SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 407

CCOHS Chemical Name: Nitrous oxide gas

Synonyms:

Dinitrogen monoxide

Dinitrogen oxide

Hyponitrous acid anhydride

Laughing gas

N20

Nitrogen hypoxide

Nitrogen monoxide

Nitrous oxide, compressed

Nitrous oxide, refrigerated liquid

Hemioxyde d’azote

Oxyde nitreux

Chemical Name French: Oxyde nitreux

Chemical Name Spanish: Oxido nitroso

CAS Registry Number: 10024-97-2

UN/NA Number(s): 1070 2201

RTECS Number(s): QX1350000

Chemical Family: Inorganic nitrogen compound / nitrogen oxide / inorganic gas

Molecular Formula: N2-0

Structural Formula: N=N=O

SECTION 2. DESCRIPTION

Appearance and Odour:

Colourless gas or refrigerated liquefied gas with a slightly sweet odour.(29,30)

Odour Threshold:

Not available

Warning Properties:

Information not available for evaluation.

Composition/Purity:

Nitrous oxide is available in medical, commercial, and high purity grades, with purities of 97-99+%. The chief impurity in the commercial product is nitrogen. Nitrogen dioxide, oxygen and carbon dioxide may also be present. It can be shipped as a refrigerated liquid (typically at -17 deg C (0 deg F) and 1848 kPa) or as a liquefied, compressed gas in high-pressure cylinders under its own vapour pressure of 5070 kPa at 21.1 deg C.(30,31) Nitrous oxide does not fall into the definition of a cryogenic liquid because its boiling point is too high. However, it is sometimes included in this category because many of the hazards and control measures are similar to cryogenic liquids.(32)

Uses and Occurrences:

The major use is as an analgesic and inhalation anesthetic in dentistry, surgery and veterinary medicine, either alone or with other anesthetics; also used for cryosurgery; a propellant for pressure or aerosol products; foaming agent for whipping cream; as an oxidizing gas for atomic absorption spectrophotometry; nitration agent for alkali metals; manufacture of other chemicals; detection of leaks in natural gas pipelines; in rocket fuel formulations; a fuel oxidant for racing vehicles; and in the manufacture of semiconductors.(1,19,29,31)

Occurs in the natural environment at concentrations of about 0.25-0.29 ppm, arising from the bacterial decomposition of organic nitrogen material in soil.(1)

SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:

Colourless gas or refrigerated, liquefied gas with a slightly sweet odour. Will not burn. OXIDIZER. Contact with combustible materials may cause fire or explosion. Explosive when mixed with fuels. COMPRESSED GAS. Confined space hazard. Gas can displace the oxygen in the air. Refrigerated liquid or escaping liquified gas may cause frostbite. REPRODUCTIVE HAZARD. Can cause embryotoxic, fetotoxic and teratogenic effects, based on human information.

POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:

Occupational exposure to nitrous oxide usually ranges between 400 and 3,000 ppm, when waste gas scavenging technology is not being used. With gas scavenging, exposures of less than 50 ppm are readily achieved.(1) Short-term health effects are not expected to occur at these relatively low exposure levels.

Exposure to concentrations of 100,000 ppm (10%) and higher can affect behaviour and the ability to carry out mental tasks. This effect has also been demonstrated in volunteers exposed to a very low concentration (50 ppm for 3-4 hours). However, this finding, at such low exposure levels, has not been confirmed in subsequent studies.(1) Reversible effects, such as delayed response to stimuli, have been consistently observed in volunteers briefly exposed to concentrations of 100,000 ppm (10%) or higher. Performing moderate to heavy work during exposure has not affected results.(2-4)

At levels of 330,000 ppm (30%), volunteers have shown reduced sensitivity to pain. Levels of 400,000-700,000 ppm (40-70%) have caused reversible blood system (hematological) changes, including depression of bone marrow activity. Levels of 500,000-700,000 ppm (50-70%) have produced a feeling of numbness (anesthesia).(5) At concentrations greater than 800,000 ppm (80%), a feeling of drunkenness (stupor) may result.(1)

Extremely high levels of nitrous oxide can displace oxygen in the air and cause health effects due to the lack of oxygen (asphyxiation).(6) At these high concentrations, the effects of oxygen deficiency may be combined with the effects of nitrous oxide toxicity. Effects of oxygen deficiency can include an increased breathing and pulse rate, disturbed muscular coordination, emotional upset, abnormal fatigue, disturbed respiration, nausea, vomiting, collapse or loss of consciousness and possible respiratory collapse and death.(7)

In cases of substance abuse, inhalation of nitrous oxide has caused unconsciousness. Vomiting and subsequent aspiration of vomit into the lungs has caused death.(8) On rare occasions, medical use of nitrous oxide as an anesthetic, without adequate accompanying oxygen, has led to prolonged unconsciousness with visual impairment, including loss of vision, in patients.(9)

Skin Contact:

Contact with the refrigerated liquid or liquefied gas escaping from its high pressure cylinder may cause frostbite. Symptoms of mild frostbite include numbness, prickling and itching in the affected area. Symptoms of more severe frostbite include a burning sensation and stiffness of the affected area. The skin may become waxy white or yellow. Blistering, tissue death and gangrene may also develop in severe cases. There is one case report of liquid nitrous oxide causing frostbite injury.(10)

There are no reports of skin irritation from gaseous nitrous oxide.

Eye Contact:

Contact with the refrigerated liquid or liquefied gas escaping from its high pressure cylinder may cause freezing of the eye. Permanent eye damage or blindness could result.

There are no reports of gaseous nitrous oxide causing eye irritation.(9)

Ingestion:

Ingestion is not an applicable route of exposure for gases.

Effects of Long-Term (Chronic) Exposure

NEUROLOGICAL EFFECTS: Repeated exposure to high concentrations of nitrous oxide can damage the peripheral nervous system. A condition called polyneuropathy has been observed. While this condition may improve over time, it is not completely reversible.

Initial signs and symptoms of polyneuropathy include numbness, a burning or prickling sensation on the skin (paresthesia), poor muscle coordination (ataxia) and clumsiness. If exposure continues, weakness, disturbances in walking (gait), impotence and signs of degeneration of the spinal cord can occur.(6,11)

One small study of dentists who used nitrous oxide occupationally did not report harmful effects.(11) However, another larger study of dentists and dental assistants heavily exposed to nitrous oxide (concentrations not provided) over several years reported an increased incidence of peripheral nervous system effects, including numbness, tingling, and weakness.(1) In 15 cases of nitrous oxide-induced polyneuropathy, two cases were dentists overexposed during routine clinical use in poorly ventilated dental clinics and 13 were cases of substance-abuse in which dentists self-administered 300,000 to 800,000 ppm (30-80%) nitrous oxide, 30 to 60 minutes/day, 2-7 days/week, for periods ranging from 3 months to several years.(12)

BLOOD FORMATION SYSTEM: Medical administration of approximately 500,000 ppm (50%) nitrous oxide over several weeks has resulted in decreased bone marrow activity and decreased numbers of circulating blood cells. Bone marrow activity usually returned to normal after treatment stopped, although fatal aplastic anemia has been reported.(11) The relevance of this health effect to occupational exposures is uncertain.

OTHER LONG-TERM (CHRONIC) EFFECTS: In one study, a mail survey showed that liver and kidney disease rates were increased for dentists and dental assistants heavily exposed to nitrous oxide.(13) No conclusions can be drawn based on this observation because of limitations, such as self-reporting biases, lack of exposure data and lack of control for other potential causes of the observed effects.

Carcinogenicity:

The International Agency for Research on Cancer (IARC) has determined that the evidence for carcinogenicity of volatile anesthetics, including nitrous oxide, to humans is inadequate.(14) One human population study specifically examined cancer incidence in dentists and dental assistants exposed to nitrous oxide. The cancer rate was not increased in male dentists. A marginal significant increase in cancer of the cervix was observed in heavily exposed females.(13) However, there may be other explanations for this small increase and no conclusions can be drawn from this study.

The International Agency for Research on Cancer (IARC) has not evaluated the carcinogenicity of this chemical.

The American Conference of Governmental Industrial Hygienists (ACGIH) has designated this chemical as not classifiable as a human carcinogen (A4).

The US National Toxicology Program (NTP) has not listed this chemical in its report on carcinogens.

Teratogenicity and Embryotoxicity:

Several human population studies among health care workers indicate that repeated exposure to volatile anesthetics, including nitrous oxide, is associated with an increased incidence of miscarriage and, to a lesser extent, developmental effects in children.(15) These observations of effects in humans are consistent with results from animal studies, despite limitations with information derived from human population studies (for example, potential reporting biases, possible confounding factors, and/or inadequate exposure data).

In a study, which examined nitrous oxide specifically, more miscarriages were observed in female dental assistants. Also, more developmental effects were observed in the children of female dental assistants.(13) The rates of miscarriage and developmental effects in children were also significantly elevated in female hospital workers exposed to volatile anesthetics, primarily nitrous oxide, compared to unexposed workers.(5) Miscarriages in female dental assistants were increased in women who worked with nitrous oxide for 3 hours/week or more in dental facilities not using scavenging equipment.(16)

In other studies, pregnancy outcome has not been affected by exposure to nitrous oxide as part of surgical procedures.(15) Veterinary workers exposed to low nitrous oxide levels (estimated to be in the range of 25 ppm) did not have more miscarriages or developmental effects in their children.(5)

Reproductive Toxicity:

Inconsistent results have been obtained in studies of the male reproductive system.(38) Some studies have shown increased miscarriages and developmental effects in the wives of dentists and hospital workers exposed to nitrous oxide.(5,13,38). Many of the positive studies have been criticized due to design flaws. In one well-conducted study, no sperm abnormalities were observed in anesthesiologists who worked for one year or more in hospitals equipped with modern gas-scavenging devices (average nitrous oxide concentration was less than 50 ppm).(5,11) Overall, the majority of studies suggest no effect on the male reproductive system.(38)

There is inadequate information to assess the effects of nitrous oxide on the female reproductive system. In one study, fertility was decreased (measured by increased time-to-pregnancy) in female dental assistants with heavy exposure to nitrous oxide (those exposed for greater than 5 hours/week).(17) No firm conclusions can be drawn from this study because of design limitations, such as possible self-reporting biases, the fact that other possible causes were not investigated (for example, age of the mother) and the relatively small number of people studied. Harmful effects were not observed in one animal study.

Mutagenicity:

Results from studies investigating mutagenicity in the blood cells of health care workers exposed to volatile anesthetics are conflicting. The available studies have not investigated the effect in people exposed to nitrous oxide alone. Mutagenicity in blood cells were reported in health care workers exposed to the anesthetic halothane, in combination with nitrous oxide. The urine of these workers was not mutagenic in a bacterial test. The specific role of nitrous oxide in producing these results cannot be determined.(18) Negative results have been obtained for nitrous oxide in bacteria and cultured mammalian cells.

Toxicologically Synergistic Materials:

The toxicity of nitrous oxide may be increased by a vitamin B12-deficient diet. One animal study indicated that exposure to nitrous oxide together with a vitamin B12-deficient diet caused reduced growth, an effect not observed with either treatment alone.(5)

Potential for Accumulation:

Nitrous oxide does not accumulate in the body. It is readily absorbed through the lungs and is transported in the blood throughout the body. It can cross the placenta. Nitrous oxide is excreted unchanged in exhaled air, but a small amount escapes through the skin.(19)

Health Comments:

Effects of long-term (chronic) overexposure to nitrous oxide are similar to those seen with vitamin B12 deficiency in the diet.(6) Nitrous oxide is thought to inactivate vitamin B12, which impairs functioning of an enzyme system which makes methionine. Methionine is used by the body to produce many molecules including thymine, a building block of DNA. Case reports of substance-abuse suggest nitrous oxide may have addictive properties.

SECTION 4. FIRST AID MEASURES

Inhalation:

This gas is a teratogen/embryotoxin. Take proper precautions to ensure your own safety before attempting rescue (e.g. wear appropriate protective equipment). Remove the source of contamination or move victim to fresh air and obtain medical advice.

Skin Contact:

GAS: No skin effects expected. LIQUEFIED GAS: Quickly remove victim from source of contamination and briefly flush with lukewarm, gently flowing water until the chemical is removed. DO NOT attempt to rewarm the affected area on site. DO NOT rub area or apply dry heat. Gently remove clothing or jewellery that may restrict circulation. Carefully cut around clothing that sticks to the skin and remove the rest of the garment. Loosely cover the affected area with a sterile dressing. DO NOT allow victim to drink alcohol or smoke. Quickly transport victim to an emergency care facility.

Eye Contact:

GAS: No eye effects expected. LIQUEFIED GAS: Quickly remove victim from source of contamination. Immediately and briefly flush with lukewarm, gently flowing water until the chemical is removed. DO NOT attempt to rewarm. Cover both eyes with a sterile dressing. DO NOT allow victim to drink alcohol or smoke. Quickly transport victim to an emergency care facility.

Ingestion:

Ingestion is not a typical route of exposures for gases or liquefied gases.

First Aid Comments:

Provide general supportive measures (comfort, warmth, rest).

Consult a doctor and/or the nearest Poison Control Centre for all serious exposures.

All first aid procedures should be periodically reviewed by a doctor familiar with the material and its conditions of use in the workplace.

SECTION 5. FIRE FIGHTING MEASURES

Flash Point:

Does not burn (nonflammable).

Lower Flammable (Explosive) Limit (LFL/LEL):

Not flammable

Upper Flammable (Explosive) Limit (UFL/UEL):

Not flammable

Autoignition (Ignition) Temperature:

Not flammable

Sensitivity to Mechanical Impact:

Stable gas or liquid. Probably not sensitive.

Sensitivity to Static Charge:

Information not available.

Combustion and Thermal Decomposition Products:

High temperatures (greater than 649 deg C) may cause decomposition to nitrogen and oxygen.(29) Nitric oxide or nitrogen dioxide gases may also form.

Fire Hazard Summary:

Does not burn (nonflammable). Nitrous oxide is a mild oxidizing agent that can ignite combustible materials such as wood, paper, oils and grease, and may support, accelerate and intensify the burning of combustible materials in a fire. Some materials that do not normally burn, may burn in an enriched nitrous oxide atmosphere. The decomposition to nitrogen and oxygen may become explosive at high temperatures, but little decomposition occurs below 649 deg C (1200 deg F). Containers or cylinders may rupture violently due to overpressurization, if exposed to fire or excessive heat for a sufficient period of time. Initially, vapours from liquefied gas are heavier than air and may linger above the spill. Extremely high levels of nitrous oxide can displace oxygen in the air to the point where there is not enough oxygen to breathe. Escaping liquefied nitrous oxide may freeze water leading to heavy icing, possibly blocking pressure relief valves.(32,33)

Extinguishing Media:

Use extinguishing media appropriate to surrounding fire conditions, such as dry chemical powder, carbon dioxide, or foam. Use water in large quantities for fires involving nitrous oxide.

Fire Fighting Instructions:

Evacuate area and fight fire from a safe distance or a protected explosion-resistant location or maximum possible distance. Approach fire from upwind to avoid hazardous vapours and toxic decomposition products. Move cylinders or containers from the fire area if this can be done without risk. Explosive decomposition may occur under fire conditions. Use extreme caution since heat may rupture containers, which may possibly rocket. Otherwise, apply water from as far a distance as possible, in flooding quantities as a spray or fog to keep fire-exposed cylinders, containers or equipment cool and absorb heat, until well after the fire is out. Take care not to block pressure relief valves. If possible, avoid spraying cold areas of equipment.

If there is a nitrous oxide leak, stop the flow of gas, if this can be done safely. Otherwise, withdraw from area and let fire burn. Remove all flammable and combustible materials from the vicinity, especially oil and grease. Do not direct water at source of leak or venting safety devices of liquid storage containers since icing may occur. Take care not to block pressure relief valves. If it is desirable to evaporate a liquefied nitrous oxide spill quickly, water spray may be used to increase the rate of evaporation if the increased vapour evolution can be controlled. DO NOT discharge a solid stream of water into liquid nitrous oxide. If liquid nitrous oxide is discharging into the air, judgment should be used in deciding whether to allow the gas to escape, or to attempt to cut off the gas flow, depending on which is safer.(31)

Nitrous oxide and its decomposition products are hazardous to health. Do not enter without wearing specialized protective equipment suitable for the situation. Firefighter’s normal protective clothing (Bunker Gear) will not provide adequate protection. A full-body encapsulating chemical resistant suit with positive pressure self-contained breathing apparatus (MSHA/NIOSH approved or equivalent) may be necessary.

NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA – Comments:

NFPA has no listing for this chemical in Codes 49 or 325.

SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 44.013

Conversion Factor:

1 ppm = 1.80 mg/m3; 1 mg/m3 = 0.557 ppm at 25 deg C (calculated)

Physical State: Gas

Melting Point: -90.8 deg C (-131.44 deg F) (Triple point) (29)

Boiling Point: -88.5 deg C (-127.4 deg F) at 101.3 kPa (29-31)

Relative Density (Specific Gravity): Not applicable (gas)

Solubility in Water: Slightly soluble (121 mg/100 g; 0.68 mL/100 mL at 20 deg C and 101.3 kPa) (29,31)

Solubility in Other Liquids: Ethanol, diethyl ether, oils, sulfuric acid (1,29,34)

Coefficient of Oil/Water Distribution (Partition Coefficient): Not applicable

pH Value: Not applicable

Viscosity-Dynamic: Gas: 0.0145 mPa.s (0.0145 centipoises) at 25 deg C (30)

Surface Tension: Liquid: 1.75 mN/m (1.75 dynes/cm) at 20 deg C in contact with vapour.(19,34)

Vapour Density: 1.53 at 25 deg C (air=1) (30) Gas: 1.947 kg/m3 at 21.1 deg C and 101.3 kPa (31)

Vapour Pressure: 5070 kPa (50 atm) (31); 5238 kPAa (51.7 atm) (29,30) at 21.1 deg C

Vapour Pressure at 50 deg C: Greater than 7000 kPa (69 atm) (estimated from graph) (31b)

Saturation Vapour Concentration: Not applicable (gas)

Evaporation Rate: Not applicable (gas)

Critical Temperature: 36.4 deg C (97.6 deg F) (30,34)

Critical Pressure: 7254 kPa (71.6 atm) (30,34)

Other Physical Properties:

ABSOLUTE DENSITY: Gas: 1.947 kg/m3 at 21.1 deg C and 101.3 kPa (31)

SECTION 10. STABILITY AND REACTIVITY

Stability:

Stable at normal temperatures. At elevated temperatures (above 649 deg C) decomposes into nitrogen and oxygen. This decomposition may become explosive at high temperatures. Decomposition will occur at lower temperatures in the presence of catalytic surfaces such as silver, platinum, cobalt, copper oxides or nickel oxides.(29,30)

Hazardous Polymerization:

Does not occur

Incompatibility – Materials to Avoid:

NOTE: Chemical reactions that could result in a hazardous situation (e.g. generation of flammable or toxic chemicals, fire or detonation) are listed here. Many of these reactions can be done safely if specific control measures (e.g. cooling of the reaction) are in place. Although not intended to be complete, an overview of important reactions involving common chemicals is provided to assist in the development of safe work practices.

COMBUSTIBLE MATERIALS (e.g. wood, paper, oil, grease) – may ignite.(29,31)

COMBUSTIBLE GASES (e.g. ammonia, carbon monoxide, hydrogen, hydrogen sulfide and phosphine) or DIETHYL ETHER – form explosive mixtures.(35,36)

POWDERED ALUMINUM, HYDRAZINE or LITHIUM HYDRIDE – form flammable mixtures, some of which may ignite spontaneously.(29,35,36)

AMORPHOUS BORON, GASEOUS SODIUM, TIN(II)OXIDE or TUNGSTEN CARBIDE – ignite when heated in nitrous oxide.(29,35,36)

HYDROGEN – lowers the ignition temperature.(35)

PHENYLLITHIUM – forms unstable lithium phenylazoxide.(29,36)

PLASTIC TUBES (e.g polyvinyl chloride, silicone rubber or red rubber) – surgical tubes have been ignited by surgical lasers or electrocautery in atmospheres enriched by nitrous oxide.(35)

SILANE – detonates very easily.(35)

Hazardous Decomposition Products:

None reported

Conditions to Avoid:

High temperatures, electric discharge, welding

Corrosivity to Metals:

Not corrosive to common structural materials, such as iron, steel, stainless steel and copper, bronze and brass.(30,31,37) Corrosive to aluminum, nickel, and nickel-copper and nickel-chromium-iron alloys at high concentrations in water.(37)

Stability and Reactivity Comments:

Electric discharge may initiate the explosive decomposition of the gas at 5-800 kPa at normal temperatures. Oxyacetylene welding repair work on or near a tank of liquefied nitrous oxide has led to a violent explosion.(35) May cause swelling of some elastomers and may dissolve some plastics.(29,31)

SECTION 11. TOXICOLOGICAL INFORMATION

Standard animal toxicity values are not available.

An LC50 (rat) value of 160 mg/m3 (6-hour exposure) has been reported.(20, unconfirmed) This value is not considered reliable since rats have tolerated short- and long-term exposures to much higher concentrations.

Effects of Long-Term (Chronic) Exposure:

Inhalation:

Harmful effects have been observed in blood formation and immune system functions and the neurological system (peripheral nervous system effects) following exposures to high concentrations. Blood Formation and Immune System Functions: Rats exposed to high concentrations (greater than 10,000 ppm (1%)) have shown impaired formation and development of blood cells (hematopoiesis). At very high concentrations (greater than 400,000 ppm (40%)), effects are observed within the first few days of exposure. In some studies, the effects have been shown to be reversible once exposure stops. Prolonged exposure has caused cell division in the bone marrow to completely stop.(1,11) In one study, mice were exposed to 50, 500 or 5000 ppm for 2 or 13 weeks. No effects were observed after two weeks. At 13 weeks, decreased liver weights and a decreased number of white blood cells were seen at all concentrations. Bone marrow activity was depressed at the middle and high concentrations, and the number of plaque-forming cells, an indicator of depressed immune response, was decreased at 5000 ppm.(21) Neurological Effects: Monkeys inhaling 150,000 ppm (15%) developed poor muscle coordination within a few days. If administration continued for more than 2 weeks, irreversible degeneration of nerve tissue in the spinal cord occurred. In rats, exposure to 700,000 ppm (70%) for 6 months did not cause neurological effects. Primates appear more sensitive than rodents to the nervous system effects of nitrous oxide.(11)

Carcinogenicity:

The International Agency for Research on Cancer (IARC) has determined that the evidence for carcinogenicity of nitrous oxide to animals is inadequate.(14) Nitrous oxide was not carcinogenic in studies conducted with mice.(11,28) In one well-conducted study, no increase in tumours was observed in mice exposed to 100,000 or 400,000 ppm (10 or 40%) for 78 weeks.(28)

Teratogenicity, Embryotoxicity and/or Fetotoxicity:

Numerous studies have investigated the effect of nitrous oxide exposure on pregnancy outcome in rats and mice. Observed effects have included embryotoxicity (increased incidence in resorptions and decreased litter size), fetotoxicity (decreased fetal weight) and teratogenicity (skeletal malformations). In several studies, maternal toxicity was observed or not addressed and therefore, these studies cannot be evaluated. In studies in which maternal toxicity was not observed, significant adverse effects were observed in the offspring in four studies (22-25) and no effects were seen in one study (26). Embryotoxicity (increased resorptions and small litter size), fetotoxicity (decreased fetal length) and teratogenicity (skeletal malformations) were observed in rats continuously exposed to 1,000 ppm nitrous oxide on days 1-19 of pregnancy. Effects were not observed at 250 or 500 ppm. Maternal toxicity was not observed.(22) In another study, embryotoxicity (increased numbers of resorptions and fetal deaths) and teratogenicity (skeletal malformations) were observed when rats were continuously exposed to 500,000 ppm (50%) for 2, 4 or 6 days starting on the eighth day of pregnancy. Maternal toxicity was not observed.(23) Offspring of rats exposed to 10,000, 100,000 or 500,000 ppm (1, 10 or 50%) for 8 hours/day throughout pregnancy had fetotoxicity (decreased fetal weights at the middle and high concentration and delayed ossification at the high concentration). Maternal toxicity was not observed.(24) More subtle developmental effects were observed in another study in which mice were exposed on a single day of pregnancy to a concentration that did not cause maternal toxicity.(25)

Reproductive Toxicity:

Studies on the effects of nitrous oxide on the male reproductive system in rodents have given conflicting results. In one study, damage to the testes was observed in rats exposed to 200,000 ppm (20%) nitrous oxide either continuously or for 8 hours/day for up to 35 days. The effects were reversible after exposure stopped. A different researcher obtained similar results.(11) In two other studies, damage to the testes was not observed in mice repeatedly exposed to up to 800,000 ppm (80%).(1,11,27) Fertility was not affected when male mice were exposed to 5,000, 50,000 or 500,000 ppm (0.5, 5 or 50%) for 9 weeks prior to mating.(26) In a study on the effect of nitrous oxide on the female reproductive system of mice, the number of oocytes (developing eggs) was not altered by exposure to 5,000, 50,000 or 500,000 ppm (0.5, 5 or 50%) for 14 weeks.(27)

SECTION 16. OTHER INFORMATION

Selected Bibliography:

(1) Nitrous oxide. In: Documentation of the threshold limit values and biological exposure indices. 6th edition. American Conference of Governmental Industrial Hygienists, 1991. p. 1134-1138

(2) Bradley, M.E., et al. The effects of nitrous oxide narcosis on the physiologic and psychologic performance of man at rest and during exercise. In: Underwater physiology V. Edited by C.J. Lambertsen. FASEB, 1976. p. 617-626

(3) Fenwick, P.B.C., et al. Changes in the pattern reversal visual evoked potential as a function of inspired nitrous oxide concentration. Electroencephalography and Clinical Neurophysiology. Vol. 57, no. 2 (1984). p. 178-183

(4) McMenemin, I.M., et al. Comparison of the effects of subanaesthetic concentrations of isoflurane or nitrous oxide in volunteers. British Journal of Anaesthesia. Vol. 60, no. 1 (January, 1988). p. 56-63

(5) Dutch Expert Committee on Occupational Standards. Health-based recommended occupational exposure limit for nitrous oxide. Labour Inspectorate, Ministry of Social Affairs and Employment, September, 1992.

(6) Lipsett, M.J., et al. Inorganic compounds of carbon, nitrogen, and oxygen: nitrous oxide (N2O). In: Patty’s industrial hygiene and toxicology. 4th edition. Edited by G.D. Clayton, et al. Volume II. Toxicology. Part F. John Wiley and Sons, 1994. p. 4591-4597

(7) Wilkenfeld, M. Simple asphyxiants. In: Environmental and occupational medicine. 2nd edition. Edited by W.N. Rom. Volume II. Little, Brown and Company, 1992. p. 535-538

(8) Suruda, A.J., et al. Fatal abuse of nitrous oxide in the workplace. Journal of Occupational Medicine. Vol. 32, no. 8 (August, 1990). p. 682-684

(9) Grant, W.M., et al. Toxicology of the Eye. 4th edition. Charles C. Thomas, 1993. p. 1056-1057

(10) Craig, D.B. Thermal injury by liquid nitrous oxide. (Letter) The Canadian Anaesthetists’ Society Journal. Vol. 29, no. 2 (March, 1982). p. 181

(11) Nitrous Oxide/N20. Edited by E.I. Eger II. Elsevier, 1985. p. 235- 247, 259-279

(12) Layzer, R.B. Myeloneuropathy after prolonged exposure to nitrous oxide. The Lancet. Vol. 2, no. 8102 (December 9, 1978). p. 1227-1230

(13) Cohen, E.N., et al. Occupational disease in dentistry and chronic exposure to trace anesthetic gases. The Journal of the American Dental Association. Vol. 101, no. 1 (July, 1980). p. 21-31

(14) Anaesthetics, volatile (group 3). In: IARC monographs on the evaluation of carcinogenic risks to humans. Supplement 7. Overall evaluations of carcinogenicity: an updating of IARC monographs volumes 1 to 42. International Agency for Research on Cancer, 1987. p. 93-95

(15) Scialli, A.R., et al. Reproductive effects of chemical, physical, and biologic agents: REPROTOX. The Johns Hopkins University Press, 1995. p. 249- 250

(16) Rowland, A.S., et al. Nitrous oxide and spontaneous abortion in female dental assistants. American Journal of Epidemiology. Vol. 141, no. 6 (March 5, 1995). p. 531-538

(17) Rowland, A.S., et al. Reduced fertility among women employed as dental assistants exposed to high levels of nitrous oxide. The New England Journal of Medicine. Vol. 327, no. 14 (October 1, 1992). p. 993-997

(18) Karelova, J., et al. Chromosome and sister-chromatid exchange analysis in peripheral lymphocytes, and mutagenicity of urine in anesthesiology personnel. International Archives of Occupational and Environmental Health. Vol. 64, no. 4 (November, 1992). p. 303-306

(19) HSDB record for nitrous oxide. Last revision date: 96/09/04

(20) RTECS database record for nitrogen oxide. Last updated: 9610.

(21) Healy, C.E., et al. Short term toxicity of nitrous oxide on the immune, hemopoietic, and endocrine systems in CD-1 mice. Toxicology and Industrial Health. Vol. 6, no. 1 (January, 1990). p. 57-70

(22) Vieira, E., et al. Effects of low concentrations of nitrous oxide on rat fetuses. Anesthesia and Analgesia. Vol. 59, no. 3 (March, 1980). p. 175- 177

(23) Fink, C.R., et al. Teratogenic activity of nitrous oxide. Nature. Vol. 214 (April 8, 1967). p. 146-148

(24) Pope, W.D.B., et al. Fetotoxicity in rats following chronic exposure to halothane, nitrous oxide, or methoxyflurane. Anesthesiology. Vol. 48, no. 1 (January, 1978). p. 11-16

(25) Koeter, H., et al. Behavioral effects in mice exposed to nitrous oxide or halothane: prenatal vs. postnatal exposure. Neurobehavioral Toxicology and Teratology. Vol. 8, no. 2 (March/April, 1986). p. 189-194

(26) Mazze, R.I., et al. Reproduction and fetal development in mice chronically exposed to nitrous oxide. Teratology. Vol. 26, no. 1 (1982). p. 11-16

(27) Mazze, R.I., et al. Germ cell studies in mice after prolonged exposure to nitrous oxide. Toxicology and Applied Pharmacology. Vol. 67, no. 3 (March 15, 1983). p. 370-375

(28) Baden, J.M., et al. Mutagenicity and toxicity studies with high pressure nitrous oxide. Toxicology Letters. Vol. 7, no. 3 (1981). p. 259-262

(29) Emergency action guide for nitrous oxide. Association of American Railroads, January, 1989

(30) Braker, W., et al. Matheson gas data book. 6th edition. Matheson Gas Products, 1980. p. 550-556

(31a) Compressed Gas Association. Handbook of compressed gases. 3rd edition. Chapman and Hall, 1990. p. 70-92, 519-525

(31b) Handbook of compressed gases. Compressed Gas Association. 4th ed. Kluwer Academic Publishers, 1999. p. 551

(32) Riklik, L. How to work safely with cryogenic liquids (P90-24E). Canadian Centre for Occupational Health and Safety, 1990

(33) Matheson guide to safe handling of compressed gases. 2nd printing. Matheson Gas Products, Inc., 1983. p. 216-225

(34) Weast, R.C., ed. Handbook of chemistry and physics. 66th edition. CRC Press, 1985-1986. p. B-120, F-34, F-64

(35) Urben, P.G., ed. Bretherick’s handbook of reactive chemical hazards. 5th edition. Volume 1. Butterworth-Heinemann Ltd., 1995. p. 1686-1688

(36) Fire protection guide to hazardous materials. 11th edition. National Fire Protection Association, 1994. NFPA 491

(37) Corrosion data survey: metals section. 6th edition. National Association of Corrosion Engineers, 1985. p. 90-1 to 91-1

(38) Tas, S., et al. Occupational hazards of the male reproductive system. Critical Reviews in Toxicology. Vol. 26, no. 2 (1996). p. 261-307

(39) Forsberg, K., et al. Quick selection guide to chemical protective clothing. 4th ed. Van Nostrand Reinhold, 2002

Information on chemicals reviewed in the CHEMINFO database is drawn from a number of publicly available sources. A list of general references used to compile CHEMINFO records is available in the database Help.

Review/Preparation Date: 1997-06-24

Revision Indicators:

US transport 1998-03-01

TLV-TWA 1998-06-01

TLV comments 1998-06-01

TDG 2002-05-29

TDG 2002-06-14

TLV basis 2004-01-04

Resistance of materials for PPE 2004-04-05

Bibliography 2006-01-18

Vapour pressure at 50 deg C 2006-01-18

Relative density 2006-09-28