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SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 748
CCOHS Chemical Name: Nitrogen dioxide

Synonyms:
Dinitrogen tetroxide
Dinitrogen tetroxide, liquefied
Nitrogen dioxide, liquefied
Nitrogen oxide
Nitrogen peroxide
Nitrogen peroxide, liquefied
Nitrogen tetroxide
Peroxyde d'azote

Chemical Name French: Dioxyde d'azote
Chemical Name Spanish: Dióxido de nitrógeno
CAS Registry Number: 10102-44-0
Other CAS Registry Number(s): 10544-72-6
UN/NA Number(s): 1067
RTECS Number(s): QW9805000
EU EINECS/ELINCS Number: 233-272-6
Chemical Family: Inorganic nitrogen compound / nitrogen oxide / inorganic gas
Molecular Formula: N-O2 or N2-O4
Structural Formula: O=N-O; O=(O)-N-N-(O)=O or O=N-O-N-(O)=O

SECTION 2. DESCRIPTION

Appearance and Odour:
Yellowish to dark brown liquid or reddish-brown gas with a pungent, suffocating odour.(21,22,23)

Odour Threshold:
Reported values vary. 0.11-0.14 ppm (minimum perceptible value) (24); 0.22 ppm (perception)(22). Odour thresholds of 0.39 ppm (25) and 5 ppm (22) have also been reported.

Warning Properties:
GOOD - TLV is more than 10 times the odour threshold.

Composition/Purity:
At room temperature, nitrogen dioxide can exist as a gas or liquid. It is a gas at or above 21.1 deg C (70 deg F) and a liquid below 21.1 deg C. At normal room temperatures, it exists as an equilibrium mixture of nitrogen dioxide (N2O) (CAS 10102-44-0) and dinitrogen tetroxide (N2O4) (CAS 10544-72- 6). Each molecule of dinitrogen tetroxide consists of 2 molecules of nitrogen dioxide which have combined. At the boiling point (21.1 deg C), the liquid contains 0.1% NO2; at 100 deg C, the liquid contains less than 1% N2O and the gas is 90% N2O and 10% N2O4. At 140 deg C, the gas is completely N2O. The physical properties reported in this review are those of an equilibrium mixture of the 2 forms.(21,22,26,27) Nitrogen dioxide is shipped in cylinders and tanks as a liquefied gas under its own vapour pressure of 101.1 kPa absolute at 21.1 deg C.(21)

Uses and Occurrences:
Used as a catalyst in certain oxidation reactions; polymerization inhibitor for acrylates; nitration agent for organic compounds and explosives; oxidizing agent; chemical intermediate for nitric acid; catalyst for sulfuric acid; manufacture of oxidized cellulose compound (hemostatic cotton); oxidizing agent for rocket fuels; floor bleaching agent; calibration gas; and for increasing the wet strength of paper.(26,28)
Nitrogen oxides (NOx), nitrogen dioxide and nitric oxide, occur naturally as a result of bacterial action on nitrogenous compounds and to a lesser extent from fires, volcanic action, and fixation by lightening. The main source of NOx air pollution is the high temperature combustion of fossil fuels used in motor vehicles and industry (especially power plants).(2)


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
Yellowish to dark brown liquid or reddish-brown gas with a pungent, suffocating odour. Will not burn. COMPRESSED GAS. STRONG OXIDIZER. Contact with combustible materials may cause fire or explosion. Confined space hazard. VERY TOXIC. May be fatal if inhaled. Extremely irritating to the respiratory tract. Causes lung injury--effects may be delayed. Reacts with moisture to form nitric acid and nitrous acid, which are CORROSIVE to the eyes and skin. May cause blindness. May cause permanent scarring. POSSIBLE MUTAGEN. May cause genetic damage based on animal information.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
Depending on the room temperature, nitrogen dioxide (NO2) may be a liquid (21 deg C and below) or a gas (above 21 deg C). Most commonly, people are exposed to nitrogen dioxide by inhalation of the gas. The gas is extremely irritating to the nose, throat and lungs. The seriousness of effects depends more on the highest concentration reached, and not necessarily on the length of exposure. The onset of some symptoms can be delayed for up to 36 hours.
Nose and throat irritation can occur at 15-25 ppm. Other symptoms can include coughing, a feeling of an inability to breathe (dyspnea), headache, and nausea. At 25-100 ppm, more severe symptoms can develop, including pneumonia (inflammation of the lungs) or bronchiolitis (inflammation of the small airways). These effects can be reversible. At concentrations exceeding 150 ppm, potentially fatal pulmonary edema (accumulation of fluid in the lungs) and progressive blockage of the small airways can occur.(1)
A three-stage response is common following exposures to high concentrations. First, the exposed person experiences cough, dyspnea, headache, nausea, irregular heart beat, fatigue, and, occasionally, a choking or smothering sensation. This first stage usually subsides once the exposure stops. During the second stage, the person feels fine and may even return to work. In the third stage, which occurs approximately 3-36 hours later, the person can develop pneumonitis (inflammation of the lungs) or pulmonary edema (accumulation of fluid in the lungs), with symptoms such as rapid breathing, increased heart rate, dyspnea, chest pain, bleeding from the lungs or small airways and cyanosis (bluish discolouration of the skin). Following an apparant recovery from initial symptoms, some people have developed severe respiratory symptoms up to one month after a short-term exposure. Permanent lung damage can result from a short-term exposure. The above symptoms are sometimes referred to as silo filler's disease, which can occur when a farmer enters a silo 18 hours to 10 days after fresh silage has been stored and is exposed to high concentrations of nitrogen dioxide.(1,2)
A small number of studies with healthy volunteers suggest that short exposures to greater than 1 ppm can have harmful effects on the respiratory system. Two- hour exposures to 1 ppm NO2 did not result in significant changes in lung function. However, increased bronchial responsiveness (the reaction of the airways to inhaled substances) was observed with exposures to greater than 1 ppm. Slight increases in airway resistance (a sign of airway obstruction) have also been observed at 2.5 and 5 ppm. Individuals with pre-existing respiratory system disorders, such as asthma, may be more sensitive to the effects of NO2.(3,4)
There is limited information which suggests that exposure to NO2 may harm the body's natural defence mechanisms against foreign materials (physical and immune system responses).(2,5,6)

Skin Contact:
No reports of skin irritation following exposure to NO2 gas were located. Liquid nitrogen dioxide (dinitrogen tetroxide) can cause chemical burns at the point of contact, but would rapidly vapourize to the gas, thus posing a more serious inhalation hazard. Liquid dinitrogen tetroxide can react with moisture on the skin to form nitric acid and nitrous acid which are corrosive.(2,7) Corrosive materials can produce permanent injury, including scarring. One case report describes workers who developed superficial skin burns when high concentrations of nitrogen dioxide gas reacted with perspiration on their skin to form nitric acid.(7)

Eye Contact:
Eye irritation has been reported in people exposed to the gas at concentrations which also cause nose and throat irritation (15-25 ppm). Liquid dinitrogen tetroxide can cause chemical burns at the point of contact, but would rapidly vapourize to the gas posing a more serious inhalation hazard. Liquid dinitrogen tetroxide will react with moisture in the eyes to form nitric acid and nitrous acid which are corrosive.(2,7) Corrosive materials can produce permanent eye damage, including blindness.

Ingestion:
Ingestion is not an applicable route of exposure for gases. If liquid dinitrogen tetroxide came into contact with the mouth, it would cause a chemical burn at the point of contact and rapidly vapourize to the gas, thus posing an inhalation hazard.

Effects of Long-Term (Chronic) Exposure

LUNG EFFECTS: Reports of lung effects from long-term exposure to low levels of NO2 are inconsistent. Respiratory tract symptoms and decreased lung function have been reported in some studies of adults with long-term exposure to less than 0.05 ppm NO2. However, several similar studies have reported no effects.(4) Decreased lung function has not been observed in bus garage workers and salt or coal miners exposed to low levels of NO2.(4) Animal studies have found that long-term exposure can result in impairment of lung function.

Carcinogenicity:

There is no human information available. No conclusions can be drawn from the limited animal information available.

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:
There is no human information available. No conclusions can be drawn from the limited animal information available.

Reproductive Toxicity:
There is no human information available. The limited animal data available has not demonstrated significant reproductive effects.

Mutagenicity:
There is no human information available. Positive results have been obtained in one study using live animals. Positive results have also been obtained in bacteria and cultured mammalian cells.

Toxicologically Synergistic Materials:
There is no information available.

Potential for Accumulation:
About 80-90% of inhaled NO2 is absorbed through the lungs. Absorbed NO2 enters the blood as the nitrite (NO2)-ion and is excreted in the urine as the nitrate (NO3)-ion.(2,4)

Health Comments:
People exposed to NO2, especially those with pre-existing lung disorders, might have enhanced sensitivity to other irritants. NO2 is usually present in a mixture with other air pollutants, and might interact with other environmental factors to produce reactive chemicals.


SECTION 4. FIRST AID MEASURES

Inhalation:
Take proper precautions to ensure your own safety before attempting rescue (e.g. wear appropriate protective equipment, use the buddy system). Remove source of contamination or move victim to fresh air. If breathing is difficult, oxygen may be beneficial if administered by trained personnel, preferably on a doctor's advice. DO NOT allow victim to move about unnecessarily. Symptoms of pulmonary edema can be delayed up to 48 hours after exposure. Immediately transport victim to an emergency care facility.

Skin Contact:
GAS: If irritation occurs, flush affected area with lukewarm, gently flowing water for at least 5 minutes. If irritation persists, obtain medical advice. LIQUID: As quickly as possible, remove contaminated clothing, shoes and leather goods (e.g. watchbands, belts). Flush contaminated area with lukewarm, gently flowing water for at least 20-30 minutes, by the clock. Immediately transport victim to an emergency care facility. Completely decontaminate clothing, shoes and leather goods before re-use or discard.

Eye Contact:
GAS: If irritation occurs, flush eye(s) with lukewarm, gently flowing water for at least 5 minutes. If irritation persists, obtain medical attention. LIQUID: Quickly and gently blot or brush away excess chemical, if any remains. Immediately flush the contaminated eye(s) with lukewarm, gently flowing water for at least 20-30 minutes, by the clock. Quickly transport victim to an emergency care facility.

Ingestion:
GAS: Ingestion is not an applicable route of exposure for gases. LIQUID: Rinse mouth with large amounts of water and obtain medical advice immediately.

First Aid Comments:
Provide general supportive measures (comfort, warmth, rest).
Consult a doctor and/or the nearest Poison Control Centre for all exposures except minor instances of skin contact.
Some recommendations in the above sections may be considered medical acts in some jurisdictions. These recommendations should be reviewed with a doctor and appropriate delegation of authority obtained, as required.
All first aid procedures should be periodically reviewed by a doctor familiar with the material and its conditions of use in the workplace.

Note to Physicians:
NOTE: By far, the most significant route of exposure is inhalation. If skin or eye contact results in irritation, it is very likely that a serious inhalation exposure has also occurred and appropriate first aid should be administered and follow-up conducted.



SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
Nonflammable gas or liquid.

Lower Flammable (Explosive) Limit (LFL/LEL):
Not applicable

Upper Flammable (Explosive) Limit (UFL/UEL):
Not applicable

Autoignition (Ignition) Temperature:
Not applicable

Sensitivity to Mechanical Impact:
Stable gas or liquid. Probably not sensitive.

Sensitivity to Static Charge:
Information not available. The electrical conductivity of the liquid has been described in one source as "quite low."(27)

Combustion and Thermal Decomposition Products:
Undergoes thermal decomposition to give nitric oxide and oxygen when heated above 160 deg C.(29) The decomposition is appreciable above 600 deg C.(26)

Fire Hazard Summary:
Nonflammable gas or liquid. Nitrogen dioxide is a strong 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 substances that do not normally burn in air will ignite or explode upon contact with the liquid or in an enriched nitrogen dioxide atmosphere. The National Fire Protection Association (NFPA) lists nitrogen tetroxide as a Class 2 oxidizer. A Class 2 oxidizer will cause a moderate increase in the burning rate or cause spontaneous ignition of combustible materials with which it comes in contact.(30) In a fire containers may rupture violently and possibly rocket releasing large amounts of extremely toxic oxidizing gases into the atmosphere. No part of a container should be subjected to a temperature higher than 52 deg C (approximately 125 deg F). Vapours from the liquefied gas are initially heavier than air and may spread along the ground.

Extinguishing Media:
Water spray or fog can be safely used to extinguish surrounding fire safely. Halons will react violently with N2O and should not be used. There is disagreement regarding the use of other extinguishing agents, such as dry chemical powder, foam and carbon dioxide. It is therefore best to use water spray or fog. However, if it is necessary to use other extinguishing agents, proceed with due caution.

Fire Fighting Instructions:
Use extreme caution. 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. Do not enter areas with high nitrogen dioxide concentrations.
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.
If there is a nitrogen dioxide leak, stop the flow of gas, if this can be done safely. Water spray or fog may be used to reduce gas from leaking containers. Remove all flammable and combustible materials from the vicinity, especially oil and grease. Do not direct water directly on leak as this may cause leak to increase. Reverse flow into cylinder may cause rupture. Take care not to block pressure relief valves. DO NOT discharge a solid stream of water into liquid nitrogen dioxide. Stay away from ends of tanks (but realize that shrapnel may travel in any direction). Withdraw immediately in case of rising sound from venting safety device or any discolouration of tanks due to fire. In an advanced or massive fire, the area should be evacuated; use unmanned hoseholders or monitor nozzles.
Nitrogen dioxide is extremely 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 - Health: 3 - Short exposure could cause serious temporary or residual injury. (nitrogen oxides)
NFPA - Flammability: 0 - Will not burn under typical fire conditions. (nitrogen oxides)
NFPA - Instability: 0 - Normally stable, even under fire conditions, and not reactive with water. (nitrogen oxides)
NFPA - Specific Hazards: Oxidizing material. (nitrogen oxides)

SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 46.01 (NO2) or 92.01 (N2O4)

Conversion Factor:
1 ppm = 1.88 mg/m3; 1 mg/m3 = 0.53 ppm at 25 deg C (nitrogen dioxide); 1 ppm = 3.76 mg/m3; 1 mg/m3 = 0.266 ppm at 25 deg C (dinitrogen tetroxide) (calculated)

Physical State: Gas
Melting Point: -11.2 deg C (11.8 deg F) at 101.3 kPa (21,22,26). Also reported as -9.3 deg C (15.3 deg F) (11,22)
Boiling Point: 21.2 deg C (70.1 deg F) at 101.3 kPa (11,21,26)
Relative Density (Specific Gravity): Not applicable (gas)
Solubility in Water: Reacts to form nitric acid and nitrous acid; nitrous acid then decomposes to nitric acid and nitric oxide.(21,22,26)
Solubility in Other Liquids: Alkalies, chloroform, carbon disulfide and concentrated nitric and sulfuric acids.(22,28)
Coefficient of Oil/Water Distribution (Partition Coefficient): Not applicable (reacts with water).
pH Value: Not applicable; solutions are very acidic.
Viscosity-Dynamic: Liquid: 0.4165 mPa.s (0.416 centipoises) at 20 deg C (21,26); Gas: 0.014 mPa.s (0.014 centipoises) at 26.8 deg C and 101.3 kPa (26)
Surface Tension: Liquid: 27.5 mN/m (27.5 dynes/cm) at 19.8 deg C in contact with vapour.(32)
Vapour Density: 1.58 (air=1) (11) Gas: 3.394 kg/m3 at 21.1 deg C and 101.3 kPa (21,26)
Vapour Pressure: 101.33 kPa (760 mm Hg) at 21.1 deg C (26,32)
Vapour Pressure at 50 deg C: Approximately 348 kPa absolute (approx. 3.43 atm) (calculated)
Saturation Vapour Concentration: Not applicable (gas)
Evaporation Rate: Not applicable (gas)
Critical Temperature: 158.2 deg C (316.8 deg F) (21,26)
Critical Pressure: 10132.5 kPa absolute (100 atm) (21,26,32)

SECTION 10. STABILITY AND REACTIVITY

Stability:
Normally stable. Nitrogen dioxide thermally decomposes to nitric oxide and oxygen when heated above 160 deg C.(29) The decomposition is appreciable above 600 deg C.(26)

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.


Nitrogen dioxide and dinitrogen teroxide are strong oxidizing agents capable of reacting explosively with many substances. For a review of the many substances nitrogen dioxide and dinitrogen tetroxide can react with, consult references 33, 34 and 35. These include: COMBUSTIBLE MATERIALS (e.g. wood, paper, oil, grease) - may cause fire or explosion upon contact.(22,29)
ACETIC ANHYDRIDE, ALCOHOLS, AMMONIA, BORON TRICHLORIDE, CALCIUM, DIMETHYL SULFOXIDE, FORMALDEHYDE (about 180 deg C), HYDROCARBONS (e.g toluene, hexane, hot cyclohexane), NITROGEN TRICHLORIDE, TRIETHYLAMINE (below 0 deg C), TETRAMETHYLTIN, UNSATURATED HYDROCARBONS (e.g. propene, 1-butene, 1,3- butadiene) (between -32 and -90 deg C) or VINYL CHLORIDE - mixtures may explode violently.(33-35)
ALUMINUM POWDER, CARBON DISULFIDE, HALOCARBONS (e.g. dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane) or NITROAROMATICS (e.g. nitrobenzene, nitrotoluene) - form detonable mixtures.(33-35)
HYDROGEN, OXYGEN - non-explosive mixtures become explosive when small amounts of nitrogen dioxide are present.(33)
CARBONYL METALS, CYCLOPENTADIENE or HYDRAZINE DERIVATIVES (e.g hydrazine, methylhydrazine, 1,1-dimethylhydrazine) - mixtures ignite on contact.(33,35)
PYRIDENE or QUINOLINE - violently attacked by the liquid dinitrogen tetroxide.(33)
METALS (e.g. reduced iron, potassium, pyrophoric manganese, sodium (slightly warm) (at ambient temperatures), METAL ACETYLIDES or CARBIDES (e.g. cesium acetylide, tungsten and ditungsten carbides) (at high temperatures) - ignite in the gas.(33-35)
MAGNESIUM FILINGS (when heated), WHITE PHOSPHORUS (warm or molten) or SULFUR - burn vigorously.(33-35)

Hazardous Decomposition Products:
Decomposes in water to form nitric acid and nitrous acid. Nitrous acid then decomposes to nitric acid and nitric oxide, especially with increased temperature.(22,26)

Conditions to Avoid:
High temperatures, moisture

Corrosivity to Metals:
Nitrogen dioxide and dinitrogen tetroxide are corrosive to copper and its alloys.(35) When dry (0.1% moisture or less), they are not corrosive to mild steel and other metals and alloys, such as carbon steel, stainless steel, aluminum and nickel and its alloys at ordinary temperatures and pressures. They are very corrosive to most metals under wet conditions (greater 10% water), except stainless steels, particularly with high chromium content, and nickel-chromium-iron-molybdenum and nickel-chromium-molybdenum alloys and aluminum.(21,22,26,36)

Stability and Reactivity Comments:
Good quality ceramic bodies, pyrex, Teflon and Kel-F films are satisfactory for handling wet or dry nitrogen dioxide or dinitrogen tetroxide.(21,26)


SECTION 11. TOXICOLOGICAL INFORMATION

LC5O (rat): 88 ppm (4-hour exposure); 115-168 ppm (1-hour exposure); 174 ppm (30-minute exposure); 201-420 ppm (15-minute exposure); 416-833 ppm (5- minute exposure).(8,9)

Eye Irritation:

At 70 ppm, nitrogen dioxide (NO2) gas caused irritation in animals. Cloudiness of the cornea (opacity) was not observed in rabbits exposed to 20 ppm for 4 hours, but was observed following exposure to 70 ppm for 8 hours.(10)

Effects of Short-Term (Acute) Exposure:

Inhalation:
Short-term exposure of animals to 40 ppm or higher at first produces symptoms such as nose irritation and severe respiratory distress. Higher concentrations have resulted in death, usually from pulmonary edema (accumulation of fluid in the lungs). Although, a small number of deaths have been caused by asphyxiation (lack of oxygen), due to spasm of the larynx. Structural changes in the respiratory tissue, including increased growth (hyperplasia) of some cell types and loss of cilia in the small airways, have been observed in rats exposed to 10-20 ppm for 24-36 hours.(8) Increased sensitivity to allergens was observed in guinea pigs exposed to 40- 70 ppm. More deaths from bacterial infections resulted after mice were exposed to 5 ppm NO2 for 3 days. After a 7-day exposure to 4 ppm, guinea pigs had increased reactivity of the respiratory tract (bronchial hyperreactivity) to inhaled substances.(3,4)

Effects of Long-Term (Chronic) Exposure:

Inhalation:
Long-term exposure to NO2 has affected the function and structure of the respiratory system, as well as natural mechanisms of defence against foreign bodies (physical and immune system responses). Rats continuously exposed to NO2 over several months showed loss of cilia in the small airways (at 0.5 ppm) and elevated respiratory rates (at 0.8 ppm). Mice exposed to 0.5 ppm for 6, 18, or 24 hours/day for 3-12 months showed early signs of emphysema (a lung disease).(11) Long-term exposure to greater than 10 ppm has produced emphysema.(1) Several studies have shown that mice exposed to 0.25-5 ppm have developed harmful changes in their immune systems.(4) Monkeys exposed to 1 ppm for 1 year show a slightly decreased immune response. Monkeys exposed to 5 ppm for 2 months, or 10 ppm for 1 month, showed a marked decrease in resistance to infections.(11) A small number of studies using rodents indicate that repeated exposure to NO2 may cause effects on the nervous system, for example, delayed response to stimuli (0.32 ppm) and subtle behavioral effects (5.0-7.5 ppm).(3)

Carcinogenicity:
Conflicting results have been obtained in the available studies. An increase in lung tumours was reported in mice exposed to 10 ppm NO2 for 6 months (a relatively short exposure duration).(12) No increase in lung tumours was observed in rats exposed to 0.04, 0.4 or 4 ppm NO2 for 17 months.(13)

Teratogenicity, Embryotoxicity and/or Fetotoxicity:
No conclusions can be drawn from the available studies, due to inadequate evaluation of maternal toxicity or insufficient details for evaluation.
Mice continuously exposed to 22 or 45 ppm NO2 on days 7-18 of pregnancy had offspring with significantly reduced birthweight and reduced neuromuscular coordination (e.g. righting reflexes). No visible signs of maternal toxicity were apparent, although it was not clear that a complete evaluation of maternal toxicity was conducted.(14) In another study, offspring were monitored for 2 months following exposure to 0.03, 0.05, 0.5 or 5 ppm, 6 hours/day throughout pregnancy. Postnatal biochemical changes in the liver and subtle effects on neuromotor and physical development were marginally apparent at 0.5 ppm and clearly apparent at 5 ppm. Maternal toxicity was not discussed.(15) Another study which reports embryotoxic and fetotoxic effects in the offspring of rats continuously exposed to 0.045 or 0.43 ppm NO2 throughout pregnancy cannot be evaluated. The study is not available in English, and therefore the results cannot be confirmed. Maternal toxicity was not discussed in the review.(16)

Reproductive Toxicity:
Female rats exposed 12 hours/day to 1.25 ppm, but not animals exposed to 0.07 ppm, for 3 months had longer estrus (fertility) cycles. This effect was reversible when exposure ended. Fertility was not affected.(16) Effects on the testes were not observed in male rats exposed to 1 ppm NO2 for 21 days.(17)

Mutagenicity:
Positive results (gene mutations and chromosomal aberrations) were observed in lung cells of rats exposed to 8-27 ppm NO2 for 3 hours.(18) In another study, negative results (in chromosomal abnormalities in sperm) were obtained in mice exposed to 10 ppm NO2.(17)
Positive results have been obtained in bacteria and cultured hamster cells (chromosomal aberrations).(19,20)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) Schlesinger, R. B. Nitrogen dioxide. In: Environmental and Occupational Medicine. 2nd edition. Edited by W.N. Rom. Little, Brown and Company, 1992. p. 503-517
(2) Lipsett, M.J., et al. Inorganic compounds of carbon, nitrogen, and oxygen: nitric oxide (NO) and nitrogen dioxide (NO2). 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. 4566-4591
(3) Lindvall, T. Health effects of nitrogen dioxide and oxidants. Scandinavian Journal of Work, Environment and Health. Vol. 11, Suppl. 3 (1985). p. 10-28
(4) Berglund, M., et al. Health risk evaluation of nitrogen oxides. Scandinavian Journal of Work, Environment and Health. Vol. 19, Suppl. 2 (1993). p. 1-72
(5) Sandstrom, T., et al. Reductions in lymphocyte subpopulations after repeated exposure to 1.5 ppm nitrogen dioxide. British Journal of Industrial Medicine. Vol. 49, no. 12 (December, 1992). p. 850-854
(6) Utell, M.J., et al. Mechanisms of nitrogen dioxide toxicity in humans. Research report number 43. Health Effects Institute, 1991.
(7) Yockey, C.C., et al. The McConnell missile accident: clinical spectrum of nitrogen dioxide exposure. Journal of the American Medical Association. Vol. 244, no. 11 (September 12, 1980). p. 1221-1223
(8) Meldrum, M. Toxicology of substances in relation to major hazards: nitrogen dioxide. Health and Safety Executive, 1992.
(9) Schieb, B.T. Criteria for a recommended standard: occupational exposure to oxides of nitrogen (nitrogen dioxide and nitric oxide). PB81-226995. National Institute for Occupational Health and Safety, March, 1976
(10) Grant, W.M., et al. Toxicology of the Eye, 4th edition. Charles C. Thomas, 1993. p. 1049-1050
(11) Nitrogen dioxide. In: Documentation of the threshold limit values and biological exposure indices. 6th edition. American Conference of Governmental Industrial Hygienists, 1991. p. 1108-1110
(12) Adkins, Jr., B., et al. Oncogenic response of Strain A/J mice to inhaled chemicals. Journal of Toxicology and Environmental Health. Vol. 17, no. 2-3 (1986). p. 311-322
(13) Ichinose, T., et al. Experimental studies on tumor promotion by nitrogen dioxide. Toxicology. Vol. 67, no. 2 (April, 1991). p. 211-225
(14) Singh, J. Nitrogen dioxide exposure alters neonatal development. NeuroToxicology. Vol. 9, no. 3 (1988). p. 545-549
(15) Tabacova, S., et al. Postnatal effects of maternal exposure to nitrogen dioxide. Neurobehavioral Toxicology and Teratology. Vol. 7 (1985). p. 785- 789
(16) Barlow, S.M., et al. Nitrogen dioxide. In: Reproductive hazards of industrial chemicals: an evaluation of animal and human data. Academic Press, 1982. p. 417-421
(17) Scialli, A. R., et al. Reproductive effects of chemical, physical and biological agents: REPROTOX. The Johns Hopkins University Press, 1995. p. 392
(18) Isomura, K., et al. Induction of mutations and chromosome aberrations in lung cells following in vivo exposure of rats to nitrogen oxides. Mutation Research. Vol. 136, no. 2 (1984). p. 119-125
(19) Tsuda, H., et al. Chromosomal aberrations and sister chromatid exchanges induced by gaseous nitrogen dioxide in cultured Chinese hamster cells. Mutation Research. Vol. 89, no. 4 (1981). p. 303-309
(20) Gorsdorf, S., et al. Nitrogen dioxide induces DNA single-strand breaks in cultured Chinese hamster cells. Carcinogenesis. Vol. 11, no. 1 (January, 1990). p. 37-41
(21) Compressed Gas Association. Handbook of compressed gases. 3rd edition. Chapman and Hall, 1990. p. 70-92, 507-512
(22) Emergency action guide for nitrogen tetroxide. Association of American Railroads, January, 1995
(23) NIOSH pocket guide to chemical hazards. National Institute for Occupational Safety and Health, June 1994. p. 228
(24) Odor thresholds for chemicals with established occupational health standards. American Industrial Hygiene Association, 1989. p. 25, 70-71
(25) Amoore, J.E. et al. Odor as an aid to chemical safety: odor thresholds compared with threshold limit values and volatiles for 214 industrial chemicals in air and water dilution. Journal of Applied Toxicology. Vol. 3, no. 6 (1983). p. 280-281
(26) Braker, W., et al. Matheson gas data book. 6th edition. Matheson
(27) Cotton, F.A., et al. Advanced inorganic chemistry: a comprehensive text. 4th edition. John Wiley and Sons, 1980. p. 426-427
(28) HSDB record for nitrogen dioxide. Last revision date: 96/07/11
(29) Chemical safety sheets. Kluwer Academic Publishers, 1991. p. 645
(30) NFPA 430. Code for the storage of liquid and solid oxidizers. 1995 edition. National Fire Protection Association, 1995. p. 430-1 to 430-16
(31) Forsberg, K., et al. Quick selection guide to chemical protective clothing. 4th ed. Van Nostrand Reinhold, 2002
(32) Weast, R.C., ed. Handbook of chemistry and physics. 66th edition. CRC Press, 1985-1986. p. B-120, D-194, F-34, F-64
(33) Urben, P.G., ed. Bretherick's handbook of reactive chemical hazards. 5th edition. Volume 1. Butterworth-Heinemann Ltd., 1995. p. 1680, 1688-1694
(34) Fire protection guide to hazardous materials. 13th ed. Edited by A.B. Spencer, et al. National Fire Protection Association, 2002. NFPA 49; NFPA 491
(35) Sigma-Aldrich library of chemical safety data. Edition II. Volume 2. Sigma-Aldrich Corporation, 1988. p. 2575A
(36) Corrosion data survey: metals section. 6th edition. National Association of Corrosion Engineers, 1985. p. 88-6,7 to 89-6,7
(37) European Communities. Commission Directive 96/54/EC. July 30, 1996

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
Resistance of materials 1998-04-01
TLV comments 1998-08-01
EU Classification 1998-11-01
EU Risk 1998-11-01
EU Safety 1998-11-01
EU Comments 1998-11-01
Bibliography 1998-11-01
TDG 2002-05-29
WHMIS detailed classification 2002-06-10
WHMIS proposed classification 2002-06-10
WHMIS health effects 2002-06-10
Emergency overview 2002-06-10
First aid skin 2002-06-10
First aid eye 2002-06-10
Handling 2002-06-14
Storage 2002-06-14
Bibliography 2003-04-19
ERPG-1 2003-06-10
ERPG-2 2003-06-10
ERPG-3 2003-06-10
WHMIS detailed classification 2003-07-24
WHMIS health effects 2003-07-24
PEL transitional comments 2003-12-04
PEL-STEL final 2003-12-04
Resistance of materials for PPE 2004-04-05
Bibliography 2004-04-05
Relative density 2006-09-28



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