Overview of all the structural information available in the, This page was last edited on 27 November 2020, at 13:13. C23H33N3O2. Shock and organ failure are indicated by disorientation, stupor, weakness, drowsiness, excessive thirst (polydipsia), low urine production (oliguria), and bloody urine (hematuria). Because ricin is stable over a wide pH range, degradation in endosomes or lysosomes offers little or no protection against ricin. Despite ricin's extreme toxicity and utility as an agent of chemical/biological warfare, it is extremely difficult to limit the production of the toxin. Vol. Ricin is a powerful poison that could be used as an agent of biological warfare or as a weapon of mass destruction (WMD). The vaccine is safe and immunogenic in mice, rabbits, and humans. Despite this, more than 1 million metric tons (1,100,000 short tons) of castor beans are processed each year, and approximately 5% of the total is rendered into a waste containing negligible concentrations of undenatured ricin toxin. [1] The median lethal dose (LD50) of ricin for mice is around 22 micrograms per kilogram of body weight via intraperitoneal injection. Castor oil is a colourless to very pale yellow liquid with a distinct taste and odor. This conclusion was based on comparison of the final weapons, rather than ricin's toxicity (LCt50 ~10 mg/min/m3). It is composed of two chains, as shown here from PDB entry 2aai , each with a specific job.The "B" chain (in blue) is the targeting mechanism, and the "A" chain (in red) is the toxic portion. 963, 1966. [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. This is indicated by edema of the eyes and lips; asthma; bronchial irritation; dry, sore throat; congestion; skin redness (erythema); skin blisters (vesication); wheezing; itchy, watery eyes; chest tightness; and skin irritation. Ricin (/ˈraɪsɪn/ RY-sin) is a lectin (a carbohydrate-binding protein) and a highly potent toxin produced in the seeds of the castor oil plant, Ricinus communis. [30], Ingestion of ricin causes pain, inflammation, and hemorrhage in the mucosal membranes of the gastrointestinal system. Latest. CGP-53153. 351, 1977. CAS #: 9009-86-3 Alternate CAS #: 9067-26-9 RTECS #: VJ2625000. He was sentenced, on 18 September 2015, to eight years imprisonment.[70]. 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. Compared to botulinum or anthrax as biological weapons or chemical weapons, the quantity of ricin required to achieve LD50 over a large geographic area is significantly more than an agent such as anthrax (tons of ricin vs. only kilogram quantities of anthrax). Gastrointestinal symptoms quickly progress to severe nausea, vomiting, diarrhea, and difficulty swallowing (dysphagia). 1073, 1979. Vol. Survivors often develop long-term organ damage. [69] Mohammed Ali from Liverpool, England was convicted after attempting to purchase 500 mg of ricin over the dark web from an undercover FBI agent. [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". Ricin is a potent toxin extracted from castor beans (Ricinus communis). The laboratory testing usually involves immunoassay or liquid chromatography-mass spectrometry.[42]. [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. Eventually this is harmful to the whole body, and death may occur. Ricin is a glycoprotein toxin (66,000 daltons) from the seed of the castor plant. Ricin Overview. Second, Ondřej Kolář, the mayor of Prague 6 municipal district, who was involved in removing the controversial statue to the Soviet-era Marshal Konev. 148, 1994. Under both the 1972 Biological Weapons Convention and the 1997 Chemical Weapons Convention , ricin is listed as a schedule 1 controlled substance. 9009-86-3 - Ricin - Searchable synonyms, formulas, resource links, and other chemical … 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. DESCRIPTION: Ricin is an extremely toxic plant protein derived from the seeds of the castor bean plant (Ricinus communis). [58], Ten days before the attack on Georgi Markov another Bulgarian defector, Vladimir Kostov, survived a similar attack. Type 2 RIPs consist of an A chain that is functionally equivalent to a type 1 RIP, covalently connected by a single disulfide bond to a B chain that is catalytically inactive, but serves to mediate transport of the A-B protein complex from the cell surface, via vesicle carriers, to the lumen of the endoplasmic reticulum (ER). Some researchers have speculated about using ricins in the treatment of cancer, as a so-called "magic bullet" to destroy targeted cells. [29][38], Deaths from ingesting castor plant seeds are rare, partly because of their indigestible seed coat, and because some of the ricin is deactivated in the stomach. In terms of structure, ricin closely resembles abrin-a, an isotoxin of abrin. Vol. 582, 1973. [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. [30], Vaccination is possible by injecting an inactive form of protein chain A. A dose of purified ricin powder the size of a few grains of table salt can kill an adult human. [11] RTB has been shown to bind to the cell surface on the order of 106-108 ricin molecules per cell surface. 259, 1979. Detecting biological and chemical agents . Acta Pharmacologica et Toxicologica, Supplementun. 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. Type 2 RIPs consist of an A chain that is functionally equivalent to a type 1 RIP, covalently connected by a single disulfide bondto a B chain that is catalytically inactive, but serves to mediate transport of the A-B protein complex from the c… As a terrorism agent, ricin can be used as a powder, a mist, a pellet, or can be dissolved in water or weak acid. If you are near a release of ricin, emergency coordinators may tell you to either evacuate the area or to “shelter in place” inside a building to avoid being exposed to the chemical. 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]. Chemical Formula: C 21 H 16 FN 3 OS. [56], Ricin has been involved in a number of incidents. [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. [30], Symptoms of ricin inhalation are different from those caused by ingestion. After Markov's death the wound on Kostov's back was examined and a ricin-laced pellet identical to the one used against Markov was removed. 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. [30], When skin or inhalation exposure occur, ricin can cause an allergy to develop. Vol. 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. Ricin could be linked to a monoclonal antibody to target malignant cells recognized by the antibody. Pharmacology and Toxicology Vol. 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. With appropriate treatment, most patients will make a decent recovery. [12], The profuse binding of ricin to surface membranes allows internalization with all types of membrane invaginations. A dose of purified ricin powder the size of a few grains of table salt can kill an adult human. Within the active site of RTA, there exist several invariant amino acid residues involved in the depurination of ribosomal RNA. Dislocation of RTA requires ER membrane-integral E3 ubiquitin ligase complexes,[23] but RTA avoids the ubiquitination that usually occurs with ERAD substrates because of its low content of lysine residues, which are the usual attachment sites for ubiquitin. National Technical Information Service. Ricin is a highly-toxic compound derived from castor plant beans. [67], The popularity of Breaking Bad inspired several real-life criminal cases involving ricin or similar substances. Ribosomes produce all of the proteins needed by a cell. Within the lumen of the ER the propolypeptide is glycosylated and a protein disulfide isomerase catalyzes disulfide bond formation between cysteines 294 and 318. First, you’re going to need a laminar flow hood or a glovebox. By ingestion, the pathology of ricin is largely restricted to the gastrointestinal tract, where it may cause mucosal injuries. The castor bean plant from which ricin is derived is a common ornamental and can be grown at home without any special care. The prime suspects were the Bulgarian secret police: Georgi Markov had defected from Bulgaria some years previously and had subsequently written books and made radio broadcasts that were highly critical of the Bulgarian communist regime. In September 1978, a Bulgarian dissident, Georgi Markov, was assassinated by a pellet of ricin … 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. [53] Ricin is easy to produce, but is not as practical or likely to cause as many casualties as other agents. Without the proteins, cells die. "Toxicology of Drugs and Chemicals," Deichmann, W.B., New York, Academic Press, Inc., 1969Vol. [10], The seeds of Ricinus communis are commonly crushed to extract castor oil. 41, Pg. at UT Southwestern. "Prehled Prumyslove Toxikologie; Organicke Latky," Marhold, J., Prague, Czechoslovakia, Avicenum, 1986Vol. [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]. A general guide is 1 to 2 mg of ricin/g of ground castor seed. 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. Ricin is one of the most poisonous substances on Earth and it's scarily easy to make. 1903), specifically Annex §2, Ch.1, Article 23, stating "... it is especially prohibited ... [t]o employ poison or poisoned arms". Where is ricin found, and how is it used? Ricin works by getting inside the cells of a person’s body and preventing the cells from making the proteins they need. The propolypeptide is further glycosylated within the Golgi apparatus and transported to protein storage bodies. Haemorrhage causes bloody feces (melena) and vomiting blood (hematemesis). 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. [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). 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. [31] Ricin is easily denatured by temperatures over 80 °C (176 °F) meaning many methods of deploying ricin would generate enough heat to denature it. [10] In 2013 a 37-year-old woman in the United States survived after ingesting 30 beans. Vol. 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 … 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. LIVER: "HEPATITIS (HEPATOCELLULAR NECROSIS), DIFFUSE", VASCULAR: BP LOWERING NOT CHARACTERIZED IN AUTONOMIC SECTION, BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY). Un­til the mid-20th cen­tu­ry, mer­cury was wide­ly used in medicine. Under both the 1972 Biological Weapons Convention and the 1997 Chemical Weapons Convention, ricin is listed as a schedule 1 controlled substance. [46] At that time it was being considered for use either as a toxic dust or as a coating for bullets and shrapnel. [49], The Soviet Union also possessed weaponized ricin. [61] On 2 October 2018, two letters suspected of containing ricin were sent to The Pentagon; one addressed to Secretary of Defense James Mattis, and the other to Chief of Naval Operations, Admiral John Richardson. If the ricin release was outside, move away from the area where the ricin was released. [3], Ricin is synthesized in the endosperm of castor oil plant seeds. There is a lot of fear and misinformation associated with this poison. The castor oil plant has many uses including natural hair growth and eyebrow and eyelash improvement. [13][14] Intracellular vesicles shuttle ricin to endosomes that are delivered to the Golgi apparatus. Ricin (rye-sin) is a chemical poison present in castor beans. It blocks protein synthesis by altering the rRNA, thus killing the cell. 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. Chemical formula-C21H16FN3OS. Kostov was standing on an escalator of the Paris metro when he felt a sting in his lower back above the belt of his trousers. The holotoxin can be taken up by clathrin-coated pits, as well as by clathrin-independent pathways including caveolae and macropinocytosis. Symptoms of poisoning depend on how you were exposed to it, for example, by inhalation, ingestion, or skin and eye exposure. The KGB developed weapons using ricin which were used outside the Soviet bloc, most famously in the Markov assassination.[50][51]. [28] The depurination event rapidly and completely inactivates the ribosome, resulting in toxicity from inhibited protein synthesis. [60] On 16 July 2014, Richardson was sentenced to 18 years in prison plus a restitution fine of $367,000. [10], Several terrorists and terrorist groups have experimented with ricin and caused several incidents of the poisons being mailed to US politicians. [37] Accidental ingestion of Ricinus communis cake intended for fertilizer has been reported to be responsible for fatal ricin poisoning in animals.
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