View source for Nitrous oxide

{{Chembox/Top|Nitrous oxide}}
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| align="center" colspan="2" bgcolor="white" | [[Image:Nitrous-oxide-3D-vdW.png|150px|Nitrous oxide - space-filling model]]
[[Image:Nitrous-oxide-dimensions-3D-balls.png|200px|Nitrous oxide's bond lengths]]<br>
[[Image:Nitrous-oxide-2D-VB.png|250px|Nitrous oxide's canonical forms]]<br>
|-
{{Chembox/SectGeneral}}
{{Chembox/Formula|N<sub>2</sub>O}}
{{Chembox/MolarMass|44.0128}}
{{Chembox/Appearance|colourless gas}}
{{Chembox/CASNo|10024-97-2}}
{{Chembox/SectProperties}}
| [[Density]] and [[Phase (matter)|phase]]
| 1222.8 kg m<sup>-3</sup> (liquid)<br />1.8 kg m<sup>-3</sup> (gas STP)
|-
{{Chembox/Solubility|water|}}
{{Chembox/MeltingPt|-90.86 °C (182.29 K)}}
{{Chembox/BoilingPt|-88.48 °C (184.67 K)}}
{{Chembox/SectStructure}}
{{Chembox/MolecularShape|linear}}
{{Chembox/DipoleMoment|0.166}}
{{Chembox/SectThermo}}
{{Chembox/DeltaHf298|+82.05}}
{{Chembox/SectHazards}} <!--  Summary only, MSDS provides more complete information -->
{{Chembox/EUClass|Oxidising ('''O''')}}
| [[NFPA 704]]
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{| border="0" cellspacing="0" cellpadding="0"
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| {{NFPA 704 | Health=2 | Flammability=0 | Reactivity=0 | Other=OX }}
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| [[List of R-phrases|R-phrases]]
| {{R8}}
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| [[List of S-phrases|S-phrases]]
| {{S38}}
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{{Chembox/SectDataPage}}
{{Chembox/SectRelated}}
{{Chembox/RelatedX|nitrogen oxide|[[Nitric oxide]]<br />[[Nitrogen dioxide]]<br />[[Dinitrogen trioxide]]<br />[[Dinitrogen tetroxide]]<br />[[Dinitrogen pentoxide]]}}
{{Chembox/RelatedCpds|[[Nitric acid]]<br />[[Nitrous acid]]}}
{{Chembox/Bottom}}
{{drugbox |
| IUPAC_name = Nitrous oxide
| image = Nitrous-oxide-3D-vdW.png
| width = 200
| CAS_number = 10024-97-2
| ATC_prefix = N01AX13
| ATC_suffix = 
| PubChem = 
| DrugBank = 
| N = 2 | O = 1
| molecular_weight = 44.0128 g/mol
| SMILES = N<sub>2</sub>O
| bioavailability = 
| metabolism = 0.004%
| elimination_half-life = 5 minutes
| excretion = [[Respiratory]]
| pregnancy_category = 
| legal_AU =
| legal_CA = 
| legal_US = 
| legal_UK = 
| legal_status = Anasthetic use allowed in the United States and Australia; Recreational use often illegal on a state-by-state basis
| routes_of_administration = [[Inhalation]]
}} 
{{CMG}}

{{EH}}

==Overview==
'''Nitrous oxide''' (also called dinitrogen oxide or dinitrogen monoxide, or sometimes '''laughing gas''') is a [[chemical compound]] with the [[chemical formula]] [[Nitrogen|N]]<sub>2</sub>[[Oxygen|O]]. At room temperature, it is a colorless [[Flammability|non-flammable]] [[gas]], with a pleasant, slightly sweet odor and taste. It is used in [[surgery]] and [[dentistry]] for its [[anaesthetic]] and [[analgesic]] effects. It is commonly known as "laughing gas" due to the euphoric effects of inhaling it, a property that has led to its non-medical use as an [[inhalant]] drug. It is also used in motor racing as an oxidizer to increase the power output of engines. Oftentimes it is incorrectly referred to as "NOS," refrencing a manufacturer of automotive nitrous oxide equipment, [[Nitrous Oxide Systems]].

[[Image:Nitrous oxide - 10 x 8g.jpg|thumb|200px|right|8g canister of nitrous oxide]]
Nitrous oxide (N<sub>2</sub>O) is a [[dissociative]] drug that can cause [[analgesia]], [[depersonalization]], [[derealization]], [[dizziness]], [[Euphoria (emotion)|euphoria]], [[flanging]] of sound, slight [[hallucination]]s and [[neurotoxicity]].

==In medicine==

Previously, nitrous oxide was typically administered by dentists through a demand-valve inhaler over the nose that only releases gas when the patient inhales through the nose; full-face masks are not commonly used by dentists, so that the patient's mouth can be worked on while the patient continues to inhale the gas.  Current use involves constant supply flowmeters which allow the proportion of nitrous oxide and the combined gas flow rate to be individually adjusted.  The masks still obviously cover only the nose.

Because nitrous oxide is minimally metabolized, it retains its potency when exhaled into the room by the patient and can pose an intoxicating and prolonged-exposure hazard to the clinic staff if the room is poorly ventilated. Where nitrous oxide is administered, a continuous-flow fresh-air ventilation system or nitrous-scavenging system is used, to prevent waste gas buildup.

Nitrous oxide is a weak general anesthetic, and so is generally not used alone in general anaesthesia. In general anesthesia it is used as a carrier gas in a 2:1 ratio with oxygen for more powerful general anaesthetic agents such as [[sevoflurane]] or [[desflurane]]. It has a MAC ([[minimum alveolar concentration]]) of 105% and a blood:gas partition coefficient of 0.46. Less than 0.004% is metabolised in humans.

==Recreational use==
Since the earliest uses of nitrous oxide for medical or dental purposes, it has also been used recreationally as an [[inhalant]], because it causes [[Euphoria (emotion)|euphoria]] and slight hallucinations. Only a small number of recreational users (such as dental office workers or medical gas technicians) have legal access to pure nitrous oxide [[canister]]s that are intended for medical or dental use. Most recreational users obtain nitrous oxide from compressed gas containers which use nitrous oxide as a propellant for whipped cream or from automotive nitrous systems.  Automotive nitrous available to the public often has ~100 ppm [[Sulfur dioxide]] added to prevent recreational use/abuse; (not hydrogen sulfide as suggested by <ref>http://www.justsayn2o.com/nitrous.obtain.html</ref>).  Inhalation of such a mixture is nearly impossible after one breath due to gagging and sooner or later, involuntary clamping off of the esophagus; (some with "sulfate" allergies could even die due to allergic reaction).  

Users typically inflate a balloon or plastic bag with nitrous oxide and inhale the gas for its effects, as the nitrous oxide expelled directly from a tank or cracker would severely damage the user's lungs due to the extremely cold temperature that it would be at.  While nitrous oxide is not a dangerous substance per se, recreational users typically do not mix it with air or oxygen (as is standard procedure in a dentist's office) and thus may risk injury or death from lack of oxygen ([[anoxia]]).  Nitrous oxide, when inhaled using a home made system consisting of a mask and/or regulator, presents more potential danger due to the automatic, continuous application. This may in turn prevent adequate oxygen from reaching the user, rendering them unconscious, subsequently leading to death due to asphyxiation.  Inhaling nitrous oxide in conjunction with an [[alkyl nitrite]] is in some circles referred to as "space surfing", as the nitrous oxide acts synergistically with the alkyl nitrite to create strong (but short-lived) euphoria, analgesia, dissociation, and in some cases, sensations of internal movement or agitation. 

The name also comes from the sound-flanging effects of nitrous oxide, which some users compare to the sound of waves crashing on a beach (hence "surfing"). While powerful, this is a potentially dangerous combination, as the CNS depressing effects of the nitrous oxide, combined with the drop in blood pressure (which is characteristic of nitrite inhalant use), may cause [[hypotension]], unconsciousness, or, in the case of extreme overdose, death. Individuals with cardiac conditions, complications arising from stroke or surgery, or chronically low blood pressure are advised not to use these two drugs simultaneously.

Nitrous oxide is used as a whipping agent due to the ease at which it migrates into and out of oils; only a few seconds of rapid shaking is enough to migrate the gas into the oily cream under pressure. Due to this ability, nitrous also easily moves throughout the body, into and out of cells, because cell membranes are oil-based lipids. Prolonged inhalation of high concentrations of nitrous oxide will cause it to migrate throughout the body into sinus cavities, the digestive tract, and into fat cells. 

An inactive person who has breathed high concentrations for 20-30 minutes but then breathes normally will still retain the gas in their body at low doses as the gas slowly migrates back out of these internal cavities. Even after several hours of not breathing the gas, sudden rapid whole-body movements such as callisthenics causes the dissolved gas to suddenly begin migrating out of fat cells, resulting in a latent dosing effect.  

Nitrous oxide can be habit-forming because of its short-lived effect (generally from 1 - 5 minutes in recreational doses) and ease of access. Death can result if it is inhaled in such a way that too little oxygen is breathed in. While the pure gas is generally not toxic, long-term use in very large quantities has been associated with [[vitamin B12]] deficiency, [[anemia]] due to reduced [[hemopoiesis]], [[neuropathy]], [[tinnitus]], and [[numbness]] in extremities.  Harmful irreversible effects that may be caused by abuse of nitrous oxide include peripheral neuropathies and limb spasms.<ref>National Institute on Drug Abuse. (2006). NIDA InfoFacts: Inhalants. Retrieved April 29, 2007, from http://www.drugabuse.gov/Infofacts/Inhalants.html</ref> Pregnant women should not use nitrous oxide as chronic use is [[teratogen]]ic and [[fetus|foetotoxic]]. One study in rats found that long term exposure to high doses of nitrous oxide may lead to [[Olney's lesions]].<ref name="Jevtovic-Todorovic"/>  Seizures, perception of time, and vision-altering perceptions are possible side effects.

=== Aerosol propellant ===
The gas is approved for use as a [[food additive]] (also known as E942), specifically as an [[aerosol spray#Propellant|aerosol spray propellant]]. Its most common uses in this context are in aerosol [[whipped cream]] canisters, [[cooking spray]]s,  and as an inert gas used to displace bacteria-inducing oxygen when filling packages of [[potato chips]] and other similar snack foods.

The gas is extremely soluble in fatty compounds.  In aerosol whipped cream, it is dissolved in the fatty cream until it leaves the can, when it becomes gaseous and thus creates foam.  Used in this way, it produces whipped cream four times the volume of the liquid, whereas whipping air into cream only produces twice the volume.  If air were used as a propellant, under increased pressure the oxygen would accelerate [[rancidification]] of the butterfat, while nitrous oxide inhibits such degradation. 

However, the whipped cream produced with nitrous oxide is unstable, and will return to a more or less liquid state within half an hour to one hour. Thus, the method is not suitable for decorating food that will not be immediately served. Similarly, [[cooking spray]], which is made from various types of oils combined with [[lecithin]] (an [[emulsifier]]), may use nitrous oxide as a [[propellant]]; other propellants used in cooking spray include food-grade [[alcohol]] and [[propane]].

Users of nitrous oxide often obtain it from whipped cream dispensers that use nitrous oxide as a propellant (see above section), for recreational use a as a euphoria-inducing [[inhalant]] drug.   It is non-harmful in small doses, but risks due to lack of oxygen do exist (see section on "Recreational use" above).

=== Rocket motors ===
Nitrous oxide can be used as an [[oxidizing agent|oxidizer]] in a [[rocket]] motor.  This has the advantages over other oxidizers that it is non-toxic and, due to its stability at room temperature, easy to store and relatively safe to carry on a flight. As a secondary benefit it can be readily decomposed to form breathing air.  it's high density and low storage pressure enable it to be highly competitive with stored high pressure gas systems.

Nitrous oxide has been the oxidizer of choice in several [[hybrid rocket]] designs (using solid fuel with a liquid or gaseous oxidizer).  The combination of nitrous oxide with [[hydroxyl-terminated polybutadiene]] fuel has been used by [[SpaceShipOne]] and others.  It is also notably used in [[amateur rocketry|amateur]] and [[high power rocket]]ry with various [[plastic]]s as the fuel. An episode of ''[[MythBusters]]'' featured a hybrid rocket built using a [[paraffin]]/powdered carbon mixture (and later [[salami]]) as its solid fuel and nitrous oxide as its oxidizer.

Nitrous oxide can also be used in a [[monopropellant rocket]].  In the presence of a heated [[catalyst]], N<sub>2</sub>O will decompose exothermically into nitrogen and oxygen, at a temperature of approximately 1300 °C. Because of the large heat release the catalytic action rapidly becomes secondary as thermal autodecomposition becomes dominant.  In a vacuum thruster, this can provide a monopropellant [[specific impulse]] (''I''<sub>sp</sub>) of as much as 180s.  While noticeably less than the ''I''<sub>sp</sub> available from [[hydrazine]] thrusters (monopropellant or [[Bipropellant rocket|bipropellant]] with [[Dinitrogen tetroxide|nitrogen tetroxide]]), the decreased toxicity makes nitrous oxide an option worth investigating. Because of its release of very high temperature oxygen as a monopropellant the addition of even small amounts of a fuel such as hydrogen rapidly increases the specific impulse and the high oxygen temperatures simplify ignition of the fuel.  ''I''<sub>sp</sub> greater than 340 seconds can be readily achieved.  its low freezing point also eases thermal management as compared to hydrazine- a valuable property on a spacecraft which may contain quantities of cryogenic propellant.

=== Internal combustion engine ===
{{main|Nitrous}}

In vehicle [[racing]], nitrous oxide (often referred to as just "[[nitrous]]" in this context to differ from the acronym NOS which is the brand Nitrous Oxide Systems) is sometimes injected into the intake manifold (or prior to the intake manifold), some systems directly inject right before the cylinder (direct port injection) to increase power. The gas itself is not flammable, but it delivers more [[oxygen]] than atmospheric air by breaking down at elevated temperatures, allowing the engine to burn more fuel and air and resulting in more powerful combustion. Nitrous oxide is stored as a compressed liquid; the [[heat of vaporization|evaporation]] and expansion of liquid nitrous oxide in the [[intake manifold]] causes a large drop in intake charge temperature, resulting in a denser charge, further allowing more air/fuel mixture to enter the cylinder. The lower temperature can also reduce [[Engine knocking|detonation]].

The same technique was used during [[World War II]] by [[Luftwaffe]] aircraft with the [[GM 1]] system to boost the power output of [[aircraft engine]]s. Originally meant to provide the Luftwaffe standard aircraft with superior high-altitude performance, technological considerations limited its use to extremely high altitudes. Accordingly, it was only used by specialized planes like high-altitude [[reconnaissance aircraft]], [[schnellbomber|high-speed bombers]] and high-altitude [[interceptor aircraft|interceptors]].

One of the major problems of using nitrous oxide in a reciprocating engine is that it can produce enough power to damage or destroy the engine. Very large power increases are possible, and if the mechanical structure of the engine is not properly reinforced, the engine may be severely damaged or destroyed during this kind of operation. It is very important with nitrous oxide augmentation of [[internal combustion engine]]s to maintain proper operating temperatures and fuel levels to prevent ''preignition'', or ''detonation'' (sometimes referred to as ''knocking'' or ''pinging'').

== Neuropharmacology ==
[[Image:N2O Medical Tanks.jpg|thumb|100px|right|Medical grade nitrous oxide tanks used in dentistry]]
Nitrous oxide shares many pharmacological similarities with other inhaled anesthetics, but there are a number of differences. Nitrous oxide is relatively [[non-polar]], has a low [[molecular weight]], and high lipid solubility. As a result it can quickly diffuse into [[phospholipid]] [[cell membranes]]. 

Like many classical anesthetics, the exact mechanism of action is still open to some conjecture. It [[NMDA receptor antagonist|antagonizes the NMDA receptor]] at partial pressures similar to those used in general anaesthesia. The evidence on the effect of N<sub>2</sub>O on [[GABA]]-A currents is mixed, but tends to show a lower potency potentiation.<ref name="mennerick">Mennerick, S., Jevtovic-Todorovic, V., Todorovic, S.M., Shen, W., Olney, J.W. & Zorumski, C.F. (1998). Effect of nitrous oxide on excitatory and inhibitory synaptic transmission in hippocampal cultures. J Neurosci, 18, 9716-26.</ref> N<sub>2</sub>O, like other [[volatile anesthetic]]s, activates twin-pore [[potassium channel]]s, albeit weakly. These channels are largely responsible for keeping neurons at the resting (unexcited) potential.<ref name="gruss">Gruss, M., Bushell, T.J., Bright, D.P., Lieb, W.R., Mathie, A. & Franks, N.P. (2004). Two-pore-domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane. Mol Pharmacol, 65, 443-52.</ref> Unlike many anesthetics, however, N<sub>2</sub>O does not seem to affect [[calcium channel]]s.<ref name="mennerick"/>

Unlike most general anesthetics, N<sub>2</sub>O appears to affect the GABA receptor. In many behavioral tests of [[anxiety]], a low dose of N<sub>2</sub>O is a successful [[anxiolytic]]. This anti-anxiety effect is partially reversed by [[benzodiazepine]] [[receptor antagonist]]s. Mirroring this, animals which have developed tolerance to the anxiolytic effects of benzodiazepines are partially tolerant to nitrous oxide.<ref name="emmanouil">Emmanouil, D.E., Johnson, C.H. & Quock, R.M. (1994). Nitrous oxide anxiolytic effect in mice in the elevated plus maze: mediation by benzodiazepine receptors. Psychopharmacology (Berl), 115, 167-72.</ref> Indeed, in humans given 30% N<sub>2</sub>O, benzodiazepine receptor antagonists reduced the subjective reports of feeling “high”, but did not alter psycho-motor performance.<ref name="zacny">Zacny, J.P., Yajnik, S., Coalson, D., Lichtor, J.L., Apfelbaum, J.L., Rupani, G., Young, C., Thapar, P. & Klafta, J. (1995). Flumazenil may attenuate some subjective effects of nitrous oxide in humans: a preliminary report. Pharmacol Biochem Behav, 51, 815-9.</ref>

The effects of N<sub>2</sub>O seem linked to the interaction between the [[endogenous]] [[opioid]] system and the descending [[noradrenergic]] system. When animals are given [[morphine]] chronically they develop tolerance to its analgesic (pain killing) effects; this also renders the animals tolerant to the analgesic effects of N<sub>2</sub>O<ref>Berkowitz, B.A., Finck, A.D., Hynes, M.D. & Ngai, S.H. (1979). Tolerance to nitrous oxide analgesia in rats and mice. Anesthesiology, 51, 309-12.</ref>.  Administration of [[antibodies]] which bind and block the activity of some endogenous opioids (not [[beta-endorphin]]), also block the antinociceptive effects of N<sub>2</sub>O.<ref name="branda">Branda, E.M., Ramza, J.T., Cahill, F.J., Tseng, L.F. & Quock, R.M. (2000). Role of brain dynorphin in nitrous oxide antinociception in mice. Pharmacol Biochem Behav, 65, 217-21.</ref> Drugs which inhibit the breakdown of endogenous opioids also potentiate the antinociceptive effects of N<sub>2</sub>O.<ref name="branda"/> Several experiments have shown that opioid receptor antagonists applied directly to the brain block the antinociceptive effects of N<sub>2</sub>O, but these drugs have no effect when injected into the [[spinal cord]]. 

Conversely, alpha-[[adrenoreceptor]] antagonists block the antinociceptive effects of N<sub>2</sub>O when given directly to the spinal cord, but not when applied directly to the brain.<ref name="guo">Guo, T.Z., Davies, M.F., Kingery, W.S., Patterson, A.J., Limbird, L.E. & Maze, M. (1999). Nitrous oxide produces antinociceptive response via alpha2B and/or alpha2C adrenoceptor subtypes in mice. Anesthesiology, 90, 470-6.</ref> Indeed, alpha2B-adrenoreceptor knockout mice or animals depleted in noradrenaline are nearly completely resistant to the antinociceptive effects of N<sub>2</sub>O.<ref>Sawamura, S., Kingery, W.S., Davies, M.F., Agashe, G.S., Clark, J.D., Koblika, B.K., Hashimoto, T. & Maze, M. (2000). Antinociceptive action of nitrous oxide is mediated by stimulation of noradrenergic neurons in the brainstem and activation of [alpha]2B adrenoceptors. J Neurosci, 20, 9242-51.</ref> It seems N<sub>2</sub>O-induced release of endogenous opioids causes disinhibition of [[brain stem]] noradrenergic neurons, which release [[norepinephrine]] into the spinal cord and inhibit pain signaling (Maze, M. and M. Fujinaga, 2000). Exactly how N<sub>2</sub>O causes the release of opioids is still uncertain.

== Safety ==
The major safety hazards of nitrous oxide come from the fact that it is a compressed liquified gas, an asphyxiation risk, and a [[dissociative]] [[anaesthetic]]. Exposure to nitrous oxide causes short-term decreases in mental performance, audiovisual ability, and manual dexterity. <ref> 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> 

A study of workers <ref> Rowland AS, Baird DD, Weinberg CR, Shore DL, Shy CM, Wilcox AJ [1992]. Reduced fertility among women employed as dental assistants exposed to high levels of nitrous oxide. New Eng J Med 327(14):993B997. </ref>
and several experimental animal studies <ref>Corbett TH, Cornell RG, Endres JL, Millard RI [1973]. Effects of low concentrations of nitrous oxide on rat pregnancy. Anesthesiology 39:299B301.</ref> <ref>Vieira E [1979]. Effect of the chronic administration of nitrous oxide 0.5% to gravid rats. Br J Anaesth 51:283B287. </ref> <ref>Vieira E, Cleaton-Jones JP, Austin JC, Moyes DG, Shaw R [1980]. Effects of low concentrations of nitrous oxide on rat fetuses. Anesth and Analgesia 59(3):175B177. </ref> <ref>Vieira E, Cleaton-Jones P, Moyes D [1983]. Effects of low intermittent concentrations of nitrous oxide on the developing rat fetus. Br J Anaesth 55:67B69. </ref>  indicate that adverse reproductive effects may also result from chronic exposure to nitrous oxide.

The [[National Institute for Occupational Safety and Health]] recommends that workers' exposure to nitrous oxide should be controlled during the administration of anesthetic gas in medical, dental, and veterinary operatories. <ref> 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 [http://www.cdc.gov/niosh/noxidalr.html]</ref>

===Chemical/physical===
At room temperature (20°C) the saturated vapour pressure is 58.5 bar, rising up to 72.45 bar at 36.4°C- the [[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= Air Liquid data on Nitrous oxide]</ref> Liquid nitrous oxide acts as a good solvent for many [[organic compounds]]; liquid mixtures and may form shock sensitive explosives.

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>[http://www.ukrocketman.com/rocketry/hybridukhistory.shtml vaseline triggered explosion of hybrid rocket]</ref>

There have also been accidents where nitrous oxide decomposition in plumbing has led to the explosion of large tanks.<ref>[http://www.hobbyspace.com/AAdmin/archive/SpecialTopics/Misc/eindhoven.pdf Nitrous Oxide Trailer Rupture July 2, 2001] Report at CGA Seminar “Safety and Reliability of Industrial Gases, Equipment and Facilities”, October 15 -17, 2001, St. Louis, Missouri by Konrad Munke, LindeGas AG</ref>

===Biological===
Nitrous oxide inactivates the cobalamin form of vitamin B{{ssub|12}} by oxidation. Symptoms of vitamin B{{ssub|12}} deficiency, including [[sensory neuropathy]], [[myelopathy]], and [[encephalopathy]], can occur within days or weeks of exposure to nitrous oxide [[anesthesia]] 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. People with normal vitamin B{{ssub|12}} levels have sufficient vitamin B{{ssub|12}} 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 anesthesia. 

Nitrous oxide has also been shown to induce early stages of [[Olney's lesions]] in the brains of rats.<ref name="Jevtovic-Todorovic">{{cite journal |author=Jevtovic-Todorovic V, Beals J, Benshoff N, Olney J |title=Prolonged exposure to inhalational anesthetic nitrous oxide kills neurons in adult rat brain |journal=Neuroscience |volume=122 |issue=3 |pages=609-16 |year=2003 |pmid=14622904}}</ref>

===Thermal===
Compressed nitrous oxide is usually stored at room temperature, but as the gas expands it quickly cools to sub-zero temperatures via the [[Joule-Thomson Effect]]. A leak or unexpected release of compressed nitrous oxide can result in an immediate and severe [[burn (injury)|burn]].

== Legality ==
In the United States, possession of nitrous oxide is legal under federal law and is not subject to [[Drug Enforcement Administration|DEA]] purview.<ref name="ccle">[http://www.cognitiveliberty.org/dll/N20_state_laws.htm Center for Cognitive Liberty and Ethics: State Laws Concerning Inhalation of Nitrous Oxide]</ref> It is, however, regulated by the [[Food and Drug Administration]] under the Food Drug and Cosmetics Act; prosecution is possible under its "misbranding" clauses, prohibiting the sale or distribution of nitrous oxide for the purpose of [[recreational drug use|human consumption]]. 

Many states have laws regulating the possession, sale, and distribution of nitrous oxide; but these are normally limited to either banning distribution to minors, or to setting an upper limit for the amount of nitrous oxide that may be sold without special license, rather than banning possession or distribution completely. In most jurisdictions, like at the federal level, sale or distribution for the purpose of recreational consumption is illegal.<ref name="ccle"/>

In the [[United Kingdom]], recreational use of nitrous oxide is illegal, though sale and possession for non-inhalant use is legal for adults over the age of 18.<ref name="erowidlaw">http://www.erowid.org/chemicals/nitrous/nitrous_law.shtml</ref>  According to Times online, and certain other sources, laughing gas is legal in the UK.<ref>http://www.timesonline.co.uk/tol/news/uk/article596797.ece</ref>

In New Zealand, the [[New Zealand Ministry of Health|Ministry of Health]] has warned that nitrous oxide is a prescription medicine, and its sale or possession without a prescription is an offence under the Medicines Act.<ref>[http://www.beehive.govt.nz/ViewDocument.aspx?DocumentID=23487 Beehive.govt.nz - Time's up for sham sales of laughing gas]</ref>  This statement would seemingly prohibit all non-medicinal uses of the chemical, though it is implied that only recreational use will be legally targeted.

== History==
The gas was first synthesized by English chemist and natural philosopher [[Joseph Priestley]] in 1775 [http://www.justsayn2o.com/], who called it ''phlogisticated nitrous air'' (see [[phlogiston]]). Priestley describes the preparation of "nitrous air diminished" by heating iron filings dampened with [[nitric acid]] in ''Experiments and Observations on Different Kinds of Air'', (1775). Priestley was delighted with his discovery: "I have now discovered an air five or six times as good as common air... nothing I ever did has surprised me more, or is more satisfactory." <ref>J. R. Partington, ''A Short History of Chemistry'', 3rd ed., Dover Publications, Inc., New York, New York, 1989, pp. 110-121.</ref> [[Humphry Davy]] in the 1790s tested the gas on himself and some of his friends, including the poets [[Samuel Taylor Coleridge]] and [[Robert Southey]]. 

They realised that nitrous oxide considerably dulled the sensation of pain, even if the inhaler were still semi-conscious. After it was publicized extensively by [[Gardner Quincy Colton]] in the United States in the 1840s, it came into use as an anaesthetic, particularly by dentists, who do not typically have access to the services of an [[anesthesiologist]] and who may benefit from a patient who can respond to verbal commands.

==Manufacture==

A gas is present in trace amounts in Earth's atmosphere as a result of high temperature reactions between nitrogen and oxygen. 
Industrially the gas is prepared by gently heating [[ammonium nitrate]], which decomposes into nitrous oxide and water vapor.

NH<sub>4</sub>NO<sub>3</sub>(s) → 2 H<sub>2</sub>O(g) + N<sub>2</sub>O(g) 

The preparation is dangerous because of N2O's tendency to explosively decompose into nitrogen and oxygen at high temperatures. (The World Trade Center and Oklahoma City bombings involved detonation of nitrous oxide produced by rapid high temperature decomposition.) N<sub>2</sub>O manufactured this way should NOT be inhaled, because it is contaminated with NO<sub>2</sub>, a corrosive, irritating gas that can cause permanent lung and genetic damage. 

The addition of various [[phosphate]]s favors formation of a purer gas at slightly lower temperatures. This reaction occurs between 170 - 240°C, temperatures where ammonium nitrate is a moderately sensitive [[explosive]] and a very powerful [[oxidizer]] (perhaps on the order of fuming [[nitric acid]]). At temperatures much above 240&nbsp;°C the [[exothermic reaction]] may accelerate this reaction up to the point of [[detonation]]. 

The mixture must be cooled to avoid such a disaster. In practice, the reaction involves a series of tedious adjustments to control the temperature to within a narrow range.  Professionals have destroyed whole neighborhoods by losing control (of the ''temperature and pressure'' in the ammonium nitrate retorts) in commercial scale processes. Examples include the Ohio Chemical debacle in [[Montreal]], 1966 and the Air Products & Chemicals, Inc. disaster in Delaware City, Delaware, 1977.   

Downstream, the hot, corrosive mixture of gases must be cooled to condense the steam and filtered to remove higher oxides of nitrogen.  Also  ammonium nitrate ''loke'' in an extremely persistent colloid will likely have to be removed.  The clean up is often done in a train of 3 gas washes; namely base, acid and base again.  Any significant amounts of nitric oxide (NO) may not necessarily be absorbed directly by the base (sodium hydroxide) washes.  

The nitric oxide impurity is sometimes chelated out with iron II (ferrous sulfate), reduced with iron metal (such as steel wool or turnings) or oxidised (example: potassium permanganate) and then absorbed in base as a higher oxide.  The first base wash may (or may not) react out much of the ammonium nitrate smoke, however this reaction generates ammonia gas, which may have to be absorbed in the acid wash. 

The direct oxidation of [[ammonia]] may someday rival the ammonium nitrate [[pyrolysis]] synthesis of nitrous oxide mentioned above.  This capital-intensive process, which originates in Japan, uses a [[manganese dioxide]]-[[bismuth oxide]] catalyst. (Suwa et al. 1961; Showa Denka Ltd.)
:2NH<sub>3</sub> + 2O<sub>2</sub> → N<sub>2</sub>O + 3H<sub>2</sub>O

Higher oxides of nitrogen are formed as impurities.  For comparison note that [[catalysis|uncatalyzed]] ammonia oxidation (i.e. combustion or explosion) goes primarily to N<sub>2</sub> and H<sub>2</sub>O. The [[Ostwald process]] oxidizes ammonia to [[nitric oxide]] (NO), using a [[platinum]] catalyst screen. (this is the beginning of the modern synthesis of nitric acid from ammonia, often much of the nitric acid is reacted with more ammonia to form ammonium nitrate and sometimes the ammonium nitrate cam be pyrolysed to . . . [see above]).

Nitrous oxide can be made by heating a solution of [[sulfamic acid]] and [[nitric acid]]. A lot of gas was made this way in Bulgaria (Brozadzhiew & Rettos, 1975).  
:HNO<sub>3</sub> + NH<sub>2</sub>SO<sub>3</sub>H → N<sub>2</sub>O + H<sub>2</sub>SO<sub>4</sub> + H<sub>2</sub>O
There is no explosive hazard in this reaction if the mixing rate is controlled.  However, as usual, toxic higher oxides of nitrogen form. 

Nitrous oxide is produced in large volumes as a by-product in the synthesis of adipic acid; one of the two reactants used in nylon manufacture.  This might become a major commercial source, but will require the removal of higher oxides of nitrogen and organic impurities.  Currently much of the gas is decomposed before release for environmental protection.  Greener proceses may prevail that substitute peroxide for nitric acid oxidation; hence no generation of oxide of nitrogen by-products.

Colorless solutions of [[hydroxylammonium chloride]] and [[sodium nitrite]] can also be used to produce N<sub>2</sub>O:
: NH<sub>3</sub>OH<sup>+</sup>Cl<sup>−</sup> + NaNO<sub>2</sub> → N<sub>2</sub>O + NaCl + H<sub>2</sub>O
If the nitrite is added to the hydroxylamine solution, the gas produced is pure enough for inhalation, and the only remaining byproduct is salt water.  However, if the hydroxylamine solution is added to the nitrite solution (nitrite is in excess), then toxic higher oxides of nitrogen are also formed.

== Nitrous oxide in the atmosphere ==
[[Image:Major greenhouse gas trends.png|thumb|350px|Greenhouse gas trends.]]
Unlike other [[nitrogen oxide]]s, nitrous oxide is a major [[greenhouse gas]].  While its radiative warming effect is substantially less than CO<sub>2</sub>, nitrous oxide's persistence in the atmosphere, when considered over a 100 year period, per unit of weight, has 296 times more impact on [[global warming]] than that per mass unit of [[carbon dioxide]] (CO<sub>2</sub>) [http://www.grida.no/climate/ipcc_tar/wg1/248.htm].  Control of nitrous oxide is part of efforts to curb greenhouse gas emissions, such as the [[Kyoto Protocol]].  Despite its relatively small concentration in the atmosphere, nitrous oxide is the third largest greenhouse gas contributor to overall global warming, behind [[carbon dioxide]] and [[methane]]. (The other nitrogen oxides contribute to global warming indirectly, by contributing to tropospheric ozone production during smog formation).

Nitrous oxide is emitted by [[bacteria]] in soils and oceans, and thus has been a part of Earth's atmosphere for eons. Agriculture is the main source of human-produced nitrous oxide: cultivating soil, the use of [[nitrogen fertilizer]]s, and animal waste handling can all stimulate naturally occurring bacteria to produce more nitrous oxide. The livestock sector (primarily cows, chickens, and pigs) produces 65% of human-related nitrous oxide [http://www.virtualcentre.org/en/library/key_pub/longshad/A0701E00.htm]. Industrial sources make up only about 20% of all anthropogenic sources, and include the production of [[nylon]] and nitric acid, and the burning of fossil fuel in internal combustion engines.

Human activity is thought to account for somewhat less than 2&nbsp;[[tera]]grams (this is multiplied by about 300 when calculated as an equivalent amount of carbon dioxide) of nitrogen oxides per year, nature for over 15&nbsp;teragrams [http://www.epa.gov/nitrousoxide/sources.html]. The global anthropogenic nitrous oxide flux is about 1&nbsp;petagram of carbon dioxide carbon-equivalents per year; this compares to 2&nbsp;petagrams of methane carbon dioxide carbon-equivalents per year, and to an atmospheric loading rate of about 3.3&nbsp;petagrams of carbon dioxide carbon-equivalents per year.

Nitrous oxide also attacks [[ozone]] in the [[stratosphere]], aggravating the excess amount of [[ultraviolet|UV]] light striking the earth's surface in recent decades, in a manner similar to various freons and related [[haloalkane|halogenated organics]]. Nitrous oxide is the main naturally-occurring regulator of stratospheric ozone.

Recent Research [http://meteo.lcd.lu/globalwarming/Crutzen/biofuels_NO2_release_2007.pdf] by Nobel Laureate [[Paul Crutzen]] suggests that emissions of Nitrous Oxide in the production of biofuels are more than enough to offset the advantages that biodiesel was hoped to have in terms of [[carbon dioxide]] emissions.  More generally this concerns the use of all Nitrogen Fertilizer.

==External links==
*[http://www.osha.gov/SLTC/healthguidelines/nitrousoxide/recognition.html Occupational Safety and Health Guideline for Nitrous Oxide]
*[http://www.vega.org.uk/video/programme/111 Paul Crutzen Interview] Freeview video of Paul Crutzen Nobel Laureate for his work on decomposition of ozone talking to Harry Kroto Nobel Laureate by the Vega Science Trust.
*[http://www.npi.gov.au/database/substance-info/profiles/67.html National Pollutant Inventory - Oxide of nitrogen fact sheet]
*[http://www.tsinghua.edu.cn/docsn/lxx/mainpage/a/Web/index_files/page0002.htm Nitrous Oxide Specs] Extremely thorough Nitrous Oxide Facts
*[http://www.cdc.gov/niosh/topics/nitrousoxide/ National Institute for Occupational Safety and Health - Nitrous Oxide]

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==References==
{{reflist}}

[[Category:Oxides]]
[[Category:Nitrogen compounds]]
[[Category:Aerosol propellants]]
[[Category:Anesthetics]]
[[Category:Dissociatives]]
[[Category:Greenhouse gases]]
[[Category:Nitrogen metabolism]]
[[Category:NMDA receptor antagonists]]
[[Category:Monopropellants]]
[[Category:Rocket oxidizers]]
[[Category:Inhalants]]
[[Category:Occupational safety and health]]

[[ar:أكسيد نيتروس]]
[[cs:Oxid dusný]]
[[da:Lattergas]]
[[de:Distickstoffmonoxid]]
[[es:Óxido nitroso]]
[[eo:Ridgaso]]
[[fr:Protoxyde d'azote]]
[[gl:Óxido nitroso]]
[[it:Ossido di diazoto]]
[[he:חמצן דו-חנקני]]
[[lt:Diazoto monoksidas]]
[[hu:Dinitrogén-oxid]]
[[nl:Lachgas]]
[[ja:亜酸化窒素]]
[[no:Dinitrogenoksid]]
[[nds:Distickstoffmonoxid]]
[[pl:Podtlenek azotu]]
[[pt:Óxido nitroso]]
[[ru:Оксид азота(I)]]
[[sr:Азотсубоксид]]
[[fi:Ilokaasu]]
[[sv:Lustgas]]
[[zh:一氧化二氮]]

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