Distickstoffoxid

log Kow = 0.36

0.36

Slightly sweetish

Weak, pleasant odor

1.266 at -128.2 °F (USCG, 1999) - Denser than water; will sink

1.799 g/L

Density: 1.226 at -89 °C (liquid); 1.967 at standard temperature and pressure

Density: 1.9775 kg/cu m (gas, 0 °C, 101.3 kPa); 793 kg/cu m (liquid, 20 °C, 101.3 kPa)

Density (at the boiling point of the liquid): 1.28 kg/l

1.266 at -128.2 °F

0.1 % at 77 °F (NIOSH, 2024)

0.1 % at 77 °F (NIOSH, 2024)

Slightly soluble in water

At 20 °C and 2 atm one liter of the gas dissolves in 1.5 liters of water

130 mL/100 mL water at 0 °C, 56.7 mL/100 mL water at 25 °C

Soluble in ethanol, ethyl ether

Danger

H270 (100%): May cause or intensify fire; oxidizer [Danger Oxidizing gases]

P220, P244, P261, P271, P282, P304+P340, P319, P336+P317, P370+P376, P403, P403+P233, P405, P410+P403, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 663 reports by companies from 15 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H270: May cause or intensify fire; oxidizer [Danger Oxidizing gases]

Chemical: Nitrogen oxide, (N2O)

Hazard Traits - Developmental Toxicity; Reproductive Toxicity

Nitrogen oxide (N2O) is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Nitrogen oxide (N2O) are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

REACH registered substance: Dinitrogen oxide (EC: 233-032-0)

Nitrous oxide: HSNO Approval: HSR001065 Approved with controls

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

Non-Flammable Gas Oxidizer

Non-Flammable Gas Oxidizer

Behavior in Fire: Will support combustion, and may increase intensity of fire. Containers may explode when heated. (USCG, 1999)

Excerpt from ERG Guide 122 [Gases - Oxidizing (Including Refrigerated Liquids)]:

· Substance does not burn but will support combustion.

· Substance does not burn but will support combustion.

Not combustible but enhances combustion of other substances. Gives off irritating or toxic fumes (or gases) in a fire. Risk of fire and explosion. See Chemical Dangers.

Spontaneous ignition occurs when nitrous oxide and lithium hydride or hydrazine are mixed.

Amorphous boron ignites when heated in dry nitrous oxide.

Does not burn but is flammable by chemical reaction and supports combustion.

Inhalation causes intense analgesia; concentrations of over 40-60% cause loss of consciousness preceded by hysteria. Contact of liquid with eyes or skin causes frostbite burn. (USCG, 1999)

Excerpt from ERG Guide 122 [Gases - Oxidizing (Including Refrigerated Liquids)]:

· Vapors may cause dizziness or asphyxiation without warning, especially when in closed or confined areas.

· Vapors may cause dizziness or asphyxiation without warning, especially when in closed or confined areas.

Nitrous oxide is a simple asphyxiant; it has caused neuropathy when abused for its euphoric effects. The TLV basis is CNS impairment, hematologic effect, and embryo/fetal damage. Rats exposed for 2 or more days to 80% NO and 20% O2 have altered hematopoiesis. At 1000 ppm, NO inactivates vitamin B12. [ACGIH] Possible frostbite from contact with liquid; [NIOSH] In substance abuse cases with peripheral neuropathy, nitrous oxide was administered at 300,000 to 800,000 ppm (30-80%) for 30-60 minutes per day, 2-7 days a week for 3 months to several years. [CHEMINFO]

2201 122

1070 122

1070 122

2201 122(refrigerated liquid)

Oxidizing Agents, Weak

Oxidizing Agents, Weak

IPCS; Poisons Information Monograph PIM381: Nitrous oxide (February 1992). Poisons Information Monographs (PIM) are a global database with evaluated information on substances commonly involved in cases of poisoning.[Available from, as of February 26, 2016 http://www.inchem.org/pages/pims.html]

NITROUS OXIDE is a weak oxidizing agent. Nonflammable but supports combustion. Can explode at high temperature (after vaporization). Vapors can undergo a violent reaction with aluminum, boron, hydrazine, lithium hydride, phenyllithium, phosphine, sodium, tungsten carbide [Bretherick, 5th ed., 1995, p. 1686]. Contact of the cold liquefied gas with water may result in vigorous or violent boiling. If the water is hot, a liquid "superheat" explosion may occur. Pressures may build to dangerous levels if liquefied gas contacts water in a closed container [Handling Chemicals Safely 1980].

NITROUS OXIDE, REFRIGERATED LIQUID is a weak oxidizing agent. Nonflammable but supports combustion. Can explode at high temperature (after vaporization). Vapors may undergo a violent reaction with aluminum, boron, hydrazine, lithium hydride, phenyllithium, phosphine, sodium, tungsten carbide [Bretherick, 5th ed., 1995, p. 1686]. Contact of the cold liquefied gas with water may result in vigorous or violent boiling. If the water is hot, a liquid "superheat" explosion may occur. Pressures may build to dangerous levels if liquefied gas contacts water in a closed container [Handling Chemicals Safely 1980].

Excerpt from ERG Guide 122 [Gases - Oxidizing (Including Refrigerated Liquids)]:

Excerpt from ERG Guide 122 [Gases - Oxidizing (Including Refrigerated Liquids)]:

In case of fire in the surroundings, use appropriate extinguishing media. In case of fire: keep cylinder cool by spraying with water. Combat fire from a sheltered position.

Fresh air, rest. Refer for medical attention.

ON FROSTBITE: rinse with plenty of water, do NOT remove clothes. Refer for medical attention .

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

· CALL 911. Then call emergency response telephone number on shipping paper. If shipping paper not available or no answer, refer to appropriate telephone number listed on the inside back cover.

· Keep combustibles (wood, paper, oil, etc.) away from spilled material.

· CALL 911. Then call emergency response telephone number on shipping paper. If shipping paper not available or no answer, refer to appropriate telephone number listed on the inside back cover.

· Keep combustibles (wood, paper, oil, etc.) away from spilled material.

Excerpt from NIOSH Pocket Guide for Nitrous oxide:

Excerpt from NIOSH Pocket Guide for Nitrous oxide:

General First Aid:

General First Aid:

(General first aid procedures)

Nitrous oxide is an oxidizer and will increase the intensity of any fire.

Exposure of the container to prolonged heat or fire can cause it to rupture violently and rocket.

· Wear positive pressure self-contained breathing apparatus (SCBA).

· Wear positive pressure self-contained breathing apparatus (SCBA).

100.0 [ppm]

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

Use water spray to cool unopened containers.

Extinguish fire using an agent suitable for type of surrounding fire. Nitrous oxide itself does not burn. Do not extinguish the fire unless the flow of gas can be stopped and any remaining gas is out of the line. Specially trained personnel may use fog lines to cool exposures and let the fire burn itself out. Vapors are heavier than air and will collect in low areas. Vapors in confined areas may explode when exposed to fire. Containers may explode in fire. Storage containers and parts of containers may rocket great distances, in many directions. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire officials and pollution control agencies. From a secure, explosion-proof location, use water spray to cool exposed containers. If cooling streams are ineffective (venting sound increases in volume and pitch, tank discolors, or shows any signs of deforming), withdraw immediately to a secure position. If cylinders are exposed to excessive heat from fire or flame contact, withdraw immediately to a secure location ... The only respirators recommended for fire fighting are self-contained breathing apparatuses that have full facepieces and are operated in a pressure-demand or other positive pressure mode.

For more Fire Fighting Procedures (Complete) data for Nitrous oxide (6 total), please visit the HSDB record page.

Keep container tightly closed in a dry and well-ventilated place. Contents under pressure.

Store in a location separate from other materials, especially flammables and combustibles. ... Nitrous oxide must be stored to avoid contact with organic peroxides, ammonia, carbon monoxide, hydrogen, hydrogen sulfide, and phosphine, since violent reactions occur. Cylinders of nitrous oxide should be stored in a cool, preferably fire-resistant area, away from heat sources.

Cylinders containing 50% nitrous oxide and 50% oxygen should be protected from the cold to prevent separation of the gases. Cylinders exposed to temperatures lower than -7 °C should be rolled at room temperature to ensure mixing or alternatively stores horizontally for 24 hours at a temperature of not less than 10 °C.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas; Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains; Methods and materials for containment and cleaning up: Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and place in container for disposal according to local regulations.

Evacuate danger area! Consult an expert! Ventilation. If in liquid state: do NOT absorb in saw-dust or other combustible absorbents. NEVER direct water jet on liquid.

Spill handling: If in a building, evacuate building and confine vapors by closing doors and shutting down HVAC systems. Restrict persons not wearing protective equipment from area of spill or leak until cleanup is complete. Remove all ignition sources. Ventilate area of spill or leak to disperse the gas. Wear chemical protective suit with self-contained breathing apparatus to combat spills. Stay upwind and use water spray to "knock down" vapor; contain runoff. Stop the flow of gas, if it can be done safely from a distance. If source is a cylinder and the leak cannot be stopped in place, remove the leaking cylinder to a safe place and repair leak or allow cylinder to empty. If flow cannot be stopped, allow it to flow into a mixture of caustic soda and slaked lime and dispose of the resulting material in a hood. Keep this chemical out of confined spaces, such as a sewer, because of the possibility of explosion, unless the sewer is designed to prevent the buildup of explosive concentrations.

Excerpt from ERG Guide 122 [Gases - Oxidizing (Including Refrigerated Liquids)]:

Excerpt from ERG Guide 122 [Gases - Oxidizing (Including Refrigerated Liquids)]:

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

Product: Burn in a chemical incinerator equipped with an afterburner and scrubber but exert extra care in igniting as this material is highly flammable. Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material; Contaminated packaging: Dispose of as unused product.

When administered alone, nitrous oxide can significantly increase cerebral blood flow and intracranial pressure. This cerebral vasodilatory capacity of /nitrous oxide/ is significantly attenuated by the simultaneous administration of intravenous agents such as opiates and propofol. By contrast, the combination of /nitrous oxide/ and inhaled agents results in greater vasodilation than the administration of the inhaled agent alone at equivalent anesthetic depth.

The abuse-related behavioral effects produced by nitrous oxide (N2O) gas have been suggested as being unique compared with other abused inhalants. The drug discrimination paradigm in animals can be used to study subjective effects of drugs in humans and to test this hypothesis. The goals of the present experiment were to establish N2O discrimination in mice and to compare its discriminative stimulus effects with those of abused volatile vapors and vapor anesthetics. Sixteen B6SJLF1/J mice were trained to discriminate between 10 min of exposure to 60% N2O+40% oxygen (O2) and 10 min of exposure to 100% O2. The time course of N2O discrimination was examined, followed by cross-substitution testing with abused vapors, volatile anesthetics, ethanol, D-amphetamine, and 2-butanol. Mice acquired the ability to discriminate between N2O and O2 in 40 days. N2O fully substituted for 10 min of exposure to 60% N2O in a concentration-dependent manner. Full substitution required 7 min of 60% N2O exposure, but the offset of stimulus effects following the cessation of exposure was more rapid. The aromatic hydrocarbon toluene almost fully substituted for N2O. 1,1,1-Trichloroethane, methoxyflurane, isoflurane, and ethanol showed lesser degrees of substitution. D-amphetamine and the odorant 2-butanol did not substitute for N2O. Given the varying degrees of incomplete substitution by test compounds, the discriminative stimulus properties of N2O and, perhaps, its subjective effects in humans are probably not unique. As none of the inhalants tested fully mimicked N2O, its overall effects may include one or more novel stimulus components.

In recent years, the glutamate theory of alcoholism has emerged as a major theory in the addiction research field and N-methyl-d-aspartate (NMDA) receptors have been shown to play a major role in alcohol craving and relapse. The NMDA receptors are considered as the primary site of action of the anesthetic gases xenon (Xe) and nitrous oxide (N2O). Despite the rapid on/off kinetics of these gases on the NMDA receptor, a brief gas exposure can induce an analgesic or antireward effect lasting several days. The aim of this study was to examine the effect of both Xe and N2O on alcohol-seeking and relapse-like drinking behavior (measured as the alcohol deprivation effect) in Wistar rats. We used 2 standard procedures-the alcohol deprivation model with repeated deprivation phases and the cue-induced reinstatement model of alcohol seeking-to study the effect of 2 brief gas exposures of either Xe, N2O, or control gas on relapse-like drinking and alcohol-seeking behavior. Here, we show that exposure to Xe during the last 24 hours of abstinence produced a trend toward reduced ethanol intake during the first alcohol re-exposure days. In addition, Xe gas exposure significantly decreased the cue-induced reinstatement of alcohol-seeking behavior. N2 O had no effect on either behavior. Xe reduces alcohol-seeking behavior in rats and may therefore also interfere with craving in human alcoholics.

The displacement curves for air, nitrogen, and oxygen gave only a single point of inflection and IC50 values of 20, 9.2, and 7.8 nmol, respectively, on in vitro (3)H-naloxone binding to rat forebrain (strain not given). Nitrous oxide at 100% and 50% caused an extra inflection point in displacement curve giving rise to 2 IC50 values of 62.9 and 57.8 nmol (for lower affinity receptor) and 0.06 and 0.06 nmol (for higher affinity receptor) for 100 and 50%, respectively.

For more Interactions (Complete) data for Nitrous oxide (26 total), please visit the HSDB record page.

Neurotoxin - Sensorimotor

Adverse effects of nitrous include:

The substance can be absorbed into the body by inhalation.

inhalation, skin and/or eye contact (liquid)

IDENTIFICATION AND USE: Nitrous Oxide is a stable, non-irritating colorless gas with slightly sweetish odor and taste. It is used as anesthetic in dentistry and surgery, propellant gas in food aerosols, leak detection. HUMAN EXPOSURE AND TOXICITY: The main complication following inhalation of nitrous oxide is varying degrees of hypoxia, affecting the functions of the heart and the brain. This may be associated with hypotension, fatal cardiac arrhythmias, headache, dizziness, anoxic brain damage, cerebral edema and permanent mental deficit. Chronic exposure can cause neurological and hematological changes including megaloblastic erythropoiesis and neurological features similar to subacute combined degeneration of the spinal cord. Nitrous oxide should not be administered for more than 24 hours because of the risk of bone marrow depression. During induction with high concentrations of nitrous oxide, the oxygen in the lungs is rapidly used up and the anoxia with increased respiratory effort causes rapid depletion of carbon dioxide in the issues. Absence of carbon dioxide and depression of the medullary centers by the anesthetic quickly lead to respiratory failure, and rarely, the patient's cerebral function fails to recover from cerebral damage caused by the prolonged anoxia. Nitrous oxide is harmless and non-irritating to the respiratory tract, but concentrations over 50 ppm reduce dexterity, cognition and motor and audiovisual skills. Neurological manifestations similar to subacute combined degeneration of the spinal cord were reported following prolonged heavy exposure to nitrous oxide in 15 patients. Poisoning manifested by symptoms such as cyanosis, hypotension and methemoglobinemia occurred in two patients anesthetized with nitrous oxide contaminated with nitric oxide. Psychological dependency on nitrous oxide may occur. Malignant hyperthermia induced by nitrous oxide anesthesia was reported in an eleven year-old girl. No convincing evidence of carcinogenicity in man has been shown by epidemiological studies. The incidence of spontaneous abortion is increased among women exposed to nitrous oxide. It has been suggested, that there is an increased incidence of congenital anomalies in the offspring of women exposed during pregnancy and of spontaneous abortion in the wives of exposed men. No adverse effects were found in a retrospective study of 175 pregnancies during which nitrous oxide was administered. By using single-cell gel electrophoresis (comet assay), the effect of nitrous oxide on DNA damage in circulating human leukocytes was determined: nitrous oxide increased DNA damage compared with nitrous oxide-free anesthesia. ANIMAL STUDIES: Sedation with 70% nitrous oxide profoundly, but transiently, reduces the activity of cortical methionine synthase but produces lasting impairment in spatial working memory in aged rats. Exposure of pregnant rats to nitrous oxide has caused fetal death, skeletal malformations and various macroscopic lesions. Exposure of pregnant cats on 9th day of gestation to anesthetic concentrations of nitrous oxide-oxygen produces fetal resorption and various skeletal anomalies. Physical dependency and withdrawal have been demonstrated in mice. A long-term study in rats exposed to low concentrations of nitrous oxide did not find increase of neoplasia. ECOTOXICITY STUDIES: High triploid rates (> 90%) were induced when newly fertilized rainbow trout (Salmo gairdneri) eggs were exposed to nitrous oxide at elevated pressure (11 atm) for 0-30 or 0-60 min following fertilization. The triploid yield was lowered following exposure for the longer time period. Triploid rates and therefore triploid yields were reduced following exposure at a lower pressure (5 atm). Treatment of eggs at 1 atm caused no alteration in the triploidy rate.

While nitrous oxide inactivates methionine synthase, intraoperative use results in a transient metabolic abnormality that soon reverses upon replacing the degrading enzyme.

/AQUATIC SPECIES/ High triploid rates (> 90%) were induced when newly fertilized rainbow trout (Salmo gairdneri) eggs were exposed to nitrous oxide (N2O) at elevated pressure (11 atm) for 0-30 or 0-60 min following fertilization. The triploid yield was lowered following exposure for the longer time period. Triploid rates and therefore triploid yields were reduced following exposure at a lower pressure (5 atm). Treatment of eggs with N2O at 1 atm caused no alteration in the triploidy rate.

Euphoria. Drowsiness. Dizziness. Unconsciousness.

ON CONTACT WITH LIQUID: FROSTBITE.

ON CONTACT WITH LIQUID: FROSTBITE.

dyspnea (breathing difficulty); drowsiness, headache; asphyxia; reproductive effects; liquid: frostbite

Nitrous oxide is found in the air as part of the earth's natural nitrogen cycle. The compound remains in the atmosphere for about 114 years(1). It is present in the environment at concentrations ranging from 0.25 to 0.29 ppm, arising from biodegradation of organic nitrogen compounds that occur in soil(2).

INDOOR: The average nitrous oxide concentration was reported as 368 ppb volume from 5 samples taken inside a rural home in Sundarijal, Nepal, sampled during December 1982 through January 1983. Heating and cooking fuel sources were wood, followed by crop residues, animal dung and charcoal(1).

RURAL/REMOTE: The average nitrous oxide concentration was reported as 307 ppb volume from 4 samples taken outside a rural home in Sundarijal, Nepal, sampled during December 1982 through January 1983(1). Tropospheric concentration of nitrous oxide was expected to reach 380 ppb in 2050, based on the 1986 growth rate of world energy consumption(2). Fifteen-year sampling was conducted from January 1997 to December 2011 in Herantut, Pahang, Malaysia. The median concentration of nitrous oxide was 2.2 ppb (min 1.9, max 3.4 ppb). Higher concentrations were observed between June and September, corresponding to mid-range transport from more urbanized and industrial areas(3).

SOURCE DOMINATED: Nitrous oxide emissions in 1992 from target groups in the Netherlands expressed as CO2-equivalents (based on the Global Warming Potential). Nitrous oxide greenhouse gas emissions for 1988, 1990 and 1992 were 4.47, 5.94 and 11.0 Ceq.y-1, respectively(1).[Table#1373]

SOURCE DOMINATED: Nitrous oxide emissions from agriculturally-derived synthetic or organic fertilizers used worldwide ranged from 0.34% to 37%(1). Application of cattle slurry to mixed clover rye grass sward in the Basque region of Spain resulted in 16.0% of the NH4-N applied being lost to the atmosphere as nitrous oxide(2). Nitrous oxide was found to be produced by combustion of natural gas, No.6 fuel oil and coal-water slurries(3). Ship emissions account for 15% of the global Nox emissions with nearly 70% emissions occurring within 400 km of land. The 2009 annual in-port emission of nitrous oxide in the Yangshan port, Hangzhou Bay, Shanghai was reported as 33 tons. Annual emissions based on activity/source are as follows (tons): at-sea, 13.7; maneuvering, 3.3; hotelling-berth, 12.2; hotelling anchorage, 3.4; resulting in total emissions of 32.6 tons/year. Ship engine emissions factors are 0.031, 0.031 and 0.080 g/kw-hr from a main engine, auxiliary engine and boiler, respectively. Annual ship emissions based on engine type are as follows (tons): main engine, 12.7; auxiliary engine, 10.9; boiler, 9.9, resulting in total emissions of 32.5 tons/year(4).

For more Atmospheric Concentrations (Complete) data for Nitrous oxide (6 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ ... /This/ study compared the states of intoxication produced by three inhaled anesthetics that represent two of the three major classes of abused inhalants ... . Isoflurane and sevoflurane represent the class of volatile substances, and nitrous oxide (N2O) comprises a class of its own. Fourteen healthy volunteers inhaled the vehicle (100% O2) and two concentrations each of isoflurane (0.1 and 0.2%), sevoflurane (0.2 and 0.4%), and N2O (15 and 30%) for 40 min each, across seven separate sessions. Drug concentrations were chosen to produce similar ratings of drug effect strength and similar impairment on a psychomotor test, the digit-symbol substitution test (DSST). Ratings of drug effect strength and performance on the DSST were similar across drugs; however, the volatile anesthetics produced greater sedation and greater impairment on three other psychomotor tests than N2O, whereas N2O produced a greater magnitude of putatively pleasant and psychedelic-like subjective effects. These results are consistent with the drugs' putative receptor mechanisms of action and confirm Balster's classification of the volatile anesthetics into a class distinct from N2O.

/HUMAN EXPOSURE STUDIES/ ... In an attempt to assess and quantitate psychomotor dysfunction, P-300 event related potentials, Symbol Digit Test, Continuous Performance Test, and Finger Tapping Test were obtained from six subjects sequentially exposed to nitrous oxide (N2O) at 0%, 10%, 20%, and 40%. With increasing concentrations of N20, there was prolongation of P-300 latency and worsening of Continuous Performance Test and Symbol Digit Test performances; P-300 amplitude and Finger Tapping Test performance were decreased by exposure to N2O. This study demonstrates a dose dependent reduction in P-300 amplitude and prolongation of P-300 latency in subjects in whom psychomotor impairment has been induced by the acute administration of N2O.

/HUMAN EXPOSURE STUDIES/ Patients having major surgery expected to last at least 2 hr were randomly assigned to nitrous oxide-free (80% oxygen, 20% nitrogen) or nitrous oxide-based (70% N2O, 30% oxygen) anesthesia. Patients and observers were blind to group identity. The primary endpoint was duration of hospital stay. Secondary endpoints included duration of intensive care stay and postoperative complications; the latter included severe nausea and vomiting, and the following major complications: pneumonia, pneumothorax, pulmonary embolism, wound infection, myocardial infarction, venous thromboembolism, stroke, awareness, and death within 30 days of surgery. ... Of 3,187 eligible patients, 2,050 consenting patients were recruited. Patients in the nitrous oxide-free group had significantly lower rates of major complications (odds ratio, 0.71; 95% confidence interval, 0.56-0.89; P = 0.003) and severe nausea and vomiting (odds ratio, 0.40; 95% confidence interval, 0.31-0.51; P < 0.001), but median duration of hospital stay did not differ substantially between groups (7.0 vs. 7.1 days; P = 0.06). Among patients admitted to the intensive care unit postoperatively, those in the nitrous oxide-free group were more likely to be discharged from the unit on any given day than those in the nitrous oxide group (hazard ratio, 1.35; 95% confidence interval, 1.05-1.73; P = 0.02). Conclusions: Avoidance of nitrous oxide and the concomitant increase in inspired oxygen concentration decreases the incidence of complications after major surgery, but does not significantly affect the duration of hospital stay. The routine use of nitrous oxide in patients undergoing major surgery should be questioned.

/HUMAN EXPOSURE STUDIES/ ... Computer based neurobehavioral evaluation system was developed to standardize data collection in epidemiological field studies of individuals at risk for neurobehavioral toxicity. Twelve men 18 to 36 yr old were tested with the neurobehavioral evaluation system 3 times, in an initial training session followed by separate drug and control sessions in randomized order. During drug sessions, subjects received a combination of 20% nitrous oxide (N2O) and 80% oxygen through a nasal mask. In control sessions subjects received 100% oxygen. Nine neurobehavioral evaluation system tests evaluating psychomotor performance, visuospatial ability, memory, and mood were administered in approx 40 min. N2O exposure impaired performance on 3 tests: continuous performance, symbol digit substitution, and finger tapping.

For more Human Toxicity Excerpts (Complete) data for Nitrous oxide (65 total), please visit the HSDB record page.

N01AX13

N - Nervous system

QN - Nervous system

N01AX13

Findings to date indicate that nitrous oxide induces opioid peptide release in the brain stem leading to the activation of descending noradrenergic neurones, which results in modulation of the nociceptive process in the spinal cord. Several receptor–effector mechanisms including dopamine receptors, α2 adrenoceptors, benzodiazepine receptors and -methyl- -aspartate (NMDA) receptors have been implicated although the relationship of one with the other is not known.

Nitrous oxide (N2O) gas is a widely used anesthetic adjunct in dentistry and medicine that is also commonly abused. Studies have shown that N2O alters the function of the N-methyl-d-aspartate (NMDA), GABAA, opioid, and serotonin receptors among others. However, the receptors systems underlying the abuse-related central nervous system effects of N2O are unclear. The present study explores the receptor systems responsible for producing the discriminative stimulus effects of N2O. B6SJLF1/J male mice trained to discriminate 10 minutes of exposure to 60% N2O + 40% oxygen versus 100% oxygen served as subjects. Both the high-affinity NMDA receptor channel blocker (+)-MK-801 maleate [(5S,10R)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] and the low-affinity blocker memantine partially mimicked the stimulus effects of N2O. Neither the competitive NMDA antagonist, CGS-19755 (cis-4-[phosphomethyl]-piperidine-2-carboxylic acid), nor the NMDA glycine-site antagonist, L701-324 [7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(1H)-quinolinone], produced N2O-like stimulus effects. A range of GABAA agonists and positive modulators, including midazolam, pentobarbital, muscimol, and gaboxadol (4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol), all failed to produce N2O-like stimulus effects. The mu-, kappa-, and delta-opioid agonists, as well as 5-hydroxytryptamine (serotonin) 1B/2C (5-HT1B/2C) and 5-HT1A agonists, also failed to produce N2O-like stimulus effects. Ethanol partially substituted for N2O. Both (+)-MK-801 and ethanol but not midazolam pretreatment also significantly enhanced the discriminative stimulus effects of N2O. Our results support the hypothesis that the discriminative stimulus effects of N2O are at least partially mediated by NMDA antagonist effects similar to those produced by channel blockers. However, as none of the drugs tested fully mimicked the stimulus effects of N2O, other mechanisms may also be involved.

N2O interferes with vitamin B12 and folate metabolism. This impairs production of methionine (from homocysteine), used to form tetrahydrofolate and thymidine during DNA synthesis.

Nitrous oxide is 35 times more soluble than nitrogen. The gas exchanges with nitrogen and diffuses into hollow viscera and body spaces potentially containing air, such as pneumothorax, paranasal sinuses and pneumoperitoneum, or into the cerebral ventricles following pneumoencephalography. This expands the body of trapped air and increases the pressure within such closed spaces. When administration is discontinued, nitrous oxide is released into the alveoli, diluting the alveolar gases. A reduction in alveolar oxygen tension may result. This is referred to as diffusion anoxia. Because of the high concentration of nitrous oxide required to produce and maintain anesthesia, hypoxia is an unavoidable accompaniment to its use. During induction with high concentrations of nitrous oxide, the oxygen in the lungs is rapidly used up and the anoxia with increased respiratory effort causes rapid depletion of carbon dioxide in the tissues. Absence of carbon dioxide and depression of the medullary centers by the anesthetic quickly lead to respiratory failure, and rarely, the patient's cerebral function fails to recover from cerebral damage caused by the prolonged anoxia. The brain suffers anoxia from the very beginning of the administration of the gas, and not from just the moment of cessation of respiratory movements. Thus, the period of anoxia may be five minutes or more, sufficient to cause permanent brain damage in the susceptible individual. The arbitrary "safe period" of eight minutes may be too long for some patients.

Nitrous oxide induces inconsistent changes in the basal levels of the thalamic nuclei. The mechanism of analgesia is believed to involve a direct intraspinal anti-nociceptive action rather than depression of limbic function. In the brain stem, responses evoked by pain stimulation are depressed, although the extent of depression may be variable. Nitrous oxide in anesthetic doses increases cerebral blood flow and intracranial pressure.

For more Mechanism of Action (Complete) data for Nitrous oxide (7 total), please visit the HSDB record page.

Gases or volatile liquids that vary in the rate at which they induce anesthesia; potency; the degree of circulation, respiratory, or neuromuscular depression they produce; and analgesic effects. Inhalation anesthetics have advantages over intravenous agents in that the depth of anesthesia can be changed rapidly by altering the inhaled concentration. Because of their rapid elimination, any postoperative respiratory depression is of relatively short duration. (From AMA Drug Evaluations Annual, 1994, p173)

A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.

The blood/gas partition coefficient is low and most of the inhaled nitrous oxide is rapidly eliminated through the lungs, though small amounts diffuse through the skin.

/Nitrous oxide/ is highly lipid soluble and rapidly absorbed and distributed throughout the body, particularly the vessel-rich regions, including the brain, heart, kidney, splanchnic circulation, and endocrine glands. The rate of nitrous oxide uptake during the first 1 or 2 min is about 1.0 L/min (at an inspired concentrations of 80%), with later uptake inversely proportional to the square root of time. /Nitrous oxide/ is relatively nonreactive and poorly soluble in blood. ... Little hepatic or renal metabolism is detectable in experimental animals, although intestinal bacteria can reduce small quantities of inhaled /nitrous oxide/ to nitrogen gas. Small amounts of inhaled /nitrous oxide/ are also eliminated through the skin and urine.

Placental transmission data: time to appear in fetus, 6 minutes; fetal/maternal concentration ratio, 0.6. /From table/

Concentration for surgical anesthesia: nitrous oxide-inhaled concn 80-85%; blood level 30-50 mg/100 mL; partition coefficients: blood/air 0.47; brain/blood 1.1; oil/blood 3; clearance rate of blood passing lung (alveolar tension) 63%.

Nitrous oxide is almost completely eliminated by the lungs, with some minimal diffusion through the skin. Nitrous oxide is not biotransformed by enzymatic action in human tissue, and 99.9% of absorbed nitrous oxide is eliminated unchanged.

Nitrous oxide has been used as an anesthetic since 1844. It has also been used as a foaming agent for whipped cream, as an oxidant in organic chemical production and as a component of rocket fuel. Occupational exposures have been measured in the 400 to 3000 ppm range without anesthetic waste gas scavenging and 50 ppm with waste gas scavenging. [ACGIH]

To oxidize organic compounds at temperatures greater than 300 °C; to make nitrites from alkali metals at their boiling points; in rocket fuel formulations (with carbon disulfide); in the preparation of whipped cream.

Anesthetic in dentistry and surgery, propellant gas in food aerosols, leak detection.

Agent in detection of leaks in natural gas pipelines

In the munitions-explosives industry, as propellant.

For more Uses (Complete) data for Nitrous oxide (7 total), please visit the HSDB record page.

2023: 100,000 - <250,000 lb

Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: Nitrogen oxide. Aggregated National Production Volume: 10 to < 50 million pounds.

Non-confidential 2012 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Nitrogen oxide. National Production Volume: Withheld.

Nitrous oxide is manufactured by the thermal decomposition of ammonium nitrate. Higher oxides of nitrogen are removed by passing the dry gas through a series of scrubbing towers.

Prepared by thermal decomposition of ammonium nitrate.

Thermal decomposition of ammonium nitrate, controlled reduction of nitriles or nitrates.

Nitrous oxide ... contains not less than 99.0%, by volume, of nitrous oxide. The remainder is chiefly nitrogen.

/Various grades available/ electronic ... technical (99.0%, liquid phase) ... CP (99.0%), UHP (99.99%), atomic absorption (99.0%), USP.

Pure, 98% min, USP (97% min)

Entonox is a 50:50 combination of nitrous oxide and oxygen ... .

Food additives

Food Additives -> ANTIOXIDANT; FOAMING_AGENT; PROPELLANT -> JECFA Functional Classes

Food Additives -> ANTIOXIDANT; FOAMING_AGENT; PROPELLANT -> JECFA Functional Classes

Cosmetics -> Propellant

Industrial Gas Manufacturing

Nitrogen oxide (N2O): ACTIVE

Nitrous oxide ... /should not/ be confused with the poisonous & irritating oxides of nitrogen.

A mixture of 20% nitrous oxide and 80% oxygen produces analgesia equivalent to 15 mg of morphine in humans.

Laughing gas