Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and 3-Quinuclidinyl benzilate: Difference between pages

{{short description|Military incapacitating agent}}

| Watchedfields = changed

| verifiedrevid = 477220191

| Name =

| ImageFile =

| ImageFileL1 = 3-quinuclidinyl benzilate.svg

| ImageNameL1 = Bonding model

| ImageFileR1 = 3-Quinuclidinyl-benzilate-balls.png

| ImageNameR1 = Ball and stick model

| IUPACName = 1-azabicyclo[2.2.2]octan-3-yl hydroxy(diphenyl)acetate

| OtherNames = BZ<br />EA-2277<br />CS-4030<br />QNB

| SystematicName =

| Section1 = {{Chembox Identifiers

| IUPHAR_ligand = 3260

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| InChIKey = HGMITUYOCPPQLE-UHFFFAOYAEb l

| CASNo=6581-06-2

| UNII_Ref = {{fdacite|changed|FDA}}

| UNII = E69DLR7470

| PubChem=23056

| SMILES = O=C(C(C1=CC=CC=C1)(C2=CC=CC=C2)O)OC3CN4CCC3CC4

| MeSHName=Quinuclidinyl+benzilate

| Section2 = {{Chembox Properties

| C=21 | H=23 | N=1 | O=3

| Appearance= White crystalline powder

| Density=

| MeltingPtC= 164 to 165

| BoilingPtC= 322

| Solubility=

| Section3 = {{Chembox Hazards

| MainHazards=

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}}{{Jargon|date=March 2024}}

'''3-Quinuclidinyl benzilate''' ('''QNB''') (IUPAC name '''1-azabicyclo[2.2.2]octan-3-yl hydroxy(diphenyl)acetate'''; [[US Army]] code '''EA-2277'''; [[NATO]] code '''BZ'''; Soviet code '''Substance 78'''<ref>{{cite magazine |last=Conant |first=Eve |date=22 November 2002 |title=More Questions Than Answers |url=http://www.newsweek.com/more-questions-answers-142453 |magazine=Newsweek |access-date=15 April 2018 }}</ref>) is an odorless and bitter-tasting military [[incapacitating agent]].<ref name=niosh>QNB: Incapacitating Agent. [https://www.cdc.gov/niosh/ershdb/EmergencyResponseCard_29750015.html Emergency Response Safety and Health Database]. National Institute for Occupational Safety and Health. Accessed April 20, 2009.</ref> BZ is an [[receptor antagonist|antagonist]] of [[muscarinic acetylcholine receptor]]s whose structure is the [[ester]] of [[benzilic acid]] with an [[Alcohol (chemistry)|alcohol]] derived from [[quinuclidine]].

==Physicochemical characteristics==

BZ is a white crystalline powder with a bitter taste. It is odorless and nonirritating with delayed symptoms several hours after contact.<ref name=niosh /><ref name=":0" /> It is stable in most solvents, with a [[half-life]] of three to four weeks in moist air; even heat-producing munitions can disperse it. It is extremely persistent in soil and water and on most surfaces. BZ is soluble in water, soluble in dilute acids, [[trichloroethylene]], [[dimethylformamide]], and most organic solvents, and insoluble with aqueous alkali.<ref name=":0">{{cite book|title=Handbook of toxicology of chemical warfare agents|publisher=Academic Press|last=Gupta|first=Ramesh C.|date=21 January 2015|isbn=978-0-12-800494-4|edition=Second|location=London|pages=152|oclc=903965588}}</ref><ref>US Army FM 3-9</ref>

==Effects==

As a powerful [[anticholinergic]] agent, BZ produces a [[syndrome]] of effects known as the [[toxidrome|anticholinergic toxidrome]]: these include both psychological and physiological effects, with the most incapacitating effect being a state of [[delirium]] characterized by [[cognitive dysfunction]], [[hallucinations]], and inability to perform basic tasks. The usual syndrome of physical anticholinergic effects are also present, including [[mydriasis]] (potentially to the point of temporary [[blindness]]), [[tachycardia]], dermal [[vasodilation]], [[xerostomia]] and [[hyperthermia]].<ref>Committee on Acute Exposure Guideline Levels; Committee on Toxicology; Board on Environmental Studies and Toxicology; Division on Earth and Life Studies; National Research Council. Washington (DC): National Academies Press (US); 2013 Apr 26.</ref> The readily-observable symptoms of the anticholinergic toxidrome are famously characterized by the [[mnemonic]] "Mad as a hatter, red as a beet, dry as a bone and blind as a bat" (and variations thereof).<ref>{{cite journal|author1=Ramjan KA |author2=Williams AJ |author3=Isbister GK |author4=Elliott EJ |title='Red as a beet and blind as a bat' Anticholinergic delirium in adolescents: lessons for the paediatrician |journal=Journal of Paediatrics and Child Health |date=November 2007|volume=43|issue=11|pages=779–780|doi=10.1111/j.1440-1754.2007.01220.x |pmid=17924941|s2cid=37914161 }}</ref>

== Toxicity ==

Based on data from more than 500 reported cases of accidental [[atropine]] overdose and deliberate poisoning, the median lethal oral dose is estimated to be approximately 450&nbsp;mg (with a shallow probit slope of 1.8). Some estimates of lethality with BZ have been grossly erroneous, and ultimately the safety margin for BZ is inconclusive due to lack of human data at higher dosage ranges, though some researchers have estimated it to be 0.5 to 3.0&nbsp;mg/kg and an LD₀₁ is 0.2 to 1.4&nbsp;mg/kg (Rosenblatt, Dacre, Shiotsuka, & Rowlett, 1977).<ref name=":3">{{cite book|last=Goodman|first=Ephraim|title=Historical contributions to the human toxicology of atropine : behavioral effects of high doses of atropine and military uses of atropine to produce intoxication|publisher=Eximdyne|year=2010|isbn=978-0-9677264-3-4|location=Wentzville, Missouri|pages=62|oclc=858939565}}</ref>

== Treatment ==

[[Antidote|Antidotes]] for BZ include 7-MEOTA, which can be administered in tablet or injection form. Atropine and [[tacrine]] (THA) have also been used as treatments, THA having been shown to reduce the effects of BZ within minutes.<ref>{{cite book|title=Handbook of toxicology of chemical warfare agents|publisher=Academic Press| last=Gupta | first=Ramesh C.|date=21 January 2015|isbn=978-0-12-800494-4|edition=Second|location=London|pages=156|oclc=903965588}}</ref><ref>{{cite book|last=Goodman |first=Ephraim|title=Historical contributions to the human toxicology of atropine: behavioral effects of high doses of atropine and military uses of atropine to produce intoxication|publisher=Eximdyne|year=2010|isbn=978-0-9677264-3-4|location=Wentzville, Missouri|pages=72|oclc=858939565}}</ref> Some military references suggest the use of [[physostigmine]] to temporarily increase synaptic acetylcholine concentrations.<ref name=niosh />

==History==

===Invention and research===

BZ was invented by the Swiss [[Pharmaceutical industry|pharmaceutical company]] [[Hoffman-LaRoche]] in 1951.<ref name=kirby/> The company was investigating anti-spasmodic agents, similar to [[tropine]], for treating gastrointestinal ailments when the chemical was discovered.<ref name=kirby/> It was then investigated for possible use in ulcer treatment, but was found unsuitable. At this time the United States military investigated it along with a wide range of possible nonlethal, psychoactive and [[psychotomimetic]] incapacitating agents including [[psychedelic drug]]s such as [[Lysergic acid diethylamide|LSD]] and [[Tetrahydrocannabinol|THC]], [[dissociative]] drugs such as [[ketamine]] and [[phencyclidine]], potent [[opioid]]s such as [[fentanyl]], as well as several glycolate [[anticholinergics]].<ref>Possible Long-Term Health Effects of Short-Term Exposure To Chemical Agents, Volume 2: Cholinesterase Reactivators, [http://books.nap.edu/openbook.php?record_id=9136&page=47 Psychochemicals] and Irritants and Vesicants. (1984)</ref><ref>[http://forgottensecrets.net/ Ketchum - Chemical Warfare: Secrets Almost Forgotten] {{Webarchive|url=https://web.archive.org/web/20221022164841/http://forgottensecrets.net/ |date=2022-10-22 }} (2006)</ref> By 1959, the [[United States Army]] showed significant interest in deploying it as a chemical warfare agent.<ref name=kirby/> It was originally designated "TK", but when it was standardized by the Army in 1961, it received the NATO code name "BZ", the Chemical Corps initially referred to BZ as CS4030, then later as EA 2277.<ref name=":3" /><ref name=kirby/> The agent commonly became known as "Buzz" because of this abbreviation and the effects it had on the mental state of the human volunteers intoxicated with it in research studies at [[Edgewood Arsenal human experiments|Edgewood Arsenal]] in Maryland.<ref name=kirby>Kirby, Reid. "[http://www.sussex.ac.uk/Units/spru/hsp/documents/CBWCB71.pdf Paradise Lost: The Psycho Agents]", ''The CBW Conventions Bulletin'', May 2006, Issue no. 71, pp. 2-3, accessed December 11, 2008.</ref> As described in retired Army psychiatrist [[James S. Ketchum|James Ketchum's]] autobiographical book ''Chemical Warfare: Secrets Almost Forgotten'' (2006), work proceeded in 1964 when a general envisioned a scheme to incapacitate an entire [[Naval trawler|trawler]] with aerosolized BZ; this effort was dubbed [[Project DORK]].<ref>{{cite web |url=https://www.wired.com/dangerroom/2007/04/the_secrets_of_/ |title=Army's Hallucinogenic Weapons Unveiled |date=April 2007 |publisher=Wired |access-date=22 August 2022 |archive-url=https://web.archive.org/web/20161224100650/https://www.wired.com/2007/04/the_secrets_of_/ |archive-date=24 December 2016}}</ref> BZ was ultimately weaponized for delivery in the [[M44 generator cluster]] and the [[M43 cluster bomb]], until all such stocks were destroyed in 1989 as part of a general downsizing of the US chemical warfare program.

In 2022 a documentary film,'' Dr Delirium and The Edgewood Experiments'', was broadcast on [[Discovery Channel|Discovery+]], featuring an interview with Ketchum not previously shown.<ref>{{cite news |title='It affected a great number of people': inside the world of shocking military drug experiments |last=Simonpillai |first=Radheyan |newspaper=The Guardian |date=9 June 2022 |url= https://www.theguardian.com/tv-and-radio/2022/jun/09/dr-delirium-and-the-edgewood-experiments-documentary}}</ref>

===Use and alleged use===

In February 1998, the British [[Ministry of Defence (United Kingdom)|Ministry of Defence]] accused [[Iraq]] of having stockpiled large amounts of a [[glycolate]] [[anticholinergic]] incapacitating agent known as ‘Agent&nbsp;15’.<ref>{{cite news |url=https://www.independent.co.uk/news/iraqi-zombie-gas-arsenal-revealed-1143947.html |archive-url=https://web.archive.org/web/20110513105334/http://www.independent.co.uk/news/iraqi-zombie-gas-arsenal-revealed-1143947.html |author1=Colin Brown |author2=Ian Burrel |date=10 February 1998|archive-date=2011-05-13 |url-access=limited |url-status=live |title=Iraqi 'zombie gas' arsenal revealed |newspaper=[[The Independent]] |place=UK}}</ref> Agent&nbsp;15 is an alleged Iraqi incapacitating agent that is likely to be chemically identical to BZ or closely related to it. Agent&nbsp;15 was reportedly stockpiled in large quantities prior to and during the [[Persian Gulf War]]. However, after the war the [[CIA]] concluded that Iraq had not stockpiled or weaponized Agent&nbsp;15.{{efn| "We assess that Iraq never went beyond research with Agent&nbsp;15 – a hallucinogenic chemical similar to BZ – or any other psychochemical. Agent&nbsp;15 became an issue after a 9&nbsp;February 1998 British press release claimed that the UK had information, thought to be reliable, that Iraq had large quantities of this chemical agent in the 1980s. UNSCOM and intelligence information indicated that Iraq researched a number of psychochemicals, including Agent&nbsp;15, BZ, and PCP; however, UNSCOM indicated it saw no evidence of Iraqi importation of large quantities, weaponization, procurement of militarily significant quantities of precursors, or industrial production of these agents."<ref>{{cite report |url=https://www.cia.gov/library/reports/general-reports-1/gulfwar/cwagents/index.htm |series=Intelligence Update |title=Chemical Warfare Agent Issues |publisher=[[U.S. Central Intelligence Agency]] |date=April 2002 |access-date=28 January 2013 |archive-date=14 April 2019 |archive-url=https://web.archive.org/web/20190414062356/https://www.cia.gov/library/reports/general-reports-1/gulfwar/cwagents/index.htm |url-status=dead }}</ref>}}<ref name="foreignpolicy-20130125">{{cite magazine |first=Jeffrey |last=Lewis |date=25 January 2013 |title=Why everyone's wrong about Assad's zombie gas |magazine=Foreign Policy |url=https://foreignpolicy.com/articles/2013/01/25/buzz_bomb |access-date=28 January 2013}}</ref>

According to Konstantin Anokhin, professor at the Institute of Normal Physiology in Moscow, BZ was the [[Moscow hostage crisis chemical agent|chemical agent used to incapacitate terrorists]] during the [[2002 Nord-Ost siege]], but at least 115&nbsp;hostages perished due to overdose;<ref>{{cite news |title=Hostages given military's nerve gas antidote |date=28 October 2002 |newspaper=[[The Guardian]] |url=https://www.theguardian.com/world/2002/oct/28/russia.richardnortontaylor}}</ref> but many other agents have also been proposed, and none definitively confirmed.

In January&nbsp;2013, an unidentified U.S. administration official, referring to an undisclosed U.S. State Department cable, claimed that "Syrian contacts made a compelling case that Agent&nbsp;15, a hallucinogenic chemical similar to BZ,<ref>{{cite report |series=Intelligence Update |title=Chemical Warfare Agent Issues |chapter=Iraqi Chemical Agents and Their Effects |publisher=[[U.S. Central Intelligence Agency]] |chapter-url=https://www.cia.gov/library/reports/general-reports-1/gulfwar/cwagents/index.htm#appendixa1 |date=April 2002 |access-date=2013-01-19 |archive-date=2019-04-14 |archive-url=https://web.archive.org/web/20190414062356/https://www.cia.gov/library/reports/general-reports-1/gulfwar/cwagents/index.htm#appendixa1 |url-status=dead }}</ref> was used in [[Homs]]".<ref>{{cite news |last=Rogin |first=Josh |date=15 January 2013 |title=Secret State Department cable: Chemical weapons used in Syria |newspaper=Foreign Policy The Cable |url=http://thecable.foreignpolicy.com/posts/2013/01/15/secret_state_department_cable_chemical_weapons_used_in_syria |access-date=16 January 2013}}</ref><ref name=reuters-20130116>{{cite news |title=U.S. plays down media report that Syria used chemical weapons |work=Reuters |date=16 January 2013 |access-date=28 January 2013 |url=https://www.reuters.com/article/us-syria-usa-chemical-idUSBRE90F00P20130116}}</ref> However, in response to these reports a [[U.S. National Security Council]] spokesman stated,

<blockquote>The reporting we have seen from media sources regarding alleged chemical weapons incidents in Syria has not been consistent with what we believe to be true about the Syrian chemical weapons program.<ref name=foreignpolicy-20130125/><ref name=reuters-20130116/></blockquote>

=== Legality ===

BZ is listed as a [[List of Schedule 2 substances (CWC)|Schedule 2 compound]] by the OPCW (Szinicz, 2005).<ref name=":2">{{cite journal|last1=Valdez|first1=Carlos A.|last2=Leif|first2=Roald N.|last3=Hok|first3=Saphon|last4=Hart|first4=Bradley R.|date=2017-07-25|title=Analysis of chemical warfare agents by gas chromatography-mass spectrometry: methods for their direct detection and derivatization approaches for the analysis of their degradation products|journal=Reviews in Analytical Chemistry|language=en|volume=37|issue=1|doi=10.1515/revac-2017-0007|s2cid=103245582 |issn=2191-0189|doi-access=free}}</ref>

==See also==

* [[Edgewood Arsenal human experiments]]

* [[EA-3167]]

* [[EA-3443]]

* [[EA-3580]]

* [[EA-3834]]

==Footnotes==

{{notelist|1}}

==References==

{{reflist}}

* {{US Army}}

==External links==

* [http://www.erowid.org/chemicals/bz/bz.shtml Erowid]—BZ Vault

* [http://www.emedicine.com/emerg/topic912.htm eMedicine]—3-Quinuclidinyl Benzilate Poisoning

* [https://web.archive.org/web/20051216122928/http://www.defensetech.org/archives/002000.html Possible Abuse of BZ by Insurgents in Iraq], Defense Tech blog, December 2005.

* [https://www.cdc.gov/niosh/ershdb/emergencyresponsecard_29750015.html Center for Disease Control]—BZ Incapacitating Agent

* Kirby, Reid. [https://www.scribd.com/doc/114637880/Paradise-Lost-The-Psycho-Agents-CBWCB71 Paradise Lost: The Psycho Agents], The CBW Conventions Bulletin, v.71, May 2006, p.1.

* [https://web.archive.org/web/20090805145324/http://fhp.osd.mil/CBexposures/pdfs/tall_timber.pdf Department of Defense]—Agent BZ use in Hawaii April through June 1966

{{U.S. chemical weapons}}

{{Chemical warfare}}

{{Hallucinogens}}

{{Muscarinic acetylcholine receptor modulators}}

{{DEFAULTSORT:Quinuclidinyl Benzilate, 3-}}

[[Category:Muscarinic antagonists]]

[[Category:Carboxylate esters]]

[[Category:Deliriants]]

[[Category:Incapacitating agents]]

[[Category:3-Quinuclidinyl esters]]

[[Category:Chemical weapons of the United States]]

[[Category:Swiss inventions]]

[[Category:Tertiary alcohols]]

[[Category:Benzilate esters]]