Nitric Oxide

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

H280 (87.4%): Contains gas under pressure; may explode if heated [Warning Gases under pressure]

H314 (100%): Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]

H318 (37.5%): Causes serious eye damage [Danger Serious eye damage/eye irritation]

H330 (87.4%): Fatal if inhaled [Danger Acute toxicity, inhalation]

H331 (12.6%): Toxic if inhaled [Danger Acute toxicity, inhalation]

H373 (34.6%): May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

P220, P244, P260, P261, P264, P264+P265, P271, P280, P284, P301+P330+P331, P302+P361+P354, P304+P340, P305+P354+P338, P316, P317, P319, P320, P321, P363, P370+P376, P403, P403+P233, P405, P410+P403, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 301 reports by companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

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

H280: Contains gas under pressure; may explode if heated [Warning Gases under pressure]

H330: Fatal if inhaled [Danger Acute toxicity, inhalation]

H370: Causes damage to organs [Danger Specific target organ toxicity, single exposure]

P220, P244, P260, P264, P270, P271, P284, P304+P340, P308+P316, P316, P320, P321, P370+P376, P403, P403+P233, P405, P410+P403, and P501 (click each P-code to see the statement)

H331: Toxic if inhaled [Danger Acute toxicity, inhalation]

P220, P244, P260, P261, P264, P270, P271, P304+P340, P308+P316, P316, P321, P370+P376, P403, P403+P233, P405, P410+P403, and P501 (click each P-code to see the statement)

Fresh air, rest.

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

Warning: Can cause permanent injury after very short exposure to small quantities. Delayed pulmonary edema can occur even following minimal early symptoms. Caution is advised.

Signs and Symptoms of Nitric Oxide Exposure: Acute exposure to nitric oxide may result in changes of the pulmonary system including pulmonary edema, pneumonitis, bronchitis, bronchiolitis and emphysema. Mild or violent coughing, hyperpnea (rapid, deep breathing), and dyspnea (difficult or labored breathing) may occur. Fatigue, drowsiness, restlessness, anxiety, mental confusion, nausea and abdominal pain may be seen. Also weak rapid pulse, dilated heart, circulatory collapse, and loss of consciousness may be noted.

Emergency Life-Support Procedures: Acute exposure to nitric oxide may require decontamination and life support for the victims. Emergency personnel should wear protective clothing appropriate to the type and degree of contamination. Air-purifying or supplied-air respiratory equipment should also be worn, as necessary. Rescue vehicles should carry supplies such as plastic sheeting and disposable plastic bags to assist in preventing spread of contamination.

Inhalation Exposure:

1. Move victims to fresh air. Emergency personnel should avoid self-exposure to nitric oxide.

2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer 100% humidified oxygen or other respiratory support.

3. Obtain authorization and/or further instructions from the local hospital for performance of other invasive procedures.

4. Rush to a health care facility.

Dermal/Eye Exposure:

1. Remove victims from exposure. Emergency personnel should avoid self-exposure to nitric oxide.

3. If eye exposure has occurred, eyes must be flushed with lukewarm water for at least 15 minutes.

4. Obtain authorization and/or further instructions from the local hospital for performance of other invasive procedures.

5. Rush to a health care facility.

Ingestion Exposure:

Note: Ingestion of nitric oxide gas is not expected to be a significant route of exposure.

1. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer 100% humidified oxygen or other respiratory support.

2. Obtain authorization and/or further instructions from the local hospital for performance of other invasive procedures.

3. Rush to a health care facility. (EPA, 1998)

General First Aid:

· Call 911 or emergency medical service.

· Ensure that medical personnel are aware of the material(s) involved, take precautions to protect themselves and avoid contamination.

· Move victim to fresh air if it can be done safely.

· Administer oxygen if breathing is difficult.

· If victim is not breathing:

-- DO NOT perform mouth-to-mouth resuscitation; the victim may have ingested or inhaled the substance.

-- If equipped and pulse detected, wash face and mouth, then give artificial respiration using a proper respiratory medical device (bag-valve mask, pocket mask equipped with a one-way valve or other device).

-- If no pulse detected or no respiratory medical device available, provide continuous compressions. Conduct a pulse check every two minutes or monitor for any signs of spontaneous respirations.

· Remove and isolate contaminated clothing and shoes.

· For minor skin contact, avoid spreading material on unaffected skin.

· In case of contact with substance, remove immediately by flushing skin or eyes with running water for at least 20 minutes.

· For severe burns, immediate medical attention is required.

· Effects of exposure (inhalation, ingestion, or skin contact) to substance may be delayed.

· Keep victim calm and warm.

· Keep victim under observation.

· For further assistance, contact your local Poison Control Center.

· Note: Basic Life Support (BLS) and Advanced Life Support (ALS) should be done by trained professionals.

Specific First Aid:

· Clothing frozen to the skin should be thawed before being removed.

Wear positive pressure breathing apparatus and full protective clothing. Move container from fire area if you can do so without risk. Stay away from ends of tanks. Spray cooling water on containers that are exposed to flames until well after fire is out. For massive fire in cargo area, use unmanned hose holder or monitor nozzles; if this is impossible, withdraw from area and let fire burn.

For small fires, use dry chemical or carbon dioxide. For large fires, use water spray, fog, or foam. (EPA, 1998)

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

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

· Keep unauthorized personnel away.

· Stay upwind, uphill and/or upstream.

· Many gases are heavier than air and will spread along the ground and collect in low or confined areas (sewers, basements, tanks, etc.).

· Ventilate closed spaces before entering, but only if properly trained and equipped.

· Do not touch or walk through spilled material.

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

· Stop leak if you can do it without risk.

· Use water spray to reduce vapors or divert vapor cloud drift. Avoid allowing water runoff to contact spilled material.

· Do not direct water at spill or source of leak.

· If possible, turn leaking containers so that gas escapes rather than liquid.

· Prevent entry into waterways, sewers, basements or confined areas.

· Isolate area until gas has dispersed.

· Ventilate the area.

Excerpt from ERG Guide 124 [Gases - Toxic and/or Corrosive - Oxidizing]:

IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area for at least 100 meters (330 feet) in all directions.

SPILL: See ERG Table 1 - Initial Isolation and Protective Action Distances on the UN/NA 1660 datasheet.

FIRE: If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2024)

Immediate precautionary measure

· Isolate spill or leak area for at least 100 meters (330 feet) in all directions.

· See Table 1 - Initial Isolation and Protective Action Distances.

· If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions.

Small spill:

- ISOLATE in all directions: 30 m (100 ft)

Large spill:

- ISOLATE in all directions: 100 m (300 ft)

- PROTECT people from downwind during DAY time: 0.1 km (0.1 mi)

- PROTECT people from downwind during NIGHT time: 0.6 km (0.4 mi)

- PROTECT people from downwind during DAY time: 0.6 km (0.4 mi)

- PROTECT people from downwind during NIGHT time: 2.2 km (1.4 mi)

Personal protection: gas-tight chemical protection suit including self-contained breathing apparatus. Shut off cylinder if possible. Isolate the area until the gas has dispersed.

1) VENTILATE AREA OF LEAK OR RELEASE TO DISPERSE GAS. 2) STOP FLOW OF GAS. IF SOURCE ... IS CYLINDER & LEAK CANNOT BE STOPPED IN PLACE, REMOVE ... CYLINDER TO SAFE PLACE IN OPEN AIR, & REPAIR LEAK OR ALLOW ... TO EMPTY.

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number P076, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

Nitric oxide is a poor candidate for incineration.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emmissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants.

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

Excerpt from ERG Guide 124 [Gases - Toxic and/or Corrosive - Oxidizing]:

Do not touch or walk through spilled material. Keep combustibles (wood, paper, oil, etc.) away from spilled material. Stop leak if you can do it without risk. Use water spray to reduce vapors or divert vapor cloud drift. Avoid allowing water runoff to contact spilled material. Do not direct water at spill or source of leak. If possible, turn leaking containers so that gas escapes rather than liquid. Prevent entry into waterways, sewers, basements or confined areas. Isolate area until gas has dispersed. Ventilate the area. (ERG, 2024)

Fireproof if in building. Keep in a well-ventilated room.

IN GENERAL, MATERIALS WHICH ARE TOXIC AS STORED OR WHICH CAN DECOMP INTO TOXIC COMPONENTS ... SHOULD BE STORED IN A COOL, WELL-VENTILATED PLACE, OUT OF DIRECT RAYS OF SUN, AWAY FROM AREAS OF HIGH FIRE HAZARD, & SHOULD BE PERIODICALLY INSPECTED ... INCOMPATIBLE MATERIALS SHOULD BE ISOLATED ... .

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

· Wear chemical protective clothing that is specifically recommended by the manufacturer when there is NO RISK OF FIRE.

· Structural firefighters' protective clothing provides thermal protection but only limited chemical protection.

Biological Exposure Indices (BEI) [ACGIH] - Methemoglobin in blood = 1.5% of hemoglobin during or at end of shift. [ACGIH]

TIH (Toxic Inhalation Hazard) - Term used to describe gases and volatile liquids that are toxic when inhaled. Some are TIH materials themselves, e.g., chlorine, and some release TIH gases when spilled in water, e.g., chlorosilanes. [ERG 2016].

0.5 [ppm]

AEGL 1: Notable discomfort, irritation, or certain asymptomatic non-sensory effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure (Unit: ppm)

AEGL 2: Irreversible or other serious, long-lasting adverse health effects or an impaired ability to escape (Unit: ppm)

AEGL 3: Life-threatening health effects or death (Unit: ppm)

NR = Not recommended due to insufficient data Short-term exposures to below 80 ppm NO should not constitute a health hazard * AEGL values for nitrogen dioxide should be used for emergency planning.

AEGLs Status: Final

0.50 [ppm]

12 [ppm]

20 [ppm]

25 ppm (30 mg/m³)

TWA 25 ppm (30 mg/m3)

25.0 [ppm]

100 ppm (NIOSH, 2024)

100.0 [ppm]

Excerpts from Documentation for IDLHs: Other animal data: Guinea pigs have survived an exposure at 175 ppm for an unstated period [Bodansky 1951]. . . . Human data: It has been stated that exposures to oxides of nitrogen between 100 and 150 ppm are dangerous for exposures of 30 to 60 minutes [Sax 1975].

See: 10102439

8 hr Time Weighted Avg (TWA): 25 ppm.

Excursion Limit Recommendation: Excursions in worker exposure levels may exceed 3 times the TLV-TWA for no more than a total of 30 minutes during a work day, and under no circumstances should they exceed 5 times the TLV-TWA, provided that the TLV-TWA is not exceeded.

Biological Exposure Index (BEI): Determinant: methemoglobin in blood; Sampling Time: during or end of shift; BEI: 1.5% of hemoglobin. The determinant may be present in biological specimens collected from subjects who have not been occupationally exposed, at a concentration which could affect interpretation of the result. Such background concentrations are incorporated in the BEI value. The determinant is nonspecific, since it is also observed after exposure to other chemicals. The biological determinant is an indicator of exposure to the chemical, but the quantitative interpretation of the measurement is ambiguous. These determinants should be used as a screening test if a quantitative test is not practical or as a confirmatory test if the quantitative test is not specific and the origin of the determinant is in question. /Methemoglobin inducers/

25 ppm as TWA; BEI issued.

25 ppm [1992]

2.5 mg/m

0.63 mg/m

CAUTION: These materials do not burn but will support combustion. Some will react violently with water.

Small Fire

· Contain fire and let burn. If fire must be fought, water spray or fog is recommended.

· Water only; no dry chemical, CO2 or Halon®.

· Do not get water inside containers.

· If it can be done safely, move undamaged containers away from the area around the fire.

· Damaged cylinders should be handled only by specialists.

Fire Involving Tanks

· Fight fire from maximum distance or use unmanned master stream devices or monitor nozzles.

· Cool containers with flooding quantities of water until well after fire is out.

· Do not direct water at source of leak or safety devices; icing may occur.

· Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank.

Nitric oxide appears as a colorless gas. Noncombustible but accelerates the burning of combustible material. Vapors heavier than air. Very toxic by inhalation and skin absorption. Heating the containers may cause them to rupture violently and rocket.

Colorless gas. (Note: Shipped as a nonliquefied compressed gas.) [NIOSH] NO is converted to NO2 spontaneously in air. [ACGIH]

COLOURLESS COMPRESSED GAS.

Colorless gas.

Colorless gas. [Note: Shipped as a nonliquefied compressed gas.]

COLORLESS GAS; BLUE LIQ

BLUISH-WHITE SNOW WHEN SOLID

Brown at high concn in air

Sharp, sweet odor

-241.1 °F at 760 mmHg (EPA, 1998)

-151.74 °C

-151.8 °C

-151.74 °C @760 [mm Hg]

-262.5 °F (EPA, 1998)

-163.6 °C

-163.3 °C

5 % (NIOSH, 2024)

7.38 ml/ 100 ml water at 0 °C; 4.6 ml/ 100 ml water at 20 °C; 2.37 ml/ 100 ml water at 60 °C

3.4 CC/100 CC SULFURIC ACID

26.6 CC/100 CC ALCOHOL

SOL IN CARBON DISULFIDE, IRON SULFATE

Solubility in water, ml/100ml at 0 °C: 7.4

1.27 at -238.36 °F (EPA, 1998) - Denser than water; will sink

1.27 AT -150.2 °C, LIQ

1.27 at -238.36 °

1.226 @25 °C

1.04(relative gas density)

1.04 (EPA, 1998) - Heavier than air; will sink (Relative to Air)

1.04 (AIR= 1)

Relative vapor density (air = 1): 1.04

26000 mmHg at 68 °F (EPA, 1998)

45600 MM HG AT -94.8 °C

34.2 atm

750 [mm Hg] @-151.9 °C

WHEN HEATED TO DECOMP, IT EMITS HIGHLY TOXIC FUMES OF /NITROGEN OXIDES/ ... .

0.0188 cP at 25 °C @ 101.325 KPa (gas)

3.293 KCAL/MOLE

Odor Threshold Low: 0.29 [ppm]

Odor Threshold High: 0.97 [ppm]

Odor thresholds from HSDB

Combines very rapidly with oxygen in the air to form nitrogen dioxide. Nitrogen dioxide reacts with water to form nitric acid and nitric oxide, reacts with alkalis to form nitrates and nitrites [Merck 11th ed. 1989].

Oxidizing Agents, Strong

Explosive

Strong Oxidizing Agent

Water-Reactive

Air-Reactive

CSL00025

METHANOL + NITRIC OXIDE

vapor can ignite in the presence of a spark

Flammable

ACS Safety Letters

CSL00194

Nitrous oxide + Nitric oxide + Sodium + Hydrogen + Sodium formate + Toluene

"A safety letter from Merck & Co. chemists titled “Nitric Oxide at High Pressure” (C&EN, Jan. 30, page 6) described two explosions during depressurization of a reaction between NO and methanol under basic conditions. The products in a model system with sodium methoxide were described as nitrous oxide and formic acid, presumably as sodium formate. A potential danger in this system should be pointed out: Sodium formate undergoes thermal decomposition to give hydrogen gas (J. Am. Chem. Soc.,DOI: 10.1021/ja02245a004), which explodes spontaneously in the presence of nitrous oxide above critical limits (J. Am. Chem. Soc., DOI: 10.1021/ja01179a036), even in the absence of a catalyst or source of ignition. The presence of hydrogen and nitrous oxide above a reaction mixture was undoubtedly the cause of an explosion and fire in my laboratory in 1981 during workup of a reaction between sodium and nitric oxide. The major product of the reaction is cis-sodium hyponitrite, which decomposes immediately in water to form sodium hydroxide and nitrous oxide. The employee, a biology major who was badly burned, had carried out the reaction a number of times without incident. This time he tried twice and failed to disperse about 30 g of sodium in toluene and, without consulting me, decided to continue the reaction. The explosion occurred as he was attempting to destroy the unreacted sodium, a lump too large to remove from the flask, by dropwise addition of water. Most of the sodium had reacted at the time of the explosion, and there was no indication of mechanical failure. At the time, I was unaware of the extreme incompatibility of the two gases, and the accident was extremely puzzling. The reaction mixture was close to room temperature and was stirred rapidly while the headspace was flushed with a stream of nitrogen. When I arrived at the laboratory a few minutes after the accident, nitrogen was still flowing from the burned-off end of the plastic tubing. Since that time, I noticed a reference to the “hydrogen explosion” in the ancient chemical literature as a way to identify nitrous oxide." (reprint of the full-text)

Medium (up to 100g)

10.1021/cen-09013-letters

Literature Reference

10/15/2022

10/14/2022

CSL00200

Nitric oxide + Nitrous oxide + Methanol

"Chemists at Merck & Co. were performing experiments using nitric oxide at high pressure (10–20 bar) when two instances of an explosion occurred during rapid depressurization of the NO headspace from a 500-mL closed reactor system. No injuries occurred, and damage was contained to the barricaded cell area. Both before and in between these events, NO had been used successfully about 100 times. Each explosion occurred after completion of the reaction, while venting through three-eighths- or one-quarter-inch i.d. Teflon-lined steel-braided tubing to atmospheric pressure. Static electricity was suspected as the ignition source that, in conjunction with the presence of an oxidant (NO) and fuel (CH3OH), would lead to combustion. To confirm this hypothesis, an investigation was conducted. Preliminary results are communicated here. The reaction system consisted of NO in conjunction with methanol under basic conditions. A literature search didn’t point to any existing cautionary notes about this reaction. Experimental ignition testing of NO systems was conducted by Fauske & Associates, which showed no combustion unless ignition energy greater than 3 J was used. This exceeds the energy typical of a static discharge, so it does not fully explain the observed combustion. Further analysis of the reaction headspace using gas chromatography/mass spectrometry revealed that N2O was formed over time from a simple model system of NO + sodium methoxide + methanol. The conversion of NO to N2O and concomitant oxidation of methanol to formic acid proceeds to 50% in about six hours. Testing showed the energy needed to ignite the headspace of methanol under 1 bar of 50/50 NO/N2O is less than 3 mJ, several orders of magnitude lower than for similar systems without N2O. On the basis of these results, the likely cause of the explosions is the combination of (a) formation of N2O gas and (b) generation of static potential caused by the rapid flow of gas and condensing methanol through the Teflon-lined tubing during rapid depressurization (while venting), which leads to sparking of sufficient energy to cause the combustible vapor to ignite. We wanted to alert the chemical process industry to risks associated with this particular procedure. Anyone contemplating use of this chemistry should thoroughly evaluate its safety. " (reprint of full text)

10.1021/cen-09005-letters

10/19/2022

NITRIC OXIDE can serve as both an oxidizing agent and as a reducing agent. Sustains the combustion of powdered aluminum [Mellor 5:209-212. 1946-47]. Enflames or explodes when mixed with vapors of carbon disulfide [Mellor 8, Supp. 2:232. 1967]. Reacts vigorously with sodium monoxide above 100 °C [Mellor 2, Supp. 2:629. 1961]. Reacts on contact with oxygen at room temperature to form brown gaseous nitrogen dioxide. Reacts with alkalis to form nitrates and nitrites [Merck 11th ed. 1989]. The liquid is very sensitive to detonation in the presence of water.

WILL REACT WITH WATER OR STEAM TO PRODUCE HEAT & CORROSIVE FUMES

CAN REACT VIGOROUSLY WITH REDUCING MATERIALS

Fluorine, combustible materials, ozone, ammonia, chlorinated hydrocarbons, metals, carbon disulfide [Note: Reacts with water to form nitric acid. Rapidly converted in air to nitrogen dioxide].

NITRIC OXIDE & CARBON DISULFIDE REACT EXPLOSIVELY WITH EMISSION OF LIGHT; MIXTURE OF NITRIC OXIDE & CHLORINE MONOXIDE CAN BE EXPLOSIVE; NITROGEN TRICHLORIDE EXPLODES ON CONTACT WITH NITRIC OXIDE; MIXTURES OF NITRIC OXIDE & OZONE EXPLODE EVEN WHEN QUANTITY OF OZONE IS SMALL.

For more Hazardous Reactivities and Incompatibilities (Complete) data for NITRIC OXIDE (10 total), please visit the HSDB record page.

Fluorine, combustible materials, ozone, NH3, chlorinated hydrocarbons, metals, carbon disulfide [Note: Reacts with water to form nitric acid. Rapidly converted in air to nitrogen dioxide.]

IDENTIFICATION: Nitric oxide is a colorless, odorless gas that is only slightly soluble in water. The main sources of nitrogen oxides (including nitric oxide) emissions are combustion processes. Fossil fuel power stations, motor vehicles and domestic combustion appliances emit nitrogen oxides, mostly in the form of nitric oxide. Nitric oxide can be present at significant concentrations in ambient air and in indoor air. HUMAN EXPOSURE: Human exposure to nitrogen oxides varies from indoors to outdoors, from cities to the countryside, and with the time of day and season. Nitric oxide is readily oxidized to nitrogen dioxide and peroxidation then occurs. Because of the concurrent exposure to some nitrogen dioxide in nitric oxide exposures, it is difficult to discriminate nitric oxide effects from nitrogen dioxide. Nitric oxide functions as an intracellular second messenger modulating a wide variety of essential enzymes, and it inhibits its own production (e.g., negative feedback). Nitric oxide activates guanylate cyclase which in turn increases intracellular cGMP levels. Nitric oxide is acknowledged as an important endogenous second messenger within several organ systems. At certain levels, inhaled nitric oxide concentrations can cause vasodilation in the pulmonary circulation without affecting the systemic circulation. The lowest effective concentration is not established. Information on pulmonary function and lung host defenses consequent to nitric oxide exposure are too limited for any conclusions to be drawn. Relatively high concentrations have been used in clinical applications for brief periods without reported adverse effects. ANIMAL STUDIES: The toxicological database for nitric oxide is small, relative to nitrogen dioxide. It is often difficult to obtain pure nitric oxide in air without some contamination with nitrogen dioxide. Endogenous nitric oxide synthesis occurs by nitric oxide formation from physiological substrate in cells of many of the organ systems such as nerve tissue, blood vessels and the immune system. Nitric oxide may be more potent than nitrogen dioxide in introducing certain changes in lung morphology. In a study examining the effects of nitric oxide on bacterial defenses, there were no statistically significant effects for either sex at any of the time points studied. In vitro data indicate that nitric oxide stimulates guanylate cyclase and leads to smooth muscle relaxation and vasodilation and functional effects on the nervous system. These effects are probably responsible for vasodilation in the pulmonary circulation and an acute bronchodilator effect of inhaled nitric oxide. Nitric oxide has an affinity for haem-bound iron which is two times higher than that of carbon monoxide. This affinity leads to the formation of methaemoglobin and the stimulation of guanylate cyclase. Furthermore, nitric oxide reacts with thiol-associated iron in enzymes and eventually displaces the iron. This is a possible mechanism for the cytotoxic effects of nitric oxide. Nitric oxide can deaminate DNA, evoke DNA chain breaks, and inhibit DNA polymerase and ribonucleotide reductase. It might be antimitogenic and inhibit T cell proliferation in rat spleen cells.

In animal primary neuronal cell cultures, excess nitric oxide is partially responsible for glutamate neurotoxicity. These glutamate derangements affect neurodegenerative disorders, including stroke, epilepsy, Alzheimer's disease, amyotrophic lateral sclerosis, and Huntington's disease. However, it is more likely that these neurotoxic mechanisms are subject to mediation through peroxynitrite, the product of an NO and superoxide anion reaction. Peroxynitrite and excess oxygen free radicals can be generated from severe cellular damage and cross the blood-brain barrier as lipid-soluble products accumulate within neuronal tissue. The newer FDA-approved iNO delivery system limits the toxicity of nitric oxide by delivering a controlled level of nitric oxide with oxygen.

Nitric oxide

◉ Summary of Use during Lactation

No information is available on breastfeeding during the therapeutic use of nitric oxide by inhalation. Nitric oxide has a half-life of only a few seconds, so exogenously administered nitric oxide cannot reach the breastmilk. Nitric oxide is metabolized to methemoglobin and nitrate, which are present in the maternal systemic circulation. Although maternal nitrate serum levels may be elevated during nitric oxide administration, this does not result in elevated breastmilk nitrate levels. Both nitric oxide and nitrate are normal components of human milk, and nitric oxide is administered directly to newborns by inhalation to treat respiratory failure. Given the above, it appears to be acceptable to breastfeed during maternal nitric oxide inhalation therapy.

◉ Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

◉ Effects on Lactation and Breastmilk

Nitric oxide produced locally in the breast may have a role in the letdown reflex at the initiation of lactation. It results in high concentrations of nitrates and nitrites in breastmilk just prior to an increase in milk production. Nitric oxide may also be involved with nipple erection.

The substance can be absorbed into the body by inhalation.

inhalation

Cough. Shortness of breath.

Redness.

irritation eyes, wet skin, nose, throat; drowsiness, unconsciousness; methemoglobinemia

Eyes, skin, respiratory system, blood, central nervous system

Methemoglobinemia - The presence of increased methemoglobin in the blood; the compound is classified as secondary toxic effect

Toxic Pneumonitis - Inflammation of the lungs induced by inhalation of metal fumes or toxic gases and vapors.

iNO's adverse effects are primarily dose-dependent, and the recommended limit for clinical use is 20 ppm for up to 14 days in a preterm infant. However, even low doses may exert cellular toxicity. Infants who received iNO and ventilation for PPHN for 1 to 4 days showed nitrotyrosine residues within their lungs, indicating potential long-term pulmonary complications. Clinical doses of iNO have also exhibited adverse effects. Infants weaning from nitric oxide, when it was withdrawn rapidly, suffered from severe rebound pulmonary vasospasm, most likely due to the actions of exogenous nitric oxide downregulating nitric oxide synthase activity.

NO can also rapidly interact with other atoms or anions to facilitate damage. It can combine with oxygen in the lungs to form nitrogen dioxide, a potent pulmonary irritant. Additionally, it can interact with a superoxide anion to form peroxynitrite. Peroxynitrite is cytogenic and can disrupt surfactant functioning within the lungs.

Clinical adverse effects of iNO include the following:

* Worsening heart failure

* Hypotension

* Pulmonary vasospasm

* Methemoglobinemia: The risk of methemoglobinemia increases with the simultaneous use of the eutectic mixture of local anesthetics. (EMLA-Lidocaine/Prilocaine)

LC50 (rat) = 1,068 mg/m3/4H

Nitric oxide (NO) is produced both by macrophages in vivo as a physiological response to infection and by a variety of cell types as an intercellular messenger. In addition, NO and nitrogen dioxide (NO2) are significant components of many combustion processes. The ubiquitous exposure of humans to nitrogen oxides (NOx), both endogenously and exogenously, may play a significant role in the carcinogenic process due to nitrosation of amines by NOx. We report here that exposure to low concentrations of NO, alone or in combination with NO2, results in significantly enhanced mutation in Salmonella typhimurium TA1535 using a modified Ames Salmonella reversion assay. The observed mutagenicity requires that the bacteria be actively dividing at the time of exposure to NO or NO2, suggesting that the nitrogen oxides, or their reaction products, function as direct-acting mutagens and that the induced lesion is easily repairable by non-dividing cells. Exposure to NO resulted in a time- and dose-dependent increase in the number of revertants approximately proportional to the square of the NO concentration from 0 to 20 ppm. NO was a more effective mutagen relative to NO2, however, the observed requirement for O2 suggests limited oxidation of NO (presumably to NO2) is necessary. Numerous lipid- and aqueous-phase inhibitors of nitrosation, as well as a number of other general antioxidants and free-radical trapping agents, were examined for their effectiveness in blocking the mutagenic effects of NO. The mutagenic activity of NO was most effectively inhibited by beta-carotene and tocopherols. BHT, dimethyl sulfoxide and mannitol also blocked the mutagenic effects of NOx but appeared less effective than beta-carotene or vitamin E, while ascorbate was ineffective as an inhibitor of mutation resulting from NO exposure.

... THE MECHANISM OF NITRIC OXIDE INTOXICATION SUGGESTS THAT IN MIXTURES WITH CARBON MONOXIDE, AS WELL AS NITROGEN DIOXIDE, ADDITIVE EFFECTS SHOULD BE ASSUMED.

The effects of nitric oxide (NO) and carbon monoxide on discrimination learning and brain activity were studied in rats. Male Long-Evans rats surgically instrumented with prefrontal and parietal electroencephalographic electrodes were exposed to 0, 100, or 500 ppm carbon monoxide or 10 or 50 ppm NO alone or in combination for 180 min. Effects on behavior (lever press task) and response to auditory stimulation were examined. Response to auditory stimulation was assessed by recording auditory evoked potentials. At the end of exposure, the rats were killed and blood carboxyhemoglobin and methemoglobin were determined. There was no significant difference between blood auditory evoked potential concn after exposure to 100 or 500 ppm carbon monoxide or 100 or 500 ppm carbon monoxide plus 10 or 50 ppm NO. Methemoglobin concn were significantly higher after exposure to 10 ppm NO plus 100 ppm carbon monoxide than after 10 ppm NO alone. Exposure to 50 ppm NO reduced the number of correct trials and the total number of lever presses significantly. Exposure to 500 ppm carbon monoxide decr the number of correct trials nonsignificantly and the total number of lever presses significantly. Combined carbon monoxide and NO exposure caused synergistic decr in number of correct trials and total number of trials. Carbon monoxide or NO caused increased amplitudes and prolonged latencies in early auditory evoked potential peaks. NO prolonged the latency of late auditory evoked potential peaks. Carbon monoxide incr the amplitude of the N150 peak, whereas NO decr its amplitude. The 10 ppm NO plus 100 ppm carbon monoxide exposure induced a combination effect that was less than additive. The 50 ppm NO plus 500 ppm carbon monoxide exposure induced an additive or synergistic effect on auditory evoked potential peak response. /It was concluded/ that NO plays a dominant role during intoxication with NO and carbon monoxide.

It as shown that preincubation of pancreatic islet cells with alpha-tocopherol significantly improves their resistance to toxic doses of nitric oxide. No protection was afforded by other antioxidants such as vitamin C or glutathione-monoethyl ester. The pathway of NO induced islet cell death involves DNA damage and excessive activation of poly(ADP-ribose)polymerase leading to irreversible depletion of intracellular NAD+. alpha-Tocopherol was found to interfere at early steps of this pathway, by preventing the occurrence of DNA strand breaks. This indicates that alpha-tocopherol directly interacts with nitric oxide or its reactive intermediates. Alpha-tocopherol is not only part of the cellular defence system against oxygen radicals but also protects eukaryotic cells from nitric oxide toxicity.

Basic treatment: Establish a patent airway. Suction if necessary. Aggressive airway management may be needed. Encourage patient to take deep breaths. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuosly with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. ... /Nitrogen oxides (NOX) and related compounds/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or in respiratory arrest. Early intubation at the first signs of upper airway obstruction may be necessary. Positive-pressure ventilation techniques with a bag-valve-mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W TKO /SRP: "To keep open", minimal flow rate/. Consider drug therapy for pulmonary edema ... . Consider the use of vasopressors to treat hypotension without signs of hypovolemia ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen. ... . Use proparacaine hydrochloride to assist eye irrigation. /Nitrogen oxides (NOX) and related compounds/

Consider the points of attack, /respiratory system, lung/ in preplacement and periodic physical examination.

CHIEF TOXIC EFFECT ... ASCRIBED TO FORMATION OF METHEMOGLOBIN & SUBSEQUENT ACTION ON CNS.

SYMPTOMATOLOGY: 1. Usually no symptoms occur at the time of exposure, with the exception of a slight cough and perhaps fatigue and nausea. Exposure to low concn may result in impaired pulmonary defense mechanisms (macrophages, cilia) with complications. ... 2. Only very concn nitrous fumes produce prompt coughing, choking, headache, nausea, abdominal pain, and dyspnea (tightness and burning pain in the chest). 3. A symptom-free period follows exposure and lasts for 5-72 hr. 4. Fatigue, uneasiness, restlessness, cough, hyperpnea, and dyspnea appear insidiously, as the adult respiratory distress syndrome gradually develops. /Nitrogen oxides/

SYMPTOMATOLOGY: 5. Increasingly rapid and shallow respirations, cyanosis, mild or violent coughing with frothy expectoration and physical signs of pulmonary edema (for example rales and rhonchi). The vital capacity is rapidly reduced. A serous exudate may develop in the pleural cavity, but its volume is usually small. 6. Anxiety, mental confusion, lethary and finally loss of consciousness. 7. A weak, rapid pulse, dilated heart, venous congestion, intense cyanosis and severe hemoconcentration. Circulatory collapse is secondary to anoxia and hemoconcentration. 8. An asphyxial death due to blockade of gas exchange in the lungs. Death commonly occurs within a few hours after the first evidence of pulmonary edema. /Nitrogen oxides/

SYMPTOMATOLOGY: 9. Sometimes a second acute phase follows the initial pulmonary reaction after a quiescent period of several weeks. Cough, tachypnea, dyspnea, fever, tachycardia and cyanosis at this stage are usually due to bronchiolitis obliterans. The relapse may be abrupt and fulminating, leading either to death or a slow convalescence. 10. In nonfatal cases, convalescence may be complicated by infectious bronchitis, bronchiolitis obliterans, pneumonia and general asthenia. Rarely diffuse pulmonary fibrosis may develop. /Nitrogen oxides/

For more Human Toxicity Excerpts (Complete) data for NITRIC OXIDE (11 total), please visit the HSDB record page.

... /IT/ IS ABOUT 1/5 AN ACUTE TOXIC AS NITROGEN DIOXIDE, ASSUMING MINIMAL CONTAMINATION WITH NO2 & ... NO SYNERGISTIC ACTION.

ANIMAL STUDIES ... CITED IN WHICH 322 PPM ... PRODUCED 60% METHEMOGLOBINEMIA AFTER 6 HR.

... EMPHYSEMATOUS LESIONS IN MICE EXPOSED TO 10 PPM OF NITROGEN DIOXIDE FOR 2 HR/DAY, 5 DAYS/WK FOR VARIOUS PERIODS UP TO 30 WEEKS. ... MICE SIMILARLY EXPOSED TO 10 PPM OF NITRIC OXIDE SHOWED MUCH MORE PRONOUNCED EMPHYSEMATOUS CHANGES.

MAIN SOURCE OF URBAN NITRIC OXIDE ... IS COMBUSTION OF FOSSIL FUELS. ESCAPE OF ... GASES FROM INDUSTRIAL PROCESSES WHERE NITRIC OXIDE IS MADE OR USED, OR FROM FERTILIZER OR EXPLOSIVE FACTORIES, CAN BE IMPORTANT IN LOCAL AREA & IN PLANTS THEMSELVES. IN GENERAL, HIGHER COMBUSTION TEMP YIELD MORE NITROGEN OXIDES.

IN MOST URBAN AREAS THE CAR IS SINGLE LARGEST PRODUCER OF NITRIC OXIDE, WHICH MOVES SO RAPIDLY FROM ENGINE CYLINDER TO COOLER EXHAUST PIPES THAT IT IS PREVENTED FROM DECOMP ...

Volatile organics and nitrogen oxides are emitted by transportation and industrial sources. Oxides of nitrogen are emitted in the combustion of fossil fuels. /Nitrogen oxides/

... RELEASED IN REACTION BETWEEN NITRIC ACID & ANY ORG MATERIAL; IN EXHAUST FROM METAL CLEANING ... FROM ELECTRIC ARC WELDING; IN ELECTROPLATING, ENGRAVING, & PHOTOGRAVURE OPERATIONS; IN DYNAMITE BLASTING ... IN DIESEL ENGINE EXHAUST; IN BURNING OF NITROCELLULOSE ... & IN COMBUSTION OF SOME SHOE POLISHES. /NITROGEN OXIDES/

NITRIC OXIDE IS CONVERTED SPONTANEOUSLY IN AIR TO NITROGEN DIOXIDE, HENCE SOME OF LATTER GAS IS INVARIABLY PRESENT WHENEVER NITRIC OXIDE IS FOUND IN AIR. AT CONCN BELOW 50 PPM ... THIS REACTION IS SLOW ... & FREQUENTLY SUBSTANTIAL CONCN ... MAY OCCUR WITH NEGLIGIBLE QUANTITIES OF NITROGEN DIOXIDE ... .

PHOTOCHEMICAL AIR POLLUTION ARISES FROM A SERIES OF ATMOSPHERIC REACTIONS. THE MAIN COMPONENTS ARE OZONE, OXIDES OF NITROGEN, ALDEHYDES, PEROXYACETYL NITRATES, AND HYDROCARBONS. ... THEY ENTER INTO THE CHEMICAL REACTIONS THAT LEAD TO FORMATION OF PHOTOCHEMICAL SMOG. /OXIDES OF NITROGEN/

IN TERMS OF AMT OF MATERIAL EMITTED ANNUALLY INTO AIR, FIVE MAJOR POLLUTANTS ACCOUNT FOR CLOSE TO 98% OF POLLUTION. ... NITROGEN OXIDES (6%). /NITROGEN OXIDES/

INDUSTRIAL EXPOSURES CAN TAKE PLACE WHEREVER NITRIC ACID IS MADE OR USED & HAS OCCURRED MOST COMMONLY WHERE METALS ARE DIPPED IN ACID BATHS. ELECTRIC ARC WELDING, & TO LESSER EXTENT GAS WELDING, CAN GENERATE HAZARDOUS CONCN. FERMENTATION OF SILAGE PRODUCES HIGH CONCN, & POISONINGS OF FARMERS HAVE OCCURRED.

APPROX 1.5 MILLION USA WORKERS ARE EXPOSED DIRECTLY OR INDIRECTLY TO OXIDES OF NITROGEN (NITRIC OXIDE, NITROGEN DIOXIDE, NITRIC ACID) THROUGH OCCUPATIONS INVOLVING WELDING, SILO FILLING & EXPLOSIVE MANUFACTURE. /FROM TABLE/

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number P076, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

Nitric oxide is a poor candidate for incineration.

/GUIDE 124: GASES - TOXIC AND/OR CORROSIVE - OXIDIZING/ Health: TOXIC; may be fatal if inhaled or absorbed through skin. Fire will produce irritating, corrosive and/or toxic gases. Contact with gas or liquefied gas may cause burns, severe injury and/or frostbite. Runoff from fire control may cause pollution. /Nitric oxide; Nitric oxide, compressed/

/GUIDE 124: GASES - TOXIC AND/OR CORROSIVE - OXIDIZING/ Fire or Explosion: Substance does not burn but will support combustion. Vapors from liquefied gas are initially heavier than air and spread along ground. These are strong oxidizers and will react vigorously or explosively with many materials including fuels. May ignite combustibles (wood, paper, oil, clothing, etc.). Some will react violently with air, moist air and/or water. Cylinders exposed to fire may vent and release toxic and/or corrosive gas through pressure relief devices. Containers may explode when heated. Ruptured cylinders may rocket. /Nitric oxide; Nitric oxide, compressed/

/GUIDE 124: GASES - TOXIC AND/OR CORROSIVE - OXIDIZING/ Public Safety: CALL Emergency Response Telephone Number ... . As an immediate precautionary measure, isolate spill or leak area for at least 100 meters (330 `feet) in all directions. Keep unauthorized personnel away. Stay upwind. Many gases are heavier than air and will spread along ground and collect in low or confined areas (sewers, basements, tanks). Keep out of low areas. Ventilate closed spaces before entering. /Nitric oxide; Nitric oxide, compressed/

/GUIDE 124: GASES - TOXIC AND/OR CORROSIVE - OXIDIZING/ Protective Clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible. /Nitric oxide; Nitric oxide, compressed/

For more DOT Emergency Guidelines (Complete) data for NITRIC OXIDE (8 total), please visit the HSDB record page.

UN 1660; Nitric oxide

IMO 2.0; Nitric oxide

49 203 30; Nitric oxide

No person may /transport,/ offer or accept a hazardous material for transportation in commerce unless that person is registered in conformance ... and the hazardous material is properly classed, described, packaged, marked, labeled, and in condition for shipment as required or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./

The International Air Transport Association (IATA) Dangerous Goods Regulations are published by the IATA Dangerous Goods Board pursuant to IATA Resolutions 618 and 619 and constitute a manual of industry carrier regulations to be followed by all IATA Member airlines when transporting hazardous materials.

The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals. Detailed recommendations for individual substances and a number of recommendations for good practice are included in the classes dealing with such substances. A general index of technical names has also been compiled. This index should always be consulted when attempting to locate the appropriate procedures to be used when shipping any substance or article.

Poison Gas Oxidizer Corrosive

UN Hazard Class: 2.3; UN Subsidiary Risks: 5.1 and 8