2). The generic term NOx includes these two but does not include nitrous oxide.
| IUPAC name
| Other names
Laughing gas, Sweet air, Protoxide of nitrogen, Hyponitrous oxide
|3D model (Jmol)||Interactive image|
|E number||E942 (glazing agents, ...)|
|UN number|| 1070 (compressed)|
|Molar mass||44.013 g/mol|
|Density||1.977 g/L (gas)|
|Melting point||−90.86 °C (−131.55 °F; 182.29 K)|
|Boiling point||−88.48 °C (−127.26 °F; 184.67 K)|
|1.5 g/L (15 °C)|
|Solubility||soluble in alcohol, ether, sulfuric acid|
|Vapor pressure||5150 kPa (20 °C)|
Refractive index (nD)
|1.000516 (0 °C, 101,325 kPa)|
|219.96 J K−1 mol−1|
Std enthalpy of
|+82.05 kJ mol−1|
|Safety data sheet||Ilo.org, ICSC 0067|
| Nitric oxide|
| Ammonium nitrate|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|(what is ?)|
Nitrous oxide, commonly known as laughing gas, nitrous, nitro, or NOS is a chemical compound with the formula N
2O. It is an oxide of nitrogen. At room temperature, it is a colorless, odorless non-flammable gas, with a slightly sweet taste. It is used in surgery and dentistry for its anaesthetic and analgesic effects. It is known as "laughing gas" due to the euphoric effects of inhaling it, a property that has led to its recreational use as a dissociative anaesthetic. It is also used as an oxidizer in rocket propellants, and in motor racing to increase the power output of engines. At elevated temperatures, nitrous oxide is a powerful oxidizer similar to molecular oxygen.
Nitrous oxide gives rise to nitric oxide (NO) on reaction with oxygen atoms, and this NO in turn reacts with ozone. As a result, it is the main naturally occurring regulator of stratospheric ozone. It is also a major greenhouse gas and air pollutant. Considered over a 100-year period, it is calculated to have between 265 and 310 times more impact per unit mass (global-warming potential) than carbon dioxide.
Nitrous oxide can be used as an oxidizer in a rocket motor. This has the advantages over other oxidisers in that it is not only non-toxic, but also, 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. Its high density and low storage pressure (when maintained at low temperature) enable it to be highly competitive with stored high-pressure gas systems.
In a 1914 patent, American rocket pioneer Robert Goddard suggested nitrous oxide and gasoline as possible propellants for a liquid-fuelled rocket. Nitrous oxide has been the oxidiser 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 and high power rocketry with various plastics as the fuel.
Nitrous oxide can also be used in a monopropellant rocket. In the presence of a heated catalyst, N
2O will decompose exothermically into nitrogen and oxygen, at a temperature of approximately 1,070 °F (577 °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 (Isp) of as much as 180 s. While noticeably less than the Isp available from hydrazine thrusters (monopropellant or bipropellant with dinitrogen tetroxide), the decreased toxicity makes nitrous oxide an option worth investigating.
Nitrous oxide is said to deflagrate somewhere around 600 °C (1,112 °F) at a pressure of 21 atmospheres. At 600 psi for example, the required ignition energy is only 6 joules, whereas N
2O at 130 psi a 2500-joule ignition energy input is insufficient.
Internal combustion engine
In vehicle racing, nitrous oxide (often referred to as just "nitrous") allows the engine to burn more fuel by providing more oxygen than air alone, resulting in a more powerful combustion. The gas itself is not flammable at a low pressure/temperature, but it delivers more oxygen than atmospheric air by breaking down at elevated temperatures. Therefore, it is often mixed with another fuel that is easier to deflagrate. Nitrous oxide is a strong oxidant roughly equivalent to hydrogen peroxide and much stronger than oxygen gas.
Nitrous oxide is stored as a compressed liquid; the 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. Nitrous oxide is sometimes injected into (or prior to) the intake manifold, whereas other systems directly inject right before the cylinder (direct port injection) to increase power.
The technique was used during World War II by Luftwaffe aircraft with the GM-1 system to boost the power output of aircraft engines. 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, high-speed bombers, and high-altitude interceptor aircraft. It could sometimes be found on Luftwaffe aircraft also fitted with another engine-boost system, MW 50, a form of water injection for aviation engines that used methanol for its boost capabilities.
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 petrol engines to maintain proper operating temperatures and fuel levels to prevent "pre-ignition", or "detonation" (sometimes referred to as "knock"). Most problems that are associated with nitrous do not come from mechanical failure due to the power increases. Since nitrous allows a much denser charge into the cylinder it dramatically increases cylinder pressures. The increased pressure and temperature can cause problems such as melting the piston or valves. It may also crack or warp the piston or head and cause pre-ignition due to uneven heating.
Automotive-grade liquid nitrous oxide differs slightly from medical-grade nitrous oxide. A small amount of sulfur dioxide (SO
2) is added to prevent substance abuse. Multiple washes through a base (such as sodium hydroxide) can remove this, decreasing the corrosive properties observed when SO
2 is further oxidised during combustion into sulfuric acid, making emissions cleaner.
The gas is approved for use as a food additive (also known as E942), specifically as an aerosol spray propellant. Its most common uses in this context are in aerosol whipped cream canisters, cooking sprays, and as an inert gas used to displace oxygen, to inhibit bacterial growth, 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, oxygen would accelerate rancidification of the butterfat; nitrous oxide inhibits such degradation. Carbon dioxide cannot be used for whipped cream because it is acidic in water, which would curdle the cream and give it a seltzer-like "sparkling" sensation.
However, the whipped cream produced with nitrous oxide is unstable and will return to a more 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 as a euphoria-inducing inhalant drug. It is not harmful in small doses, but risks due to lack of oxygen do exist (see Recreational use below).
Nitrous oxide has been used for anaesthesia in dentistry since December 1844, where Horace Wells made the first 12–15 dental operations with the gas in Hartford. Its debut as a generally accepted method, however, came in 1863, when Gardner Quincy Colton introduced it more broadly at all the Colton Dental Association clinics, that he founded in New Haven and New York City. The first devices used in dentistry to administer the gas, known as Nitrous Oxide inhalers, were designed in a very simple way with the gas stored and breathed through a breathing bag made of rubber cloth, without a scavenger system and flowmeter, and with no addition of oxygen/air. Today these simple and somewhat unreliable inhalers have been replaced by the more modern relative analgesia machine, which is an automated machine designed to deliver a precisely dosed and breath-actuated flow of nitrous oxide mixed with oxygen, for the patient to inhale safely. The machine used in dentistry is designed as a simplified version of the larger anaesthetic machine used by hospitals, as it doesn't feature the additional anaesthetic vaporiser and medical ventilator. The purpose of the machine allows for a simpler design, as it only delivers a mixture of nitrous oxide and oxygen for the patient to inhale, in order to depress the feeling of pain while keeping the patient in a conscious state.
Relative analgesia machines typically feature a constant-supply flowmeter, which allow the proportion of nitrous oxide and the combined gas flow rate to be individually adjusted. The gas is administered by dentists through a demand-valve inhaler over the nose, which will only release gas when the patient inhales through the nose. Because nitrous oxide 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 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 scavenger system is used to prevent a waste-gas buildup.
Hospitals administer nitrous oxide as one of the anaesthetic drugs delivered by anaesthetic machines. Nitrous oxide is a weak general anaesthetic, and so is generally not used alone in general anaesthesia. In general anaesthesia it is used as a carrier gas in a 2:1 ratio with oxygen for more powerful general anaesthetic drugs such as sevoflurane or desflurane. It has a minimum alveolar concentration of 105% and a blood/gas partition coefficient of 0.46.
Analgesic, antidepressant, etc
The medical grade gas tanks, with the trade name Entonox and Nitronox contain a mixture with 50%, but this will normally be diluted to a lower percentage upon the operational delivery to the patient. Inhalation of nitrous oxide is frequently used to relieve pain associated with childbirth, trauma, oral surgery, and acute coronary syndrome (includes heart attacks). Its use during labour has been shown to be a safe and effective aid for birthing women. Its use for acute coronary syndrome is of unknown benefit.
In Britain and Canada, Entonox and Nitronox are commonly used by ambulance crews (including unregistered practitioners) as a rapid and highly effective analgesic gas.
Nitrous oxide is also gaining interest as a substitute gas for carbon dioxide in laparoscopic surgery. It has been found to be as safe as carbon dioxide with better pain relief.
Nitrous oxide can cause analgesia, depersonalisation, derealisation, dizziness, euphoria, and some sound distortion. Research has also found that it increases suggestibility and imagination. Inhalation of nitrous oxide for recreational use, with the purpose of causing euphoria and/or slight hallucinations, began as a phenomenon for the British upper class in 1799, known as "laughing gas parties". Until at least 1863, a low availability of equipment to produce the gas, combined with a low usage of the gas for medical purposes, meant it was a relatively rare phenomenon that mainly happened among students at medical universities. When equipment became more widely available for dentistry and hospitals, most countries also restricted the legal access to buy pure nitrous oxide gas cylinders to those sectors. Despite only medical staff and dentists today being legally allowed to buy the pure gas, a Consumers Union report from 1972 found that the use of the gas for recreational purpose was [then] still taking place, based upon reports of its use in Maryland 1971, Vancouver 1972, and a survey made by Dr. Edward J. Lynn of its non-medical use in Michigan 1970.
It was not uncommon [in the interviews] to hear from individuals who had been to parties where a professional (doctor, nurse, scientist, inhalation therapist, researcher) had provided nitrous oxide. There also were those who work in restaurants who used the N
2O stored in tanks for the preparation of whip cream. Reports were received from people who used the gas contained in aerosol cans both of food and non-food products. At a recent rock festival nitrous oxide was widely sold for 25 cents a balloon. Contact was made with a "mystical-religious" group that used the gas to accelerate arriving at their transcendental-meditative state of choice. Although a few, more sophisticated users employed nitrous oxide-oxygen mixes with elaborate equipment, most users used balloons or plastic bags. They either held a breath of N
2O or rebreathed the gas. There were no adverse effects reported in the more than one hundred individuals surveyed.
In Australia, nitrous oxide bulbs are known as nangs, possibly derived from the sound distortion perceived by consumers.
In the United Kingdom, nitrous oxide is used by almost half a million young people at nightspots, festivals and parties. In August 2015, the London Borough of Lambeth Council banned the use of the drug for recreational purposes, making offenders liable to an on-the-spot fine of up to £1,000.
Mechanism of action
The pharmacological mechanism of action of N
2O in medicine is not fully known. However, it has been shown to directly modulate a broad range of ligand-gated ion channels, and this likely plays a major role in many of its effects. It moderately blocks NMDA and β2-subunit-containing nACh channels, weakly inhibits AMPA, kainate, GABAC, and 5-HT3 receptors, and slightly potentiates GABAA and glycine receptors. It has also been shown to activate two-pore-domain K+
channels. While N
2O affects quite a few ion channels, its anaesthetic, hallucinogenic, and euphoriant effects are likely caused predominantly or fully via inhibition of NMDA receptor-mediated currents. In addition to its effects on ion channels, N
2O may act to imitate nitric oxide (NO) in the central nervous system, and this may be related to its analgesic and anxiolytic properties.
In behavioural tests of anxiety, a low dose of N
2O is an effective anxiolytic, and this anti-anxiety effect is associated with enhanced activity of GABAA receptors, as it is partially reversed by benzodiazepine receptor antagonists. Mirroring this, animals which have developed tolerance to the anxiolytic effects of benzodiazepines are partially tolerant to N
2O. Indeed, in humans given 30% N
2O, benzodiazepine receptor antagonists reduced the subjective reports of feeling "high", but did not alter psychomotor performance, in human clinical studies.
The analgesic effects of N
2O are 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 pain-killing effects, and this also renders the animals tolerant to the analgesic effects of N
2O. Administration of antibodies which bind and block the activity of some endogenous opioids (not β-endorphin) also block the antinociceptive effects of N
2O. Drugs which inhibit the breakdown of endogenous opioids also potentiate the antinociceptive effects of N
2O. Several experiments have shown that opioid receptor antagonists applied directly to the brain block the antinociceptive effects of N
2O, but these drugs have no effect when injected into the spinal cord.
Conversely, α2-adrenoceptor antagonists block the pain reducing effects of N
2O when given directly to the spinal cord, but not when applied directly to the brain. Indeed, α2B-adrenoceptor knockout mice or animals depleted in norepinephrine are nearly completely resistant to the antinociceptive effects of N
2O. Apparently N
2O-induced release of endogenous opioids causes disinhibition of brain stem noradrenergic neurons, which release norepinephrine into the spinal cord and inhibit pain signalling. Exactly how N
2O causes the release of endogenous opioid peptides is still uncertain.
In rats, N
2O stimulates the mesolimbic reward pathway via inducing dopamine release and activating dopaminergic neurons in the ventral tegmental area and nucleus accumbens, presumably through antagonisation of NMDA receptors localised in the system. This action has been implicated in its euphoric effects, and notably, appears to augment its analgesic properties as well.
However, it is remarkable that in mice, N
2O blocks amphetamine-induced carrier-mediated dopamine release in the nucleus accumbens and behavioural sensitisation, abolishes the conditioned place preference (CPP) of cocaine and morphine, and does not produce reinforcing (or aversive) effects of its own. Studies on CPP of N
2O in rats is mixed, consisting of reinforcement, aversion, and no change. In contrast, it is a positive reinforcer in squirrel monkeys, and is well known as a drug of abuse in humans. These discrepancies in response to N
2O may reflect species variation or methodological differences. In human clinical studies, N
2O was found to produce mixed responses similarly to rats, reflecting high subjective individual variability.
Neurotoxicity and neuroprotection
Like other NMDA antagonists, N
2O was suggested to produce neurotoxicity in the form of Olney's lesions in rodents upon prolonged (several hour) exposure. However, new research has arisen suggesting that Olney's lesions do not occur in humans, and similar drugs like ketamine are now believed not to be acutely neurotoxic. It has been argued that, because N
2O has a very short duration under normal circumstances, it is less likely to be neurotoxic than other NMDA antagonists. Indeed, in rodents, short-term exposure results in only mild injury that is rapidly reversible, and permanent neuronal death only occurs after constant and sustained exposure. Nitrous oxide may also cause neurotoxicity after extended exposure because of hypoxia. This is especially true of non-medical formulations such as whipped-cream chargers (also known as "whippets" or "nangs"), which are not necessarily mixed with oxygen.
Nitrous oxide at 75-vol% reduce ischemia-induced neuronal death induced by occlusion of the middle cerebral artery in rodents, and decrease NMDA-induced Ca2+ influx in neuronal cell cultures, a critical event involved in excitotoxicity.
The major safety hazards of nitrous oxide come from the fact that it is a compressed liquefied gas, an asphyxiation risk, and a dissociative anaesthetic. Exposure to nitrous oxide causes short-term decreases in mental performance, audiovisual ability, and manual dexterity. Abusing nitrous oxide can lead to oxygen deprivation resulting in loss of blood pressure, fainting and even heart attacks.
Long-term exposure can cause vitamin B12 deficiency, numbness, reproductive side effects (in pregnant females), and other problems (see Biological). 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. People can be exposed to nitrous oxide in the workplace by breathing it in or getting the liquid on their skin or in their eyes. The National Institute for Occupational Safety and Health (NIOSH) has set a Recommended exposure limit (REL) of 25 ppm (46 mg/m3) exposure to waste anaesthetic.
At room temperature (20 °C (68 °F)) the saturated vapour pressure is 50.525 bar, rising up to 72.45 bar at 36.4 °C (97.5 °F)—the critical temperature. The pressure curve is thus unusually sensitive to temperature. Liquid nitrous oxide acts as a good solvent for many organic compounds; liquid mixtures 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). Some common building materials such as stainless steel and aluminium can act as fuels with strong oxidisers such as nitrous oxide, as can contaminants, which can ignite due to adiabatic compression.
Nitrous oxide inactivates the cobalamin form of vitamin B12 by oxidation. Symptoms of vitamin B12 deficiency, including sensory neuropathy, myelopathy, and encephalopathy, can occur within days or weeks of exposure to nitrous oxide anaesthesia in people with subclinical vitamin B12 deficiency. Symptoms are treated with high doses of vitamin B12, but recovery can be slow and incomplete. People with normal vitamin B12 levels have stores to make the effects of nitrous oxide insignificant, unless exposure is repeated and prolonged (nitrous oxide abuse). Vitamin B12 levels should be checked in people with risk factors for vitamin B12 deficiency prior to using nitrous oxide anaesthesia.
Nitrous oxide reductase is an important enzyme which limits the emission of the gas to the atmosphere.
2O is a greenhouse gas with a large global warming potential (GWP). When compared to carbon dioxide (CO
2O has 298 times the ability per molecule of gas to trap heat in the atmosphere. N
2O is produced naturally in the soil during the microbial processes of nitrification and denitrification.
The United States of America signed and ratified the United Nations Framework Convention on Climate Change (UNFCCC) in 1992, agreeing to inventory and assess the various sources of greenhouse gases that contribute to climate change. The agreement requires parties to "develop, periodically update, publish and make available... national inventories of anthropogenic emissions by sources and removals by sinks of all greenhouse gases not controlled by the Montreal Protocol, using comparable methodologies...". In response to this agreement, the U.S. is obligated to inventory anthropogenic emissions by sources and sinks, of which agriculture is a key contributor. In 2008, agriculture contributed 6.1% of the total U.S. greenhouse gas emissions and cropland contributed nearly 69% of total direct nitrous oxide (N
2O) emissions. Additionally, estimated emissions from agricultural soils were 6% higher in 2008 than 1990.
According to 2006 data from the United States Environmental Protection Agency, industrial sources make up only about 20% of all anthropogenic sources, and include the production of nylon, and the burning of fossil fuel in internal combustion engines. Human activity is thought to account for 30%; tropical soils and oceanic release account for 70%. However, a 2008 study by Nobel Laureate Paul Crutzen suggests that the amount of nitrous oxide release attributable to agricultural nitrate fertilizers has been seriously underestimated, most of which would presumably come under soil and oceanic release in the Environmental Protection Agency data. Atmospheric levels have risen by more than 15% since 1750. Nitrous oxide also causes ozone depletion. A new study suggests that N2O emission currently is the single most important ozone-depleting substance (ODS) emission and is expected to remain the largest throughout the 21st century.
Nitrous oxide can be prepared by careful heating of ammonium nitrate, which decomposes into nitrous oxide and water vapour. The addition of various phosphate salts favours formation of a purer gas at slightly lower temperatures. One of the earliest commercial producers was George Poe.
3 → 2 H
2O + N
This reaction can be difficult to control, resulting in detonation.
3 + (NH4)2SO4 → Na2SO4 + 2N
- 2 (NH2)2CO + 2 HNO
4 → 2 N
2O + 2 CO
2 + (NH4)2SO4 + 2H
- 2 NH
3 + 2 O
2 → N
2O + 3 H
Hydroxylammonium chloride reacts with sodium nitrite to give nitrous oxide. If the nitrite is added to the hydroxylamine solution, the only remaining by-product 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.
3OHCl + NaNO
2 → N
2O + NaCl + 2 H
3 with SnCl
2 and HCl has also been demonstrated:
- 2 HNO
3 + 8 HCl + 4 SnCl
2 → 5 H
2O + 4 SnCl
4 + N
- H2N2O2→ H2O + N2O
Of the entire anthropogenic N
2O emission (5.7 teragrams N
2O-N per year), agricultural soils provide 3.5 teragrams N
2O–N per year. Nitrous oxide is produced naturally in the soil during the microbial processes of nitrification, denitrification, nitrifier denitrification and others:
- aerobic autotrophic nitrification, the stepwise oxidation of ammonia (NH
3) to nitrite (NO−
2) and to nitrate (NO−
3) (e.g., Kowalchuk and Stephen, 2001),
- anaerobic heterotrophic denitrification, the stepwise reduction of NO−
3 to NO−
2, nitric oxide (NO), N
2O and ultimately N
2, where facultative anaerobe bacteria use NO−
3 as an electron acceptor in the respiration of organic material in the condition of insufficient oxygen (O
2) (e.g. Knowles, 1982), and
- nitrifier denitrification, which is carried out by autotrophic NH
3−oxidizing bacteria and the pathway whereby ammonia (NH
3) is oxidised to nitrite (NO−
2), followed by the reduction of NO−
2 to nitric oxide (NO), N
2O and molecular nitrogen (N
2) (e.g., Webster and Hopkins, 1996; Wrage et al., 2001).
- Other N
2O production mechanisms include heterotrophic nitrification (Robertson and Kuenen, 1990), aerobic denitrification by the same heterotrophic nitrifiers (Robertson and Kuenen, 1990), fungal denitrification (Laughlin and Stevens, 2002), and non-biological process chemodenitrification (e.g. Chalk and Smith, 1983; Van Cleemput and Baert, 1984; Martikainen and De Boer, 1993; Daum and Schenk, 1998; Mørkved et al., 2007).
2O emissions are reported to be controlled by soil chemical and physical properties such as the availability of mineral N, soil pH, organic matter availability, and soil type, and climate related soil properties such as soil temperature and soil water content (e.g., Mosier, 1994; Bouwman, 1996; Beauchamp, 1997; Yamulki et al. 1997; Dobbie and Smith, 2003; Smith et al. 2003; Dalal et al. 2003).
Properties and reactions
Nitrous oxide is a colourless, non-toxic gas with a faint, sweet odour.
2O is inert at room temperature and has few reactions. At elevated temperatures, its reactivity increases. For example, nitrous oxide reacts with NaNH
2 at 460 K (187 °C) to give NaN
- 2 NaNH
2 + N
2O → NaN
3 + NaOH + NH
Nitrous oxide is emitted by bacteria in soils and oceans, and is thus a part of Earth's atmosphere. Agriculture is the main source of human-produced nitrous oxide: cultivating soil, the use of nitrogen fertilisers, 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. Industrial sources make up only about 20% of all anthropogenic sources, and include the production of nylon, and the burning of fossil fuel in internal combustion engines. Human activity is thought to account for 40%; tropical soils and oceanic release account for the rest.
Nitrous oxide reacts with ozone in the stratosphere. Nitrous oxide is the main naturally occurring regulator of stratospheric ozone. Nitrous oxide is a major greenhouse gas. Considered over a 100-year period, it has 298 times more impact per unit weight than carbon dioxide. Thus, despite its low concentration, nitrous oxide is the fourth largest contributor to these greenhouse gases. It ranks behind water vapour, carbon dioxide, and methane. Control of nitrous oxide is part of efforts to curb greenhouse gas emissions.
The gas was first synthesised by English natural philosopher and chemist Joseph Priestley in 1772, who called it phlogisticated nitrous air (see phlogiston). Priestley published his discovery in the book Experiments and Observations on Different Kinds of Air (1775), where he described how to produce the preparation of "nitrous air diminished", by heating iron filings dampened with nitric acid.
The first important use of nitrous oxide was made possible by Thomas Beddoes and James Watt, who worked together to publish the book Considerations on the Medical Use and on the Production of Factitious Airs (1794). This book was important for two reasons. First, James Watt had invented a novel machine to produce "Factitious Airs" (i.e. nitrous oxide) and a novel "breathing apparatus" to inhale the gas. Second, the book also presented the new medical theories by Thomas Beddoes, that tuberculosis and other lung diseases could be treated by inhalation of "Factitious Airs".
The machine to produce "Factitious Airs" had three parts: A furnace to burn the needed material, a vessel with water where the produced gas passed through in a spiral pipe (for impurities to be "washed off"), and finally the gas cylinder with a gasometer where the gas produced, "air", could be tapped into portable air bags (made of airtight oily silk). The breathing apparatus consisted of one of the portable air bags connected with a tube to a mouthpiece. With this new equipment being engineered and produced by 1794, the way was paved for clinical trials, which began when Thomas Beddoes in 1798 established the "Pneumatic Institution for Relieving Diseases by Medical Airs" in Hotwells (Bristol). In the basement of the building, a large-scale machine was producing the gases under the supervision of a young Humphry Davy, who was encouraged to experiment with new gases for patients to inhale. The first important work of Davy was examination of the nitrous oxide, and the publication of his results in the book: Researches, Chemical and Philosophical (1800). In that publication, Davy notes the analgesic effect of nitrous oxide at page 465 and its potential to be used for surgical operations at page 556.
Despite Davy's discovery that inhalation of nitrous oxide could relieve a conscious person from pain, another 44 years elapsed before doctors attempted to use it for anaesthesia. The use of nitrous oxide as a recreational drug at "laughing gas parties", primarily arranged for the British upper class, became an immediate success beginning in 1799. While the effects of the gas generally make the user appear stuporous, dreamy and sedated, some people also "get the giggles" in a state of euphoria, and frequently erupt in laughter.
The first time nitrous oxide was used as an anaesthetic drug in the treatment of a patient was when dentist Horace Wells, with assistance by Gardner Quincy Colton and John Mankey Riggs, demonstrated insensitivity to pain from a dental extraction on 11 December 1844. In the following weeks, Wells treated the first 12–15 patients with nitrous oxide in Hartford, and according to his own record only failed in two cases. In spite of these convincing results being reported by Wells to the medical society in Boston already in December 1844, this new method was not immediately adopted by other dentists. The reason for this was most likely that Wells, in January 1845 at his first public demonstration to the medical faculty in Boston, had been partly unsuccessful, leaving his colleagues doubtful regarding its efficacy and safety. The method did not come into general use until 1863, when Gardner Quincy Colton successfully started to use it in all his "Colton Dental Association" clinics, that he had just established in New Haven and New York City. Over the following three years, Colton and his associates successfully administered nitrous oxide to more than 25,000 patients. Today, nitrous oxide is used in dentistry as an anxiolytic, as an adjunct to local anaesthetic.
However, nitrous oxide was not found to be a strong enough anaesthetic for use in major surgery in hospital settings. Being a stronger and more potent anaesthetic, sulfuric ether was instead demonstrated and accepted for use in October 1846, along with chloroform in 1847. When Joseph Thomas Clover invented the "gas-ether inhaler" in 1876, it however became a common practice at hospitals to initiate all anaesthetic treatments with a mild flow of nitrous oxide, and then gradually increase the anaesthesia with the stronger ether/chloroform. Clover's gas-ether inhaler was designed to supply the patient with nitrous oxide and ether at the same time, with the exact mixture being controlled by the operator of the device. It remained in use by many hospitals until the 1930s. Although hospitals today are using a more advanced anaesthetic machine, these machines still use the same principle launched with Clover's gas-ether inhaler, to initiate the anaesthesia with nitrous oxide, before the administration of a more powerful anaesthetic.
As a patent medicine
Colton's popularization of nitrous oxide led to its adoption by a number of less than reputable quacksalvers, who touted it as a cure for consumption, scrofula, catarrh, and other diseases of the blood, throat, and lungs. Nitrous oxide treatment was administered and licensed as a patent medicine by the likes of C. L. Blood and Jerome Harris in Boston and Charles E. Barney of Chicago.
In the United States, possession of nitrous oxide is legal under federal law and is not subject to DEA purview. 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 human consumption.
Many states have laws regulating the possession, sale, and distribution of nitrous oxide. Such laws usually ban distribution to minors or limit the amount of nitrous oxide that may be sold without special license. For example, in the state of California, possession for recreational use is prohibited and qualifies as a misdemeanour.
In New Zealand, the 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. This statement would seemingly prohibit all non-medicinal uses of the chemical, though it is implied that only recreational use will be legally targeted.
In India, for general anaesthesia purposes, nitrous oxide is available as Nitrous Oxide IP. India's gas cylinder rules (1985) permit the transfer of gas from one cylinder to another for breathing purposes. This law benefits remote hospitals, which would otherwise suffer as a result of India's geographic immensity. Nitrous Oxide IP is transferred from bulk cylinders (17,000 litres [600 cu ft] capacity gas) to smaller pin-indexed valve cylinders (1,800 litres [64 cu ft] of gas), which are then connected to the yoke assembly of Boyle's machines. Because India's Food & Drug Authority (FDA-India) rules state that transferring a drug from one container to another (refilling) is equivalent to manufacturing, anyone found doing so must possess a drug manufacturing license.
- Tarendash, Albert S. (2001). Let's review: chemistry, the physical setting (3rd ed.). Barron's Educational Series. p. 44. ISBN 0-7641-1664-9.
- "Overview of Greenhouse Gases – Nitrous Oxide" (PDF). US EPA. Page 164 (document header listing). Retrieved 19 March 2014.
- "U.S. Greenhouse Gas Inventory Report: 1990-2013" (PDF). US EPA. April 2015. page 60. Retrieved 19 August 2015.
- "WHO Model List of Essential Medicines" (PDF). World Health Organization. October 2013. p. 6. Retrieved 22 April 2014.
- Berger, Bruno (5 October 2007). "Is nitrous oxide safe?" (PDF). Swiss Propulsion Laboratory. pp. 1–2.
...Self pressurizing (Vapor pressure at 20°C is ~50.1 bar...Nontoxic, low reactivity -> rel. safe handling (General safe ???)...Additional energy from decomposition (as a monopropellant: ISP of 170 s)...Specific impulse doesn’t change much with O/F...[page 2] N2O is a monopropellant (as H2O2 or Hydrazine...)
- Goddard, R. H. (1914) "Rocket apparatus" U.S. Patent 1,103,503
- Nitrous Oxide Safety. Space Propulsion Group (2012)
- Munke, Konrad (2 July 2001) Nitrous Oxide Trailer Rupture, Report at CGA Seminar "Safety and Reliability of Industrial Gases, Equipment and Facilities", 15–17 October 2001, St. Louis, Missouri
- "Scaled Composites Safety Guidelines for N
2O" (PDF). Scaled Composites. 17 June 2009. Retrieved 29 December 2013.
For example, N2O flowing at 130 psi in an epoxy composite pipe would not react even with a 2500 J ignition energy input. However, at 600 psi, the required ignition energy was only 6 J.
- FR-5904. Pratt & Whitney Aircraft.
- Cline, Allen W. (January 2000) "Engine Basics: Detonation and Pre-Ignition". CONTACT! Magazine
- "Holley performance products, FAQ for Nitrous Oxide Systems". Holley. Retrieved 18 December 2013.
- Sneader W (2005). Drug Discovery –A History. (Part 1: Legacy of the past, chapter 8: systematic medicine, pp. 74–87). John Wiley and Sons. ISBN 978-0-471-89980-8. Retrieved 21 April 2010.
- Miller AH (1941). "Technical Development of Gas Anesthesia". Anesthesiology journal. 2 (4): 398–409. doi:10.1097/00000542-194107000-00004. Archived from the original on 19 December 2014.
- Copeland, Claudia. "Nitrous Oxide Analgesia for Childbirth". Pregnancy.org.
- O'Connor RE; Brady W; Brooks SC; Diercks, D.; Egan, J.; Ghaemmaghami, C.; Menon, V.; O'Neil, B. J.; et al. (2010). "Part 10: acute coronary syndromes: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care". Circulation. 122 (18 Suppl 3): S787–817. doi:10.1161/CIRCULATIONAHA.110.971028. PMID 20956226.
- Gillman, M. A.; Lichtigfeld, F. J. (2004). "Enlarged double-blind randomised trial of benzodiazepines against psychotropic analgesic nitrous oxide for alcohol withdrawal". Addictive Behaviors. 29 (6): 1183–1187. doi:10.1016/j.addbeh.2004.03.015. PMID 15236821.
- Rammohan A, Manimaran AB, Manohar RR, Naidu RM; Manimaran; Manohar; Naidu (2011). "Nitrous oxide for pneumoperitoneum: no laughing matter this! A prospective single blind case controlled study". Int J Surg. 9 (2): 173–6. doi:10.1016/j.ijsu.2010.10.015. PMID 21059420.
- Rammohan, A.; Manimaran, A. B.; Manohar, R. R.; Naidu, R. M. (2011). "Nitrous oxide for pneumoperitoneum: No laughing matter this! A prospective single blind case controlled study". International Journal of Surgery. 9 (2): 173–176. doi:10.1016/j.ijsu.2010.10.015. PMID 21059420.
- Nagele, Peter; A. Duma, M. Kopec, M. A. Gebara, A. Parsoei, M. Walker, A. Janski, V. N. Panagopoulos, P. Cristancho, J. P. Miller, C. F. Zorumski, C. R. Conway (2015). "Nitrous Oxide for Treatment-Resistant Major Depression: A Proof-of-Concept Trial". Biological Psychiatry. 78 (1): 10–18. doi:10.1016/j.biopsych.2014.11.016. Cite uses deprecated parameter
- Newport, D. Jeffrey; et al (2015). "Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression". American Journal of Psychiatry. 172 (10): 950–966. doi:10.1176/appi.ajp.2015.15040465. Cite uses deprecated parameter
- Giannini, A. J. (1991). Miller, N. S., ed. Volatiles. New York: Marcel Dekker. p. 396. ISBN 0-8247-8474-X.
- Whalley MG, Brooks GB; Brooks (2009). "Enhancement of suggestibility and imaginative ability with nitrous oxide". Psychopharmacology (Berl). 203 (4): 745–52. doi:10.1007/s00213-008-1424-0. PMID 19057896.
- Brecher EM (1972). "Consumers Union Report on Licit and Illicit Drugs, Part VI – Inhalants and Solvents and Glue-Sniffing". Consumer Reports Magazine. Retrieved 18 December 2013.
- Lynn, Edward J.; Walter, Richard G.; Harris, Lance A.; Dendy, Robert; James, Mary (1972). "Nitrous Oxide: It's a Gas" (PDF). Journal of Psychoactive Drugs. Journal of Psychedelic Drugs. 5: 1–7. doi:10.1080/02791072.1972.10471462.
- "nang". Urban Dictionary. Retrieved 29 August 2011.
- "'Nanging' out: the rise of nitrous oxide as a Sydney party drug". The Sydney Morning Herald.
- "Warning over laughing gas misuse". The Guardian. 9 August 2014. Retrieved 9 August 2014.
- "Lambeth Council bans laughing gas as recreational drug". BBC News. 17 August 2015. Retrieved 17 August 2015.
- Yamakura T, Harris RA; Harris (2000). "Effects of gaseous anaesthetics nitrous oxide and xenon on ligand-gated ion channels. Comparison with isoflurane and ethanol". Anesthesiology. 93 (4): 1095–101. doi:10.1097/00000542-200010000-00034. PMID 11020766.
- Mennerick S, Jevtovic-Todorovic V, Todorovic SM, Shen W, Olney JW, Zorumski CF; Jevtovic-Todorovic; Todorovic; Shen; Olney; Zorumski (1998). "Effect of nitrous oxide on excitatory and inhibitory synaptic transmission in hippocampal cultures". Journal of Neuroscience. 18 (23): 9716–26. PMID 9822732.
- Gruss M, Bushell TJ, Bright DP, Lieb WR, Mathie A, Franks NP; Bushell; Bright; Lieb; Mathie; Franks (2004). "Two-pore-domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane". Molecular Pharmacology. 65 (2): 443–52. doi:10.1124/mol.65.2.443. PMID 14742687.
- Emmanouil DE, Quock RM; Quock (2007). "Advances in Understanding the Actions of Nitrous Oxide". Anesthesia Progress. 54 (1): 9–18. doi:10.2344/0003-3006(2007)54[9:AIUTAO]2.0.CO;2. PMC 1821130. PMID 17352529.
- Emmanouil, D. E., Johnson, C. H. & Quock, R. M.; Johnson; Quock (1994). "Nitrous oxide anxiolytic effect in mice in the elevated plus maze: mediation by benzodiazepine receptors". Psychopharmacology. 115 (1–2): 167–72. doi:10.1007/BF02244768. PMID 7862891.
- Zacny, J.P., Yajnik, S., Coalson, D., Lichtor, J.L., Apfelbaum, J.L., Rupani, G., Young, C., Thapar, P. & Klafta, J.; Yajnik; Coalson; Lichtor; Apfelbaum; Rupani; Young; Thapar; Klafta (1995). "Flumazenil may attenuate some subjective effects of nitrous oxide in humans: a preliminary report". Pharmacology Biochemistry and Behavior. 51 (4): 815–9. doi:10.1016/0091-3057(95)00039-Y. PMID 7675863.
- Berkowitz, B. A., Finck, A. D., Hynes, M. D. & Ngai, S. H.; Finck; Hynes; Ngai (1979). "Tolerance to nitrous oxide analgesia in rats and mice". Anesthesiology. 51 (4): 309–12. doi:10.1097/00000542-197910000-00006. PMID 484891.
- Branda, E. M., Ramza, J. T., Cahill, F. J., Tseng, L. F. & Quock, R. M.; Ramza; Cahill; Tseng; Quock (2000). "Role of brain dynorphin in nitrous oxide antinociception in mice". Pharmacology Biochemistry and Behavior. 65 (2): 217–21. doi:10.1016/S0091-3057(99)00202-6.
- Guo, T. Z., Davies, M. F., Kingery, W. S., Patterson, A. J., Limbird, L. E. & Maze, M.; Davies; Kingery; Patterson; Limbird; Maze (1999). "Nitrous oxide produces antinociceptive response via alpha2B and/or alpha2C adrenoceptor subtypes in mice". Anesthesiology. 90 (2): 470–6. doi:10.1097/00000542-199902000-00022. PMID 9952154.
- Sawamura, S., Kingery, W. S., Davies, M. F., Agashe, G. S., Clark, J. D., Koblika, B. K., Hashimoto, T. & Maze, M.; Kingery; Davies; Agashe; Clark; Kobilka; Hashimoto; Maze (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 (24): 9242–51. PMID 11125002.
- Maze M, Fujinaga M; Fujinaga (2000). "Recent advances in understanding the actions and toxicity of nitrous oxide". Anaesthesia. 55 (4): 311–4. doi:10.1046/j.1365-2044.2000.01463.x. PMID 10781114.
- Sakamoto S, Nakao S, Masuzawa M, Inada T, Maze M, Franks NP, Shingu K (2006). "The differential effects of nitrous oxide and xenon on extracellular dopamine levels in the rat nucleus accumbens: a microdialysis study". Anesthesia and Analgesia. 103 (6): 1459–63. doi:10.1213/01.ane.0000247792.03959.f1. PMID 17122223.
- Benturquia N, Le Marec T, Scherrmann JM, Noble F; Le Marec; Scherrmann; Noble (2008). "Effects of nitrous oxide on dopamine release in the rat nucleus accumbens and expectation of reward". Neuroscience. 155 (2): 341–4. doi:10.1016/j.neuroscience.2008.05.015. PMID 18571333.
- Lichtigfeld FJ, Gillman MA; Gillman (1996). "Role of dopamine mesolimbic system in opioid action of psychotropic analgesic nitrous oxide in alcohol and drug withdrawal". Clinical Neuropharmacology. 19 (3): 246–51. doi:10.1097/00002826-199619030-00006. PMID 8726543.
- Koyanagi S, Himukashi S, Mukaida K, Shichino T, Fukuda K; Himukashi; Mukaida; Shichino; Fukuda (2008). "Dopamine D2-like receptor in the nucleus accumbens is involved in the antinociceptive effect of nitrous oxide". Anesthesia and Analgesia. 106 (6): 1904–9. doi:10.1213/ane.0b013e318172b15b. PMID 18499630.
- David HN, Ansseau M, Lemaire M, Abraini JH; Ansseau; Lemaire; Abraini (2006). "Nitrous oxide and xenon prevent amphetamine-induced carrier-mediated dopamine release in a memantine-like fashion and protect against behavioral sensitization". Biological Psychiatry. 60 (1): 49–57. doi:10.1016/j.biopsych.2005.10.007. PMID 16427030.
- Benturquia N, Le Guen S, Canestrelli C, Lagente V, Apiou G, Roques B, Noble F (2007). "Specific blockade of morphine- and cocaine-induced reinforcing effects in conditioned place preference by nitrous oxide in mice". Neuroscience. 149 (3): 477–86. doi:10.1016/j.neuroscience.2007.08.003. PMID 17905521.
- Ramsay DS, Watson CH, Leroux BG, Prall CW, Kaiyala KJ; Watson; Leroux; Prall; Kaiyala (2003). "Conditioned place aversion and self-administration of nitrous oxide in rats". Pharmacology, Biochemistry, and Behavior. 74 (3): 623–33. doi:10.1016/S0091-3057(02)01048-1. PMID 12543228.
- Wood RW, Grubman J, Weiss B; Grubman; Weiss (1977). "Nitrous oxide self-administration by the squirrel monkey". The Journal of Pharmacology and Experimental Therapeutics. 202 (3): 491–9. PMID 408480.
- Zacny JP, Galinkin JL; Galinkin (1999). "Psychotropic drugs used in anesthesia practice: abuse liability and epidemiology of abuse". Anesthesiology. 90 (1): 269–88. doi:10.1097/00000542-199901000-00033. PMID 9915336.
- Dohrn CS, Lichtor JL, Coalson DW, Uitvlugt A, de Wit H, Zacny JP; Lichtor; Coalson; Uitvlugt; De Wit; Zacny (1993). "Reinforcing effects of extended inhalation of nitrous oxide in humans". Drug and Alcohol Dependence. 31 (3): 265–80. doi:10.1016/0376-8716(93)90009-F. PMID 8462415.
- Walker DJ, Zacny JP; Zacny (2001). "Within- and between-subject variability in the reinforcing and subjective effects of nitrous oxide in healthy volunteers". Drug and Alcohol Dependence. 64 (1): 85–96. doi:10.1016/S0376-8716(00)00234-9. PMID 11470344.
- Jevtovic-Todorovic V, Beals J, Benshoff N, Olney JW; Beals; Benshoff; Olney (2003). "Prolonged exposure to inhalational anesthetic nitrous oxide kills neurons in adult rat brain". Neuroscience. 122 (3): 609–16. doi:10.1016/j.neuroscience.2003.07.012. PMID 14622904.
- Nakao S; Nagata A; Masuzawa M; Miyamoto, E; Yamada, M; Nishizawa, N; Shingu, K (2003). "NMDA receptor antagonist neurotoxicity and psychotomimetic activity". Masui. the Japanese Journal of Anesthesiology (in Japanese). 52 (6): 594–602. PMID 12854473.
- Jevtovic-Todorovic V, Benshoff N, Olney JW; Benshoff; Olney (2000). "Ketamine potentiates cerebrocortical damage induced by the common anaesthetic agent nitrous oxide in adult rats". British Journal of Pharmacology. 130 (7): 1692–8. doi:10.1038/sj.bjp.0703479. PMC 1572233. PMID 10928976.
- Jevtovic-Todorovic V, Carter LB; Carter (2005). "The anesthetics nitrous oxide and ketamine are more neurotoxic to old than to young rat brain". Neurobiology of Aging. 26 (6): 947–56. doi:10.1016/j.neurobiolaging.2004.07.009. PMID 15718054.
- Slikker, W.; Zou, X.; Hotchkiss, C. E.; Divine, R. L.; Sadovova, N.; Twaddle, N. C.; Doerge, D. R.; Scallet, A. C.; Patterson, T. A.; Hanig, J. P.; Paule, M. G.; Wang, C. (2007). "Ketamine-Induced Neuronal Cell Death in the Perinatal Rhesus Monkey". Toxicological Sciences. 98 (1): 145–158. doi:10.1093/toxsci/kfm084. PMID 17426105.
- Sun, Lin; Qi Li; Qing Li; Yuzhe Zhang; Dexiang Liu; Hong Jiang; Fang Pan; David T. Yew (November 2012). "Chronic ketamine exposure induces permanent impairment of brain functions in adolescent cynomolgus monkeys". Addiction Biology. 19 (2): 185–94. doi:10.1111/adb.12004. PMID 23145560.
- Abraini JH, David HN, Lemaire M; David; Lemaire (2005). "Potentially neuroprotective and therapeutic properties of nitrous oxide and xenon". Annals of the New York Academy of Sciences. 1053: 289–300. Bibcode:2005NYASA1053..289A. doi:10.1196/annals.1344.025. PMID 16179534.
- De Vasconcellos, K; Sneyd, J. R. (2013). "Nitrous oxide: Are we still in equipoise? A qualitative review of current controversies". British Journal of Anaesthesia. 111 (6): 877–85. doi:10.1093/bja/aet215. PMID 23801743.
- Flippo, T. S.; Holder Jr, W. D. (1993). "Neurologic Degeneration Associated with Nitrous Oxide Anesthesia in Patients with Vitamin B12 Deficiency". Archives of Surgery. 128 (12): 1391–5. doi:10.1001/archsurg.1993.01420240099018. PMID 8250714.
- JACQUES H. ABRAINI,HÉLÈNE N. DAVID, MARC LEMAIRE (2005) Potentially Neuroprotective and Therapeutic Properties of Nitrous Oxide and Xenon http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2005.tb00036.x/full
- 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.
- Teenager dies after 'taking laughing gas' at party in Bexley. London Evening Standard
- 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
- "CDC – NIOSH Pocket Guide to Chemical Hazards – Nitrous oxide". www.cdc.gov. Retrieved 2015-11-21.
- Nitrous oxide. Air Liquide Gas Encyclopedia.
- "Vaseline triggered explosion of hybrid rocket". Ukrocketman.com.
- "Safetygram 20: Nitrous Oxide" (PDF). Airproducts.com. Archived from the original (PDF) on 1 September 2006.
- Giannini, A.J. (1999). Drug Abuse. Los Angeles: Health Information Press. ISBN 1-885987-11-0.
- Conrad, Marcel (4 October 2006). "Pernicious Anemia". Retrieved 2 June 2008.
- Rowland, A.S.; Baird, D.D.; Weinberg, C.R.; Shore, D.L.; Shy, C.M.; Wilcox, A.J. (1992). "Reduced fertility among women employed as dental assistants exposed to high levels of nitrous oxide". The New England Journal of Medicine. 327 (14): 993–7. doi:10.1056/NEJM199210013271405. PMID 1298226.
- Vieira, E.; Cleaton-Jones, P.; Austin, J.C.; Moyes, D.G.; Shaw, R. (1980). "Effects of low concentrations of nitrous oxide on rat fetuses". Anesthesia and Analgesia. 59 (3): 175–7. doi:10.1213/00000539-198003000-00002. PMID 7189346.
- Vieira, E. (1979). "Effect of the chronic administration of nitrous oxide 0.5% to gravid rats". British journal of anaesthesia. 51 (4): 283–7. doi:10.1093/bja/51.4.283. PMID 465253.
- Vieira, E; Cleaton-Jones, P; Moyes, D. (1983). "Effects of low intermittent concentrations of nitrous oxide on the developing rat fetus". British journal of anaesthesia. 55 (1): 67–9. doi:10.1093/bja/55.1.67. PMID 6821624.
- Schneider, Lisa K.; Wüst, Anja; Pomowski, Anja; Zhang, Lin; Einsle, Oliver (2014). "Chapter 8. No Laughing Matter: The Unmaking of the Greenhouse Gas Dinitrogen Monoxide by Nitrous Oxide Reductase". In Peter M.H. Kroneck and Martha E. Sosa Torres. The Metal-Driven Biogeochemistry of Gaseous Compounds in the Environment. Metal Ions in Life Sciences. 14. Springer. pp. 177–210. doi:10.1007/978-94-017-9269-1_8.
- "40 CFR Part 98 – Revisions to the Greenhouse Gas Reporting Rule and Final Confidentiality | U.S. EPA" (PDF). Environmental Protection Agency. 15 November 2013. Retrieved 19 March 2014.
- Sloss, Leslie L. (1992). Nitrogen Oxides Control Technology Fact Book. William Andrew. p. 6. ISBN 978-0-8155-1294-3.
- "2011 U.S. Greenhouse Gas Inventory Report | Climate Change – Greenhouse Gas Emissions | U.S. EPA". Epa.gov. Retrieved 11 April 2011.
- "FULL TEXT OF THE CONVENTION, ARTICLE 4(1) (a)". Unfccc.int. 31 December 1998. Archived from the original on 24 January 2011. Retrieved 11 April 2011.
- "Sources and Emissions – Where Does Nitrous Oxide Come From?". U.S. Environmental Protection Agency. 2006. Retrieved 2 February 2008.
- Crutzen, P. J.; Mosier, A. R.; Smith, K. A.; Winiwarter, W. (2008). "N2O release from agro-biofuel production negates global warming reduction by replacing fossil fuels". Atmospheric Chemistry and Physics. 8 (2): 389–395. doi:10.5194/acp-8-389-2008.
- "Climate Change 2007: The Physical Sciences Basis". IPCC. Retrieved 30 April 2007.
- Ravishankara, A. R.; Daniel, J. S.; Portmann, R. W. (2009). "Nitrous Oxide (N2O): The Dominant Ozone-Depleting Substance Emitted in the 21st Century". Science. 326 (5949): 123–5. Bibcode:2009Sci...326..123R. doi:10.1126/science.1176985. PMID 19713491.
- Grossman, Lisa (28 August 2009). "Laughing gas is biggest threat to ozone layer". NewScientist.
- Reimer R. A.; Slaten C. S.; Seapan M.; Lower M. W.; Tomlinson P. E. (1994). "Abatement of N2O emissions produced in the adipic acid industry". Environmental progress. 13 (2): 134–137. doi:10.1002/ep.670130217.
- Shimizu, A.; Tanaka, K. & Fujimori, M. (2000). "Abatement of N2O emissions produced in the adipic acid industry". Chemosphere – Global Change Science. 2 (3–4): 425–434. doi:10.1016/S1465-9972(00)00024-6.
- Holleman, A. F.; Wiberg, E. (2001). Inorganic Chemistry. San Diego: Academic Press. ISBN 0-12-352651-5.
- "George Poe is Dead". Washington Post. 3 February 1914. Retrieved 29 December 2007.
Cousin of Famous Poet and Noted as a Scientist. Inventor of the Respirator. Also First to Liquefy Nitrous Oxide. Cadet at Virginia Military Institute at Time of Battle of Newmarket. Mentioned for the Nobel Prize for Scientific Attainment in Chemistry. Prof. George Poe, a cousin of the poet Edgar Allan Poe, a noted scientist and inventor, who had been mentioned for the Nobel prize for scientific attainment, a former resident of Washington, died in Norfolk, Virginia, yesterday of general paralysis. Prof. Poe was in his sixty-eighth year.
- "Nitrous oxide plant". Sanghi Organization. Archived from the original on 27 November 2013. Retrieved 18 December 2013.
- "Nitrogen Family". chemistry.tutorvista.com
- "Preparation of Nitrous Oxide from Urea, Nitric Acid and Sulfuric Acid".
- Suwa T, Matsushima A, Suziki Y, Namina Y (1961). "Synthesis of Nitrous Oxide by Oxidation of Ammonia". Kohyo Kagaku Zasshi, Showa Denka Ltd. 64: 1879–1888.
- Egon Wiberg, Arnold Frederick Holleman (2001) Inorganic Chemistry, Elsevier ISBN 0-12-352651-5
- IPCC, 2006
- Housecroft, Catherine E. & Sharpe, Alan G. (2008). "Chapter 15: The group 15 elements". Inorganic Chemistry (3rd ed.). Pearson. p. 464. ISBN 978-0-13-175553-6.
- Steinfeld, H.; Gerber, P.; Wassenaar, T.; Castel, V.; Rosales, M. & de Haan, C. (2006). "Livestock's long shadow – Environmental issues and options". Fao.org. Retrieved 2 February 2008.
- "Nitrous Oxide Emissions". U.S. Environmental Protection Agency. Retrieved 31 March 2016.
- "4.1.1 Sources of Greenhouse Gases". IPCC TAR WG1 2001. Retrieved 21 September 2012.
- Keys, T.E. (1941). "The Development of Anesthesia". Anesthesiology. 2 (5): 552–574. Bibcode:1982AmSci..70..522D. doi:10.1097/00000542-194109000-00008. Archived from the original on 12 January 2014.
- Priestley J (1776). "Experiments and Observations on Different Kinds of Air". 2 (3).
- Davy H (1800). Researches, chemical and philosophical –chiefly concerning nitrous oxide or dephlogisticated nitrous air, and its respiration. Printed for J. Johnson.
- Erving, H. W. (1933). "The Discoverer of Anæsthesia: Dr. Horace Wells of Hartford". The Yale Journal of Biology and Medicine. 5 (5): 421–430. PMC 2606479. PMID 21433572.
- Wells H (1847). A history of the discovery, of the application of nitrous oxide gas, ether, and other vapours, to surgical operations. J. Gaylord Wells.
- Desai SP, Desai MS, Pandav CS (2007). "The discovery of modern anaesthesia-contributions of Davy, Clarke, Long, Wells and Morton". Indian J Anaesth. 51 (6): 472–8.
- "Alleged Forgery". The Inter Ocean. 1877-09-28. p. 8. Retrieved 2015-10-26.
- "A Man of Ominous Name". The Inter Ocean. 1890-02-19. Retrieved 2015-10-26.
- "US Nitrous Oxide Laws (alphabetically) Based on a search of online free legal databases. Conducted May 2002". Center for Cognitive Liberty and Ethics.
- "CAL. PEN. CODE § 381b : California Code – Section 381b". Lp.findlaw.com.
- Anderton, Jim (26 June 2005). "Time's up for sham sales of laughing gas". Beehive.govt.nz.
|Wikimedia Commons has media related to Nitrous oxide.|
- Occupational Safety and Health Guideline for Nitrous Oxide
- 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.
- National Pollutant Inventory – Oxide of nitrogen fact sheet
- National Institute for Occupational Safety and Health – Nitrous Oxide
- CDC – NIOSH Pocket Guide to Chemical Hazards – Nitrous Oxide
- Nitrous Oxide FAQ
- Erowid article on Nitrous Oxide
- Nitrous oxide fingered as monster ozone slayer, Science News
- Dental Fear Central article on the use of nitrous oxide in dentistry