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SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 511
CCOHS Chemical Name: Nitromethane

Synonyms:
Nitrocarbol
NM

Chemical Name French: Nitrométhane
Chemical Name Spanish: Nitrometano
CAS Registry Number: 75-52-5
UN/NA Number(s): 1261
RTECS Number(s): PA9800000
EU EINECS/ELINCS Number: 200-876-6
Chemical Family: Aliphatic nitro compound / nitroalkane / mononitroalkane / nitromethane
Molecular Formula: C-H3-N-O2
Structural Formula: CH3-N(=O)-O

SECTION 2. DESCRIPTION

Appearance and Odour:
Colourless, oily liquid with a mild, fruity odour.(9,13) Some sources describe the odour as disagreeable.(10,13,15)

Odour Threshold:
3.5 ppm (method not reported) (14); 100 ppm (cited as 250 mg/m3) (method not reported) (9)

Warning Properties:
NOT RELIABLE - the reported odour thresholds are above or near the TLV. The irritation threshold is reported to be 200 ppm (500 mg/m3) which is well above the TLV.(9)

Composition/Purity:
Nitromethane is available in grades of purity of 95-99+%.(21) It may contain other nitroalkanes, such nitroethane and nitropropane, ketones, aldehydes, propionitrile and water as impurities. Nitromethane may be transported in 55 gallon drums. The drum head space must be filled with nitrogen to reduce the risk of adiabatic compression. Nitromethane can be transported in bulk when mixed with a variety of dilutants or desensitizers to make it less sensitive to shock. These desensitizers with the minimum content by weight are 1,2-butylene oxide (40%), cyclohexanone (25%), 1,4-dioxane (35%), methanol (45%), 1-nitropropane (48%), 2-nitropropane (47%) and 1,1,1-trichloroethane (50%).(16)

Uses and Occurrences:
Nitromethane is used as a chemical intermediate in the synthesis of many useful compounds, such as nitro and amino alcohols (alkanolamines), pesticides, chloropicrin (a soil fumigant), bronopol (a biocide), and ranitidine (an anti-ulcer drug). It is also used as a rocket fuel, as a component of drag racing and hobby (model) car fuels and as a military propellant; in explosive applications, particularly in shaped charges, which are often used for targeted undersea explosions and line trenching; as a stabilizer for halogenated hydrocarbons, such as 1,1,1,-trichloroethane; as a solvent for cyanoacrylate adhesives, acrylic coatings, cellulose compounds, polymers and waxes; and for cleaning electronic circuit boards.(16,18)
Nitromethane occurs in car exhaust condensate and cigarette smoke.(26)

SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
Colourless, oily liquid with a mild, fruity odour. Some sources describe the odour as disagreeable. FLAMMABLE LIQUID AND VAPOUR. Can decompose at high temperatures forming toxic gases, such as nitrogen oxides. Closed containers may rupture and explode if heated. DANGEROUSLY REACTIVE. Shock- and heat-sensitive. Heating, increased pressure, impact or extreme shock can cause an explosion. Addition of acids, bases or metal oxides may form shock sensitive mixtures. Forms very sensitive explosive metallic salts. TOXIC. May be harmful if inhaled. Vapour may cause headache, nausea, dizziness, drowsiness and confusion. May cause lung injury-effects may be delayed. POSSIBLE CANCER HAZARD - may cause cancer, based on animal information.


POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
Nitromethane readily forms high vapour concentrations at room temperatures and should be considered toxic by this route of exposure. Inhalation exposure is expected to cause respiratory irritation and central nervous system (CNS) effects, such as headache, tiredness, nausea and vomiting. There is no specific human information for nitromethane, but these effects have been seen following exposure to closely related chemicals and in animals exposed to nitromethane. Pulmonary edema (a life-threatening accumulation of fluid in the lungs) was seen in animals that died following exposure to high concentrations. The symptoms of pulmonary edema (chest pain and shortness of breath) can be delayed for up to 24 hours after exposure The irritation threshold for nitromethane is reported to be 200 ppm.(9)

Skin Contact:
Nitromethane is not expected to be irritating, based on animal information.
Animal studies indicate that nitromethane is not absorbed through the skin in harmful amounts.

Eye Contact:
Nitromethane vapour, mist or liquid is probably not irritating, based on animal information. Nitromethane is described in some sources as an eye irritant, but no details are provided.(5,12,15)

Ingestion:
Nitromethane is not expected to be very toxic, based on animal toxicity values. If ingested nitromethane may cause gastrointestinal tract irritation and CNS effects such as nausea, vomiting and diarrhea. Ingestion of nitromethane is unlikely to occur in an occupational setting.

Effects of Long-Term (Chronic) Exposure

Nervous System:
It is not possible to draw firm conclusions based on two case reports of peripheral neuropathy developing following occupational exposure to nitromethane.
Two employees exposed to nitromethane for 1-2 months by inhalation and skin contact developed severe peripheral neuropathy. The nitromethane was sprayed onto a headlight from a small spray bottle then wiped off with a rag. One employee (a 26-year old woman) initially noted weakness in her hands, legs and feet. The other employee (a 23-year old man) complained of foot numbness, and pain and swelling in both legs and feet. Both employees were subsequently diagnosed with severe peripheral neuropathy. Following removal from exposure, one employee reported significant, although not complete improvement. The other continued to show significant symptoms 8 months after exposure stopped. Airborne concentrations of nitromethane ranged from 10 to 20 ppm (8-hour time-weighted average). Other chemicals in the work environment included cyanoacrylates and methyl methacrylate. Firm conclusions cannot be drawn because of the very small number of cases and the possibility that the effects observed may have been due to other factors, including the combination of exposures in this particular work environment.(35)

Skin:
Repeated or prolonged exposure to nitromethane can dry the skin and may cause mild irritation.

Skin Sensitization:
There is not enough information available to conclude that nitromethane is an occupational sensitizer.
Allergic contact dermatitis of the hands (red, itchy, cracked and/or blistered skin) occurred in 4 women who worked with an adhesive solvent containing nitromethane (concentration not reported) for 1-2 months to more than a year. In all cases, patch tests confirmed reaction to nitromethane, and avoidance of exposure resulted in recovery. Previous history of allergies was not discussed for any of the cases.(8) Negative results were reported in one unconfirmed animal study.

Carcinogenicity:

Nitromethane is possibly carcinogenic to humans, based on animal evidence.(28) There is no human information available. Nitromethane increased the incidence of Harderian gland and lung tumours (males and females) and hepatocellular adenomas (females only) in mice exposed by inhalation. Nitromethane also increased the incidence of benign and malignant mammary gland tumours in female rats exposed by inhalation.

The International Agency for Research on Cancer (IARC) has concluded that this chemical is possibly carcinogenic to humans (Group 2B).

The American Conference of Governmental Industrial Hygienists (ACGIH) has designated this chemical as an animal carcinogen (A3).

The US National Toxicology Program (NTP) has listed this chemical as reasonably anticipated to be a human carcinogen.

Teratogenicity and Embryotoxicity:
There is no human or animal information available.

Reproductive Toxicity:
There is no human information available. Effects on some reproductive parameters (sperm motility and fertility cycle length) have been observed in rats and/or mice exposed to high concentrations by inhalation. However, firm conclusions cannot be drawn because there were no studies that evaluated reproductive outcome located.
Nitromethane has been detected in mother's milk.(21)

Mutagenicity:
No human studies have been reported. Information available from short-term tests indicates that nitromethane is not mutagenic.

Toxicologically Synergistic Materials:
There is no information available.

Potential for Accumulation:
Probably does not accumulate. Nitromethane is absorbed through the lungs and from the gastrointestinal tract. There is no evidence of sufficient absorption through the skin to cause toxic effects.(11)

SECTION 4. FIRST AID MEASURES

Inhalation:
This product is flammable and a possible carcinogen. Take proper precautions to ensure your own safety before attempting rescue (e.g. wear appropriate protective equipment and remove any sources of ignition). 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. Obtain medical advice immediately.

Skin Contact:
Avoid direct contact. Wear chemical protective clothing, if necessary. As quickly as possible, flush with lukewarm, gently flowing water for at least 5 minutes or until the chemical is removed. Under running water, remove contaminated clothing, shoes and leather goods (e.g. watchbands, belts). Obtain medical advice immediately. Completely decontaminate clothing, shoes and leather goods before re-use or discard.

Eye Contact:
Avoid direct contact. Wear chemical protective gloves, if necessary. Immediately flush the contaminated eye(s) with lukewarm, gently flowing water for 5 minutes or until the chemical is removed, while holding the eyelid(s) open. Obtain medical advice immediately.

Ingestion:
NEVER give anything by mouth if victim is rapidly losing consciousness, is unconscious or convulsing. Have victim rinse mouth thoroughly with water. DO NOT INDUCE VOMITING. Have victim drink 240 to 300 mL (8 to 10 oz) of water to dilute material in stomach. If vomiting occurs naturally, rinse mouth and repeat administration of water. 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 inhalation or 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:
Absorbed nitromethane (via skin contact or ingestion) can interfere with the most widely used colorimetric method (Jaffe reaction) used to measure creatinine. This interference can result in the measurement of unusually elevated serum creatinine concentrations, which could lead to inappropriate treatment. Enzymatic measurement of creatinine will ensure accurate measurement of creatinine, even in the presence of nitromethane.(30)


SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
35-35.6 deg C (95-96 deg F) (Tag closed cup) (16,18)

Lower Flammable (Explosive) Limit (LFL/LEL):
7.3% at 33 deg C (18,26)

Upper Flammable (Explosive) Limit (UFL/UEL):
No reliable values located. A value of 63% has been reported in one source (12), but cannot be validated.

Autoignition (Ignition) Temperature:
418 deg C (785 deg F) (16,18)

Sensitivity to Mechanical Impact:
Nitromethane is relatively insensitive to mechanical impact under conditions of normal pressure and temperature. However, it has been detonated using combinations of increased temperature, pressure, shock, impact and confinement. Contamination with many different chemicals (e.g. amines or oxygen-bearing acids) can sensitize nitromethane to severe shock (e.g. firing of commercial caps, gun fire and mechanical impact) leading to explosion of the nitromethane.

Sensitivity to Static Charge:
Nitromethane will not accumulate static charge, since it has a high electrical conductivity.(12,37) Mixtures of nitromethane vapour and air at concentrations in the flammable range may be ignited by a static discharge of sufficient energy.

Electrical Conductivity:
5 x 10(5) pS/m at 25 deg C (12)

Minimum Ignition Energy:
Not available

Combustion and Thermal Decomposition Products:
Nitrogen oxides are formed in a fire.(13,21) Incomplete combustion may also produce irritating fumes and acrid smoke. At high temperatures (355 deg C) and high pressures (1216-2027 kPa), hydrogen cyanide, ethyl cyanide, and formaldehyde can also be formed.(42)

Fire Hazard Summary:
Flammable and dangerously reactive liquid. Can release vapours that form explosive mixtures with air at, or above, 35 deg C. Vapours are heavier than air and may travel a considerable distance to a source of ignition and flash back to a leak or open container. During a fire irritating/toxic oxides of nitrogen and carbon monoxide may be generated. Vapours can accumulate in confined spaces, resulting in toxicity, flammability and explosivity hazards. If liquid nitromethane is heated under confinement (a closed container), a rapid build-up of pressure inside the container can result in an explosive rupture, with a sudden release of large amounts of flammable gas. Rapid compression of the liquid under conditions that prevent heat from escaping (adiabatic conditions) can result in explosion. Nitromethane is more sensitive to detonation if contaminated with a number of chemicals (e.g. amines or oxygen-bearing acids). With a severe shock, explosion can occur.

Extinguishing Media:
Carbon dioxide, appropriate foam, water spray or fog.(13,21) Nitromethane fires can be readily extinguished by water. (18) Special "alcohol resistant fire-fighting foams" are recommended for use with any polar flammable liquid that is slightly soluble or completely soluble (like nitromethane) in water. Fire fighting foam manufacturers should be consulted for recommendations regarding types of foams and application rates.

Extinguishing Media to be Avoided:
DO NOT use dry chemical extinguishers containing sodium or potassium bicarbonates. Alkaline bicarbonates appear to extinguish the fire when first applied, but later contribute to reignition.(18)

Fire Fighting Instructions:
Use extreme caution since explosive decomposition may occur under fire conditions and heat may rupture containers. Fight fire from a protected, explosion-resistant location or maximum possible distance. Approach fire from upwind to avoid hazardous vapours and toxic decomposition products.
If fire occurs in the vicinity of nitromethane, use unmanned monitors and hoseholders to keep cooling streams of water on fire-exposed tanks or containers until well after the fire is out. Stay away from ends of tanks. Withdraw immediately in case of rising sound from venting safety device or any discolouration of tank due to fire.
In an advanced or massive fire, the area should be evacuated; use unmanned hoseholders or monitor nozzles. If this is is not possible, withdraw from fire area and do not attempt to fight the fire.
If a leak or spill has not ignited, use water spray to cool and disperse the vapours. Water spray may also be used to dilute spills to nonflammable mixtures and to flush spills away from ignition sources. Solid streams of water may be ineffective and spread material.
Tanks or drums should not be approached directly after they have been involved in a fire or heated by exposure, until they have completely cooled down. Clean-up or salvage operations should not be attempted until the nitromethane is cooled.(17)

Protection of Fire Fighters:
Nitromethane and its decomposition products are inhalation hazards. Firefighters may enter the area if positive pressure self-contained breathing apparatus (NIOSH approved or equivalent) and full Bunker Gear is worn.


NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA - Health: 2 - Intense or continued (but not chronic) exposure could cause temporary incapacitation or possible residual injury.
NFPA - Flammability: 3 - Liquids and solids that can be ignited under almost all ambient temperature conditions.
NFPA - Instability: 4 - Readily capable of detonation or explosive decomposition or explosive reaction at normal temperatures and pressures.

SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 61.04

Conversion Factor:
1 ppm = 2.49 mg/m3; 1 mg/m3 = 0.40 ppm at 25 deg C (calculated)

Physical State: Liquid
Melting Point: -28.55 deg C (-19.4 deg F) (16,18)
Boiling Point: 101.2 deg C (214 deg F) (16,18,37,38)
Relative Density (Specific Gravity): 1.138 at 20 deg C (16,18); 1.132 at 25 deg C (10,37) (water = 1)
Solubility in Water: Soluble (10.5 g/100 mL at 20 deg C (18); 11.1 g/100 mL at 25 deg C (16,38))
Solubility in Other Liquids: Soluble in all proportions in aromatic hydrocarbons, alcohols, ethers, esters, ketone and lower carboxylic acids; limited solubility in alkanes and cycloalkanes (11,18)
Coefficient of Oil/Water Distribution (Partition Coefficient): Log P (oct) = 0.35 (39)
pH Value: 6.4 (0.01 Molar aqueous solution at 25 deg C) (10,18)
Acidity: Weak acid (17)
Dissociation Constant: pKa = 10.12 at 25 deg C (37)
Viscosity-Dynamic: 0.647 mPa.s (0.647 centipoises) at 20 deg C (16,18); 0.61-0.63 mPa.s (0.61-0.63 centipoises) at 25 deg C (17,38)
Viscosity-Kinematic: 0.57 mm2/s (0.57 centistokes) at 20 deg C; 0.54-0.56 mm2/s ( 0.54-0.56 centistokes) at 25 deg C (calculated)
Saybolt Universal Viscosity: 27.5 Saybolt Universal Seconds at 37.8 deg C (100 deg F) (calculated)
Surface Tension: 37.48 mN/m (37.48 dynes/cm at 20 deg C) (16,18,40); 36.53 mN/m (36.53 dynes/cm) at 25 deg C (calculated) (38,40)
Vapour Density: 2.11 (air = 1)
Vapour Pressure: 3.64 kPa (27.3 mm Hg) at 20 deg C (calculated) (18); 4.77 kPa (35.8 mm Hg) at 25 deg C (calculated) (37,41)
Saturation Vapour Concentration: 36000 ppm (3.6%) at 20 deg C; 47000 ppm (4.7%) at 25 deg C (calculated)
Evaporation Rate: 1.39 (n-butyl acetate = 1) (16,18); 9 (diethyl ether = 1) (evaporation number) (16,18)
Henry's Law Constant: 2.90 Pa.m3/mol (cited as 2.86 x 10(-5) atm.m3/mol) at 25 deg C (41); log H = -2.93 (dimensionless constant; calculated)

Other Physical Properties:
DIELECTRIC CONSTANT: 37.27 at 20 deg C (37)

SECTION 10. STABILITY AND REACTIVITY

Stability:
Nitromethane is normally stable at room temperature and pressure. However, with certain combinations of increased temperature and pressure, extreme shock, impact, confinement, and contamination, it can exhibit explosive characteristics.

Explosive Properties:
Under normal temperature and pressure, pure nitromethane is relatively insensitive to shock and does not readily explode. However, with certain combinations of increased temperature and pressure, extreme shock, impact, confinement and contamination, it can exhibit explosive characteristics.

Oxidizing Properties:
Nitromethane acts as a mild oxidizing agent.(17,27,42) The oxidation process may be accelerated at elevated temperatures.(42)

Self-Reactive Properties:
Under certain combinations of temperature, pressure, severe shock, impact, confinement and contamination, nitromethane can exhibit explosive characteristics. There are three general types of conditions under which nitromethane can decompose and potentially explode: heating liquid nitromethane under confinement, which is especially hazardous as the liquid approaches the critical temperature (315 deg C); rapid compression where heat generated cannot escape to the external environment (adiabatic compression); and contamination with certain chemicals (e.g. amines or oxygen-bearing acids), which cause nitromethane to become shock sensitive.

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.


ACIDS (e.g. formic, nitric, sulfuric or phosphoric acids), ALKALI METALS (e.g. potassium or sodium), INORGANIC BASES (e.g. potassium hydroxide, ammonium hydroxide or sodium carbonate), AMINES (e.g. aniline, diaminoethane, methylamine or morpholine) - increases the sensitivity of nitromethane to detonation.(27,42) Alkalis form salts which are explosive when dry.(13,21,27)
HYDRAZINE AND METHANOL - hydrazine strongly sensitizes nitromethane and its mixtures with methanol to detonation.(27)
STRONG OXIDIZING AGENTS (e.g. perchloric acid, perchlorates or peroxides) - mixtures may explode.(17,21)
ACETONE, AMMONIUM SALTS, TRIMETHYLSILYL IODIDE- form explosive mixtures.(27)
ALUMINUM CHLORIDE - mixtures with nitromethane and organic matter can explode.(13,27)
HALOFORMS - mixtures with chloroform or bromoform are detonable.(27)
METAL OXIDES (e.g. cobalt, nickel, chromium, lead, mercury or silver oxides) - increases the sensitivity of nitromethane to heat and detonation.(27)
HYDROCARBONS (e.g. alkenes, acetylenes) - nitromethane may act as a mild oxidant and should not be mixed with readily oxidizable compounds, since explosions may occur.(17,27) Mixtures of nitromethane and solvents which are to be heated above 101 deg C should first be tested in small-scale explosion tests.(27)
CALCIUM HYPOCHLORITE - delayed, but violent reaction.(13,27)
CARBON DISULFIDE - forms the unstable acid, nitroethanedithioic acid, the salts of which are explosive.(27)
ALKALI METAL HYDRIDES (e.g. sodium hydride, lithium tetrahydroaluminate) - reaction is explosively violent, due to the formation of the alkali aci-nitromethanide.(27)
SILVER NITRATE - aqueous silver nitrate may react to form the shock-sensitive silver fulminate.(27)
UREA PERCHLORATE - liquid mixtures are extremely powerful explosives.(27)
ALKYLMETAL HALIDES (e.g. diethyl aluminum bromide or methyl zinc iodide) - contact causes ignition.(27)
ACTIVATED CARBON - The heat of adsorption is very high, therefore, is a potential fire hazard.(27)

Hazardous Decomposition Products:
None reported.

Conditions to Avoid:
Sparks, open flames, shock, high temperatures, high pressure, adiabatic compression.

Corrosivity to Metals:
Nitromethane is not corrosive to aluminum, cast iron, carbon steel (if no water is present), stainless steels (such as 300 series and 400 series), copper (if no acid is present), nickel-based alloys, such as Hastelloy, tantalum, titanium and zirconium.(43,44,45) Aluminum and stainless steel are resistant to corrosion by wet nitromethane.(18)

Corrosivity to Non-Metals:
Nitromethane attacks some plastics, such as acrylonitrile- butadiene-styrene (ABS), chlorinated polyvinyl chloride (CPVC), nylon, polyvinyl chloride (PVC) and polyesters; elastomers, such as chloroprene, ethylene vinyl acetate (EVA), Viton, natural rubber and silicone rubbers, neoprene, niltrile buna-N (NBR), and polyurethane; and coatings, such as coal tar, epoxy polyamide and vinyls.(43,46,47) The following materials are resistant to nitromethane: Plastics, such as acrylics, Teflon, polyethylene and polypropylene; elastomers, such as butyl rubber, ethylene-propylene, fluorocarbon elastomers, isoprene, polyester and fiberglass, and styrene- butadiene (SBR); and coatings, such as polyester.(43,46,47)

Stability and Reactivity Comments:
As a general rule, extreme caution should be used in attempting any untried reactions, or making unusual combinations.(17)
The higher nitroparaffins, benzene, xylene, methanol, 1-butanol, 1-butyl acetate, amyl acetate, di-n-butyl phthalate and di-n-butyl sebacate inhibit the propagation of the explosion of nitromethane.(42)

SECTION 11. TOXICOLOGICAL INFORMATION

LD50 (oral, rat): 940 mg/kg (20)
LD50 (oral, mouse): 950 mg/kg (20)
LD50 (oral, rat): 1478 mg/kg (22)

LD50 (dermal, rabbit): greater than 2000 mg/kg (22)

Eye Irritation:

Nitromethane is not irritating to the eyes.

No irritation (as scored by the Draize method) was observed in rabbits when 0.1 mL nitromethane was applied to the eyes.(22) Mild irritation (increased density of the cornea) was observed in eyes of rabbits after administration of 0.1 mL nitromethane (maximum average score 3.2/110 at 24 hours). However, the untreated eye of 5/6 rabbits also showed increased corneal density. Therefore, firm conclusions cannot be drawn from this study.(49) No eye irritation was observed among guinea pigs and rabbits exposed to vapour concentrations of 500 ppm or more.(3)

Skin Irritation:

Nitromethane is not irritating to the skin.

No irritation was seen in a standard Draize test using rabbits (score: 0).(22) No irritation was observed when nitromethane was applied to the skin of rabbits or guinea pigs.(1,3) These studies provide only limited details regarding experimental methods.

Effects of Short-Term (Acute) Exposure:

Inhalation of high concentrations has produced central nervous system (CNS) effects (rapid breathing, increased activity, and loss of coordination) and signs of respiratory irritation in exposed animals. Sciatic nerve degeneration was observed in rats exposed to 375 ppm and greater. Very high oral doses have also produced signs of CNS depression and liver damage.

Inhalation:
Rats and mice were exposed to 0, 94, 188, 375, 750 or 1500 ppm for 16 days. All animals survived to the end of the study. The mean body weight of male rats exposed to 1500 ppm was slightly decreased. Rapid breathing and increased activity were observed early in the study and reduced activity and loss of coordination in the hindlimbs were observed near the end of the study in rats exposed to 1500 ppm. Reduced activity and slow breathing were observed in mice exposed to 1500 ppm. A concentration-related increase in absolute and relative liver weights and minimal to mild degeneration of the olfactory epithelium were observed in rats and mice. Sciatic nerve degeneration was present in rats exposed to 375 ppm or greater. Rats exposed to 750 or 1500 ppm also had reduced myelin around sciatic axons.(36) A 6-hour exposure to 10,000 ppm or a 2-hour exposure to 30,000 ppm resulted in the death of 2/2 rabbits and 2/2 guinea pigs. A 3-hour exposure to 10,000 ppm or a 1-hour exposure to 30,000 ppm resulted in the death of 2/2 guinea pigs but both rabbits survived. All animals survived a 1-hour exposure to 10,000 ppm. Initial signs of toxicity were restlessness and slight irritation to the respiratory tract. Central nervous system (CNS) effects were observed one half to one hour after exposure to 30,000 or 50,000 ppm, while 5 hours elapsed before CNS effects were observed after exposure to 10,000 ppm. Liver damage and acute pulmonary congestion with edema (a life-threatening accumulation of fluid in the lungs) was seen in animals that died. No deaths occurred when 2 rabbits, 2 guinea pigs and a monkey were exposed to 500 ppm for a total of 140 hours (daily exposures of 6 hours). No evidence of blood effects was seen in any exposure groups.(3) Rats (4/group) were exposed to 1000, 4000, 6000 or 8000 ppm for 4 hours. At 6000 and 8000 ppm, the exposed animals showed unresponsiveness during exposure, and convulsions after exposure. Two rats had respiratory injury at 8000 ppm. Death occurred in 1/4 rats exposed to 6000 ppm and in 3/4 rats exposed to 8000 ppm. No to minimal toxic signs were observed at 1000 and 4000 ppm.(50) No signs or very weak signs of methemoglobinemia (a condition in which the oxygen-carrying component of the blood is converted to an inactive form) were seen in rats exposed to concentrations of 13000 ppm for 6 hours or 2500 ppm for 4 days. No harmful effects were observed in rats exposed to 500 ppm for 3 weeks.(24)

Skin Contact:
No harmful effects were observed when nitromethane was applied to the skin of rabbits or guinea pigs.(1,3) These studies provide very limited details regarding experimental methods.

Ingestion:
Lethal doses (750 to 1000 mg/kg) caused progressive weakness and collapse, unsteadiness and incoordination, and changes in respiration (first slow breathing and later increasingly rapid breathing). There were no changes in blood chemistry and there was no methemoglobin formation. Liver damage were seen in animals that died.(3) Slight liver damage was seen in dogs given a dose of 125 mg/kg (20% nitromethane emulsified in 0.2% methylcellulose). Liver damage became more severe with increasing dose (500 to 1500 mg/kg). Kidney damage was observed only at doses of 1500 mg/kg. All animals received higher doses (500 mg/kg and above) died within approximately 30 hours or were killed due to severe toxicity.(4)

Effects of Long-Term (Chronic) Exposure:

Inhalation of 375 ppm and above for 13 weeks has caused degeneration of the sciatic nerve and hemolytic anemia in rats and evidence of upper respiratory tract irritation in rats and mice. In a two-year study, evidence of upper respiratory tract irritation was observed in mice exposed to 188 ppm and above. Signs of liver damage were observed in young male rats given high oral doses for 15 weeks.

Inhalation:
Rats and mice were exposed to 0, 94, 188, 375, 750 or 1500 ppm for 13 weeks. All animals survived to the end of the study. Body weight and body weight gain were reduced in male rats exposed to 1500 ppm. Hindlimb paralysis was observed in rats exposed to 750 and 1500 ppm. Forelimb and hindlimb grip strength was decreased in rats exposed to 1500 ppm. Minimal to mild degeneration of the sciatic nerve was observed in rats exposed to 375 ppm. Concentration-related microcytic, responsive anemia was also observed in rats, especially at 375 ppm and greater. Evidence of hemolysis included the presence of Heinz bodies and increased mean cell hemoglobin and methemoglobin concentration. Minimal to mild hyperplasia was observed in the bone marrow of rats (at 750 ppm and greater for males; 188 ppm and greater for females). Mice in the 1500 ppm group had minimal extramedullary hematopoiesis of the spleen. Both rats and mice experienced olfactory epithelial degeneration (at 375 ppm and greater) and respiratory epithelial hyaline droplets (at 375 ppm and greater for mice and at 750 ppm and greater for rats).(36) Rats were exposed to 0, 94, 188 or 375 ppm and mice were exposed to 0, 188, 375 or 750 ppm for 103 weeks. No hindlimb paralysis was observed in the rats. An increased incidence of nasal lesions with degeneration and metaplasia of the olfactory epithelium and degeneration of the respiratory epithelium were observed in mice exposed to 188 ppm and above. Carcinogenic effects were observed in female rats and male and female mice. These effects are described under "Carcinogenicity" below.(36) No significant effects were noted in rats exposed to 0, 100 or 200 ppm for 2 years.(31) Male rabbits and male rats were exposed to 0, 98 or 745 ppm for up to 24 weeks. Mild signs of toxicity were noted in animals exposed to 98 ppm. Moderate signs of toxicity were seen following exposure to 745 ppm. A reduction in body weight gain was observed in rats exposed to 745 ppm and hematocrit and hemoglobin levels were slightly depressed from 10 days through 6 months. An effect on the thyroid (depressed thyroxin levels) was seen in rabbits at both concentrations. Some evidence of pulmonary edema and other pulmonary abnormalities was observed in rabbits exposed to both concentrations for 1 month.(5)

Ingestion:
Young male rats were given drinking water containing 0.1, 0.2, 0.5, 1 or 2% nitromethane for up to 15 weeks. The rats would not consume water containing 0.5, 1 or 2%. Several animals in each of these groups died or were destroyed by their cage mates and these experimental groups were discontinued. In the 0.25% group, 7/10 rats survived and in the 0.1% group; 6/10 rats survived. Approximate doses were 500 mg/kg/day (0.1%) or 1000 mg/kg/day (0.2%). Survivors showed reduced weight gain and signs of liver damage.(4)

Skin Sensitization:
Nitromethane did not cause skin sensitization in intradermal sensitization testing in guinea pigs.(22) The study protocol and data are not available for evaluation.

Carcinogenicity:
The International Agency for Research on Cancer (IARC) has concluded there is sufficient evidence for the carcinogenicity of nitromethane to experimental animals.(28)
Mice were exposed by inhalation to 0, 188, 375 or 750 ppm for 103 weeks. Significant increases in the incidence of Harderian gland tumours (males and females), alveolar/bronchiolar tumours (males and females) and hepatocellular adenomas (females) were observed. Under the conditions of this study, there was clear evidence of carcinogenic activity in male and female mice.(36) Rats were exposed by inhalation to 0, 94, 188 or 375 ppm for 103 weeks. Significant increases were observed in the incidences of mammary gland fibroadenomas and mammary gland carcinomas in females. Under the conditions of this study, there was clear evidence of carcinogenic activity in female rats and no evidence of carcinogenic activity in male rats.(36) In another study, a significant increase in tumours was not observed in rats exposed by inhalation to 0, 100 or 200 ppm for 2 years.(31)

Reproductive Toxicity:
Effects on some reproductive parameters (sperm motility and fertility cycle length) have been observed in rats and/or mice exposed to high concentrations by inhalation. However, firm conclusions cannot be drawn because there were no studies that evaluated reproductive outcome located.
Rats and mice were exposed to 375, 750 or 1500 ppm for 13 weeks. A dose-related decrease in sperm motility was observed. The decrease was significant at 750 and 1500 ppm in rats and at all concentrations for mice. In the 1500 ppm group, body weight as well as weight of cauda, epididymis and testis were decreased in rats. A dose-related increase in fertility cycle length was observed in female mice.(36)

Mutagenicity:
The available information indicates that nitromethane is not mutagenic.
Negative results were obtained for micronucleus formation in the peripheral blood erythrocytes of mice exposed by inhalation to 1500 ppm for 13 weeks.(36) Negative results were also obtained in the bone marrow micronucleus test in mice exposed twice to doses up to 1830 mg/kg by intraperitoneal administration.(25) This route of exposure is not considered relevant to occupational situations.
Negative results were obtained in 3 tests using cultured mammalian cells (sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells and the micronucleus test in Syrian hamster embryo cells). Positive results were obtained one test that used a high concentration of nitromethane (cell transformation in Syrian hamster embryo cells).(33,36) Negative results were obtained in several tests using bacteria, both with and without metabolic activation.(2,23,25,28,29,34) One study reports positive results in one strain of Salmonella typhimurium (TA 1535), in the presence of metabolic activation.(32)
Negative results were obtained in the sex-linked recessive lethal assay in Drosophila (fruit flies).(25)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) A review of toxicological studies on the nitroparaffins with particular emphasis on 2-nitropropane. IMC Chemical Group, 1977 (NIOSH Control No: 00136155)
(2) Chiu, C.W., et al. Mutagenicity of some commercially available nitro compounds for salmonella typhimurium. Mutation Research. Vol. 58 (1978). p. 11-22
(3) Machle, W., et al. The physiological response of animals to some simple mononitroparaffins and to certain derivatives of these compounds. Journal of Industrial Hygiene and Toxicology. Vol. 22, no. 8 (Oct. 1940). p. 315-332
(4) Weatherby, J.H. Observations on the toxicity of nitromethane. AMA Archives of Industrial Health. Vol. 11 (1955). p. 102-106
(5) Lewis, T.R., et al. Subchronic inhalation toxicity of nitromethane and 2-nitropropane. Journal of Environmental Pathology and Toxicology. Vol. 2, no. 5 (1979). p. 233-249
(6) Information profiles on potential occupational hazards: nitroparaffins (SRC TR 81-617). Second Draft. National Institute for Occupational Safety and Health, 1981. p. 1-29 (NIOSHTIC Control No.: 00188273)
(7) Nitromethane. In: Documentation of the threshold limit values and biological exposure indices. 7th ed. E-O. American Conference of Governmental Industrial Hygienists (ACGIH), 2001
(8) Webb, K.G., et al. Occupational allergic contact dermatitis to nitromethane. American Journal of Contact Dermatitis. Vol. 13, no. 4 (Dec. 2002). p. 201-202
(9) Ruth, J.H. Odor thresholds and irritation levels of several chemical substances: a review. American Industrial Hygiene Association Journal. Vol. 47 (Mar. 1986). p. A142-A151
(10) Nitromethane. In: The Merck index: an encyclopedia of chemicals, drugs and biologicals. Edited by M.J. O'Neil, et al. 13th ed. Merck and Company, 2001. p. 1186
(11) Doepker, C.L. Aliphatic nitro, nitrate and nitrite compounds. In: Patty's Toxicology. 5th ed. Edited by E. Bingham, et al. Vol. 4. John Wiley and Sons, 2001. p. 553-632
(12) Nitromethane. In: Chemical safety sheets: working safely with hazardous chemicals. Kluwer Academic Publishers, 1991. p. 648
(13) Fire protection guide to hazardous materials. 13th ed. Edited by A.B. Spencer, et al. National Fire Protection Association, 2002. NFPA 325; NFPA 49; NFPA 491
(14) Amoore, J.E., et al. Odor as an aid to chemical safety : odor thresholds compared with threshold limit values and volatilities for 214 industrial chemicals in air and water dilution. Journal of Applied Toxicology. Vol. 3, no. 6 (1983). p. 272-290
(15) Nitromethane. In: NIOSH pocket guide to chemical hazards. National Institute for Occupational Safety and Health, June 1997
(16) Markofsky, S.B. Nitrocompounds, aliphatic. In: Ullmann's encyclopedia of industrial chemistry. 5th completely revised ed. Vol. A 17. VCH Publishers, 1991. p. 401-409
(17) Nitroparaffins and their hazards. Research report no. 12. The National Board of Fire Underwriters, 1959
(18) Bollmeier, Jr., A.F. Nitroparaffins. In: Kirk-Othmer encyclopedia of chemical technology. 4th ed. Vol. 17. John Wiley and Sons, 1996. p. 205-225
(19) Forsberg, K., et al. Quick selection guide to chemical protective clothing. 4th ed. Van Nostrand Reinhold, 2002
(20) Subbotin, V.G. Hygienic assessment of nitromethane and other nitroparaffins from the standpoint of the sanitary protection of water bodies. Hygiene and Sanitation. Vol. 32, no. 9 (1967). p. 320-324
(21) Nitromethane. Sigma-Aldrich Website. Sigma-Aldrich Corporation. MSDS. Date updated: 2002-05. Available at: <www.sigmaaldrich.com/suite7> (Password required)
(22) IMC. Acute toxicity profile, epidemiological data and environmental fate studies with cover letter dated 051689. Date produced: Oct. 20, 1982. Angus Chemical Co. EPA/OTS 86-890000232. NTIS/OTS0516767.
(23) Mortelmans, K., et al. Salmonella mutagenicity test: II. Results from the testing of 270 chemicals. Environmental Mutagenesis. Vol 8, suppl. 7 (1986). p. 1-119
(24) Dequidt, J., et al. Experimental toxicological study of several nitroparaffins. IV Nitromethane (NM). Bulletin de la Societe de Pharmacie de Lille (1972). p. 29-35 (English translation : IMC Chemical Group, Inc. (NIOSH Control No.: 00136155))
(25) Gocke, E., et al. Mutagenicity of cosmetics ingredients licensed by the European Communities. Mutation Research. Vol. 90 (1981). p. 91-109
(26) Verschueren, K. Handbook of environmental data on organic chemicals. 4th ed. Vol. 2. John Wiley and Sons, Inc., 2001. p. 1631-1632
(27) Urben, P.G., ed. Bretherick's reactive chemical hazards database. [CD-ROM]. 6th ed. Version 3.0. Butterworth-Heinemann Ltd., 1999
(28) International Agency for Research on Cancer (IARC). Nitromethane. In: IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 77. Some industrial chemicals. World Health Organization, 2000. p. 487-501
(29) Lofroth, G., et al. Structure-activity relationship of nitroalkane-induced mutagenicity in the Ames salmonella assay. Genetic Toxicology of Environmental Chemicals, Part B: Genetic Effects and Applied Mutagenesis. Alan R. Liss, 1986. p. 149-155
(30) Mullins, M.E., et al. Intoxication with nitromethane-containing fuels: don't be "fueled" by the creatinine. Clinical Toxicology. Vol. 36, no. 4 (1998). p. 315-320
(31) Griffin, T.B., et al. Chronic inhalation exposure of rats to nitromethane. Ecotoxicology and Environmental Safety. Vol. 34 (1996). p. 109-117
(32) Ong, T., et al. Mutagenicity results of selected industrial chemicals. Proceedings of the First NCI/EPA/NIOSH Collaborative Workshop: Progress Report on Joint Environmental and Occupational Cancer Studies. May 6-8, 1980. p. 470-479, 487
(33) Gibson, D.P., et al. Induction of micronuclei in Syrian hamster embryo cells: comparison to results in the SHE cell transformation assay for National Toxicology Program test chemicals. Mutation Research. Vol. 392 (1997). p. 61-70
(34) Dayal, R., et al. Comparison of the hepatotoxicity in mice and the mutagenicity of three nitroalkanes. Fundamental and Applied Toxicology. Vol. 13 (1989). p. 341-348
(35) Page, E.H., et al. Peripheral neuropathy in workers exposed to nitromethane. American Journal of Industrial Medicine. Vol. 40 (2001). p. 107-113
(36) NTP technical report on the toxicology and carcinogenesis studies of nitromethane (CAS no. 75-52-5) in F344/N rats and B6C3F1 mice (inhalation studies). National Toxicology Program. NTP TR 461. US Department of Health and Human Services, 1997
(37) Dean, J.A. Lange's handbook of chemistry. 15th ed. McGraw-Hill, Inc., 1999. p. 1.284, 5.51, 5.100, 5.124, 5.145, 8.62, 8.161
(38) Lide, D.R., ed. Handbook of chemistry and physics. [CD-ROM]. Chapman and Hall/CRCnetBASE 1999
(39) Syracuse Research Corporation. Interactive LogKow (KowWin) Database Demo. Date unknown. Available at: <syrres.com/esc/kowdemo.htm>
(40) Jasper, J.J. Surface tension of pure liquid compounds. In: Compilation of data of some 2200 pure liquid compounds. Journal of Physical and Chemical Reference Data. Vol. 1, no. 4 (1972). p. 928
(41) Syracuse Research Corporation. The Physical Properties Database (PHYSPROP). Interactive PhysProp Database Demo. Date unknown. Available at: <www.syrres.com/esc/physdemo.htm>
(42) Makovky, A., et al. Nitromethane; physical properties, thermodynamics, kinetics of decomposition, and utilization as fuel. Chemical Reviews. Vol. 58 (1958). p. 627-644
(43) Schweitzer, P.A. Corrosion resistance tables: metals, nonmetals, coatings, mortars, plastics, elastomers and linings, and fabrics. 4th ed. Part B, E-O. Marcel Dekker, Inc., 1995. p. 2037-2040
(44) Corrosion data survey: metals section. 6th ed. National Association of Corrosion Engineers, 1985. p. 88-10 to 89-10
(45) Pruett, K.M. Chemical resistance guide for metals and alloys: a guide to chemical resistance of metals and alloys. Compass Publications, 1995. p. 230-241
(46) Corrosion data survey: nonmetals section. 5th ed. National Association of Corrosion Engineers, 1983. p. 238 (8-10)
(47) Pruett, K.M. Chemical resistance guide for elastomers II: a guide to chemical resistance of rubber and elastomeric compounds. Compass Publications, 1994. p. C260-C265
(48) European Economic Community. Commission Directive 93/72/EEC. Sept. 1, 1993
(49) Food and Drug Research Labs. Primary eye irritation study of nitromethane in New Zealand white rabbits with cover letter dated 050989. Date produced: Mar. 15, 1989. W.R. Grace & Co. EPA/OTS 86-890000306. NTIS/OTS0519071.
(50) Haskell Laboratories. Preliminary toxicity studies on nitromethane and simulated hair sprays containing nitromethane or other inhibitors with cover sheet dated 061289. Date produced: May 26, 1961. EPA/OTS 86-890000841. NTIS/OTS0520957.
(51) Report on Carcinogens. 11th ed. US Department of Health and Human Services, Public Health Service, National Toxicology Program

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: 2004-06-21

Revision Indicators:
Carcinogenicity 2005-02-02
Bibliography 2005-02-02



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