Ricin: Chemistry, Sources, Exposures, Toxicology and Medical Aspects

Abstract

The chapter covers the origins of ricin toxin, which is present in the seeds of the many cultivars of the castor oil plant. The structure and biogenesis of the dimeric (A and B chain toxin) ricin (RCA 60 ) is described, compared with the related, but less toxic, Ricinus agglutinin (RCA 120 ) and the toxic activity of ricin, the N ‐glycosidase activity of the A chain, is explained. The intoxication process is further described and developed through in vitro and in vivo studies, which then focus on several possible routes of exposure. These include inhalation, that route which has been the primary focus of military‐oriented research through oral and parenteral routes of intoxication; histopathology and symptomatology are described, using evidence from human cases of ricin poisoning, wherever possible. Information is then presented on the development of medical countermeasures against ricin poisoning, including pretreatment approaches (vaccines) and postexposure approaches, which include antitoxins. More novel and currently research‐based studies are considered, including inhibitors of N ‐glycosidase, substrate competitors or approaches to interfere with the binding of the ricin B chain to galactose moieties.

Production, Characterisation and Testing of an Ovine Antitoxin against Ricin; Efficacy, Potency and Mechanisms of Action

“…A significant number of fatal and sub-lethal cases of human intoxication have been reported following accidental or deliberate ingestion or from parenteral exposure to ricin [ 4 ]. The development of prophylactic and post-exposure therapies for ricin intoxication has been on-going for many years [ 5 , 6 ] and a continued requirement for the development of medical countermeasures for ricin has been identified [ 7 ]. At present, however, there is no specific prophylactic or post-exposure therapy available for the clinical management of individuals exposed to ricin.…”

“…The toxin then enzymatically inactivates the ribosome though depurination of a single adenine residue in the 28 S ribosomal subunit. This event inactivates the 60 S ribosomal subunit, disrupts protein synthesis and results in cell death [ 1 , 6 ]. A single ricin molecule has been hypothesised to have the potential to inactivate multiple ribosomes and consequently killing a cell [ 16 , 17 , 18 ].…”

Ricin and Saxitoxin: Two Natural Products That Became Chemical Weapons

“…Castor seeds contain notable amounts of ricin ranging (depending on the origin of the seeds) from 0.1% to 4.0% of the weight of the bean . For the manufacturing of castor oil, ricin has to be deactivated.…”

“…12 Castor seeds contain notable amounts of ricin ranging (depending on the origin of the seeds) from 0.1% to 4.0% of the weight of the bean. 13 For the manufacturing of castor oil, ricin has to be deactivated. Deactivation of ricin occurs during the extraction process if the temperature used is higher than 80 °C.…”

Short- and long-term outcomes of pulmonary exposure to a sublethal dose of ricin in mice

“…Previous studies in rodents and non-human primates demonstrated that following pulmonary exposure to lethal dose of ricin, the injury is mostly confined to the lungs, including marked interstitial pneumonia associated with pro-inflammatory cytokine release, massive neutrophil infiltration, vascular hyperpermeability, perivascular and alveolar edema, hemorrhages, diffuse airway epithelial cell and alveolar macrophage death. Eventually, the extensive pneumonia, which involves massive cell infiltration and excessive accumulation of pleural fluids leads to respiratory insufficiency and death [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] . This damage to the lungs is classified as acute lung injury, which can develop to acute respiratory distress syndrome (ARDS) 12 .…”