Is CBD Oil Safe and Beneficial to Take Before Surgery?
Individuals scheduled for surgery should always disclose their CBD or cannabis use to the surgeon and anesthesiologist who would handle the procedure.
Also, patients should ask the presiding surgical doctor if they should be ingesting any cannabinoid at all, and take that advice seriously.
CBD for Anxiety
Some people may be interested in using CBD to manage anxiety before surgery. This interest is understandable since the compound has been shown to possess anti-anxiety characteristics that might benefit those who are anxious about an upcoming operation.
A study published in the Journal of Psychopharmacology found that CBD decreases anxiety levels in individuals with a social anxiety disorder (SAD) with results indicating that, relative to placebo, CBD was associated with significantly decreased subjective anxiety (1).
In the said study, the brain scans showed that CBD regulates chemical uptake and blood flow in the brain.
CBD can help people with anxiety disorders by impacting the CB1 cannabinoid receptors in the brain and modifying the signaling process of serotonin (the “feel-good” chemical) receptors.
However, note that taking CBD too close to a surgery schedule could pose risks, especially since many doctors still do not quite understand the full effects of CBD oil.
CBD vs Anticoagulants
Individuals on any anticoagulant (blood thinner) medication should altogether avoid taking CBD or any cannabis-related product long before going to surgery.
Blood coagulation studies show that CBD showed mild anticoagulating effects (2). Research indicates that CBD can potentially exacerbate bleeding after surgery and slow down wound healing, especially for those who suffer from any clotting disorder.
Whenever one takes CBD or any medicine, it passes through the digestive system to the liver, where an enzymatic pathway, called the cytochrome P450 (CYP450) family of enzymes, metabolizes or breaks down the substance ingested.
Liver enzymes CYP450 process about 60% of all medications, including blood thinners, like warfarin. When used with blood thinners, CBD may decrease how quickly the liver breaks down some medications.
In theory, taking CBD, along with some pharmaceuticals that are broken down by the liver, may increase the concentration and side effects of the drug (3).
A 2017 study showed that CBD is broken down further via the same liver pathways as most prescription anticoagulants (4).
This metabolism is dose-dependent but can affect the potency of the drug. Therefore, those who are taking prescription blood thinners should always consult with their doctor before starting a CBD regimen.
Patients should insist on regular blood checks, as CBD and cannabis can decrease the degradation of the drugs (such as warfarin) in their body, and doses should be adjusted accordingly.
Taking CBD in conjunction with anticoagulants can cause serious complications that may put an individual’s health or life at risk.
CBD vs Anesthetic Risk
Anesthetic risk has many variables and is often related to one’s unique medical issues and specific surgery.
Individuals who use cannabis products do so in many ways, forms and amounts. Thus, CBD’s effect on the body is difficult to predict when combined with a wide variety of anesthetic agents and techniques.
Currently, there is not enough evidence to say that cannabis alone increases one’s anesthetic risk when stopped at an appropriate time.
Still, it is recommended that one abstains from cannabis use as long as possible before surgery.
Below is the minimum time a patient would be expected to stop before receiving an anesthetic, as suggested by the Royal Victoria Regional Health Centre of Canada (5).
|Cannabidiol (CBD)||Cannabis (Marijuana)|
|Oral Dosing/Ingested: Stop 4 hours before surgery||Ingested: Stop 12 hours before surgery|
|Smoked/Vaporized: Stop 12 hours before surgery|
The attending anesthesiologist has a legal obligation to provide patients with the safest care possible during surgery.
However, there may be rare occasions when surgery is delayed, postponed, or canceled at the doctor’s discretion.
Still, under no circumstances shall anyone intoxicated (affected by any drug or alcohol) can receive an anesthetic for non-emergency surgery.
With CBD’s numerous purported therapeutic characteristics, there are several ways that it may benefit individuals in the days before surgery.
However, most experts would suggest avoiding CBD in the hours before a surgical procedure, the same time a doctor recommends avoiding other medications, beverages, and foods.
Thus, those who use CBD regularly or took any CBD in the days before surgery must inform their doctor and their anesthesiologist first.
On the other hand, those who are looking to try CBD for the first time must only do so after consulting with a doctor experienced in cannabis use.
- Crippa JA et al.Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report.J Psychopharmacol. 2011 Jan;25(1):121-30. DOI: 10.1177/0269881110379283. Epub 2010 Sep 9. DOI: 10.1177/0269881110379283.
- Coetzee C, Levendal RA, van de Venter M, Frost CL. Anticoagulant effects of a Cannabis extract in an obese rat model. 2007;14(5):333–337. https://doi.org/10.1016/j.phymed.2006.02.004.
- MedlinePlus. (2020, Jan 21). Cannabidiol. Retrieved from https://medlineplus.gov/druginfo/natural/1439.html.
- Grayson L, Vines B, Nichol K, Szaflarski JP; UAB CBD Program. An interaction between warfarin and cannabidiol, a case report. Epilepsy Behav Case Rep. 2017;9:10–11. Published 2017 Oct 12. DOI:10.1016/j.ebcr.2017.10.001.
- The Royal Victoria Regional Health Centre. (2018, Nov 29). Cannabis Before Surgery. Retrieved from https://www.rvh.on.ca/surgery/SiteAssets/SitePages/preoped/Cannabis%20Before%20Surgery%20Patient%20Information%20Sheet.pdf.
|Date of Peer Review: October 2002|
|TYPES OF HAZARD / EXPOSURE||ACUTE HAZARDS / SYMPTOMS||PREVENTION||FIRST AID / FIRE FIGHTING|
|FIRE||Not combustible. Gives off irritating or toxic fumes (or gases) in a fire.||In case of fire in the surroundings: use appropriate extinguishing media.|
|Inhalation||Cough. Sore throat. Drowsiness. Weakness. Unconsciousness. See Notes.||Ventilation, local exhaust, or breathing protection.||Fresh air, rest. Artificial respiration may be needed. Refer for medical attention.|
|Skin||Redness. Dry skin.||Protective gloves.||Remove contaminated clothes. Rinse skin with plenty of water or shower.|
|Eyes||Redness. Pain.||Safety spectacles, or eye protection in combination with breathing protection.||First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then take to a doctor.|
|Ingestion||(See Inhalation).||Do not eat, drink, or smoke during work.||Rinse mouth. Refer for medical attention.|
|SPILLAGE DISPOSAL||PACKAGING & LABELLING|
|Ventilation. Collect leaking and spilled liquid in sealable containers as far as possible. Absorb remaining liquid in sand or inert absorbent and remove to safe place. (Extra personal protection: self-contained breathing apparatus).||EU Classification|
|Keep in a well-ventilated room.|
|PHYSICAL STATE; APPEARANCE:|
COLOURLESS LIQUID, WITH CHARACTERISTIC ODOUR.
The vapour is heavier than air and may accumulate in lowered spaces causing a deficiency of oxygen.
The substance decomposes on heating producing toxic and corrosive fumes (hydrogen chloride, hydrogen fluoride). Attacks some plastic and rubber.
OCCUPATIONAL EXPOSURE LIMITS:
TLV: 75 ppm as TWA; A4; (ACGIH 2002).
MAK: 20 ppm; Peak limitation category: II(8); Pregnancy risk group: C; (DFG 2002).
|ROUTES OF EXPOSURE:|
The substance can be absorbed into the body by inhalation of its vapour and by ingestion.
A harmful contamination of the air can be reached rather quickly on evaporation of this substance at 20°C.
EFFECTS OF SHORT-TERM EXPOSURE:
The substance is irritating to the eyes, the skin and the respiratory tract. The substance may cause effects on the central nervous system and cardiovascular system. Exposure at high levels may result in unconsciousness.
|Boiling point: 56.5°C|
Relative density (water = 1): 1.52
Solubility in water: poor
Vapour pressure, kPa at 20°C: 23.3
Relative vapour density (air = 1): 1.9
|Relative density of the vapour/air-mixture at 20°C (air = 1): 1.12|
Explosive limits, vol% in air: 4.25-?
|Other names: Anesthetic compound no. 347, NCS-115944, Alyrane, Efrane, Ohio 347. Other CAS numbers: (+)-enflurane CAS 22194-21-4; (-)-enflurane CAS 22194-22-5. Check oxygen content before entering area. High concentrations in the air cause a deficiency of oxygen with the risk of unconsciousness or death.|
|© IPCS, CEC 1999|
SECTION 1. CHEMICAL IDENTIFICATION
CHEMINFO Record Number: 407
CCOHS Chemical Name: Nitrous oxide gas
Hyponitrous acid anhydride
Nitrous oxide, compressed
Nitrous oxide, refrigerated liquid
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)
Information not available for evaluation.
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
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
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)
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.
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 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.
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)
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.
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)
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
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.
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.
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 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
Does not burn (nonflammable).
Lower Flammable (Explosive) Limit (LFL/LEL):
Upper Flammable (Explosive) Limit (UFL/UEL):
Autoignition (Ignition) Temperature:
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)
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
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
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)
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:
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:
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)
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)
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
(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
US transport 1998-03-01
TLV comments 1998-06-01
TLV basis 2004-01-04
Resistance of materials for PPE 2004-04-05
Vapour pressure at 50 deg C 2006-01-18
Relative density 2006-09-28