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Ricin

12:52 AM // 0 comments // sb blogger // Category: Biological Toxins , Ricin , Weapons //

Site of Action
Ricin is a member of a class of plant toxins known as type 2 ribosome inactivating proteins. It has two subunits held together by a covalent bond (a disulfide bridge.) The B subunit binds to specific structures on the surface of a cell stimulating its uptake. The A subunit is carried along with it and is an enzyme (an N-glycosidase) that catalyzes the removal of a specific component from the ribosomal RNA that could be compared to removing the keystone from and arch and causing inactivation of the ribosome. The loss of protein synthesis leads to cell death and tissue damage. The catalytic action, meaning that a single molecule of the toxin can inactivate many ribosomes, makes the protein particularly effective.
Source
The protein is extracted from the seed of the castor bean plant(Ricinus communis): a widely used, attractive and rapidly growing ornamental vine that is also grown on a large scale for castor oil production.
Castor oil manufacturers are to be encouraged to use hot-press rather than cold-press methods to extract castor oil to minimize the recovery of ricin from the waste.




Symptoms
  • By ingestion:
    • abdominal pain,
    • vomiting,
    • diarrhea, bloody diarrhea
    • damage to major organs:
      • liver,
      • kidney,
      • spleen
  • By inhalation:
    • weakness,
    • fever,
    • nausea,
    • dyspnea (difficulty breathing),
    • cough,
    • pulmonary edema
    • arthralgia (pain in the joints).
Onset of Symptoms
Within a few hours by ingestion and within 18-24 hours by inhalation. If a lethal dose is experienced, time to death is a matter of a few days.
Rapid diagnostic assay
ELISA's are available for the detection of ricin. In the event of its use as a weapon, clustering of patients with similar symptoms may be the first and only clue. Particular attention in a BW environment must be paid to the lungs as inhalation toxicity will be the most likely form of poisoning, diagnosis may be by elimination of other possibilities, including:
  • inhalation anthrax,
  • Q fever,
  • tularemia,
  • Staphylococcal enterotoxin B,
  • phosgene.
Antidote
None available. Possible antidotes include sugar analogs that prevent ricin binding to its target and the AIDS drug AZT that may inhibit the catalytic subunit.
Supportive Care
Symptoms are treated. For inhalation exposure, breathing is supported and pulmonary edema is treated. Exposure by ingestion is treated by absorbing the toxin onto generous quantities of superactivated charcoal and the digestive tract is then cleared out with a cathartic.
Inactivation
Decontamination with dilute bleach or soap and water.
 
International Disease Classification Codes for Ricin Poisoning
Disease
ICD-9-CM
ICD-10
Toxic effect of berries & other
plants eaten as food
988.2
T62.1



Toxicity
Route
LD50(micrograms/kg)
Intravenous
3.0
Intraperitoneal
2.6



Chemical Properties
Structure

This is a set of four representations of ricin prepared from structural information in the Brookhaven Protein Data Bank viewed using the ChIME plug-in for Netscape. A larger image can be seen by clicking on each of the images.
  1. TopLeft: The blue strand is the A chain that has the toxic enzymic activity (an RNA N-glycosidase) of the protein and the green strand is the B chain responsible for binding to cells and being taken up by them. The ribbon-like winding of the A-chain shows it highly ordered structure.
  2. Top Right: A space filling view showing the atoms forming the surface of the molecule. The chains are color coded as above. The red areas are the sugar side chains of the protein that play a role in binding to the cell surface.
  3. Bottom Left: A ball and stick representation.
  4. A conformational presentation showing the regions of higher order structure in the molecule.
CA Name
Ricin
Trivial Names
  • Ricinus communis lectin

Note: This is not to be confused with Ricinus communis agglutinin, which is also toxic, but significantly less so than ricin.
Registry Number
9009-86-3
RTECS Number
VJ2625000
Molecular
Formula
Not applicable
Molecular
weight
The active dimer has a molecular weight of 60,000 with subunit molecular weights of 30,000.
Solubility
Freely soluble in water and dilute acetic acid.
pKa in water
Complete synthesis
No, and unlikely because of the ready availability of the raw material as waste from castor oil manufacture.


Agent Properties
Ricin is about 1,000-fold less toxic than botulin and is considered of marginal toxicity or effectiveness in comparison to it or Staphylococcal enterotoxin B, requiring tons to be delivered for effective battlefield use. However, hundreds of thousands of tons of castor seed waste containing 1-2% ricin are produced every year. The protein is relatively easily extracted from such waste and his means that such stockpiles are not out of the question. It has also been suggested that ricin can be used in combination with other biological agents to increase their effectiveness. Inhalation of ricin can damage the lungs easing the entry of pathogens spread through aerosols.
The protein is relatively robust and when freeze-dried, it forms a powder that disperses readily. Researchers are instructed not to freeze dry ricin because of this hazard.
Ricin is a valuable research tool and the catalytic subunit is being investigated for use in the treatment of cancers. When it is bound to an antibody that recognizes cancer cells, then it may be taken up by the cancer cells and ultimately kill them. This is known as an immunotoxin and the Australia group makes specific exclusions in the monitoring of ricin for such use.
Terrorist Acquisition and Attempted Use.
There have been at least two prosecutions in the United States under the Biological Weapons Anti-Terrorism act of 1989 for illegal possession of ricin powder. Ricin is seen as attractive as a terror weapon to fringe groups and a number of books and videos describe the small scale preparation of the protein. Some web sites describing the synthesis have been taken down.
Beginning in October 2003, someone known only as "Fallen Angel" started sending small quantities of crude ricin preparations to US politicians, including the President. Fallen Angel was objecting to new laws that required truckers to take longer rest breaks.
Assassination with Ricin: the strange case of the Bulgarian dissidents
Two Bulgarian dissidents who had been close to Communist President Todor Shivkov before disillusionment and defection fell prey to a bizarre assassination plot that is often compared to something out of James Bond or the Avengers.
The first effort: against Vladimir Kostov in Paris in August 1978 failed, although he was very ill for some time. The second, against BBC World Service commentator Georgi Markov, was successful. In September 1978, as he was walking across Waterloo Bridge in London on his way to Bush House (BBC World Service headquarters) when he was bumped by a man carrying an umbrella and felt a sharp pain. The man apologized and walked off and Markov fell ill within hours.
Markov told doctors what had happened and after his death a minute metal ball was recovered from his right thigh. The tiny sphere, 0.6 millimeters across (smaller than the ball of a ballpoint pen), had been exquisitely engineered as a carrier for poison with two holes 0.2 millimeters across (each made using a different technology) and traces of ricin were found in them.
A re-examination of Kostov found a similar ball in his back. He had been protected at the time of the attack by a heavy sweater that gave enough resistance to prevent complete penetration of the ball.
The interpretation placed on events, and subsequently confirmed, was that technicians at the Soviet KGB had modified an umbrella to turn it into a syringe that could deliver the poison. The KGB had previously used a version of this technique with briefcases as the delivery vehicle.
Zhivkov was unforgiving of those who betrayed him, especially the voluble and passionate Markov, but he did his regime as much damage as Markov could have done had he lived.


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