Several incidents involving contamination of residences and buildings due to ricin production or dissemination have occurred in recent years. Although no approved therapeutics are currently based on ricin, it does have the potential to be used in the treatment of tumors, as a "magic bullet" to destroy targeted cells. It is a stable substance and does not break down easily in typical indoor or outdoor temperatures. Ricin is highly poisonous if inhaled or injected, but less so when ingested. The quaternary structure of ricin is a globular, glycosylated heterodimer of approximately 60–65 kDa. Toxin: Abrin, a protein synthesis inhibitor, which is located in the seeds. Threatening agents are biological organisms or chemicals that could cause harm to people’s health. [40], Most acute poisoning episodes in humans are the result of oral ingestion of castor beans, 5–20 of which could prove fatal to an adult. However, investigators possessing less than 1000 mg (1g) are exempt from regulation. The chemical synonyms of Ricin (CAS NO.9009-86-3) are Pyridine, 4- [5- (4-fluorophenyl)-2- [4- (methylsulfinyl)phenyl]-1H-imidaz ; 4- (4-Fluorophenyl)-2- (4-methylsulfinylphenyl)-5- (4-pyridyl)1H-imidazol and 4- [4- (4-Fluorophenyl)-2- (4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine .The … Mer­cury. Within the lumen of the ER the propolypeptide is glycosylated and a protein disulfide isomerase catalyzes disulfide bond formation between cysteines 294 and 318. Ricin works its harm by destroying small parts of cells, called ribosomes. Use of ricin as an adjuvant has potential implications for developing mucosal vaccines. wt1-ricin a. 31, Pg. Jan van Aken, a German expert on biological weapons, explained in a report for The Sunshine Project that Al Qaeda’s experiments with ricin suggest their inability to produce botulinum or anthrax. If any of these native internalization sequences are present in a therapeutic agent, the drug will be internalized by, and kill, untargeted non-tumorous cells as well as targeted cancerous cells. The purpose of this fact sheet is to help separate fact from fiction regarding ricin poisoning. 11002), and is subject to strict reporting requirements by facilities that produce, store, or use it in significant quantities.[45]. However, it was believed at the time that Bulgaria would not have been able to produce the pellet, and it was also believed that the KGB had supplied it. [30], Ingestion of ricin causes pain, inflammation, and hemorrhage in the mucosal membranes of the gastrointestinal system. Earlier, Soviet dissident Aleksandr Solzhenitsyn also suffered (but survived) ricin-like symptoms after an encounter in 1971 with KGB agents. The targets should have been: First, Zdeněk Hřib, the mayor of Prague (capital of the Czech Republic), who was involved in renaming a square in Prague, "Pod Kaštany", where the Russian embassy is situated, to the Square of Boris Nemtsov, an opposition politician assassinated in the Kremlin in 2015. If the ricin release was outside, move away from the area where the ricin was released. Since at least World War I, governments have investigated its use on the battlefield. [46] At that time it was being considered for use either as a toxic dust or as a coating for bullets and shrapnel. A general guide is 1 to 2 mg of ricin/g of ground castor seed. Ricin is classified as a type 2 ribosome-inactivating protein (RIP). [30], An antidote has been developed by the UK military, although it has not yet been tested on humans. [15] Ricin molecules are thought to follow retrograde transport via early endosomes, the trans-Golgi network, and the Golgi to enter the lumen of the endoplasmic reticulum (ER).[16]. [30], Vaccination is possible by injecting an inactive form of protein chain A. Acta Pharmacologica et Toxicologica, Supplementun. Ricin causes severe diarrhea and vomiting, and victims can die of circulatory shock or organ failure; inhaled ricin can cause fatal pulmonary edema or respiratory failure. Some researchers have speculated about using ricins in the treatment of cancer, as a so-called "magic bullet" to destroy targeted cells. In terms of structure, ricin closely resembles abrin-a, an isotoxin of abrin. A protein phytotoxin from the seeds of Ricinus communis, the castor oil plant. However, bacterial toxins, such as diphtheria toxin, which is used in denileukin diftitox, an FDA-approved treatment for leukemia and lymphoma, have proven to be more practical. The castor oil plant has many uses including natural hair growth and eyebrow and eyelash improvement. As a terrorism agent, ricin can be used as a powder, a mist, a pellet, or can be dissolved in water or weak acid. It is a triglyceride in which approximately 90 percent of fatty acid chains are ricinoleates. The propolypeptide is cleaved within protein bodies by an endopeptidase to produce the mature ricin protein that is composed of a 267 residue A chain and a 262 residue B chain that are covalently linked by a single disulfide bond.[4]. Third, Pavel Novotný, the mayor of Prague's southwestern Řeporyje district. [67], The popularity of Breaking Bad inspired several real-life criminal cases involving ricin or similar substances. The holotoxin can be taken up by clathrin-coated pits, as well as by clathrin-independent pathways including caveolae and macropinocytosis. National Technical Information Service. [4] The ricin precursor protein is 576 amino acid residues in length and contains a signal peptide (residues 1–35), the ricin A chain (36–302), a linker peptide (303–314), and the ricin B chain (315–576). In 1978 Bulgarian defector Vladimir Kostov survived a ricin attack similar to the one on Georgi Markov, probably due to his body's production of antibodies. The poison ricin is found naturally in castor beans. RTA has rRNA N-glycosylase activity that is responsible for the cleavage of a glycosidic bond within the large rRNA of the 60S subunit of eukaryotic ribosomes. Whereas type 1 RIPs are composed of a single protein chain that possesses catalytic activity, type 2 RIPs, also known as holotoxins, are composed of two different protein chains that form a heterodimeric complex. [15] Although the exact mechanism of the event is unknown, key amino acid residues identified include tyrosine at positions 80 and 123, glutamic acid at position 177, and arginine at position 180. Castor oil is a vegetable oil pressed from castor beans. [39] Rauber and Heard have written that close examination of early 20th century case reports indicates that public and professional perceptions of ricin toxicity "do not accurately reflect the capabilities of modern medical management". [26] RTA specifically and irreversibly hydrolyses the N-glycosidic bond of the adenine residue at position 4324 (A4324) within the 28S rRNA, but leaves the phosphodiester backbone of the RNA intact. Ricin Overview. [44], Ricin is classified as an extremely hazardous substance in the United States as defined in Section 302 of the US Emergency Planning and Community Right-to-Know Act (42 U.S.C. [5] The N-terminal signal sequence delivers the prepropolypeptide to the endoplasmic reticulum (ER) and then the signal peptide is cleaved off. Ricin is part of the white mash that is produced when processing castor beans into castor oil. [64][65] Later, the Czech president Miloš Zeman claimed that the police protection of Zdeněk Hřib is a publicity stunt. If the lethal dose of ricin is 0.5 mg, that would put the lethal dose of cyanide at 3000 kg, and rattlesnake venom at 6000 kg. Vol. 74, Pg. [33][34] Another antidote developed by the US military has been shown to be safe and effective in lab mice injected with antibody-rich blood mixed with ricin, and has had some human testing. [56], Ricin has been involved in a number of incidents. During World War II the United States and Canada undertook studying ricin in cluster bombs. [19] Roles for the ER chaperones GRP94,[20] EDEM[21] and BiP[22] have been proposed prior to the 'dislocation' of RTA from the ER lumen to the cytosol in a manner that uses components of the endoplasmic reticulum-associated protein degradation (ERAD) pathway. It causes fever, cough, weakness, abdominal pain, vomiting, diarrhea, dehydration, and death. This toxin is more poisonous than ricin. [6] Ricin toxin A chain and ricin toxin B chain are of similar molecular weights, approximately 32 kDa and 34 kDa, respectively. Chemical formula-C21H16FN3OS. The KGB denied any involvement, although high-profile KGB defectors Oleg Kalugin and Oleg Gordievsky have since confirmed the KGB's involvement. Depurination of adenine results in a neutral ribose on an intact phosphodiester RNA backbone. 351, 1977. Ricin is a powerful poison that could be used as an agent of biological warfare or as a weapon of mass destruction (WMD). Interest in it continued for a short period after World War II, but soon subsided when the US Army Chemical Corps began a program to weaponize sarin. Zeman also confused ricin with castor oil and claimed that ricin is a non-poisonous laxative. "Toxicology of Drugs and Chemicals," Deichmann, W.B., New York, Academic Press, Inc., 1969Vol. In 1978, the Bulgarian dissident Georgi Markov was assassinated by Bulgarian secret police who surreptitiously shot him on a London street with a modified umbrella using compressed gas to fire a tiny pellet contaminated with ricin into his leg. Ricin and Weapons . Ricin uses an effective strategy shared by many bacterial and plant toxins, as described in the previous Molecule of the Month on cholera toxin. Synonyms. [29][30] It prevents cells from assembling various amino acids into proteins according to the messages it receives from messenger RNA in a process conducted by the cell's ribosome (the protein-making machinery) – that is, the most basic level of cell metabolism, essential to all living cells and thus to life itself. [68] Daniel Milzman, a 19-year-old former Georgetown University student, was charged with manufacturing ricin in his dorm room, as well as the intent of "[using] the ricin on another undergraduate student with whom he had a relationship". Neurochemical Research. 582, 1973. When inhaled or injected, just a few grains of it can kill an adult, due to its high toxicity: refining the pulp of as few as eight beans can create a dangerous amount of ricin. He developed a fever, but recovered. As ricin is not oil-soluble, little is found in the extracted castor oil. Haemorrhage causes bloody feces (melena) and vomiting blood (hematemesis). LIVER: "HEPATITIS (HEPATOCELLULAR NECROSIS), DIFFUSE", VASCULAR: BP LOWERING NOT CHARACTERIZED IN AUTONOMIC SECTION, BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY). Oleate and linoleates are the other significant components. Death typically occurs within 3–5 days of exposure. Existing treatments emphasize minimizing the effects of the poison. Ricin is resistant, but not impervious, to digestion by peptidases. To display its ribosome-inactivating function, the ricin disulfide bond must be reductively cleaved. 1903), specifically Annex §2, Ch.1, Article 23, stating "... it is especially prohibited ... [t]o employ poison or poisoned arms". TIME COURSE: Physical findings and signs of abrin exposure can occur after a symptom-free (latent) period of a few hours to several days.Effects following ingestion of abrin are somewhat rapid in the beginning, generally occurring within a few hours of ingestion. It can also be toxic if dust contacts the eyes or if it is absorbed through damaged skin. [13][14] Intracellular vesicles shuttle ricin to endosomes that are delivered to the Golgi apparatus. of Defense, Office of the Secretary of Defense, National Defense Research Institute (U.S.) (2000). Vol. It is easily extracted from the castor bean meal that remains as a by-product of castor oil production. Because ricin is stable over a wide pH range, degradation in endosomes or lysosomes offers little or no protection against ricin. [10] The remaining spent crushed seeds, called variously the "cake", "oil cake", and "press cake", can contain up to 5% ricin. When ingested, gastrointestinal symptoms can manifest within six hours; these symptoms do not always become apparent. [2], Ricin is classified as a type 2 ribosome-inactivating protein (RIP). Learn how and when to remove this template message, Emergency Planning and Community Right-to-Know Act, "EFSA Scientific Opinion: Ricin (from Ricinus communis) as undesirable substances in animal feed – Scientific Opinion of the Panel on Contaminants in the Food Chain", "P02879 Ricin precursor – Ricinus communis (Castor bean)", "Mutational analysis of the Ricinus lectin B-chains. 9009-86-3 - Ricin - Searchable synonyms, formulas, resource links, and other chemical … Under both the 1972 Biological Weapons Convention and the 1997 Chemical Weapons Convention, ricin is listed as a schedule 1 controlled substance. The characteristics of the enzymatic activity of ricin A-chain with ribosomes and with rRNA", "Inhibition by ricin of protein synthesis in vitro: 60 S ribosomal subunit as the target of the toxin", "CDC – The Emergency Response Safety and Health Database: Biotoxin: RICIN – NIOSH", "Ricin as a weapon of mass terror – separating fact from fiction", "Human trial proves ricin vaccine safe, induces neutralizing antibodies; further tests planned", University of Texas Southwestern Medical Center, "Vaccine for ricin toxin developed at Detrick lab", "Survived after ingesting 30 castor beans", "HHS and USDA Select Agents and Toxins 7 CFR Part 331, 9 CFR Part 121, and 42 CFR Part 73", "40 C.F.R. It has completed two successful clinical trials. Swallowing castor beans rarely proves to be fatal unless the bean is thoroughly chewed. Ricin, one of the most poisonous naturally occurring substances, has a long history as a chemical weapon. October 2, 2018. Attenuation was … The dust cloud concept could not be adequately developed, and the coated bullet/shrapnel concept would violate the Hague Convention of 1899 (adopted in U.S. law at 32 Stat. [48] Though there were plans for mass production and several field trials with different bomblet concepts, the end conclusion was that it was no more economical than using phosgene. Ricin is a highly toxic, naturally occurring lectin produced in the seeds of castor oil plant. Second, Ondřej Kolář, the mayor of Prague 6 municipal district, who was involved in removing the controversial statue to the Soviet-era Marshal Konev. The model proposed by Mozingo and Robertus,[8] based on X-ray structures, is as follows: Ricin is very toxic if inhaled, injected, or ingested. 2, Pg. [10] The extracted oil is also heated to more than 80 °C (176 °F) to denature any ricin that may be present. [59] Another was sent to the offices of Mayors Against Illegal Guns in Washington, D.C. A letter containing ricin was also alleged to have been sent to American President Barack Obama at the same time. DESCRIPTION: Ricin is an extremely toxic plant protein derived from the seeds of the castor bean plant (Ricinus communis). [52], Ricin is several orders of magnitude less toxic than botulinum or tetanus toxin, but the latter are harder to come by. -, Pg. (1S,3aS,3bS,5aR,9aR,9bS,11aS)-N- (2-cyanopropan-2-yl)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno [5,4-f]quinoline-1-carboxamide. It agglutinates cells, is proteolytic, and causes lethal inflammation and hemorrhage if taken internally. The KGB developed weapons using ricin which were used outside the Soviet bloc, most famously in the Markov assassination.[50][51]. For example, on 29 May 2013 two anonymous letters sent to New York City Mayor Michael Bloomberg contained traces of it. [62] A letter was received on 23 July 2019 at Pelican Bay State Prison in California which claimed to contain a suspicious substance. Ricin, toxic protein (toxalbumin) occurring in the beanlike seeds of the castor-oil plant (Ricinus communis).Ricin, discovered in 1888 by German scientist Peter Hermann Stillmark, is one of the most toxic substances known. [11] RTB has been shown to bind to the cell surface on the order of 106-108 ricin molecules per cell surface. IUPAC name- 4- [4- (4-Fluorophenyl)-2- (4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine. The major problem with ricin is that its native internalization sequences are distributed throughout the protein. All of these three politicians had received police protection. "Prehled Prumyslove Toxikologie; Organicke Latky," Marhold, J., Prague, Czechoslovakia, Avicenum, 1986Vol. Ricin is a glycoprotein toxin (66,000 daltons) from the seed of the castor plant. 149281-19-6. There is no cure for Ricin poisoning, and medical treatment is simply supportive. Kuntal Patel from London attempted to poison her mother with abrin after the latter interfered with her marriage plans. If the ricin has been ingested recently, the stomach can be flushed by ingesting activated charcoal or by performing gastric lavage. By Dan Nosowitz. When a ricin-laced pellet was removed from the small of his back it was found that some of the original wax coating was still attached. As little as 10mg of VX, outlawed by the 1997 Chemical Weapons Convention, can kill a human in just a few minutes. [10], Several terrorists and terrorist groups have experimented with ricin and caused several incidents of the poisons being mailed to US politicians. Galactose-binding ability of the 2 gamma subdomain of Ricinus communis agglutinin B-chain", "Inhibition of coated pit formation in Hep2 cells blocks the cytotoxicity of diphtheria toxin but not that of ricin toxin", "Retrograde transport pathways utilised by viruses and protein toxins", "Protein disulphide-isomerase reduces ricin to its A and B chains in the endoplasmic reticulum", "Ricin A chain insertion into endoplasmic reticulum membranes is triggered by a temperature increase to 37 {degrees}C", "Cytosolic chaperones influence the fate of a toxin dislocated from the endoplasmic reticulum", "EDEM is involved in retrotranslocation of ricin from the endoplasmic reticulum to the cytosol", "Folding-competent and folding-defective forms of ricin A chain have different fates after retrotranslocation from the endoplasmic reticulum", "The proteasome cap RPT5/Rpt5p subunit prevents aggregation of unfolded ricin A chain", "RNA N-glycosidase activity of ricin A-chain. The goal of this study was to determine whether ricin bioactivity could be attenuated in reasonable time via simple modifications of the indoor environment. In the mammalian cell cytosol, RTA then undergoes triage by the cytosolic molecular chaperones Hsc70 and Hsp90 and their co-chaperones, as well as by one subunit (RPT5) of the proteasome itself, that results in its folding to a catalytic conformation,[20][25] which de-purinates ribosomes, thus halting protein synthesis. While other plants contain the protein chains found in ricin, both protein chains must be present to produce toxic effects. A promising approach for ricin is to use the non-toxic B subunit (a lectin) as a vehicle for delivering antigens into cells, thus greatly increasing their immunogenicity. RICIN: UN #: 3172 GUIDE 153. Within two to five days of exposure to ricin, effects of ricin on the central nervous system, adrenal glands, kidneys, and liver appear. Chemical structure and … An actress, Shannon Richardson, was later charged with the crime, to which she pleaded guilty that December. In September 1978, a Bulgarian dissident, Georgi Markov, was assassinated by a pellet of ricin … The United States investigated ricin for its military potential during World War I. Ricinine | C8H8N2O2 | CID 10666 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists… [60] On 16 July 2014, Richardson was sentenced to 18 years in prison plus a restitution fine of $367,000. It is of special concern because of its potential use as a biological weapon.Accidental exposure to ricin is rare and results primarily from the ingestion of castor seeds. Augerson, William S.; Spektor, Dalia M.; United States Dept. A dose of purified ricin powder the size of a few grains of table salt can kill an adult human. C23H33N3O2. [12], The profuse binding of ricin to surface membranes allows internalization with all types of membrane invaginations. Vol. -, Pg. There is no cure or antidote for ricin … Possible treatments include intravenous fluids or electrolytes, airway management, assisted ventilation, or giving medications to remedy seizures and low blood pressure. Detecting biological and chemical agents . The laboratory testing usually involves immunoassay or liquid chromatography-mass spectrometry.[42]. Ricin is a naturally occurring protein derived from the beans of the castor oil plant, Ricinus communis. In addition, the mannose-type glycans of ricin are able to bind to cells that express mannose receptors. Its boiling point is 313 °C (595 °F) and its density is 0.961 g/cm 3. [1] The median lethal dose (LD50) of ricin for mice is around 22 micrograms per kilogram of body weight via intraperitoneal injection. Ribosomes produce all of the proteins needed by a cell. Effects of ricin poisoning depend on whether ricin was inhaled, ingested or injected. Sarcin-ricin loop substrate binds RTA active site with target adenine stacking against tyr80 and tyr123. [10] In 2013 a 37-year-old woman in the United States survived after ingesting 30 beans. With appropriate treatment, most patients will make a decent recovery. [35], Symptomatic and supportive treatments are available for ricin poisoning. You will need to have some way to purge the glovebox and thought must be given to the discharge from these two items. [10], The seeds of Ricinus communis are commonly crushed to extract castor oil. 1073, 1979. Ricin is considered both a chemical and biological weapon and is explicitly prohibited by the Biological and Toxin Weapons Convention and Schedule 1 of the Chemical Weapons Convention. CGP-53153. [53] Ricin is easy to produce, but is not as practical or likely to cause as many casualties as other agents. [49], The Soviet Union also possessed weaponized ricin. UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 6 (GalNAc-T6) Synonyms GALNAC-T6, GalNAcT6. Human Toxicology. -, Pg. [24] Thus, RTA avoids the usual fate of dislocated proteins (destruction that is mediated by targeting ubiquitinylated proteins to the cytosolic proteasomes). [29] Blood, plasma, or urine ricin or ricinine concentrations may be measured to confirm diagnosis. Vol. The ricin content of castor bean varies with the growing conditions and genetics of the plant (Millard and LeClaire, 2008). First, you’re going to need a laminar flow hood or a glovebox. Both type 1 and type 2 RIPs are functionally active against ribosomes in vitro; however, only type 2 RIPs display cytotoxicity due to the lectin-like properties of the B chain. Chemical and Pharmaceutical Bulletin. The Cas Register Number of Ricin is 9009-86-3.
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