(Taken from Wekipedia)
Sarin, or
GB, is an
organophosphorus compound with the formula
[(CH3)2CHO]CH3P(O)F. It is a colorless, odorless liquid,
[4] used as a
chemical weapon owing to its extreme potency as a
nerve agent. It has been classified as a
weapon of mass destruction[5] in
UN Resolution 687. Production and stockpiling of sarin was outlawed by the
Chemical Weapons Convention of 1993, and it is classified as a
Schedule 1 substance.
Sarin can be lethal even at very low concentrations, with death
following within one minute after direct ingestion due to suffocation
from lung muscle paralysis, unless some antidotes, typically
atropine or
Biperiden and
pralidoxime, are quickly administered to a person.
[4] People who absorb a non-lethal dose, but do not receive immediate medical treatment, may suffer permanent neurological damage.
Production and structure
Sarin is a
chiral molecule because it has four chemically different
substituents attached to the
tetrahedral phosphorus center.
[6] The S
P form (the
(–) optical isomer) is the more active
enantiomer due to its greater
binding affinity to
acetylcholinesterase.
[7][8] The P-F bond is easily broken by
nucleophilic
agents, such as water and hydroxide. At high pH, sarin decomposes
rapidly to nontoxic phosphonic acid derivatives. It is usually
manufactured and weaponized as a
racemic mixture—an equal mixture of both enantiomeric forms—by the
alcoholysis reaction of
methylphosphonyl difluoride with
isopropyl alcohol:
Isopropylamine is also included in the reaction to neutralize the
hydrogen fluoride byproduct. As a
binary chemical weapon, it can be generated
in situ by this same reaction.
A by-product of sarin production is
diisopropyl methylphosphonate (DIMP), which degrades into
isopropyl methylphosphonic acid (IMPA).
[9]
Biological effects
Sarin (red), acetylcholinesterase (yellow), acetylcholine (blue)
Like other nerve agents, sarin attacks the
nervous system by stopping nerve endings in muscles from switching off. Death will usually occur as a result of
asphyxia due to the inability to control the muscles involved in breathing function.
Specifically, sarin is a potent
inhibitor of acetylcholinesterase,
[10] an enzyme that degrades the
neurotransmitter acetylcholine after it is released into the synaptic cleft. In vertebrates, acetylcholine is the neurotransmitter used at the
neuromuscular junction,
where signals are transmitted between neurons from the central nervous
systems to muscle fibres. Normally, acetylcholine is released from the
neuron to stimulate the muscle, after which it is degraded by
acetylcholinesterase, allowing the muscle to relax. A build-up of
acetylcholine in the synaptic cleft, due to the inhibition of
cholinesterase, means the neurotransmitter continues to act on the
muscle fibre, so that any nerve impulses are effectively continually
transmitted.
Sarin acts on cholinesterase by forming a
covalent bond with the particular
serine residue at the active site. Fluoride is the
leaving group, and the resulting
phosphoester is robust and biologically inactive.
[11][12]
Its mechanism of action resembles that of some commonly used insecticides, such as
malathion. In terms of biological activity, it resembles
carbamate insecticides, such as
Sevin, and the medicines
pyridostigmine,
neostigmine, and
physostigmine.
Degradation and shelf life
The most important chemical reactions of phosphoryl halides is the
hydrolysis of the bond between phosphorus and the fluoride. This P-F bond is easily broken by nucleophilic agents, such as water and
hydroxide. At high
pH, sarin decomposes rapidly to nontoxic
phosphonic acid derivatives.
[13][14]
The initial breakdown of sarin is into isopropyl methylphosphonic acid
(IMPA), a chemical that is not commonly found in nature except as a
breakdown product of sarin. IMPA then degrades into methylphosphonic
acid (MPA), which can also be produced by other organophosphates.
[15]
Sarin degrades after a period of several weeks to several months. The
shelf life can be shortened by impurities in precursor materials.
According to the
CIA, some Iraqi sarin had a shelf life of only a few weeks, owing mostly to impure precursors.
[16]
Its otherwise-short shelf life can be extended by increasing the purity of the precursor and intermediates and incorporating
stabilizers such as
tributylamine. In some formulations, tributylamine is replaced by
diisopropylcarbodiimide (DIC), allowing sarin to be stored in
aluminium casings. In
binary chemical weapons, the two precursors are stored separately in the same
shell
and mixed to form the agent immediately before or when the shell is in
flight. This approach has the dual benefit of solving the stability
issue and increasing the safety of sarin munitions.
Effects and treatment
Sarin has a high
volatility
(ease with which a liquid can turn into a gas) relative to similar
nerve agents, therefore inhalation can be very dangerous and even vapor
concentrations may immediately penetrate the skin. A person’s clothing
can release sarin for about 30 minutes after it has come in contact with
sarin gas, which can lead to exposure of other people.
[17]
People who absorb a non-lethal dose but do not receive immediate
appropriate medical treatment may suffer permanent neurological damage.
Even at very low concentrations, sarin can be fatal. Death may follow
in one minute after direct ingestion of a lethal dose unless
antidotes, typically
atropine and
pralidoxime, are quickly administered.
[4] Atropine, an
antagonist to
muscarinic acetylcholine receptors,
is given to treat the physiological symptoms of poisoning. Since
muscular response to acetylcholine is mediated through nicotinic
acetylcholine receptors, atropine does not counteract the muscular
symptoms. Pralidoxime can regenerate
cholinesterases if administered within approximately five hours.
Biperiden, a synthetic acetylcholine antagonist, has been suggested as an alternative to atropine due to its better
blood–brain barrier penetration and higher efficacy.
[18]
Sarin is 26 times more deadly than
cyanide.
[19] The
LD50 of subcutaneously injected sarin in mice is 172 μg/kg.
[20] Treatment measures have been described.
[21]
Initial symptoms following exposure to sarin are a runny nose, tightness in the chest and constriction of the
pupils. Soon after, the victim has difficulty breathing and experiences
nausea
and drooling. As the victim continues to lose control of bodily
functions, the victim vomits, defecates and urinates. This phase is
followed by
twitching and jerking. Ultimately, the victim becomes comatose and suffocates in a series of convulsive
spasms. Moreover, common mnemonics for the symptomatology of organophosphate poisoning, including sarin gas, are the "killer B's" of
bronchorrhea and
bronchospasm because they are the leading cause of death,
[22] and
SLUDGE - Salivation, Lacrimation, Urination, Defecation, Gastrointestinal distress, and Emesis.
Diagnostic tests
Controlled studies in healthy men have shown that a nontoxic 0.43 mg
oral dose administered in several portions over a 3 day interval caused
average maximum depressions of 22 and 30%, respectively, in plasma and
erythrocyte cholinesterase levels. A single acute 0.5 mg dose caused
mild symptoms of intoxication and an average reduction of 38% in both
measures of cholinesterase activity. Sarin in blood is rapidly degraded
either
in vivo or
in vitro. Its primary inactive metabolites have
in vivo serum half-lives of approximately 24 hours. The serum level of unbound
isopropylmethylphosphonic acid
(IMPA), a sarin hydrolysis product, ranged from 2-135 µg/L in survivors
of a terrorist attack during the first 4 hours post-exposure. Sarin or
its metabolites may be determined in blood or urine by gas or liquid
chromatography, while cholinesterase activity is usually measured by
enzymatic methods.
[23]
History
Sarin was discovered in 1938 in
Wuppertal-Elberfeld in Germany by scientists at
IG Farben attempting to create stronger pesticides; it is the most toxic of the four
G-Series nerve agents made by Germany. The compound, which followed the discovery of the
nerve agent tabun, was named in honor of its discoverers:
Schrader,
Ambros, Gerhard Ritter and Van der Linde.
[24]
Use as a weapon
In mid-1939, the formula for the agent was passed to the
chemical warfare section of the
German Army Weapons Office,
which ordered that it be brought into mass production for wartime use. A
number of pilot plants were built, and a high-production facility was
under construction (but was not finished) by the end of
World War II. Estimates for total sarin production by Nazi Germany range from 500 kg to 10 tons.
[25] Though sarin,
tabun and
soman were incorporated into
artillery shells, Germany did not use nerve agents against
Allied targets.
- 1950s (early): NATO adopted sarin as a standard chemical weapon, and both the USSR and the United States produced sarin for military purposes.
- 1953: 20-year-old Ronald Maddison, a Royal Air Force engineer from Consett, County Durham, died in human testing of sarin at the Porton Down chemical warfare testing facility in Wiltshire, England. Ten days after his death an inquest
was held in secret which returned a verdict of "misadventure". In 2004,
the inquest was reopened and, after a 64-day inquest hearing, the jury
ruled that Maddison had been unlawfully killed by the "application of a
nerve agent in a non-therapeutic experiment."[26]
- 1956: Regular production of sarin ceased in the United States,
though existing stocks of bulk sarin were re-distilled until 1970.
- March 1988: Over the span of two days in March, the ethnic Kurd city of Halabja in northern Iraq (population 70,000) was bombarded with chemical and cluster bombs, which included sarin, in the Halabja poison gas attack. An estimated 5,000 people died.[27]
- April 1988: Sarin was used four times against Iranian soldiers in April 1988 at the end of the Iran–Iraq War, helping Iraqi forces to retake control of the al-Faw Peninsula during the Second Battle of al-Faw.
Using satellite imagery, the United States assisted Iraqi forces in
locating the position of the Iranian troops during those attacks.[28]
- 1993: The United Nations Chemical Weapons Convention
was signed by 162 member countries, banning the production and
stockpiling of many chemical weapons, including sarin. It went into
effect on 29 April 1997, and called for the complete destruction of all
specified stockpiles of chemical weapons by April 2007.[29]
- 1994: The Japanese religious sect Aum Shinrikyo released an impure form of sarin in Matsumoto, Nagano, killing eight people and harming over 200. (see Matsumoto incident)
- 1995: Aum Shinrikyo sect released an impure form of sarin in the Tokyo Metro. Thirteen people died. (see Sarin gas attack on the Tokyo subway)
- 1998: In the US, Time Magazine and CNN ran false news stories alleging that in 1970 U.S. Air Force A-1E Skyraiders engaged in a covert operation called Operation Tailwind, in which they deliberately dropped sarin-containing weapons on U.S. troops who had defected in Laos. CNN and Time Magazine later retracted the stories and fired the producers responsible.[30]
- 2004: Iraqi insurgents detonated a 155 mm shell containing binary precursors for sarin near a U.S. convoy in Iraq.
The shell was designed to mix the chemicals as it spins during flight.
The detonated shell released only a small amount of sarin gas, either
because the explosion failed to mix the binary agents properly or
because the chemicals inside the shell had degraded with age. Two United
States soldiers were treated after displaying the early symptoms of
exposure to sarin.[31]
- 21 August 2013: Sarin was used in an attack in the Ghouta region of the Rif Dimashq Governorate of Syria during the Syrian civil war.[32] Varying[33] sources gave a death toll of 322[34] to 1,729.[35]
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