Editing Nitrous oxide (section)

== Safety ==

Nitrous oxide is a significant [[occupational hazard]] for surgeons, dentists and nurses. Because the gas is minimally metabolised in humans (with a rate of 0.004%), it retains its potency when exhaled into the room by the patient, and can intoxicate the clinic staff if the room is poorly ventilated, with potential chronic exposure. A continuous-flow fresh-air [[ventilation (architecture)|ventilation system]] or {{chem|N|2|O}} [[scavenger system]] may be needed to prevent waste-gas buildup.{{citation needed|date=August 2022}} The [[National Institute for Occupational Safety and Health]] recommends that workers' exposure to nitrous oxide should be controlled during the administration of anaesthetic gas in medical, dental and veterinary operators.<ref>[https://www.cdc.gov/niosh/docs/94-100/ CDC.gov NIOSH Alert: Controlling Exposures to Nitrous Oxide During Anesthetic Administration]. Cincinnati, OH: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 94-100</ref> It set a [[recommended exposure limit]] (REL) of 25 [[Parts-per notation|ppm]] (46&nbsp;mg/m<sup>3</sup>) to escaped anaesthetic.<ref>{{Cite web|title =NIOSH Pocket Guide to Chemical Hazards – Nitrous oxide|url = https://www.cdc.gov/niosh/npg/npgd0465.html|website = CDC|access-date = 2015-11-21}}</ref>

Exposure to nitrous oxide causes short-term impairment of cognition, audiovisual acuity, and manual dexterity, as well as spatial and temporal disorientation,<ref>[https://www.cdc.gov/niosh/docs/1970/77-140.html Criteria for a recommended standard: occupational exposure to waste anesthetic gases and vapors]. Cincinnati, OH: U.S. Department of Health, Education, and Welfare, Public Health Service, Center for Disease Control, National Institute for Occupational Safety and Health, DHEW (NIOSH) Publication No. 77B140.</ref> putting the user at risk of accidental injury.<ref name="Mike Jay 22–25"/>

Nitrous oxide is [[neurotoxic]], and medium or long-term habitual consumption of significant quantities can cause neurological harm with the potential for permanent damage if left untreated.<ref name=nangs>{{cite journal |vauthors=Evans EB, Evans MR |title=Nangs, balloons and crackers: Recreational nitrous oxide neurotoxicity |journal=Aust J Gen Pract |volume=50 |issue=11 |pages=834–838 |date=November 2021 |pmid=34713284 |doi=10.31128/AJGP-10-20-5668 |s2cid=240153502 |type=Review|doi-access=free }}</ref><ref name="bbc.co.uk"/> It is believed that, like other [[NMDA receptor antagonist]]s, {{chem|N|2|O}} produces [[Olney's lesions]] in rodents upon prolonged (several hour) exposure.<ref name="pmid14622904">{{cite journal |year=2003|title=Prolonged exposure to inhalational anesthetic nitrous oxide kills neurons in adult rat brain|journal=Neuroscience|volume=122|issue=3|pages=609–16|doi=10.1016/j.neuroscience.2003.07.012|pmid=14622904|vauthors=Jevtovic-Todorovic V, Beals J, Benshoff N, Olney JW|s2cid=9407096}}</ref><ref name="pmid12854473">{{cite journal|year=2003|title=NMDA receptor antagonist neurotoxicity and psychotomimetic activity|journal=Masui. The Japanese Journal of Anesthesiology|language=ja|volume=52|issue=6|pages=594–602|pmid=12854473|vauthors=Nakao S, Nagata A, Masuzawa M, Miyamoto E, Yamada M, Nishizawa N, Shingu K}}</ref><ref name="pmid10928976">{{cite journal |year=2000|title=Ketamine potentiates cerebrocortical damage induced by the common anaesthetic agent nitrous oxide in adult rats|journal=British Journal of Pharmacology|volume=130|issue=7|pages=1692–8|doi=10.1038/sj.bjp.0703479|pmc=1572233|pmid=10928976 |vauthors=Jevtovic-Todorovic V, Benshoff N, Olney JW}}</ref><ref name="pmid15718054">{{cite journal|last2=Carter|year=2005|title=The anesthetics nitrous oxide and ketamine are more neurotoxic to old than to young rat brain|journal=Neurobiology of Aging|volume=26|issue=6|pages=947–56|doi=10.1016/j.neurobiolaging.2004.07.009|pmid=15718054|author=Jevtovic-Todorovic V, Carter LB|s2cid=25095727}}</ref>
However, because it is normally expelled from the body rapidly, it is less likely to be neurotoxic than other NMDAR antagonists.<ref name="pmid16179534">{{cite journal |year=2005|title=Potentially neuroprotective and therapeutic properties of nitrous oxide and xenon|journal=Annals of the New York Academy of Sciences|volume=1053|issue=1|pages=289–300|bibcode=2005NYASA1053..289A|doi=10.1111/j.1749-6632.2005.tb00036.x|pmid=16179534 |vauthors=Abraini JH, David HN, Lemaire M|s2cid=34160112}}</ref> In rodents, short-term exposure results in only mild injury that is rapidly reversible, and neuronal death occurs only after constant and sustained exposure.<ref name="pmid14622904" /> Nitrous oxide may also cause neurotoxicity after extended exposure because of [[hypoxia (medical)|hypoxia]]. This is especially true of non-medical formulations such as [[whipped-cream charger]]s ("whippits" or "nangs"),<ref>{{cite journal|pmid=23801743|doi=10.1093/bja/aet215|year=2013|last1=De Vasconcellos|first1=K.|title=Nitrous oxide: Are we still in equipoise? A qualitative review of current controversies|journal=British Journal of Anaesthesia|volume=111|issue=6|pages=877–85|last2=Sneyd|first2=J. R.|doi-access=free}}</ref> which contain no oxygen gas.<ref name="Middleton 2012 p.">{{cite book|title=Physics in anaesthesia|last=Middleton|first=Ben|publisher=Scion Pub. Ltd|year=2012|isbn=978-1-904842-98-9|location=Banbury, Oxfordshire, UK}}</ref>

In reports to poison control centers, heavy users (≥400 g or ≥200 L of {{N2O}} gas in one session) or frequent users (regular, i.e., daily or weekly) have developed signs of [[peripheral neuropathy]]: [[ataxia]] (gait abnormalities) or [[paresthesia]] (perception of sensations such as tingling, numbness, or prickling, mostly in the extremities). Such early signs of neurological damage indicate [[chronic toxicity]].<ref>{{cite journal|doi=10.1016/j.drugpo.2021.103519|year=2022|last1=van Riel|first1=A.J.H.P.|title=Alarming increase in poisonings from recreational nitrous oxide use after a change in EU-legislation, inquiries to the Dutch Poisons Information Center|journal=International Journal of Drug Policy|volume=100|page=103519|pmid=34753046|doi-access=free}}</ref>

Nitrous oxide might have therapeutic use in treating [[stroke]]. In a rodent model, nitrous oxide at 75% by volume reduced ischemia-induced neuronal death induced by occlusion of the middle cerebral artery, and decreased NMDA-induced Ca<sup>2+</sup> influx in neuronal cell cultures, a cause of [[excitotoxicity]].<ref name="pmid16179534" />

Occupational exposure to ambient nitrous oxide has been associated with DNA damage, due to interruptions in DNA synthesis.<ref>{{cite web |last1=Randhawa |first1=G. |last2=Bodenham |first2=A. |title=The increasing recreational use of nitrous oxide: history revisited |url=https://academic.oup.com/bja/article/116/3/321/2566058 |journal=British Journal of Anaesthesia |volume=116 |issue=3 |pages=321–324 |language=en |doi=10.1093/bja/aev297 |pmid=26323292 |date=1 March 2016}}</ref> This correlation is dose-dependent<ref>{{cite journal |last1=Wrońska-Nofer |first1=Teresa |last2=Nofer |first2=Jerzy-Roch |last3=Jajte |first3=Jolanta |last4=Dziubałtowska |first4=Elżbieta |last5=Szymczak |first5=Wiesław |last6=Krajewski |first6=Wojciech |last7=Wąsowicz |first7=Wojciech |last8=Rydzyński |first8=Konrad |title=Oxidative DNA damage and oxidative stress in subjects occupationally exposed to nitrous oxide (N<sub>2</sub>O) |journal=Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis |date=1 March 2012 |volume=731 |issue=1 |pages=58–63 |doi=10.1016/j.mrfmmm.2011.10.010 |pmid=22085808 }}</ref><ref>{{cite journal |title=DNA damage induced by nitrous oxide: Study in medical personnel of operating rooms |journal=Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis |date=18 June 2009 |volume=666 |issue=1–2 |pages=39–43 |doi=10.1016/j.mrfmmm.2009.03.012 |pmid=19439331 |last1=Wrońska-Nofer |first1=Teresa |last2=Palus |first2=Jadwiga |last3=Krajewski |first3=Wojciech |last4=Jajte |first4=Jolanta |last5=Kucharska |first5=Małgorzata |last6=Stetkiewicz |first6=Jan |last7=Wąsowicz |first7=Wojciech |last8=Rydzyński |first8=Konrad |bibcode=2009MRFMM.666...39W }}</ref> and does not appear to extend to casual recreational use; however, further research is needed to confirm the level of exposure needed to cause damage.

Inhalation of pure nitrous oxide causes oxygen deprivation, resulting in low blood pressure, fainting, and even heart attacks. This can occur if the user inhales large quantities continuously, as with a strap-on mask connected to a gas canister or other inhalation system, or prolonged breath-holding.{{citation needed|date=August 2024}}

Long-term exposure to nitrous oxide may cause [[Vitamin B12 deficiency|vitamin B{{ssub|12}} deficiency]].  This can cause serious neurotoxicity if the user has preexisting vitamin B{{ssub|12}} deficiency.<ref>{{Cite journal|last2=Holder|first2=W. D. Jr.|year=1993|title=Neurologic Degeneration Associated with Nitrous Oxide Anesthesia in Patients with Vitamin B12 Deficiency|journal=Archives of Surgery|volume=128|issue=12|pages=1391–5|doi=10.1001/archsurg.1993.01420240099018|pmid=8250714|last1=Flippo|first1=T. S.}}</ref> It inactivates the cobalamin form of vitamin B{{ssub|12}} by oxidation. Symptoms of vitamin B{{ssub|12}} deficiency, including [[Peripheral neuropathy|sensory neuropathy]], [[myelopathy]] and [[encephalopathy]], may occur within days or weeks of exposure to nitrous oxide anaesthesia in people with subclinical vitamin B{{ssub|12}} deficiency. Symptoms are treated with high doses of vitamin B{{ssub|12}}, but recovery can be slow and incomplete.<ref>{{cite book |last=Giannini |first=A.J. |year=1999 |title=Drug Abuse |place=Los Angeles |publisher=Health Information Press |isbn=978-1-885987-11-2 |url-access=registration |url=https://archive.org/details/drugabuse00ajam }}</ref> People with normal vitamin B{{ssub|12}} levels have stores to make the effects of nitrous oxide insignificant, unless exposure is repeated and prolonged (nitrous oxide abuse). Vitamin B{{ssub|12}} levels should be checked in people with risk factors for vitamin B{{ssub|12}} deficiency prior to using nitrous oxide anaesthesia.<ref>{{Cite web |last=Conrad |first=Marcel |title=Pernicious Anemia |website=Medscape |date=4 October 2006 |url=http://www.emedicine.com/med/topic1799.htm |access-date=2 June 2008}}</ref>

Several experimental studies in rats indicate that chronic exposure of pregnant females to nitrous oxide may have adverse effects on the developing fetus.<ref name="Vieira1980">{{cite journal|pmid=7189346 |year=1980 |last1=Vieira |first1=E. |last2=Cleaton-Jones |first2=P. |last3=Austin |first3=J.C. |last4=Moyes |first4=D.G. |last5=Shaw |first5=R. |title=Effects of low concentrations of nitrous oxide on rat fetuses |volume=59 |issue=3 |pages=175–7 |journal=Anesthesia and Analgesia |doi=10.1213/00000539-198003000-00002|s2cid=41966990 |doi-access=free }}</ref><ref>{{cite journal|pmid=465253 |year=1979 |last1=Vieira |first1=E. |title=Effect of the chronic administration of nitrous oxide 0.5% to gravid rats |volume=51 |issue=4 |pages=283–7 |journal=British Journal of Anaesthesia |doi=10.1093/bja/51.4.283|doi-access=free }}</ref><ref>{{cite journal|pmid=6821624 |year=1983 |last1=Vieira |first1=E |last2=Cleaton-Jones |first2=P |last3=Moyes |first3=D. |title=Effects of low intermittent concentrations of nitrous oxide on the developing rat fetus |volume=55 |issue=1 |pages=67–9 |journal=British Journal of Anaesthesia |doi=10.1093/bja/55.1.67|doi-access=free }}</ref>

At room temperature ({{Convert|20|C|disp=sqbr}}) the saturated vapour pressure is 50.525 bar, rising up to 72.45&nbsp;bar at {{convert|36.4|C}}—the [[Critical point (thermodynamics)|critical temperature]]. The pressure curve is thus unusually sensitive to temperature.<ref>[http://encyclopedia.airliquide.com/encyclopedia.asp?LanguageID=11&CountryID=19&Formula=&GasID=55&UNNumber= Nitrous oxide] {{Webarchive|url=https://web.archive.org/web/20160330004038/http://encyclopedia.airliquide.com/encyclopedia.asp?LanguageID=11&CountryID=19&Formula=&GasID=55&UNNumber= |date=30 March 2016 }}. Air Liquide Gas Encyclopedia.</ref> As with many strong oxidisers, contamination of parts with fuels have been implicated in rocketry accidents, where small quantities of nitrous/fuel mixtures explode due to "[[water hammer]]"-like effects (sometimes called "dieseling"—heating due to [[adiabatic]] compression of gases can reach decomposition temperatures).<ref>{{cite web|url=http://www.ukrocketman.com/rocketry/hybridukhistory.shtml |title=Vaseline triggered explosion of hybrid rocket |publisher=Ukrocketman.com}}</ref> Some common building materials such as stainless steel and aluminium can act as fuels with strong oxidisers such as nitrous oxide, as can contaminants that may ignite due to adiabatic compression.<ref>{{cite web|url=http://www.airproducts.com/nr/rdonlyres/8c46596e-2f7d-4895-b12a-e54cd63e1996/0/safetygram20.pdf |archive-url=https://web.archive.org/web/20060901093045/http://www.airproducts.com/nr/rdonlyres/8c46596e-2f7d-4895-b12a-e54cd63e1996/0/safetygram20.pdf |archive-date=1 September 2006 |title=Safetygram 20: Nitrous Oxide |publisher=Airproducts.com}}</ref> There also have been incidents where nitrous oxide decomposition in plumbing has led to the explosion of large tanks.<ref name="Munke" />