N-Methylformamide

59.06720

59.07

204-624-6

XPE4G7Y986

1087

3051

DTXSID0025608

C1163

2924199090

29.10000

-1

N-methylformamide is a clear colorless liquid with a slight amine odor. (NTP, 1992)

0.9961 g/cm³ @ Temp: 25 °C

-5.4 °C

180-185 °C

111ºC

1.431-1.433

Micible with water.Ether immiscible

0.808mmHg at 25°C

Relative vapour density (air = 1): 2.04

pKa = -0.04 @ 20 °C

Dielectric constant: 200.1 @ 15 °C; 182.4 @ 25 °C

Water soluble.

Amides and Imides

N-METHYLFORMAMIDE is incompatible with benzene sulfonyl chloride. It is also incompatible with strong oxidizing agents, acids, bases and acid chlorides. It may react with chlorine, bromine, nitrates, nitric acid, triethylaluminum, potassium permanganate, chromic acid, chromic anhydride, chromium trioxide, borohydrides, hydrides, thionyl chloride, metallic sodium, phosphorus trioxide, diborane, (octafluoroisobutyrate + sodium nitrite) and (perchloryl fluoride + potassium methyl 4,4-dinitrobutyrate). (NTP, 1992)

613 °F (NTP, 1992)

II

NONH for all modes of transport

1

R21; R61

S45-S53

LQ3000000

T

Separated from oxidants.

Solution: A 25% aqueous solution is stable at room temperature for at least one week (NMR).

P201-P280-P308 + P313

H312-H360

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

VIOLENT REACTION WITH BENZENE SULFONYL CHLORIDE.

This chemical is combustible. (NTP, 1992)|Combustible.

|Danger|H312: Harmful in contact with skin [Warning Acute toxicity, dermal]|P201, P202, P280, P281, P302+P352, P308+P313, P312, P322, P363, P405, and P501|H302 (23.58%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P264, P270, P280, P281, P301+P312, P302+P352, P305+P351+P338, P308+P313, P312, P322, P330, P337+P313, P363, P405, and P501|Aggregated GHS information provided by 229 companies from 12 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H303: May be harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P264, P270, P280, P281, P302+P352, P305+P351+P338, P307+P311, P308+P313, P312, P314, P321, P322, P337+P313, P363, P405, and P501

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992)|Use powder, carbon dioxide. In case of fire: keep drums, etc., cool by spraying with water.

SMALL SPILLS AND LEAKAGE: If you should spill this chemical, use absorbent paper to pick up all liquid spill material. Seal the absorbent paper, as well as any of your clothing which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Wash any surfaces you may have contaminated with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this material under ambient temperatures and keep away from oxidizers. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

A very dangerous fire hazard when exposed to heat or flame.

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.

/N-methylformamide/ is an eye irritant.

Personal protection: chemical protection suit including self-contained breathing apparatus. Collect leaking liquid in covered containers.

Separated from oxidants.

No indication can be given about the rate at which a harmful concentration of this substance in the air is reached on evaporation at 20 °C.

The substance is irritating to the eyes. The substance may cause effects on the liver. This may result in liver impairment.

NO open flames.

Use ventilation.

Protective gloves.

Wear safety goggles.

N-Methylformamide has been detected in cigarette smoke(1).

SIMULTANEOUS TREATMENT OF PREGNANT RATS AND MICE WITH SODIUM NITRITE (0.5-0.75% IN DRINKING WATER ON DAYS 11-15 OF GESTATION) AND N-METHYLUREA, N,N'-DIMETHYLUREA OR N,N,N-TRIMETHYLUREA (1000, 1000 OR 500 MG/KG IP, RESPECTIVELY, ON DAY 11 OR 13 OF GESTATION) PRODUCED THE SAME TERATOGENIC EFFECTS AS TREATMENT WITH THE NITROSYLATED HOMOLOGS OF THESE METHYLUREAS. TREATMENT OF RATS WITH SODIUM NITRITE & N-METHYLFORMAMIDE PRODUCED GREATER TERATOGENIC EFFECTS THAN TREATMENT WITH N-ALKYL CARBOXYLIC ACID AMIDE ALONE.|N-METHYLFORMAMIDE (1.8 G/KG IV) DECR HYPERTENSION INDUCED BY INDIRECTLY ACTING AMINES TYRAMINE & EPHEDRINE.|Admin of NMF on 4 consecutive days enhanced the sleeping time caused by pentobarbital in male rats to 565% of controls & reduced to a moderate extent the activities of rat hepatic cytochrome P-450 & cytochrome c reductase.|Like dimethylformamide NMF or its metabolites appear to interact with the metab of ethanol. Admin of 2 or 20 mmol/kg NMF to rats 3 or 18 hr before ethanol (both orally) induced an elevation in blood acetaldehyde levels. In the case of high doses of NMF admin 18 hr before alcohol, the level of ethanol in the blood was also raised significantly over controls.

LD50 BALB/C Mouse ip 2.3 g/kg|LD50 BALB/C Mouse iv 1.58 g/kg|LD50 BALB/C Mouse oral 2.6 g/kg|LD50 BALB/C Mouse im 2.7 g/kg|For more Non-Human Toxicity Values (Complete) data for N-METHYLFORMAMIDE (11 total), please visit the HSDB record page.

N-Methylformamide's production and use as an intermediate in the synthesis of pesticides; as an extraction solvent for aromatic hydrocarbons(1); and in the manufacture of methyl isocyanate(2); may result in its release to the environment through various waste streams(SRC). N-Methylformamide has been detected in cigarette smoke(3). N-Methylformamide may be also released to the atmosphere as a result of the photolysis of dimethylamine or trimethylamine(4), and may occur in water as a result of photolysis of the aquatic herbicide fluridone(5).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 7(SRC), determined from a log Kow of -0.97(2) and a regression-derived equation(3), indicates that N-methylformamide is expected to have very high mobility in soil(SRC). Volatilization of N-methylformamide from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.0X10-8 atm-cu m/mole(SRC), derived from its vapor pressure, 0.25 mm Hg(4), and water solubility, 1.0X10+6 mg/l(5). N- Methylformamide is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 0.25 mm Hg(4). N-methylformamide has been shown to biodgrade by microorgansism obtained through soil enrichment(6), suggesting that N-methylformamide may biodegrade in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 7(SRC), determined from a log Kow of -0.97(2) and a regression-derived equation(3), indicates that N-methylformamide is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.0X10-8 atm-cu m/mole(SRC), derived from its vapor pressure, 0.25 mm Hg(4), and water solubility, 1.0X10+6 mg/l(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). N-Methylformamide, present at 400 mg/l, reached 4%, 98%, and 100% of its theoretical BOD in 3 hrs, 3 days, and 7 days, respectively, using an industrial activated sludge inoculum and the Zahn-Wellens test(8). Using the BOD test, N-methylformamide achieved 2% of its theoretical BOD after 5 days(8), suggesting that N-methylformamide may biodegrade in the aquatic environment(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), N-methylformamide, which has a vapor pressure of 0.253 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere(SRC). Vapor-phase N-methylformamide is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 57 hours(SRC), calculated from its rate constant of 6.8X10-12 cu cm/molecule-sec at 25 °C(SRC) determined using a structure estimation method(3).

The rate constant for the vapor-phase reaction of N-methylformamide with photochemically-produced hydroxyl radicals has been estimated as 6.8X10-12 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 57 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). N-Methylformamide is not expected to undergo hydrolysis in the environment since amides hydrolyze very slowly under environmental conditions(2) nor to directly photolyze due to the lack of absorption in the environmental UV spectrum (>290 nm).

An estimated BCF of 3 was calculated for N-methylformamide(SRC), using a log Kow of -0.97(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of N-methylformamide is estimated as 7(SRC), using a log Kow of -0.97(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that N-methylformamide is expected to have very high mobility in soil(SRC).

The Henry's Law constant for N-methylformamide is estimated as 2.0X10-8 atm-cu m/mole(SRC) based upon its vapor pressure, 0.253 mm Hg(1), and water solubility, 1.0X10+6 mg/l(2). This Henry's Law constant indicates that N-methylformamide is expected to be essentially nonvolatile from water surfaces(3). N-Methylformamide is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

Occupational exposure to N-methylformamide may occur through inhalation and dermal contact with this compound at workplaces where N-methylformamide is produced or used(SRC). The concn of N-methylformamide in urine was 7.7 mg/l and 23.3 mg/l before shift and after shift, respectively, for workers exposed to N,N-dimethylformamide at a synthetic leather factory(1). N-Methylformamide is a metabolite of N,N-dimethylformamide(1).

The concn of N-methylformamide in urine was 7.7 mg/l and 23.3 mg/l before shift and after shift, respectively, for workers exposed to N,N-dimethylformamide at a synthetic leather factory(1). N-Methylformamide is a metabolite of N,N-dimethylformamide(1).

NMF is an investigational anticancer drug... .

Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)|Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells. (See all compounds classified as Radiation-Sensitizing Agents.)

8 healthy male subjects were exposed to dimethylformamide vapor at a concn of 8.79 + or - 0.33 ppm for 6 hr/day for 5 consecutive days. All urine voided by the subjects was collected from the beginning of the first exposure to 24 hr past the end of the last exposure & each sample was analyzed for monomethylformamide. Monomethylformamide was rapidly eliminated from the body with urine values peaking within a few hr following the end of each exposure period. The mean for the 7 hr (end of exposure) sample was 4.74 ug/ml urine or 736.8 ug.|Dimethylformamide reached an average level of 2.8 mg/l in the blood of subjects exposed to 21 ppm of the vapor for 4 hr, & was undetectable at 4 hr after the exposure; the metabolite, methylformamide, averaged between 1 & 2 mg/l in the blood & this level was maintained for at least 4 hr after exposure. Maximal blood levels of about 14 & 8 mg/l were observed for dimethylformamide & methylformamide, respectively, at 0 & 3 hrs, after a 4 hr exposure to 87 ppm of the vapor. Repeated daily exposures to 21 ppm of dimethylformamide did not result in accumulation of the chemical or its metabolite in blood. /Dimethylformamide and methylformamide/

It is known that dimethylformamide is metabolized in man by sequential N-demethylation to methylformamide & formamide, which are largely eliminated in the urine.|In mice, NMF is metabolized mainly to carbon dioxide, which is exhaled with the breath, & to methylamine, which is excreted with the urine. Of the radioactivity injected with [C14]formyl-NMF (400 mg/kg), 39% was exhaled as carbon dioxide. The amount of the drug excreted unchanged in the urine in mice was only 26% & 15% of the dose was metabolized to methylamine. A mercapturate, N-acetyl-S-(N-methylcarbamoyl)cysteine was identified as a major metabolite of NMF in the urine of mice, rats, & patients. Formation of the novel metabolite involves oxidation of the formyl moiety & subsequent conjugation with glutathione. On GLC analysis of the urine of mice which had received NMF, small amounts of formamide were also detected. Some evidence suggests that this metabolite was actually N-hydroxy-methylformamide, the immediate product of N-methyl-C-hydroxylation of NMF, & not formamide. N-Hydroxymethylformamide, like N-hydroxymethyl-N-methylformamide, the principal metabolite of dimethylformamide, is thermally labile & breaks down to give formamide & formaldehyde; but it is stable in aqueous soln. In alkaline soln N-hydroxymethylformamide undergoes facile hydrolysis. Only 14% of the radioactivity injected with [C14]methyl-NMF was exhaled as labeled carbon dioxide. Formate was not a urinary metabolite of NMF in mice.|N-methylformamide has known human metabolites that include Methyl Isocyanate.

The mechanism by which NMF causes hepatotoxicity is currently under investigation. Evidence is accumulating which suggests that a reactive metabolite of NMF is involved. In vitro NMF was cytotoxic only at concns in the 0.1 M range whereas the maximum NMF concn in the plasma of animals which showed evidence of hepatotoxicity was below 0.01 M. The hypothesis that a reactive metabolite is formed which might be responsible for NMF-induced hepatotoxicity is supported by the following findings: 1) NMF caused the depletion of hepatic glutathione levels in vivo, & in hepatocytes in vitro; 2) an NMF metabolite (or metabolites) was covalently bound to liver microsomal protein; & 3) pretreatment of mice with cysteine or N-acetylcysteine protected against NMF-induced hepatotoxicity. Liver mitochondria may be a target for the reactive metab, as NMF has been shown to inhibit the ability of mouse liver mitochondria to sequester calcium ions when a hepatotoxic dose was admin ip.

SYMPTOMS: Symptoms of exposure to this compound include irritation of the mucous membranes and upper respiratory tract. Other symptoms include liver damage, eye irritation with discomfort, tearing or blurring of vision, skin irritation with discomfort or rash, abnormalities of liver function with jaundice, temporary nervous system depression with anesthetic effects such as dizziness, headache, confusion, incoordination and loss of consciousness. ACUTE/CHRONIC HAZARDS: This compound may be absorbed through the skin and cause skin irritation. It may also irritate the eyes, mucous membranes and upper respiratory tract. When heated to decomposition it emits toxic fumes of carbon monoxide, carbon dioxide and nitrogen oxides. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Fresh air, rest. Refer for medical attention.

Rinse skin with plenty of water or shower.

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

The major potential of NMF is its ability to cause liver damage. NMF is also teratogenic & embryotoxic. It appears to be more toxic than its methyl homologue, dimethylformamide, or its N-desmethyl analogue, formamide.|As NMF is an investigational anticancer drug, a number of clinical trials have been conducted with this chemical. The first clinical evaluation was initiated in 1956. Five patients were treated with NMF; all but one patient received the drug orally. The dose ranged from 0.1-4 g/day for 2-36 days. All patients showed symptoms of toxicity- chiefly anorexia, nausea, & vomiting. Hepatic damage as measured by liver function tests was seen in all patients at total doses between 80-870 mg/kg. The liver damage appeared to be reversible with cessation of treatment. Autopsy exam of the liver of one patient showed irregular lobular disorganization, some large hepatocytes & areas of liver regeneration.|... /NMF was administered/ iv & orally to 19 patients at a starting dose of 300 mg/sq m/day for 5 days. Treatment cycles were repeated every 2 wk & doses were escalated to 1200 mg/sq m/day for 5 days. /In another study/ 35 patients /were treated/ with NMF iv at doses ranging from 125-3125 mg/sq m weekly every 6 wk. The principal toxic effects of NMF were general malaise, nausea, vomiting & anorexia. Biochemical disturbances included reversible elevation of serum levels of transaminases in several patients. The occurrence of raised serum enzyme levels did not seem to be related to the dose. Other toxic symptoms were peripheral neuropathy & alcohol intolerance in a few patients.|/N-methylformamide/ is an eye irritant.

methylformamide

The substance can be absorbed into the body by inhalation, through the skin and by ingestion.

Cough.

Redness. Pain.

All other basic organic chemical manufacturing|Formamide, N-methyl-: ACTIVE

A HPLC method with UV detection was used for the determination of low mol wt amides in pharmaceutical matrixes. The method was based on Zorbax C8 or Alltech C18 column, mobile phase consisting of 3-5% MeCN in 0.1M phosphate buffer, & flow rate of 1-1.5 ml/min at the room temperature. By strongly retaining the sample matrix & allowing the amide analyte to elute, the method can be generally applied to many types of org matrix for pharmaceutical & agricultural products. /Amides/

N-METHYLFORMAMIDE WHEN PRESENT IN URINE IN CONCN BETWEEN 5 & 500 UL/L CAN BE MEASURED BY DIRECT INJECTION OF AN ALIQUOT OF A SPECIMEN ON A CHROMOSORB 103 COLUMN OF A GAS CHROMATOGRAPH. THE SENSITIVITY OF THE METHOD CAN BE INCREASED TO MEASURE 0.5 UL/L OF N-METHYLFORMAMIDE BY CHROMATOGRAPHING DICHLOROMETHANE EXTRACTS OF CONCENTRATED URINE RESIDUES.|Methylformamide concentrations in urine may be determined by flame-ionization gas chromatography, involving direct sample introduction.|/Determination of dimethylformamide and N-methylformamide by gas chromatography/.