Ricin toxin

CLINICAL SYMPTOMS, SIGNS, AND PATHOLOGY Oral Intoxication Injection Inhalation Cause of Death 

Immunization and Passive Protection Supportive and Specific Chemotherapy 

Colonel, Veterinary Corps, U.S. Army Commander, U.S. Army Medical Research Institute of Infectious Diseases 

Ricin toxin, found in the bean of the castor plant, Ricinis communis, is one of the most toxic and easily produced plant toxins. It is a lectin consisting of two polypeptide chains, the A-chain and the B-chain, linked by a disulfide bond. It is one of a group of dichain ribosome-inactivating proteins, which are specific for the depurination of a single adenosine in ribosomal ribonucleic acid (RNA).1 The active chain (ie, the A-chain) has the ability to modify catalytically the 28S subunit of 

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Ricin (toxin from Castor bean Ricinus communis) [A chain 96638-28-7 B chain 96638-29-8] Mr -60,000, amorphous. Crude ricin, obtained by aqueous extraction and (NH4)2S04 pptn, was chromatographed on a galactosyl-Sepharose column with sequential elution of pure ricin. The second peak was due to ricin agglutinin. [Simmons and Russell Anal Biochem 146 206 1985.) Inhibitor of protein synthesis. EXTREMELY DANGEROUS, USE EXTREME CARE [instructions accompany product]. 

Category B agents There are eleven Category B agents as follows brucellosis, epsilon toxin (clostridium perfringens), glanders, melioidosis, psittacosis, Q fever, ricin toxin, staphylococcus enterotoxin B, typhus fever, viral encephalitis, and water safety threats. 

Ricin toxin— Ricinus communis (castor beans)... 

Ricin (toxin from Castor bean [Ricinus communis]) [96628-29-8]. Crude ricin, obtained by... 

Ricin toxin— Ricinus communis (castor beans) B Castor beans About 8 h Unlikely Standard Fever, N, Cough, chest discomfort, resp difficulty, joint pain, progressing to pulm edema and resp failure Typically fatal w/in 72 h Primarily supportive Tx pulm edema... 

Ricin toxin consists of two protein moieties connected by a disulphide bridge. Chain A (Mw 32 kD) blocks the ribosomal activity, and chain B (Mw 34 kD) is responsible for cell entry of the A chain. 

FIGURE 1 Empirical phase diagram for ricin toxin A-chain generated using CD molar ellipticity at 208 nm, ANS fluorescence, and intrinsic Trp fluorescence intensity data. Labels indicate the state of the protein within the same region of color based on evaluation of a compilation of data sets. (Reproduced with permission from ref. 62.)... 

Peek, L. J., Brey, R. N., and Middaugh, C. R. (2007), A rapid, three-step process for the preformulation of a recombinant ricin toxin A-chain vaccine, J. Pharm. Sci., 96,44-60. 

Ricin and abrin have played important roles in the history of clinical medicine and biomedical research. Ricin is commonly used as a part of immunotoxins for elinieal tumor research and application, although the detailed meehanism of its funetion is still under investigation (Stirpe and Battelli, 2006 Rao et al, 2005). At present, a major effort in biomedical research is under way to target the toxins and pursue malignant eells. Novel in vitro approaehes of using ricin toxins in cancer therapy have proven sueeessful however, further in vitro and animal studies are needed to confirm its potential (Wang et al, 2007). 

Lemley, P.V., Wright, D.C. (1991). Active immunization after passive monoclonal antibody and ricin toxin challenge (abstract 029), 10th World Congress on Animal, Plant, and Microbial Toxins. Singapore, China. 

Two commercial vaccines based on virosome technology are currendy on the market. Epaxal (Berna Biotech Ltd, Bern, Switzerland), a hepatitis A vaccine, has inactivated hepatitis A virus particles adsorbed on the surface of the immunopotentiating reconstituted influenza virosomes (IRIV). In Inflexal V (Berna Biotech Ltd) the virosome components themselves are the vaccine protective antigens (185). Recently, in phase I study liposome-encapsulated malaria vaccine (containing monophosphoryl lipid A as adjuvant in the bilayer), the formulation showed induction of higher level of anti-malaria antibody in human volunteers (186). Some liposomal formulations are under investigation in preclinical studies against Yersina pestis, ricin toxin and Ebola Zaire virus (77, 187). 

Data on exposnre throngh ingestion are also limited. There are no reported cases of ingestion of pure ricin toxin. Nevertheless, the signs and symptoms of exposure to the pure toxin are probably similar to those following ingestion of masticated... 

Franz, D.R. and Jaax, N.K. (1997). Ricin toxin. In Textbook of Military Medicine, Part I Warfare, Weaponry, and the Casualty. Medical Aspects of Chemical and Biological Warfare. Sidell, F.R., Takafuji, E.T., and Franz, D.R. (eds). Office of the Surgeon General, Department of the Army, Washington, D.C., pp. 631-642. 

Frankel, A., Welsh, P., Richardson, J. and Robertas, J.D. (1990) Role of arginine 180 and glutamic acid 177 of ricin toxin A chain in enzymatic inactivation of ribosomes. Mol Cell Biol, 10, 6257-6263. 

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. 

Hegde, R. and Fodder, S.K. (1998) Evolution of tetrameric lectin Ricinus communis agglutinin from two variant groups of ricin toxin dimers. Eur J Biochem, 254, 596-601. 

Kirby, R. (2004) Ricin Toxin A Military History. Army Chemical Review, 38-40. 

Leith, A.G., Griffiths, G.D. and Green, M.A. (1988) Quantification of ricin toxin using a highly sensitive avidin/biotin enzyme-linked immunosorbent assay. J Eorensic Sci Soc, 28, 227-236. 

Lemley, P.V. and Creasia, D.A. (1995) USA 5,453,271, Vaccine against Ricin Toxin. September 26, 1995. Lemley, P.V. and Wright, D.C. (1992) Mice are actively immunized after passive monoclonal antibody... 

Lindstrom, A.L., Erlandsen, S.L., Kersey, J.H. and Pennell, C.A. (1997) An in vitro model for toxin-mediated vascular leak syndrome ricin toxin A chain increases the permeability of human endothelial cell monolayers. Blood, 90, 2323. 

Tang, J., Xie, J., Shao, N. and Yan, Y. (2006) The DNA aptamers that specifically recognize ricin toxin are selected by two in vitro selection methods. Electrophoresis, 27, 1303-1311. 

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