Ricin toxin lethality

Griffiths, G.D., Bailey, S.C., Hambrook, J.L., Keyte, M., Jayasekera, P., Miles, J. and Williamson, E. (1997) Liposomally-encapsulated ricin toxoid vaccine delivered intratracheally elicits a good immune response and protects against a lethal pulmonary dose of ricin toxin. Vaccine, 15, 1933-1939. 

Ricin toxin is found in the beans of the castor plant, Ricinus communis. It is one of the most lethal and easily produced plant toxins. The toxin is present in the entire plant but is concentrated in its seeds. Ricin can be in the form of apowder, mist, or pellet, or dissolved in water or weak acid. It is a very stable substance and is not affected by extremes in temperature. Castor beans are processed throughout the world to make castor oil. Ricin is part of the waste mash produced when castor oil is made. Ricin irreversibly blocks protein synthesis. Ricin has some potential medical uses, such as bone marrow transplants and cancer treatment (to kill cancer cells). 

Food may be contaminated with toxins produced by bacteria, such as botulinum toxin. This is produced by the bacterium Clostridium botulinum and is one of the two most potent toxins known to humans (the other being ricin). As little as one hundred-millionth of a gram (1 X 10-8 g) of the toxin would be lethal for a human. Fortunately, the toxin is destroyed by heat so that cooked food is unlikely to be contaminated (although the bacterial spores are quite resistant). The bacteria grow in the absence of air (they are anaerobic), and consequently, the foodstuffs most likely to be contaminated are those that are bottled or canned and eaten without cooking, for example, raw or lightly cooked fish. 

As with some of the other chemicals discussed in this book, the possibility of using ricin as a drug, in particular for the treatment of cancer, has been explored. The possibility of attaching the part of the toxin that is lethal to cells, to antibodies, which would then target cancer cells, is being studied. 

Funatsu, G., Funatsu, M. (1970). Isolation and chemical properties of various types of ricin. Jpn. J. Med. Sci. Biol. 23 342-4 Gareth, D., Griffiths, G.D., Rice, P., Allenby, A.C., Bailey, S.C., Upshall, D.G. (1995). Inhalation toxicology and histopa-thology of ricin and abrin toxins. Inhal. Toxicol. 7 269-88 Gill, D.M. (1982). Bacterial toxins a table of lethal amounts. Microbiol. Rev. 46 86-94. 

Abrin is a plant source Type 2 RIP. It is found in Abrus precatorius (rosary pea, Indian licorice, jequirity bean). The toxicology of abrin is considered to be very similar to ricin. A similar Abrus toxin is pulchellin, produced by A. pul-chellus (Millard and LeClaire, 2008). The rosary pea has been reported to be more toxic than castor beans (Griffiths et al, 1994). Species sensitivity is variable and horses are considered to be the most sensitive. The mature goat is considered to be a more resistant species and 2 g of seed/kg body weight is reported as a lethal dose. The lethal dose for cattle is reported at 600 mg of seed/kg body weight. It is likely that abrin is denatured in the rumen (Burrows and Tyrl, 2001). 

Injected ricin kills laboratory animals in a concentration- and time-dependent manner with steep lethality curves (Fodstad et al., 1976, 1979 Olsnes and Pihl, 1977). After administration of ricin to experimental animals by injection, there is a characteristic time delay before signs of intoxication appear. The delay time decreases with increasing amounts of toxin, but it is always several hours, perhaps reflecting the time required for sufficient toxin to reach the target ribosome and disrupt protein synthesis (Olsnes and Pihl, 1977 Fodstad et al., 1979). In laboratory rats, for example, liver protein biosynthesis is unchanged compared with control levels for the first 3 h after injection (i.p.) with 500 pg/kg ricin, but steadily declines to approximately 15% of that of control groups by 10 h (Lin et al., 1971). 

Ricin and related type 2 RIP plant toxins are comparably lethal to laboratory mice under controlled conditions (Table 17.3). Variations in the LD50 values for a single toxin reported by different laboratories are comparable with variations among different toxins. Few controlled animal studies are available for several of these toxins, and comparisons among laboratories are limited by differences in toxin preparations, animal strains, and methodologies employed. The postexposure observation period is a particularly important variable for example, the literature values for the acute toxicity of abrin vary by 80-fold depending on whether intoxicated animals are observed for 24 or 48 h after exposure (Dickers et al., 2003). 

There are likely differences among species in susceptibility to related plant toxins but, as with ricin, these are often obscured by interlaboratory variability. In one comparative study of abrin (i.v.) lethality in different animals, the MED for mice was 10-fold greater (0.7 pg/kg) than that for rabbits (0.03-0.06 pg/kg), with rats and guinea pigs showing intermediate sensitivity (Fodstad et al., 1979) these findings parallel those for ricin (Table 17.2). 

Comparison of the Parenteral Lethality of Ricin and Related Toxins in Laboratory Mice... 

As with other protein toxin weapons, we expect that the generation of primary or secondary ricin aerosols, especially within an enclosed space, poses a potential biological warfare or bioterrorism risk (LeClaire and Pitt, 2005 Millard, 2005). Due to the technical challenges of generating highly toxic and persistent protein aerosols, we expect the risk of lethality to be less than the risk of operational disruption, prolonged incapacitation from ocular or respiratory tract inflammation, and increased burden on medical and logistical assets. 

It is is the third most toxic substance known after plutonium and botulism it is a protein toxin that is extracted from the castor bean (Ricinus communis). The USA Centers for Disease Control (CDC) considers 500 pg to be the lethal dose of ricin in humans if exposure is from injection or inhalation. Ricin is poisonous if inhaled, injected, or ingested, acting by the inhibition of protein synthesis. While there is no known antidote, the US military has developed a vaccine. 

Other investigators (Marsden et al, 2004) introduced an inhibitor peptide into the ricin A chain which completely eliminated the in vivo cy-totoxicty of the protein, was non-toxic when injected into rats and elicited an immune response that protected the animals from an intratracheal ricin dose of five times the LD50. Most recently, a fragment of the ricin A chain has been identified which has no enzymic activity, does not induce vascular leak syndrome, is very stable and completely protects mice from subsequent exposure to a lethal ricin challenge when the toxin is administered either by intraperitoneal injection or whole-body aerosol exposure (Olsen et al, 2004 Lebeda and Olson, 1999 McHugh et al, 2004). 

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. No antidotes are known for mycotoxins. Treatment is supportive and symptomatic. 

The amounts of toxin needed to obtain the desired effect are exceedingly small. For example, about 30 grams of the toxin ricin, easily concealed in a pocket, would be sufficient to lethally poison one batch of 150 pounds of meat, enough to produce 1,500 hot dogs. 46 The threat is real. And the knowledge required is not esoteric ... 

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