Editing Sarin (section)

==Health effects==
[[File:Sarin Wirkungsweise.png|thumb|upright| Biological effects of sarin in the neuromuscular junction. Sarin (red), acetylcholinesterase (yellow), acetylcholine (blue){{Clarify|date=February 2024}}]]{{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 junction]]s. Death usually occurs as a result of [[asphyxia]] due to the inability to control the muscles involved in breathing.<ref name=":1">{{cite book |last=Vohra |first=Rais |title=Poisoning & Drug Overdose |publisher=McGraw Hill |year=2022 |edition=8th |language=English |chapter=Organophosphorus and carbamate insecticides}}</ref>

Initial symptoms following exposure to sarin are a [[runny nose]], tightness in the chest, and [[pupil constriction|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 [[muscle contraction|twitching]] and jerking. Ultimately, the person becomes comatose and suffocates in a series of convulsive [[spasm]]s. 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,<ref>{{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}}</ref> and [[SLUDGE syndrome|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.<ref name=":1"/>

Sarin has a high [[volatility (chemistry)|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.<ref name="CDC">{{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}}</ref>

===Management===
Treatment measures have been described.<ref name=CDC/> Treatment is typically with the [[antidote]]s [[atropine]] and [[pralidoxime]].<ref name=niosh/> Atropine, an [[receptor antagonist|antagonist]] to [[muscarinic acetylcholine receptor]]s, is given to treat the physiological symptoms of poisoning. Since muscular response to acetylcholine is mediated through [[nicotinic acetylcholine receptor]]s, atropine does not counteract the muscular symptoms. Pralidoxime can regenerate [[cholinesterase]]s 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.<ref>{{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}}</ref>

===Mechanism of action===
Sarin is a potent [[acetylcholinesterase inhibitor|inhibitor of acetylcholinesterase]],<ref>{{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}}</ref> 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 [[neuron]]s 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 [[biological activity|biologically inactive]].<ref>{{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}}.</ref><ref>{{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}}</ref>

Its mechanism of action resembles that of some commonly used [[insecticide]]s, such as [[malathion]]. In terms of biological activity, it resembles [[carbamate]] insecticides, such as [[Carbaryl|Sevin]], and the medicines [[pyridostigmine]], [[neostigmine]], and [[physostigmine]].

===Diagnostic tests===
Controlled studies in healthy men have shown that a nontoxic 0.43&nbsp;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&nbsp;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 [[metabolite]]s 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&nbsp;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.<ref>{{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}}</ref>

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.<ref>{{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}}</ref><ref>{{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}}</ref>

===Toxicity===
As a nerve gas, sarin in its purest form is estimated to be 26 times more deadly than [[cyanide]].<ref>{{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}}</ref> The [[median lethal dose|LD<sub>50</sub>]] of [[subcutaneous injection|subcutaneously injected]] sarin in mice is 172 μg/kg.<ref>{{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}}</ref>

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&nbsp;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/m<sup>3</sup> value is for general population).<ref>{{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}}</ref> This number represents the estimated lethal concentration for 50% of exposed victims, the [[median lethal dose#Conventions|LCt<sub>50</sub>]] value. The [[median lethal dose#Conventions|LCt<sub>95</sub>]] or [[median lethal dose#Conventions|LCt<sub>100</sub>]] value is estimated to be 40–83 mg per cubic meter for exposure time of two minutes.<ref>{{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/}}</ref><ref>{{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}}</ref> 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.<ref>{{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}}</ref> 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 LCt<sub>50</sub>:

* [[Hydrogen cyanide]], 2,860&nbsp;mg/(min·m<sup>3</sup>)<ref name=":0">{{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}}</ref> – Sarin is 81 times more lethal
* [[Phosgene]], 1,500&nbsp;mg/(min·m<sup>3</sup>)<ref name=":0"/> – Sarin is 43 times more lethal
* [[Sulfur mustard]], 1,000&nbsp;mg/(min·m<sup>3</sup>)<ref name=":0"/> – Sarin is 28 times more lethal
* [[Chlorine]], 19,000&nbsp;mg/(min·m<sup>3</sup>)<ref>{{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}}</ref> – Sarin is 543 times more lethal