Sarin#Production and structure

File:Sarin Wirkungsweise.png{{Broader|Organophosphate poisoning}}

Like some other nerve agents that affect the neurotransmitter acetylcholine, sarin attacks the nervous system by interfering with the degradation of the neurotransmitter acetylcholine at neuromuscular junctions. Death usually occurs as a result of asphyxia due to the inability to control the muscles involved in breathing.{{cite book |last=Vohra |first=Rais |title=Poisoning & Drug Overdose |publisher=McGraw Hill |year=2022 |edition=8th |language=English |chapter=Organophosphorus and carbamate insecticides}}

Initial symptoms following exposure to sarin are a runny nose, tightness in the chest, and constriction of the pupils (miotic action). Soon after, the person will have difficulty breathing and experience nausea and drooling. This progresses to losing control of bodily functions, which may cause the person to vomit, defecate, and urinate. This phase is followed by twitching and jerking. Ultimately, the person becomes comatose and suffocates in a series of convulsive spasms. Common mnemonics for the symptomatology of organophosphate poisoning, including sarin, are the "killer Bs" of bronchorrhea and bronchospasm because they are the leading cause of death,{{cite journal |last=Gussow |first=Leon |title=Nerve Agents: Three Mechanisms, Three Antidotes |journal=Emergency Medicine News |publisher=Wolters Kluwer |location=Alphen aan den Rijn, Netherlands |volume=27 |issue=7 |page=12 |date=July 2005 |doi=10.1097/00132981-200507000-00011}} and SLUDGE – salivation, lacrimation, urination, defecation, gastrointestinal distress, and emesis (vomiting). Death may follow in one to ten minutes after direct inhalation, but may also occur after a delay ranging from hours to several weeks, in cases where exposure is limited but no antidote is applied.

Sarin has a high volatility (ease with which a liquid can turn into vapour) relative to similar nerve agents, making inhalation very easy, and may even absorb through 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.{{cite web |title=Facts About Sarin |publisher=Centers for Disease Control and Prevention |date=November 18, 2015 |url=https://www.cdc.gov/chemicalemergencies/factsheets/sarin.html |access-date=March 20, 2024}}

Treatment measures have been described. Treatment is typically with the antidotes atropine and pralidoxime. 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.{{cite journal |last=Shim |first=TM |author2=McDonough JH |title=Efficacy of biperiden and atropine as anticonvulsant treatment for organophosphorus nerve agent intoxication |journal=Archives of Toxicology |date=May 2000 |volume=74 |issue=3 |pages=165–172 |pmid=10877003 |s2cid=13749842 |doi=10.1007/s002040050670 |bibcode=2000ArTox..74..165S |url=https://apps.dtic.mil/sti/pdfs/ADA385192.pdf |access-date=April 29, 2018 |url-status=live |archive-url=https://web.archive.org/web/20170923164236/http://www.dtic.mil/get-tr-doc/pdf?AD=ADA385192 |archive-date=September 23, 2017}}

Sarin is a potent inhibitor of acetylcholinesterase,{{cite journal |vauthors=Abu-Qare AW, Abou-Donia MB |title=Sarin: health effects, metabolism, and methods of analysis |journal=Food and Chemical Toxicology |publisher=Elsevier |location=Amsterdam, Netherlands |volume=40 |issue=10 |pages=1327–33 |date=October 2002 |pmid=12387297 |doi=10.1016/S0278-6915(02)00079-0}} 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 peripheral nervous system 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 acetylcholinesterase, means the neurotransmitter continues to act on the muscle fibre, so that any nerve impulses are effectively continually transmitted.

Sarin acts on acetylcholinesterase by forming a covalent bond with the particular serine residue at the active site. Fluoride is the leaving group, and the resulting organo-phosphoester is robust and biologically inactive.{{cite journal |vauthors=Millard CB, Kryger G, Ordentlich A, etal |title=Crystal Structures of Aged Phosphonylated Acetylcholinesterase: Nerve Agent Reaction Products at the Atomic Level |journal=Biochemistry |volume=38 |issue=22 |pages=7032–9 |date=June 1999 |pmid=10353814 |s2cid=11744952 |doi=10.1021/bi982678l}}. See {{Proteopedia|1cfj}}.{{cite journal |last1=Hörnberg |first1=Andreas |last2=Tunemalm |first2=Anna-Karin |last3=Ekström |first3=Fredrik |title=Crystal Structures of Acetylcholinesterase in Complex with Organophosphorus Compounds Suggest that the Acyl Pocket Modulates the Aging Reaction by Precluding the Formation of the Trigonal Bipyramidal Transition State |journal=Biochemistry |volume=46 |issue=16 |pages=4815–4825 |year=2007 |pmid=17402711 |doi=10.1021/bi0621361}}

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.

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 acetylcholinesterase levels. A single acute 0.5 mg dose caused mild symptoms of intoxication and an average reduction of 38% in both measures of acetylcholinesterase 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 isopropyl methylphosphonic acid (IMPA), a sarin hydrolysis product, ranged from 2–135 μg/L in survivors of a terrorist attack during the first four hours post-exposure. Sarin or its metabolites may be determined in blood or urine by gas or liquid chromatography, while acetylcholinesterase activity is usually measured by enzymatic methods.{{cite book |last1=Baselt |first1=Randall C. |last2=Cravey |first2=Robert H. |title=Disposition of Toxic Drugs and Chemicals in Man |publisher=Biomedical Publications |location=Seal Beach, California |date=2017 |isbn=978-0-8151-0547-3 |pages=1926–1928 |url=https://archive.org/details/dispositionoftox00base |url-access=registration}}

A newer method called "fluoride regeneration" or "fluoride reactivation" detects the presence of nerve agents for a longer period after exposure than the methods described above. Fluoride reactivation is a technique that has been explored since at least the early 2000s. This technique obviates some of the deficiencies of older procedures. Sarin not only reacts with the water in the blood plasma through hydrolysis (forming so-called 'free metabolites'), but also reacts with various proteins to form 'protein adducts'. These protein adducts are not so easily removed from the body, and remain for a longer period of time than the free metabolites. One clear advantage of this process is that the period, post-exposure, for determination of sarin exposure is much longer, possibly five to eight weeks according to at least one study.{{cite report |title=Fluoride Ion Regeneration of Sarin (GB) from Minipig Tissue and Fluids Following Whole-Body GB Vapor Exposure |date=July 2003 |publisher=United States Army |last=Jakubowski |display-authors=etal |url=https://apps.dtic.mil/sti/tr/pdf/ADA484093.pdf |access-date=March 20, 2024 |url-status=live |archive-url=https://web.archive.org/web/20160102095524/http://www.dtic.mil/dtic/tr/fulltext/u2/a484093.pdf |archive-date=January 2, 2016}}{{cite journal |title=Improvements of the Fluoride Reactivation Method for the Verification of Nerve Agent Exposure |last=Degenhardt |display-authors=etal |date=July 2004 |journal=Journal of Analytical Toxicology |publisher=Oxford University Press |location=Oxfordshire, England |volume=28 |issue=5 |pages=364–371 |pmid=15239857 |doi=10.1093/jat/28.5.364 |doi-access=free}}

As a nerve gas, sarin in its purest form is estimated to be 26 times more deadly than cyanide.{{cite web |title=Sarin gas as chemical agent – ThinkQuest- Library |url=http://library.thinkquest.org/27393/dreamwvr/agents/sarin1.htm |access-date=August 13, 2007 |url-status=dead |archive-url=https://web.archive.org/web/20070808094319/http://library.thinkquest.org/27393/dreamwvr/agents/sarin1.htm |archive-date=August 8, 2007}} The LD₅₀ of subcutaneously injected sarin in mice is 172 μg/kg.{{cite journal |last=Inns |first=RH |author2=NJ Tuckwell |author3=JE Bright |author4=TC Marrs |title=Histochemical Demonstration of Calcium Accumulation in Muscle Fibres after Experimental Organophosphate Poisoning |journal=Hum Exp Toxicol |date=July 1990 |volume=9 |issue=4 |pages=245–250 |pmid=2390321 |bibcode=1990HETox...9..245I |s2cid=20713579 |doi=10.1177/096032719000900407}}

Sarin is highly toxic, whether by contact with the skin or breathed in. The toxicity of sarin in humans is largely based on calculations from studies with animals. The lethal concentration of sarin in air is approximately 28–35 mg per cubic meter per minute for a two-minute exposure time by a healthy adult breathing normally (exchanging 15 liters of air per minute, lower 28 mg/m³ value is for general population).{{cite book |title=Chemical Warfare Agents: Biomedical and Psychological Effects, Medical Countermeasures, and Emergency Response |last1=Lukey |first1=Brian J. |last2=Romano |first2=James A. Jr. |last3=Salem |first3=Harry |date=April 11, 2019 |publisher=CRC Press |isbn=978-0-429-63296-9 |language=en |url=https://books.google.com/books?id=DQqWDwAAQBAJ&q=exponent+lethality+vx&pg=PA174}} This number represents the estimated lethal concentration for 50% of exposed victims, the LCt₅₀ value. The LCt₉₅ or LCt₁₀₀ value is estimated to be 40–83 mg per cubic meter for exposure time of two minutes.{{cite book |title=Review of Acute Human-Toxicity Estimates for GB (Sarin) |last=Toxicology |first=National Research Council (US) Committee on |date=1997 |publisher=National Academies Press (US) |language=en |url=https://www.ncbi.nlm.nih.gov/books/NBK233733/}}{{cite journal |last1=Bide |first1=R. W. |last2=Armour |first2=S. J. |last3=Yee |first3=E. |date=2005 |title=GB toxicity reassessed using newer techniques for estimation of human toxicity from animal inhalation toxicity data: new method for estimating acute human toxicity (GB) |journal=Journal of Applied Toxicology |volume=25 |issue=5 |pages=393–409 |issn=0260-437X |pmid=16092087 |s2cid=8769521 |doi=10.1002/jat.1074}} Calculating effects for different exposure times and concentrations requires following specific toxic load models. In general, brief exposures to higher concentrations are more lethal than comparable long time exposures to low concentrations.{{cite book |title=Chemical Warfare Agents: Biomedical and Psychological Effects, Medical Countermeasures, and Emergency Response |last1=Lukey |first1=Brian J. |last2=Romano |first2=James A. Jr. |last3=Salem |first3=Harry |date=April 11, 2019 |publisher=CRC Press |isbn=978-0-429-63296-9 |language=en |url=https://books.google.com/books?id=DQqWDwAAQBAJ&q=exponent+lethality+vx&pg=PA171}} There are many ways to make relative comparisons between toxic substances. The list below compares sarin to some current and historic chemical warfare agents, with a direct comparison to the respiratory LCt₅₀:

• Hydrogen cyanide, 2,860 mg/(min·m³){{cite book |title=US Army Field Manual 3–11.9 Potential Military Chemical/Biological Agents and Compounds |publisher=United States Department of Defense |year=2005}} – Sarin is 81 times more lethal
• Phosgene, 1,500 mg/(min·m³) – Sarin is 43 times more lethal
• Sulfur mustard, 1,000 mg/(min·m³) – Sarin is 28 times more lethal
• Chlorine, 19,000 mg/(min·m³){{cite book |title=US Army Field Manual 3–9 Potential Military Chemical/Biological Agents and Compounds |publisher=United States Department of Defense |year=1990 |pages=71}} – Sarin is 543 times more lethal

Sarin is a chiral molecule because it has four chemically distinct substituents attached to the tetrahedral phosphorus center.{{cite book |last=Corbridge |first=D. E. C. |title=Phosphorus: An Outline of its Chemistry, Biochemistry, and Technology |publisher=Elsevier |location=Amsterdam, Netherlands |date=1995 |isbn=0-444-89307-5}} The S_P form (the (–) optical isomer) is the more active enantiomer due to its greater binding affinity to acetylcholinesterase.{{cite journal |last1=Kovarik |first1=Zrinka |last2=Radić |first2=Zoran |last3=Berman |first3=Harvey A. |last4=Simeon-Rudolf |first4=Vera |last5=Reiner |first5=Elsa |last6=Taylor |first6=Palmer |title=Acetylcholinesterase active centre and gorge conformations analysed by combinatorial mutations and enantiomeric phosphonates |journal=Biochemical Journal |publisher=Portland Press |location=London, England |date=March 2003 |volume=373 |pages=33–40 |pmid=12665427 |issue=Pt. 1 |pmc=1223469 |doi=10.1042/BJ20021862}}{{cite journal |title=Nerve agent stereoisomers: analysis, isolation and toxicology |last1=Benschop |first1=H. P. |last2=De Jong |first2=L. P. A. |journal=Accounts of Chemical Research |publisher=American Chemical Society |location=Washington DC |date=1988 |volume=21 |issue=10 |pages=368–374 |doi=10.1021/ar00154a003}} 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 almost always manufactured as a racemic mixture (a 1:1 mixture of its enantiomeric forms) as this involves a much simpler synthesis while providing an adequate weapon.

A number of production pathways can be used to create sarin. The final reaction typically involves attachment of the isopropoxy group to the phosphorus with an alcoholysis with isopropyl alcohol. Two variants of this final step are common. One is the reaction of methylphosphonyl difluoride with isopropyl alcohol, which produces a racemic mixture of sarin enantiomers with hydrofluoric acid as a byproduct:

:File:Sarin synth with racemic stereochemistry.png

The second process, known as the "Di-Di" process, uses equimolar quantities of methylphosphonyl difluoride (Difluoro) and methylphosphonyl dichloride (Dichloro). This reaction gives sarin, hydrochloric acid and others minors byproducts. The Di-Di process was used by the United States for the production of its unitary sarin stockpile.{{cite book |chapter=Chemical Weapons Technology |chapter-url=https://irp.fas.org/threat/mctl98-2/p2sec04.pdf |via=Federation of American Scientists |title=The Militarily Critical Technologies List Part II: Weapons of Mass Destruction Technologies (ADA 330102) |publisher=U.S. Department of Defense |author=Office of the Under Secretary of Defense for Acquisition and Technology |date=February 1998 |access-date=September 4, 2020}}

The scheme below shows a generic example that employs the Di-Di method as the final esterification step; in reality, the selection of reagents and reaction conditions dictate both product structure and yield. The choice of enantiomer of the mixed chloro fluoro intermediate displayed in the diagram is arbitrary, but the final substitution is selective for chloro over fluoro as the leaving group. Inert atmosphere and anhydrous conditions (Schlenk techniques) are used for synthesis of sarin and other organophosphates.

:File:Sarin-di-di-process-by-AHRLS-2011.png{{clear-left}}

As both reactions leave considerable acid in the product, sarin produced in bulk by these methods has a short half life without further processing, and would be corrosive to containers and damaging to weapons systems. Various methods have been tried to resolve these problems. In addition to industrial refining techniques to purify the chemical itself, various additives have been tried to combat the effects of the acid, such as:

• Tributylamine was added to US sarin produced at Rocky Mountain Arsenal.{{cite journal |title=Nerve Gas: America's Fifteen Year Struggle for Modern Chemical weapons |last=Kirby |first=Reid |date=January 2006 |journal=Army Chemical Review |url=http://www.wood.army.mil/chmdsd/images/pdfs/Jan-June%202006/Kirby-Nerve%20Gas.pdf |access-date=December 29, 2015 |url-status=dead |archive-url=https://web.archive.org/web/20170211021417/http://www.wood.army.mil/chmdsd/images/pdfs/Jan-June%202006/Kirby-Nerve%20Gas.pdf |archive-date=February 11, 2017}}
• Triethylamine was added to UK sarin, with relatively poor success.{{cite book |title=The Determination of Free Base in Stabilised GB |publisher=UK Ministry of Supply |year=1956 |location=United Kingdom |url=https://apps.dtic.mil/sti/tr/pdf/AD0090924.pdf |url-status=live |access-date=March 20, 2024 |archive-url=https://web.archive.org/web/20140828035415/http://www.dtic.mil/dtic/tr/fulltext/u2/090924.pdf |archive-date=August 28, 2014}} The Aum Shinrikyo cult experimented with triethylamine as well.{{cite web |title=New Information Revealed By Aum Shinrikyo Death Row Inmate Dr. Tomomasa Nakagawa |last=Tu |first=Anthony |url=http://www.foi.se/Global/V%C3%A5ra%20tj%C3%A4nster/Konferenser%20och%20seminarier/CBW%20symposium/Proceedings/Tu.pdf}}
• N,N-Diethylaniline was used by Aum Shinrikyo for acid reduction.{{cite news |title=The Sarin Gas Attack in Japan and the Related Forensic Investigation |date=June 2001 |publisher=OPCW |last=Seto |first=Yasuo |url=https://www.opcw.org/media-centre/news/2001/06/sarin-gas-attack-japan-and-related-forensic-investigation}}
• N,N′-Diisopropylcarbodimide was added to sarin produced at Rocky Mountain Arsenal to combat corrosion.{{cite book |title=Chemical agent and munition disposal summary of the U.S. army's experience |publisher=United States Army |year=1987 |pages=B-30 |url=http://apps.dtic.mil/dtic/tr/fulltext/u2/a193351.pdf |url-status=live |archive-url=https://web.archive.org/web/20150719010335/http://www.dtic.mil/dtic/tr/fulltext/u2/a193351.pdf |archive-date=July 19, 2015}}
• Isopropylamine was included as part of the M687 155 mm field artillery shell, which was a binary sarin weapon system developed by the US Army.{{cite news |last=Hedges |first=Michael |date=May 18, 2004 |title=Shell said to contain sarin poses questions for U.S. |work=Houston Chronicle |page=A1 |url=https://www.chron.com/news/nation-world/article/artillery-shell-with-sarin-poses-dilemma-for-u-s-1974450.php |access-date=December 30, 2015 |url-status=live |archive-url=https://web.archive.org/web/20151012210347/http://www.chron.com/news/nation-world/article/Artillery-shell-with-sarin-poses-dilemma-for-U-S-1974450.php |archive-date=October 12, 2015}}

Another byproduct of these two chemical processes is diisopropyl methylphosphonate, formed when a second isopropyl alcohol reacts with the sarin itself and from disproportionation of sarin, when distilled incorrectly. The factor of its formation in esterification is that as the concentration of DF-DCl decreases, the concentration of sarin increases, the probability of DIMP formation is greater. DIMP is a natural impurity of sarin, that is almost impossible to be eliminated, mathematically, when the reaction is a 1 mol-1 mol "one-stream".cit-OPDC. The preparatory manual to chemical warfare. Vol 1: Sarin.

:{{chem2 | (CH3)2CHO- + CH3P(O)FOCH(CH3)2 -> CH3P(O)(OCH(CH3)2)2 + F- }}

This chemical degrades into isopropyl methylphosphonic acid.{{cite web |work=Agency for Toxic Substances and Disease Registry |title=Toxic Substances Portal – Diisopropyl Methylphosphonate (DIMP) |url=https://wwwn.cdc.gov/TSP/PHS/PHSLanding.aspx?id=967&tid=203}}

File:Sarin test rabbit.jpg), 1970]]

The most important chemical reactions of phosphoryl halides is the hydrolysis of the bond between phosphorus and the fluorine atom. 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.{{cite web |title=Nerve agents |publisher=OPCW |url=http://www.opcw.org/about-chemical-weapons/types-of-chemical-agent/nerve-agents/}}{{Housecroft1st|page=317}} 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 (this is useful for detecting the recent deployment of sarin as a weapon). IMPA then degrades into methylphosphonic acid (MPA), which can also be produced by other organophosphates.Ian Sample, The Guardian, September 17, 2013, [https://www.theguardian.com/world/2013/sep/17/sarin-deadly-history-nerve-agent-syria-un Sarin: the deadly history of the nerve agent used in Syria]

Sarin with residual acid 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.{{cite web |publisher=United States Central Intelligence Agency |date=July 15, 1996 |title=Stability of Iraq's Chemical Weapon Stockpile |url=https://fas.org/irp/gulf/cia/960715/72569.htm |access-date=August 3, 2007}}

Along with nerve agents such as tabun and VX, sarin can have a short shelf life. Therefore, it is usually stored as two separate precursors that produce sarin when combined.{{cite news |title=Key Points on Sarin: The 'Most Volatile' of Nerve Agents |author=Russell Goldmanpril |date=April 6, 2017 |newspaper=New York Times |url=https://www.nytimes.com/2017/04/06/world/middleeast/sarin-nerve-agent.html}} Sarin's 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.

Sarin was discovered in 1938 in Wuppertal-Elberfeld in Germany by scientists at IG Farben who were 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: chemist Gerhard Schrader, chemist Otto Ambros, chemist {{interlanguage link|Gerhard Ritter (chemist)|lt=Gerhard Ritter|de|Gerhard Ritter (Chemiker)|display=yes}}, and from Heereswaffenamt Hans-Jürgen von der Linde.{{cite book |author=Richard J. Evans |title=The Third Reich at War, 1939–1945 |year=2008 |publisher=Penguin |isbn=978-1-59420-206-3 |page=[https://archive.org/details/thirdreichatwar00evan_1/page/n710 669] |url=https://archive.org/details/thirdreichatwar00evan_1 |url-access=registration |access-date=January 13, 2013}}

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. Pilot plants were built, and a 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.{{cite news |title=A Short History of the Development of Nerve Gases |publisher=Noblis |url=http://noblis.com/MissionAreas/nsi/BackgroundonChemicalWarfare/HistoryofChemicalWarfare/Pages/HistoryNerveGas.aspx |url-status=dead |archive-url=https://web.archive.org/web/20110429191343/http://noblis.com/MissionAreas/nsi/BackgroundonChemicalWarfare/HistoryofChemicalWarfare/Pages/HistoryNerveGas.aspx |archive-date=April 29, 2011}}

Though sarin, tabun, and soman were incorporated into artillery shells, Germany did not use nerve agents against Allied targets. Adolf Hitler refused to initiate the use of gases such as sarin as weapons.{{cite book |title=Hitler's Miracle Weapons: The Secret History Of The Rockets And Flying Crafts Of The Third Reich; from the V-1 to the A-9: Unconventional Short- and Medium-Range Weapons |last=Georg |first=Friedrich |page=49 |publisher=Helion |date=2003 |isbn=978-1-87-462262-8 |url=https://books.google.com/books?id=KAYhAQAAIAAJ}}

File:Demonstration cluster bomb.jpg warhead cutaway, showing M134 Sarin bomblets (c. 1960)]]

File:Sarin Gas against animals - weapons experiment.ogg

• 1950s (early): NATO adopted sarin as a standard chemical weapon. 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".{{cite news |work=BBC News Online |title=Nerve gas death was 'unlawful' |date=November 15, 2004 |url=http://news.bbc.co.uk/1/hi/england/wiltshire/4013767.stm}}
• 1957: Regular production of sarin chemical weapons ceased in the United States, though existing stocks of bulk sarin were re-distilled until 1970.
• 1970: During Operation Tailwind, America may have deployed Sarin gas against the Communist Pathet Lao, alongside American defectors to the Laotian Communists.{{cite book |last1=Churchill |first1=Ward |title=On the Justice of Roosting Chickens |publisher=AK Press |page=240}}
• 1976: Chile's intelligence service, DINA, assigned biochemist Eugenio Berríos to develop Sarin gas within its program Proyecto Andrea, to be used as a weapon against its opponents.{{cite web |last=Blixen |first=Samuel |title=Pinochet's Mad Scientist |website=Consortium News |date=January 13, 1999 |url=http://www.consortiumnews.com/1999/c011399a.html}} One of DINA's goals was to package it in spray cans for easy use, which, according to testimony by former DINA agent Michael Townley, was one of the planned procedures in the 1976 assassination of Orlando Letelier. Berríos later testified that it was used in a number of assassinations and it was planned to be used to kill inhabitants, through poisoning the water supply of Argentine capital Buenos Aires, in case Operation Soberanía took place.{{cite news |title=Towley reveló uso de gas sarín antes de ser expulsado de Chile |newspaper=El Mercurio |date=September 19, 2006 |language=es}}{{cite news |work=New York Times |title=Plot to kill Letelier said to involve nerve gas |date=December 13, 1981 |url=https://www.nytimes.com/1981/12/13/us/plot-to-kill-letelier-said-to-involve-nerve-gas.html |access-date=June 8, 2015}}
• March 1988: Halabja chemical attack; Over two days in March, the ethnic Kurdish city of Halabja in northern Iraq (population 70,000) was bombarded by Saddam Hussein's Iraqi Air Force jets with chemical bombs including sarin. An estimated 5,000 people died, almost all civilians.{{cite news |work=BBC News |title=1988: Thousands die in Halabja gas attack |date=March 16, 1988 |url=http://news.bbc.co.uk/onthisday/hi/dates/stories/march/16/newsid_4304000/4304853.stm |access-date=October 31, 2011}}
• April 1988: Iraq used Sarin four times against Iranian soldiers 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.
• 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 April 29, 1997, and called for the complete destruction of all specified stockpiles of chemical weapons by April 2007.{{cite web |title=Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction |publisher=Organisation for the Prohibition of Chemical Weapons |url=http://www.opcw.org/html/db/cwc/eng/cwc_frameset.html |access-date=March 27, 2011}} When the convention entered force, the parties declared worldwide stockpiles of 15,047 tonnes of sarin. As of November 28, 2019, 98% of the stockpiles have been destroyed.{{cite report |author=Organisation for the Prohibition of Chemical Weapons |date=November 30, 2016 |title=Report of the OPCW on the Implementation of the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on Their Destruction in 2015 |chapter-url=https://www.opcw.org/documents-reports/annual-reports/ |chapter=Annex 3 |page=42 |access-date=March 8, 2017}}
• 1994: Matsumoto incident; the Japanese religious sect Aum Shinrikyo released an impure form of sarin in Matsumoto, Nagano, killing eight people and harming over 500. The Australian sheep station Banjawarn was a testing ground.
• 1995: Tokyo subway sarin attack; the Aum Shinrikyo sect released an impure form of sarin in the Tokyo Metro. Twelve people died, and over 6,200 people received injuries.{{cite report |pages=91,95,100 |chapter=Chapter 3 – Rethinking the Lessons of Tokyo |chapter-url=http://www.stimson.org/books-reports/ataxia-the-chemical-and-biological-terrorism-threat-and-the-us-response/ |title=Ataxia: The Chemical and Biological Terrorism Threat and the US Response |author=Amy E. Smithson and Leslie-Anne Levy |publisher=Henry L. Stimson Centre |date=October 2000 |id=Report No. 35 |access-date=January 6, 2017 |url-status=dead |archive-url=https://web.archive.org/web/20150924110431/http://www.stimson.org/books-reports/ataxia-the-chemical-and-biological-terrorism-threat-and-the-us-response/ |archive-date=September 24, 2015}}{{cite news |last1=Martin |first1=Alex |title=1995 Aum sarin attack on Tokyo subway still haunts, leaving questions unanswered |work=The Japan Times Online |date=March 19, 2018 |url=https://www.japantimes.co.jp/news/2018/03/19/national/crime-legal/1995-aum-sarin-attack-tokyo-subway-still-haunts-leaving-questions-unanswered/}}
• 2002: Pro-Chechen militant Ibn al-Khattab may have been assassinated with sarin by the Russian government.{{cite news |title=More of Kremlin's Opponents Are Ending Up Dead |date=August 21, 2016 |work=The New York Times |url=https://www.nytimes.com/2016/08/21/world/europe/moscow-kremlin-silence-critics-poison.html}}{{cite journal |title=The chemical weapons convention and OPCW: the challenges of the 21st century |author=Ian R Kenyon |date=June 2002 |journal=The CBW Conventions Bulletin |publisher=Harvard Sussex Program on CBW Armament and Arms Limitation |issue=56 |page=47 |url=http://www.fas.harvard.edu/~hsp/bulletin/cbwcb56.pdf}}
• May 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 spun 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.{{cite news |title=Bomb said to hold deadly Sarin gas explodes in Iraq |last=Brunker |first=Mike |date=May 17, 2004 |publisher=MSNBC |url=https://www.nbcnews.com/id/wbna4997808 |access-date=August 3, 2007}}
• March 2013: Khan al-Assal chemical attack; Sarin was used in an attack on a town west of Aleppo city in Syria, killing 28 and wounding 124.{{cite news |last=Barnard |first=Anne |title=Syria and Activists Trade Charges on Chemical Weapons |newspaper=The New York Times |date=March 19, 2013 |url=https://www.nytimes.com/2013/03/20/world/middleeast/syria-developments.html?pagewanted=all |access-date=March 19, 2013}}
• August 2013: Ghouta chemical attack; Sarin was used in multiple simultaneous attacks in the Ghouta region of the Rif Dimashq Governorate of Syria during the Syrian Civil War.{{cite news |last=Murphy |first=Joe |title=Cameron: British scientists have proof deadly Sarin gas was used in chemical weapons attack |date=September 5, 2013 |newspaper=The Daily Telegraph |df=mdy-all |url=https://www.independent.co.uk/news/world/middle-east/cameron-british-scientists-have-proof-deadly-sarin-gas-was-used-in-chemical-weapons-attack-8800528.html |url-status=live |archive-url=https://web.archive.org/web/20130906013530/http://www.independent.co.uk/news/world/middle-east/cameron-british-scientists-have-proof-deadly-sarin-gas-was-used-in-chemical-weapons-attack-8800528.html |archive-date=September 6, 2013}} Varying{{cite news |title=Syria: Thousands suffering neurotoxic symptoms treated in hospitals supported by MSF |publisher=Médecins Sans Frontières |date=August 24, 2013 |df=mdy-all |url=http://www.msf.org/article/syria-thousands-suffering-neurotoxic-symptoms-treated-hospitals-supported-msf |access-date=August 24, 2013 |url-status=live |archive-url=https://web.archive.org/web/20130826214418/http://www.msf.org/article/syria-thousands-suffering-neurotoxic-symptoms-treated-hospitals-supported-msf |archive-date=August 26, 2013}} sources gave a death toll of 322{{cite news |title=NGO says 322 died in Syria 'toxic gas' attacks |agency=AFP |date=August 25, 2013 |url=http://www.ndtv.com/article/world/322-died-in-syria-toxic-gas-attacks-ngo-410028 |access-date=August 24, 2013}} to 1,729.{{cite news |title=Bodies still being found after alleged Syria chemical attack: opposition |publisher=Dailystar.com.lb |url=http://www.dailystar.com.lb/News/Middle-East/2013/Aug-22/228268-bodies-still-being-found-after-alleged-syria-chemical-attack-opposition.ashx |access-date=August 24, 2013 |url-status=dead |archive-url=https://web.archive.org/web/20190305230820/http://www.dailystar.com.lb/News/Middle-East/2013/Aug-22/228268-bodies-still-being-found-after-alleged-syria-chemical-attack-opposition.ashx |archive-date=March 5, 2019}}
• April 2017: Khan Shaykhun chemical attack: The Syrian Air Force released sarin gas in rebel-held Idlib Province in Syria during an airstrike.{{cite news |title=Chemical attack of 4 April 2017 (Khan Sheikhoun): Clandestine Syrian chemical weapons programme |language=en |url=http://www.diplomatie.gouv.fr/IMG/pdf/170425_-_evaluation_nationale_-_anglais_-_final_cle0dbf47-1.pdf |access-date=April 26, 2017}}{{cite news |title=Syrian regime dropped sarin on rebel-held town in April, UN confirms |last=Chulov |first=Martin |date=September 6, 2017 |work=The Guardian |language=en-GB |issn=0261-3077 |url=https://www.theguardian.com/world/2017/sep/06/syrian-regime-dropped-sarin-on-rebel-held-town-in-april-un-confirms |access-date=December 29, 2017}}
• April 2018: Victims of the Douma chemical attack in Syria reported to have symptoms consistent with exposure to sarin and other agents. On July 6, 2018, the Fact-Finding Mission (FFM) of the OPCW published their interim report. The report stated that, "The results show that no organophosphorous [sarin] nerve agents or their degradation products were detected in the environmental samples or in the plasma samples taken from alleged casualties". The chemical agent used in the attack was later identified as elemental chlorine.{{cite report |title=OPCW Issues Fact-Finding Mission Reports on Chemical Weapons Use Allegations in Douma, Syria in 2018 and in Al-Hamadaniya and Karm Al-Tarrab in 2016 |publisher=Organisation for the Prohibition of Chemical Weapons |date=July 6, 2018 |url=https://www.opcw.org/news/article/opcw-issues-fact-finding-mission-reports-on-chemical-weapons-use-allegations-in-douma-syria-in-2018-and-in-al-hamadaniya-and-karm-al-tarrab-in-2016/ |access-date=July 14, 2018

}}

• July 2023: The U.S. destroyed the last of its declared chemical weapons, a sarin nerve agent-filled M55 rocket, on July 7, 2023.{{cite web |title=U.S. destroys last of its declared chemical weapons |website=CBS |date=July 7, 2023 |url=https://www.cbsnews.com/news/us-destroys-last-chemical-weapons/ |access-date=July 11, 2023}}

• Chlorosarin
• Ethylsarin
• Thiosarin
• Gulf War syndrome

{{Reflist|30em}}

• [http://www.gulfweb.org/bigdoc/report/appgb.html Material Safety Data Sheet]
• [https://fas.org/irp/gulf/cia/960715/72569.htm CIA memo: The Stability of Iraq's Chemical Weapons Stockpile]
• [https://www.cdc.gov/chemicalemergencies/factsheets/sarin.html CDC Sarin fact sheet]
• [https://www.cdc.gov/niosh/ershdb/EmergencyResponseCard_29750001.html CDC Sarin Emergency Response Card]

{{Chemical agents}}

{{U.S. chemical weapons}}

{{Acetylcholine metabolism and transport modulators}}

{{Oxygen compounds}}

{{Fluorine compounds}}

{{Phosphorus compounds}}

Category:Acetylcholinesterase inhibitors

Category:Chemical weapons of the United States

Category:Cold War weapons of the Soviet Union

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Category:German chemical weapons program

Category:German inventions of the Nazi period

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Category:Methylphosphonofluoridates

Category:Soviet chemical weapons program

Category:Substances discovered in the 1930s

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Category:United Kingdom chemical weapons program