Ricin

N-acetyl cysteine (NAC) in animal studies, NAC administered intratracheally 45-60 min after high-dose phosgene exposure significantly reduced development of pulmonary edema (15,34). The appropriate dose for humans would be 20 mL of a 20% NAC solution administered via nebulizer. However, there is no evidence for using this regimen in humans, and the FDA has not approved its use for prophylactic treaunent of phosgene exposure (34). 

Ibuprofen studies in rats, mice, and rabbits revealed that parenteral or intraperito-neal adminishation of ibuprofen during the asymptomatic phase following phosgene exposure was effective in preventing pulmonary edema. However, there is no evidence of its effectiveness in human victims and the FDA has not approved its use for this purpose. In addition, a dose comparable to those used in the animal smdies, would require giving patients at least 25-50mg kg orally (34). 

Positive airway pressure ventilation some experts recommend using positive pressure ventilation during the early, asymptomatic phase following phosgene exposure to prevent pulmonary edema. While positive pressure ventilation may reduce fluid accumulation, stabilize the intra-alveolar surfactant film and suppress arteriovenous shunts, many asymptomatic patients will find the treatment unacceptable (34). In addition, resources for providing prophylactic positive pressure ventilation may not be available in a mass-casualty situation. 

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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). 

Ricin [9009-86-3], a phytotoxin found in the seeds of the castor oil plant Acinus communis, conjugated to murine monoclonal antibody (Immunogen Corp.), has been approved by the U.S. Food and Dmg Administration (FDA) for the treatment of patients with B-ceU leukemia and lymphoma (59). 

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]. 

Rieinine is not markedly toxic the poisonous character of castor-oil seeds is due to a more complex substance, ricin, the activity of which can be destroyed by heat. 

Ricinus, m. castor-oil plant, -ijl, n. castor oil. -(ilsaure, /. ricinoleic acid. -Slseife, /. caator-soap, -olsulfosaure, /. castor-oil sulfonic acid, -samen, m. castor bean, -saure, /. ricinic (ricinoleic) acid, -seife, /. castor-oil soap. 

Ricin, an extremely toxic molecule isolated from the castor bean, inactivates eukaryotic 28S tibosomal RNA by providing the N-glycolytic cleavage or removal of a single adenine. 

Ricin Cytotoxic glycoprotein derived from seeds ofthe castor plant... 

K Sandvig, S Olsnes. (1982). Entry of toxic proteins abrin, modeccin, ricin, and diphtheria toxin into cells. I. Requirement for Ca2+. J Biol Chem 257 7495-7503. 

Toxins (typically high molecular weight proteins), such as botulinum toxin, ricin, or Staphyloccocal enterotoxin (SEB) or T-2 toxin (which actually is a small molecule). 

Fredriksson, S. Hulst, A. G. Artursson, E. de Jong, A. L. Nilsson, C. van Baar, B. L. Forensic identification of neat ricin and of ricin from crude castor bean extracts by mass spectrometry. Anal. Chem. 2005, 77,1545-1555. 

Reported applications of DSS include crosslinking the A and B subunits of ricin (Montesano et al., 1982), studying human somatotropin and the components of the lactogenic-binding sites of rat liver (Caamano et al., 1983), crosslinking CSF-1 to its cell-surface receptor (Morgan... 

Figure 21.2 Conceptualized construction of an A-B subunit protein toxin (left). The B chain contains a binding region for docking onto cell surfaces, while the A chain contains a catalytic site that produces cytotoxic affects intracellularly. The two subunits are joined by a disulfide bond that is reductively cleaved at the cellular level to allow the A subunit to affect cell death. A molecular model of ricin is on the right.

Figure 21.2 illustrates the basic structure of these common two-subunit toxins, showing schematically their major characteristics. The molecular model of ricin is from Rutenber et al. (1991), RSCB structure No. 2aai. 

Due to the extraordinary toxicity of intact ribosome-inactivating toxins like ricin, abrin, and modeccin, purification and handling of these proteins must be done with extreme care. Even dust from crude seed powders or lyophilized proteins should be considered dangerous. During... 

The following method calls for mixing activated antibody with ricin A chain at a ratio of 2 mg antibody per mg of A chain. Adjustments to the amount of antibody and A chain initially dissolved in the reaction buffers should be done to anticipate this ratio. 

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