Ricin toxin injection

The first signs of ricin intoxication in laboratory animals are typically lethargy and refusal to eat, followed later by a rapid drop in body temperature with characteristic shivering, and, ultimately, hypotension death is usually delayed until 10 h to 5 days after exposure, depending on the amount of toxin injected and the species of animal (Flexner, 1897 Waller et al., 1966 Balint, 1974 Fodstad et al., 1979). Laboratory animals surviving the first 6-7 days after injection of sublethal doses of... 

The incubation period for ricin is dependent on the route of transmission. If the toxin is inhaled, the incubation is about 8 h. The incubation period for ingestimi is a few hours to days. If ricin is injected under the skin, the incubation period could be immediate to several hours, depending on the location of injection and the dose of toxin injected. 

Ricin would probably be aerosolized, but it could also be used by an assassin who might prepare it for ingestion or injection. Ricin is not nearly as potent as the C. botulinum toxin, and thus would have to be produced in very large quantities for large-scale use. 

The initial symptoms of ricin poisoning are gastroenteritis, in which there is bleeding, followed by arrythmias of the heart, depression of the central nervous system, coma, and then death. The toxin is especially potent when injected, whereas a single castor bean can be eaten without... 

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). 

The B-lymphocytes may represent one of the preferential targets of ricin toxicity in vivo. Lymphatic tissues from animals exposed to ricin show extensive hyperplasia and cellular necrosis with edema, hyperemia, and hemorrhage (Waller et al., 1966). Rats injected (i.m.) with ricin or abrin develop numerous apoptotic-like bodies in ileal crypts, para-aortic lymph nodes, and Peyer s patches (Griffiths et al., 1987). The finding of apoptosis in whole animals may be due to a direct effect of ricin on cells of the lymphatic tissue, as is observed with isolated cells in vitro, or it may partly reflect the numerous pathological sequelae of toxin exposure, including severe shock (Griffiths et al., 1988 Howat, 1988). 

Injection (i.v.) of laboratory rats with I-ricin resulted in an accumulation of about 70% of the toxin in the spleen, liver, and muscle at 30 m, with detectable levels decreasing to about 11 % of injected toxin by 24 h after exposure (Ramsden et al., 1989). Injection (i.m.) of rats with ricin showed concentration of the toxin at the injection site and the ipsilateral para-aortic lymph nodes beginning as early as 4—8 h after exposure (Griffiths et al., 1986). 

A 20 year old man allegedly attempted suicide by injection (s.c.) of an unknown amount of ricin from crude castor seed extract (Targosz et al., 2002). The victim entered the hospital about 36 h after injecting the toxin with symptoms of nausea, dizziness, weakness, chest and abdominal pain, and myalgia with paraesthesia of the extremities. Signs included hypotension, anuria, metabolic acidosis, and a bleeding diathesis. Hepatorenal and cardiorespiratory failure preceded death from an asystolic arrest approximately 54 h after injection. 

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). 

Enzyme-linked immunosorbent assays (for blood or other body fluids)50 or immunohistochemical techniques (for direct analysis of tissues) may be useful in confirming ricin intoxication. However, because ricin is bound very quickly regardless of route of challenge, and metabolized before excretion, identification in body fluids or tissues is difficult. In rats exposed to ricin labeled with iodine 125 by intravenous injection, the radioactive label was found in liver (46%), muscle (13%), and spleen (9%) 30 minutes after intravenous injection.51 Ricin was quickly cleared from the animals, with only 11% remaining after 24 hours 70% was excreted in the urine as low-molecular-weight metabolites. Attempts at identification of the toxin may also include introduction of biological autopsy materials into mice or cultured cells and neutralization through the use of specific antibodies. 

Ricin is not an infectious agent but rather is a potent protein toxin produced from castor beans (Figure 3.5). Castor beans are common worldwide and the toxin is easy to produce. It makes a good bioweapon (better for assassination than for mass exposure) because it is stable and can be administered by several routes (inhalation, oral, or injection). Although ricin is not as deadly as some toxins, the ease of its production makes it attractive as a weapon. It has been especially attractive for small terrorist organizations that lack funds for obtaining more deadly weapons. Aerosol would be the most effective delivery method, but it is difficult to produce ricin particles in the 5-micron range so it is less useful for mass exposures. 

Three routes of ricin exposure are known to exist for humans and animals inhalation, natural infection by ingestion, and injection. Depending on the route of exposure (such as injection), as little as 500 pg of ricin could be enough to kiU an adult. A 500-pg dose of ricin would be about the size of the head of a pin. A much greater amount would be required to kill a human being by either the inhalation or ingestion routes. Toxins are not usually transmitted person-to-person or animal-to-animal. Secondary aerosolization is not thought to be of concern. 

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