Ricin lethality

Other Lethal Agents. There are a number of substances, many found in nature, which are known to be more toxic than nerve agents (6). None has been weaponized. Examples of these toxic natural products include shellfish poison, isolated from toxic clams puffer fish poison, isolated from the viscera of the puffer fish the active principle of curare "heart poisons" of the digitaUs type the active principle of the sea cucumber active principles of snake venom and the protein ricin, obtained from castor beans (See Castor oil). 

Eiklid, K., Olsnes, S., and Pihl, A. (1980) Entry of lethal doses of abrin, ricin, and modeccin into the cytosol of Hela cells. Exp. Cell Res. 126, 321-326. 

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. 

Candidate vaccines under development are immunogenic and confer protection against lethal aerosol exposures. Recent animal studies have shown that either active immunization or passive prophylaxis may be effective against intravenous or intraperitoneal intoxication with ricin (Poh et al, 1994). In the case of inhalational exposure, active immunization or prophylactic administration of aerosolized specific anti-ricin antibody may also be effective (Poli et al, 1994). Unfortunately, these applications may not be clinically available since they are still under investigation. 

Davis, J.H. (1978). Abrus precatorius (rosary pea). The most common lethal plant poison. J. F/orzWaMerf. Hi i oc. 65 188-91. Day, P.J., Pinheiro, T.J., Roberts, L.M., Lord, J.M. (2002). Binding of ricin A-chain to negatively charged phospholipid vesicles leads to protein structural changes and destabilizes the lipid hilayer. Biochemistry 41 2836-43. 

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. 

Wilhehnsen, C.L., Pitt, M.L. (1996). Lesions of acute inhaled lethal ricin intoxication in rhesus monkeys. Vet. Pathol. 33 296-302. 

Balint (1974) and later Zhang et al. (1994) foimd that at the lethal dose in rabbits, ricin caused hemorrhage and necrosis. Christiansen et al. (1994) foimd that the release of norepinephrine from sympathetic nerves in the vasculature is not impaired by ricin. The CDC, under signs and symptoms of ricin poisoning that may be encountered, cite cardiovascular collapse (hypovolemic shock). 

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). 

Transdermal exposure to ricin is not serious, since it is not well absorbed through the skin. Oral exposure, for example by ingestion of castor beans, can cause severe gastroenteritis, gastrointestinal hemorrhage, and death due to circulatory collapse. Parenteral injection of ricin is rapidly fatal, as is aerosol exposure the lethal dose by these routes is 5-10 micrograms/kg (8). 

Ricin is a biomolecule frequently in the news because of its potential use as a bioterrorism agent. Ricin is a small protein (65 kd) found in the seeds of the castor oil plant, Riemus communis. It is indeed a deadly molecule, because as little as 500 xg is lethal to an adult human, and a single molecule can inhibit all protein synthesis in a cell, resulting in cell death. 

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). 

Comparison of the Lethal Effects of Ricin in Different Animals... 

Animal Lethal Dose of Ingested Castor Seed (g/kg) Lethal Dose of Injected (i.m.) Ricin (p.g/kg) Lethal Dose of Injected (i.p. or i.v.) Ricin (pig/kg) Relative Resistance to Injected (s.c.) Ricin ... 

Lethal dose determined from a single study using a highly purified preparation of ricin the postexposure observation interval was 3 days for goat and unspecified for other animals (Field, 1910 Hunt et al., 1918). 

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). 

Outside of limited descriptions or subjective commentary describing surviving animals of acute lethality studies, little is published describing the sublethal or chronic effects of ricin on specific... 

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