mycotoxin T-2

Chemical Abstracts Service registry no.	21259-20-1
Source	Produced by Fusarium tricinctum, which is a fungal contaminant of grains such as wheat and corn
Structure	T-2 3a,4b,8a-12,13-epoxytrichothec-9-ene-3,4,8,15-tetrol, 4,15-diacetate 8-(3-methylbutanoate), C 24H 34O 9  Nivalenol   3a,4b,7a-12,13-epoxy-3,4,7,15-tetrahydroxytrichothec- 9-en-8-one, C 15H 20O 7
LD 50	4.0 mg/kg (oral)
Symptoms	The onset of symptoms may vary from 1 to 12 hours. Symptoms include blisters, necrosis of tissues, dizziness, nausea, vomiting, diarrhea, hemorrhage, and death.
Mechanism	hemorrhagic substance
Properties	T-2: mw 466.53; mp 151-152ƒ C Nivalenol: mw 312.32
Routes	Ingestion, inhalation

Trichothecene mycotoxins were implicated as a chemical warfare agent in Southeast Asia. Initial suspicions were raised in the summer of 1975, when there were multiple reports among Hmong and Cambodian refugees of light aircraft dumping a yellow-green powder, causing vomiting and involuntary defecation. The powder was followed by the dropping of a munition that detonated in the air to produce a dense red haze that drifted down into the green-yellow dust, causing oral hemorrhaging followed by asphyxiation. Mortality rates were described as high. A UN commission was formed, but investigators were denied access to the areas where attacks reportedly took place. There are similar reports dating from the late 1960s in Yemen as well as from Ethiopia and Afghanistan in 1979-81. It has been estimated that there were more than 6,300 deaths in Laos, 1,000 in Cambodia, and 3,000 in Afghanistan. All attacks were alleged to have occurred in remote areas, which made confirmation of attacks and recovery of agent extremely difficult. Much controversy has centered about the veracity of eyewitness and victim accounts, as well as on the quality of the forensic evidence.

Other fungal toxins include:

mycotoxin F 2 3,4,5,6,9,10-hexahydro-14,16-dihydroxy -3-methyl-1H-2-benzoxacyclotetradecin-1,7(8H)-dione, a mycotoxin produced by numerous species of Fusarium. It inhibits fertility.
aflatoxin b1 2,3,6a,9a-tetrahydro-4-methoxycyclopenta[ c]furo [ 3',2:4,5]furo[ 2,3-h][ 1][benzopyran-1,11-dione, is a mutagenic mycotoxin produced by Aspergillusflavus, a fungus that can grow on many grains and nuts. Aflatoxin b1 causes liver cancer.

References

• Wade, N., Science, 1981, 214, 34.
• Rosen, R. T.; Rosen, J. T., Biomed. Mass Spectrom., 1982, 9, 443.
• Gilbert, J.; Shepherd, M. J., A survey of aflatoxins in peanut butters, nuts and nut confectionery products by HPLC with fluorescence detection, Food Addit. Contam., 1985, 2, 171-183.
• The Merck Index, 11 ed., Budavari, S.; O'Niel, M. J.; Smith, A.; Heckelmanm, P. E., Eds., Merck & Co.: Rahway, 1989, compound no. 9711, p.1541.

Saxitoxin

Chemical Abstracts Service registry no.	35554-08-6
Source	Produced by bacteria that grow in other organisms, including the dinoflagellates Gonyaulax catenella and G. tamarensis; which are consumed by the Alaskan butter clam Saxidomus giganteus and the California sea mussel, Mytilus californianeus. The toxin can be isolated from S. giganteus or M. californianeus.
Structure
LD 50	10 mg/kg (oral); 2.0 mg/kg (inhalation)
Symptoms	numbness, muscle weakness, respiratory paralysis
Mechanism	Cholinesterase inhibitor
Properties	mw 299.29 C 10H 17N 7O 4
Routes	Ingestion, inhalation

Saxitoxin is also known as Mytilotoxin.

Reference

• The Merck Index, 11 ed., Budavari, S.; O'Niel, M. J.; Smith, A.; Heckelmanm, P. E., Eds., Merck & Co.: Rahway, 1989, compound no. 8344, p. 1330.

Tetrodotoxin

Chemical Abstracts Service registry no.	4368-28-9
Source	Found in the liver, gonads, intestines, and skin of many species of the order Tetraodontidae, including the globe fish Spheroides rubripes.
Structure	Octahydro-12-(hydroxymethyl)-2-imino-5,9:7,10a-dimethano -10aH-[ 1,3]dioxocino[ 6,5-d]pyrimidine-4,7,10,11,12-pentol
LD 50	334 mg/kg by ingestion
Symptoms	Numbness, tingling of the lips and inner mouth surfaces, weakness, paralysis of the limbs and chest muscles, and a drop in blood pressure have been reported within as little as 10 minutes after exposure. Death can occur within 30 minutes.
Mechanism	Ion-channel neurotoxin; the guanidinium moiety of tetrodotoxin lodges in the sodium channel of a nerve cell.
Properties	mw 319.27, C 11H 17N 3O 8
Routes	Ingestion, inhalation, skin absorption

Tetrodotoxin is responsible for fugu (puffer fish) food poisoning. Personal importation of fugu into the United States is prohibited; however fugu chefs certified by the Ministry of Health and Welfare of Japan are allowed to import fugu into the US. When properly cleaned and prepared, the fugu flesh or musculature is edible and considered a delicacy by some Japanese. One meal sells for the equivalent of $400. Despite strict regulation, fugu causes approximately 50 deaths annually in Japan.

It has been claimed that tetrodotoxin is the active ingredient in zombie powder, used by Voodoo priests to induce a death-like trance. The zombie is given just enough tetrodotoxin to incapacitate him or her, then is revived and kept under control by the use of other drugs. However, claims concerning zombification are poorly documented.

References

• The Merck Index, 11 ed., Budavari, S.; O'Niel, M. J.; Smith, A.; Heckelmanm, P. E., Eds., Merck & Co.: Rahway, 1989, compound no. 9175, p. 1456.
• Davis, W., Passage of Darkness : The Ethnobiology of the Haitian Zombie, Univ. of North Carolina Press: Chapel Hill, 1988.

Other References

• Gill, D. M., Bacterial toxins: a table of lethal amounts, Microbiol. Rev., 1982, 46, 86-94.