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N-Methylformamide

PubChem CID
31254
Structure
N-Methylformamide_small.png
N-Methylformamide_3D_Structure.png
N-Methylformamide__Crystal_Structure.png
Molecular Formula
Synonyms
  • N-METHYLFORMAMIDE
  • 123-39-7
  • Methylformamide
  • Formamide, N-methyl-
  • Monomethylformamide
Molecular Weight
59.07 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-03-26
  • Modify:
    2025-01-25
Description
N-methylformamide is a clear colorless liquid with a slight amine odor. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
N-methylformamide is a member of the class of formamides having a N-methyl substituent. It is functionally related to a formamide.
N-Methylformamide has been reported in Erythrophyllum delesserioides with data available.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
N-Methylformamide.png

1.2 3D Conformer

1.3 Crystal Structures

1 of 2
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CCDC Number
Associated Article
Crystal Structure Data
Crystal Structure Depiction
Crystal Structure Depiction

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

N-methylformamide
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C2H5NO/c1-3-2-4/h2H,1H3,(H,3,4)
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

ATHHXGZTWNVVOU-UHFFFAOYSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

CNC=O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C2H5NO
Computed by PubChem 2.2 (PubChem release 2021.10.14)
C2H5NO

2.3 Other Identifiers

2.3.1 CAS

123-39-7

2.3.2 European Community (EC) Number

2.3.3 UNII

2.3.4 ChEBI ID

2.3.5 ChEMBL ID

2.3.6 DSSTox Substance ID

2.3.7 HMDB ID

2.3.8 ICSC Number

2.3.9 KEGG ID

2.3.10 Metabolomics Workbench ID

2.3.11 NCI Thesaurus Code

2.3.12 Nikkaji Number

2.3.13 NSC Number

2.3.14 Wikidata

2.3.15 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • methylformamide
  • monomethylformamide
  • N-methylformamide
  • NSC 3051

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
59.07 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
-1
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
0
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
59.037113783 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
59.037113783 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
29.1 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
4
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
20
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

N-methylformamide is a clear colorless liquid with a slight amine odor. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
Colorless liquid; [ICSC] Pale yellow or colorless liquid; [Alfa Aesar MSDS]
Liquid
COLOURLESS VISCOUS LIQUID.

3.2.2 Boiling Point

356 to 365 °F at 760 mmHg (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
180-185 °C
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1037
182.5 °C

3.2.3 Melting Point

-40 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
-5.4 °C
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1037
-3.8 °C
-3 °C

3.2.4 Flash Point

208 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
98 °C
Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. 2nd ed. Volume II: Nitrogen and Phosphorus Solvents. Amsterdam-New York-Oxford: Elsevier, 1990., p. 169
98 °C c.c.

3.2.5 Solubility

greater than or equal to 100 mg/mL at 68 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
Very soluble in acetone, ethanol.
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V3 2813
Miscible in water
Riddick, J.A., W.B. Bunger, Sakano T.K. Techniques of Chemistry 4th ed., Volume II. Organic Solvents. New York, NY: John Wiley and Sons., 1985., p. 655
1000 mg/mL at 25 °C
Solubility in water: good
Water miscible
Ethanol miscible
Ether immiscible

3.2.6 Density

1.011 at 66 °F (NTP, 1992) - Denser than water; will sink
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
0.9961 g/cu cm @ 25 °C
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1037
Density (at 20 °C): 1.003 g/cm³

3.2.7 Vapor Density

Relative vapor density (air = 1): 2.04

3.2.8 Vapor Pressure

0.2 mmHg at 77 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
0.25 [mmHg]
0.253 mm Hg @ 25 °C
Daubert, T.E., R.P. Danner. Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, D.C.: Taylor and Francis, 1989.

3.2.9 LogP

log Kow = -0.97
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 4
-0.97
HANSCH,C ET AL. (1995)
-0.0624

3.2.10 Stability / Shelf Life

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

3.2.11 Autoignition Temperature

613 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

3.2.12 Decomposition

When heated to decomposition it emits toxic fumes of /nitrogen oxides/.
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2243

3.2.13 Viscosity

1.99 mN/s/m @ 15 °C; 1.65 mN/s/m @ 25 °C
Dean, J.A. Handbook of Organic Chemistry. New York, NY: McGraw-Hill Book Co., 1987., p. 4-68

3.2.14 Surface Tension

37.96 dynes/cm @ 30 °C; 35.02 dynes/cm @ 50 °C
Dean, J.A. Handbook of Organic Chemistry. New York, NY: McGraw-Hill Book Co., 1987., p. 4-68

3.2.15 Refractive Index

Index of refraction: 1.4319 @ 20 °C/D
Lide, DR (ed.). CRC Handbook of Chemistry and Physics. 81st Edition. CRC Press LLC, Boca Raton: FL 2000, p. 3-166

3.2.16 Dissociation Constants

pKa = -0.04 @ 20 °C
Riddick, J.A., W.B. Bunger, Sakano T.K. Techniques of Chemistry 4th ed., Volume II. Organic Solvents. New York, NY: John Wiley and Sons., 1985., p. 655

3.2.17 Kovats Retention Index

Standard non-polar
793 , 722
Standard polar
1615

3.2.18 Other Experimental Properties

Dielectric constant: 200.1 @ 15 °C; 182.4 @ 25 °C
Dean, J.A. Handbook of Organic Chemistry. New York, NY: McGraw-Hill Book Co., 1987., p. 4-68

3.3 Chemical Classes

3.3.1 Solvents

Solvents -> Amides (<C10)

4 Spectral Information

4.1 1D NMR Spectra

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1D NMR Spectra
NMR: 9350 (Sadtler Research Laboratories Spectral Collection)
2 of 4
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1D NMR Spectra

4.1.1 1H NMR Spectra

1 of 2
Instrument Name
Varian A-60
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Sigma-Aldrich Co. LLC.
Catalog Number
M46705
Copyright
Copyright © 2021-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2021 John Wiley & Sons, Inc. All Rights Reserved.
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4.1.2 13C NMR Spectra

1 of 2
Copyright
Copyright © 2002-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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2 of 2
Copyright
Copyright © 2002-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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4.1.3 15N NMR Spectra

1 of 2
Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
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2 of 2
Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
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4.1.4 17O NMR Spectra

1 of 2
Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
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2 of 2
Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
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4.2 Mass Spectrometry

4.2.1 GC-MS

1 of 6
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Spectra ID
Instrument Type
EI-B
Ionization Mode
positive
Top 5 Peaks

30.0 99.99

28.0 85.67

59.0 80.69

29.0 36.48

15.0 13.69

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Notes
instrument=HITACHI M-80
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MoNA ID
MS Category
Experimental
MS Type
GC-MS
MS Level
MS1
Instrument
HITACHI M-80
Instrument Type
EI-B
Ionization Mode
positive
Top 5 Peaks

30 99.99

28 85.67

59 80.69

29 36.48

15 13.69

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License
CC BY-NC-SA

4.2.2 Other MS

1 of 2
Other MS
MASS: NIST 143 (NIST/EPA/MCDC Mass Spectral Database 1990 version); NBS 304 (National Bureau of Standards)
2 of 2
Authors
MASS SPECTROSCOPY SOC. OF JAPAN (MSSJ)
Instrument
HITACHI M-80
Instrument Type
EI-B
MS Level
MS
Ionization Mode
POSITIVE
Ionization
ENERGY 70 eV
Top 5 Peaks

30 999

28 857

59 807

29 365

15 137

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License
CC BY-NC-SA

4.3 UV Spectra

(H2O) max = The spectrum E = shows an end absorption with a small shoulder at 280 nm.

4.4 IR Spectra

IR Spectra
IR: 10961 (Sadtler Research Laboratories Prism Collection)

4.4.1 FTIR Spectra

1 of 2
Instrument Name
Bruker IFS 85
Technique
Cell
Copyright
Copyright © 1989, 1990-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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2 of 2
Technique
Layer between KBr
Source of Sample
Fluka
Copyright
Copyright © 1989, 1990-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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4.4.2 ATR-IR Spectra

Source of Sample
Aldrich
Catalog Number
473936
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4.3 Near IR Spectra

1 of 2
Instrument Name
INSTRUMENT PARAMETERS=INST=BRUKER,RSN=19577,REO=2,CNM=HEI,ZFF=2
Technique
NIR Spectrometer= BRUKER IFS 88
Source of Spectrum
Prof. Buback, University of Goettingen, Germany
Copyright
Copyright © 1989, 1990-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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2 of 2
Instrument Name
INSTRUMENT PARAMETERS=INST=BRUKER,RSN=19577,REO=2,CNM=HEI,ZFF=2
Technique
NIR Spectrometer= BRUKER IFS 88
Source of Spectrum
Prof. Buback, University of Goettingen, Germany
Copyright
Copyright © 1989, 1990-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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4.4.4 Vapor Phase IR Spectra

1 of 2
Instrument Name
DIGILAB FTS-14
Technique
Vapor Phase
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Instrument Name
Bruker IFS 85
Technique
Gas-GC
Copyright
Copyright © 1989, 1990-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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4.5 Chromatograms

4.5.1 HPLC

HPLC
Column: µBondapak C 3.9 mm i.d. x 30 cm Mobile Phase: 3% CH3CN Flow Rate: 1 mL/min Detection: UV at 220 nm Sample Preparation: 8 mg/mL in mobile phase or internal standard solution Internal Standard: dimethylacetamide (2mg/mL in mobile phase) Retention Volume: 4.5 mL (NSC - 3051) 9.0 mL (I.S.)

6 Chemical Vendors

7 Drug and Medication Information

7.1 Therapeutic Uses

NMF is an investigational anticancer drug... .
Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. 2nd ed. Volume II: Nitrogen and Phosphorus Solvents. Amsterdam-New York-Oxford: Elsevier, 1990., p. 175

8 Food Additives and Ingredients

8.1 Associated Foods

9 Pharmacology and Biochemistry

9.1 MeSH Pharmacological Classification

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

9.2 Absorption, Distribution and Excretion

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.
Krivanek ND et al; J Occup Med 20 (3): 179-182 (1978)
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/
Baselt, R.C. Biological Monitoring Methods for Industrial Chemicals. 2nd ed. Littleton, MA: PSG Publishing Co., Inc. 1988., p. 128

9.3 Metabolism / Metabolites

It is known that dimethylformamide is metabolized in man by sequential N-demethylation to methylformamide & formamide, which are largely eliminated in the urine.
Baselt, R.C. Biological Monitoring Methods for Industrial Chemicals. 2nd ed. Littleton, MA: PSG Publishing Co., Inc. 1988., p. 128
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.
Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. 2nd ed. Volume II: Nitrogen and Phosphorus Solvents. Amsterdam-New York-Oxford: Elsevier, 1990., p. 170
N-methylformamide has known human metabolites that include Methyl Isocyanate.
S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560

9.4 Mechanism of Action

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.
Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. 2nd ed. Volume II: Nitrogen and Phosphorus Solvents. Amsterdam-New York-Oxford: Elsevier, 1990., p. 174

9.5 Transformations

10 Use and Manufacturing

10.1 Uses

Sources/Uses
Used to make pesticides and methyl isocyanate and as an extraction solvent for aromatic hydrocarbons; [HSDB] Photodegradation product of Fluridone (herbicide) and metabolite of dimethylformamide (CAS# 68-12-2); [REPROTOX]
REPROTOX - Scialli AR, Lione A, Boyle Padgett GK. Reproductive Effects of Chemical, Physical, and Biological Agents. Baltimore: The Johns Hopkins University Press, 1995.
Industrial Processes with risk of exposure
Farming (Pesticides) [Category: Industry]
The substance is used as an intermediate in the synthesis of pesticides; extraction solvent for aromatic hydrocarbons.
Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New York, NY. 2001, p. V2 1495
In the manufacture of methyl isocyanate.
Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p. V14 (1995) 907

10.2 Methods of Manufacturing

BY HEATING THE METHYLAMINE SALT; OR BY REACTION OF METHYLAMINE WITH METHYL OR ETHYL FORMATE
SRI
Methyl formate + methylamine (amide formation)
Ashford, R.D. Ashford's Dictionary of Industrial Chemicals. London, England: Wavelength Publications Ltd., 1994., p. 583

10.3 General Manufacturing Information

EPA TSCA Commercial Activity Status
Formamide, N-methyl-: ACTIVE

11 Identification

11.1 Analytic Laboratory Methods

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/
Snorek SV et al; J Chromatog; 458 : 287-93 (1988)

11.2 Clinical Laboratory Methods

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.
BARNES JR, HENRY NW II; AMER IND HYG ASS J 35 (2): 84-7 (1974)
Methylformamide concentrations in urine may be determined by flame-ionization gas chromatography, involving direct sample introduction.
Baselt, R.C. Biological Monitoring Methods for Industrial Chemicals. 2nd ed. Littleton, MA: PSG Publishing Co., Inc. 1988., p. 129
/Determination of dimethylformamide and N-methylformamide by gas chromatography/.
Cechova-Wicarova O; Prac Lek 37 (10): 384-5 (1985)

12 Safety and Hazards

12.1 Hazards Identification

12.1.1 GHS Classification

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Pictogram(s)
Irritant
Health Hazard
Signal
Danger
GHS Hazard Statements

H312 (100%): Harmful in contact with skin [Warning Acute toxicity, dermal]

H319 (61.1%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H360 (93.7%): May damage fertility or the unborn child [Danger Reproductive toxicity]

Precautionary Statement Codes

P203, P264+P265, P280, P302+P352, P305+P351+P338, P317, P318, P321, P337+P317, P362+P364, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 221 reports by companies from 13 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.

12.1.2 Hazard Classes and Categories

Acute Tox. 4 (100%)

Eye Irrit. 2 (61.1%)

Repr. 1B (93.7%)

Reproductive toxicity - category 1B

Acute toxicity - category 4

12.1.3 Health Hazards

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)

National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.1.4 Fire Hazards

This chemical is combustible. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
Combustible.

12.1.5 Hazards Summary

An eye irritant; May cause liver injury; [ICSC] TLV Basis: Embryo/fetal injury; teratogenic effects; liver injury; A more recent phase I study using oral administration of NMF found elevated hepatic enzymes, mild myelosuppression and worsening of preexistent toxic peripheral neuropathies at 700 mg/m2 (227 mg/kg); [ACGIH] An eye irritant; May cause liver injury; Peripheral neuropathy has been observed in patients during clinical trials; Teratogenic and embryotoxic; Emergency treatment: Dimethylformamide; [HSDB] An eye, mucous membrane, and upper respiratory tract irritant; Can be absorbed through skin; May cause temporary nervous system depression and liver damage; [CAMEO] Irritating to rabbit eyes; Dramatically reduced body weights and increased liver enzymes in 2-week inhalation study of rats at highest dose (970 mg/m3); In rats fed by gavage, over 50% of fetuses malformed at the highest dose tested (75 mg/kg/day), a maternally toxic dose; Similar results obtained in study of rabbits; [EPA HPV] Causes hepatitis in five-day, intermittent, intravenous study of dogs; [RTECS] Embryotoxic in animals at doses maternally toxic; [REPROTOX] An irritant; [Alfa Aesar MSDS] See Dimethylformamide.
ACGIH - Documentation of the TLVs and BEIs, 7th Ed. Cincinnati: ACGIH Worldwide, 2020.
REPROTOX - Scialli AR, Lione A, Boyle Padgett GK. Reproductive Effects of Chemical, Physical, and Biological Agents. Baltimore: The Johns Hopkins University Press, 1995.

12.1.6 Fire Potential

A very dangerous fire hazard when exposed to heat or flame.
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2243

12.1.7 Skin, Eye, and Respiratory Irritations

/N-methylformamide/ is an eye irritant.
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2243

12.2 Safety and Hazard Properties

12.2.1 Lower Explosive Limit (LEL)

1.8 % (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.2.2 Upper Explosive Limit (UEL)

19.7 % (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.3 First Aid Measures

Inhalation First Aid
Fresh air, rest. Refer for medical attention.
Skin First Aid
Rinse skin with plenty of water or shower.
Eye First Aid
First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.
Ingestion First Aid
Rinse mouth. Rest. Refer for medical attention .

12.3.1 First Aid

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)

National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.4 Fire Fighting

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)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
Use powder, carbon dioxide. In case of fire: keep drums, etc., cool by spraying with water.

12.5 Accidental Release Measures

12.5.1 Spillage Disposal

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

12.5.2 Disposal Methods

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.

12.5.3 Preventive Measures

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.

12.6 Handling and Storage

12.6.1 Nonfire Spill Response

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)

National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.6.2 Safe Storage

Separated from oxidants.

12.7 Exposure Control and Personal Protection

12.7.1 Threshold Limit Values (TLV)

1.0 [ppm]
1 ppm as TWA; (skin)

12.7.2 Inhalation Risk

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.

12.7.3 Effects of Short Term Exposure

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

12.7.4 Personal Protective Equipment (PPE)

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)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.7.5 Preventions

Fire Prevention
NO open flames.
Inhalation Prevention
Use ventilation.
Skin Prevention
Protective gloves.
Eye Prevention
Wear safety goggles.
Ingestion Prevention
Do not eat, drink, or smoke during work.

12.8 Stability and Reactivity

12.8.1 Air and Water Reactions

Water soluble.

12.8.2 Reactive Group

Amides and Imides

12.8.3 Reactivity Profile

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)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.8.4 Hazardous Reactivities and Incompatibilities

VIOLENT REACTION WITH BENZENE SULFONYL CHLORIDE.
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2243

12.9 Transport Information

12.9.1 EC Classification

Symbol: T; R: 61-21; S: 53-45; Note: E

12.10 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: Formamide, N-methyl-
California Safe Cosmetics Program (CSCP) Reportable Ingredient

Hazard Traits - Reproductive Toxicity

Authoritative List - EC Annex VI CMRs - Cat. 1B

Report - if used as a fragrance or flavor ingredient

REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
Methylformamide: Does not have an individual approval but may be used under an appropriate group standard

12.11 Other Safety Information

Chemical Assessment

IMAP assessments - Formamide, N-methyl-: Environment tier I assessment

IMAP assessments - Formamide, N-methyl-: Human health tier I assessment

12.11.1 Toxic Combustion Products

When heated to decomposition it emits toxic fumes of /nitrogen oxides/.
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2243

13 Toxicity

13.1 Toxicological Information

13.1.1 Exposure Routes

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

13.1.2 Symptoms

Inhalation Exposure
Cough.
Eye Exposure
Redness. Pain.

13.1.3 Adverse Effects

Neurotoxin - Acute solvent syndrome

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

Reproductive Toxin - A chemical that is toxic to the reproductive system, including defects in the progeny and injury to male or female reproductive function. Reproductive toxicity includes developmental effects. See Guidelines for Reproductive Toxicity Risk Assessment.

13.1.4 Acute Effects

13.1.5 Toxicity Data

LC50 (rat) > 10,760 mg/m3/4hr
ToxicityData
Rat(po): LD50 4000 mg/kg
Journal of Reproduction and Fertility, 4,219,(1962)
ToxicityData
Rat(po): LD50 3500 mg/kg
Journal of Reproduction and Fertility, 4,219,(1962)
ToxicityData
Mouse(po): LD50 2600 mg/kg
Toxicology (Elsevier), 34,173,(1985)
ToxicityData
Mouse(ip): LD50 2300 mg/kg
Toxicology (Elsevier), 34,173,(1985)
ToxicityData
Mouse(sc): LD50 3100 mg/kg
Dissertation Abstracts International, 40,549,(1979)
ToxicityData
Mouse(iv): LD50 1580 mg/kg
Toxicology (Elsevier), 34,173,(1985)
ToxicityData
Mouse(im): LD50 2700 mg/kg
Toxicology (Elsevier), 34,173,(1985)
ToxicityData
Dog(iv): LD10 1262 mg/kg
National Technical Information Service, PB82- 232158

13.1.6 Interactions

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.
HAFEN P ET AL; Z KREBSFORSCH KLIN ONKOL 80 (4): 269-76 (1973)
N-METHYLFORMAMIDE (1.8 G/KG IV) DECR HYPERTENSION INDUCED BY INDIRECTLY ACTING AMINES TYRAMINE & EPHEDRINE.
PHAM-HUU CHANH ET AL; AGRESSOLOGIE 14 (4): 251-8 (1973)
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.
Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. 2nd ed. Volume II: Nitrogen and Phosphorus Solvents. Amsterdam-New York-Oxford: Elsevier, 1990., p. 173
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.
Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. 2nd ed. Volume II: Nitrogen and Phosphorus Solvents. Amsterdam-New York-Oxford: Elsevier, 1990., p. 173

13.1.7 Human Toxicity Excerpts

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.
Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. 2nd ed. Volume II: Nitrogen and Phosphorus Solvents. Amsterdam-New York-Oxford: Elsevier, 1990., p. 172
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.
Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. 2nd ed. Volume II: Nitrogen and Phosphorus Solvents. Amsterdam-New York-Oxford: Elsevier, 1990., p. 175
... /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.
Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. 2nd ed. Volume II: Nitrogen and Phosphorus Solvents. Amsterdam-New York-Oxford: Elsevier, 1990., p. 175
/N-methylformamide/ is an eye irritant.
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2243

13.1.8 Non-Human Toxicity Excerpts

... IN ANIMALS ... FORMAMIDE & MONOMETHYLFORMAMIDE HAVE BEEN SHOWN EXPERIMENTALLY TO BE TERATOGENS /ADMIN BY MOUTH OR PERCUTANEOUSLY/.
International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 137
N-METHYLFORMAMIDE (1.8 G/KG IV) INCR RESP OUTPUT IN ANESTHETIZED DOGS, RESP RHYTHM, AND DIFFERENTIAL ARTERIAL PRESSURE.
PHAM-HUU CHANH ET AL; AGRESSOLOGIE 14 (4): 251-8 (1973)
ACUTE TOXICITY OF FORMAMIDES TO RATS AND MICE WAS IN INCR ORDER: FORMAMIDE, N-METHYLFORMAMIDE, N,N-DIMETHYLFORMAMIDE, N-ETHYLFORMAMIDE, AND N,N-DIETHYLFORMAMIDE. MICE WERE MORE SUSCEPTIBLE THAN RATS. THE COMPOUNDS INDUCED TESTICULAR LESIONS.
PHAM-HUU CHANH ET AL; THERAPIE 26 (3): 409-24 (1971)
MONOMETHYLFORMAMIDE ADMIN BY STOMACH TUBE TO RABBITS FROM 6TH-18TH DAY PAST INSEMINATION SHOWED EMBRYOTOXIC & WEAKLY TERATOGENIC EFFECTS AT CONCN NOT TOXIC TO MOTHER. RABBIT WAS MORE SENSITIVE TO MONOMETHYLFORMAMIDE THAN OTHER SPECIES, WITH FETAL ANOMALIES INDUCED AT DOSES MATERNALLY ACCEPTABLE.
MERKLE J ET AL; ARZNEIM-FORSCH 30 (9): 1557-62 (1980)
For more Non-Human Toxicity Excerpts (Complete) data for N-METHYLFORMAMIDE (7 total), please visit the HSDB record page.

13.1.9 Non-Human Toxicity Values

LD50 BALB/C Mouse ip 2.3 g/kg
Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. 2nd ed. Volume II: Nitrogen and Phosphorus Solvents. Amsterdam-New York-Oxford: Elsevier, 1990., p. 172
LD50 BALB/C Mouse iv 1.58 g/kg
Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. 2nd ed. Volume II: Nitrogen and Phosphorus Solvents. Amsterdam-New York-Oxford: Elsevier, 1990., p. 172
LD50 BALB/C Mouse oral 2.6 g/kg
Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. 2nd ed. Volume II: Nitrogen and Phosphorus Solvents. Amsterdam-New York-Oxford: Elsevier, 1990., p. 172
LD50 BALB/C Mouse im 2.7 g/kg
Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. 2nd ed. Volume II: Nitrogen and Phosphorus Solvents. Amsterdam-New York-Oxford: Elsevier, 1990., p. 172
For more Non-Human Toxicity Values (Complete) data for N-METHYLFORMAMIDE (11 total), please visit the HSDB record page.

13.2 Ecological Information

13.2.1 Environmental Fate / Exposure Summary

N-Methylformamide's production and use as an intermediate in the synthesis of pesticides, as an extraction solvent for aromatic hydrocarbons, and in the manufacture of methyl isocyanate may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 0.25 mm Hg at 25 °C indicates N-methylformamide will exist solely as a vapor in the ambient atmosphere. Vapor-phase N-methylformamide will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 57 hours. If released to soil, N-methylformamide is expected to have very high mobility based upon an estimated Koc of 7. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 2.0X10-8 atm-cu m/mole. N-Methylformamide has been shown to biodgrade by microorganisms obtained through soil enrichment. If released into water, N-methylformamide is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. 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; therefore, N-methylformamide may biodegrade in the aquatic environment. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected since amides hydrolyze very slowly at environmental conditions. Occupational exposure to N-methylformamide may occur through inhalation and dermal contact with this compound at workplaces where N-methylformamide is produced or used. Monitoring data indicate that the general population may be exposed to N-methylformamide via inhalation of cigarette smoke. (SRC)

13.2.2 Artificial Pollution Sources

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).
(1) Verschueren K; Handbook of Environmental Data on Organic Chemicals. 4th ed. NY, NY: John Wiley and Sons, 2: 1495 (2001)
(2) Richter RH, Priester RD; Kirk-Othmer Encycl Chem Technol 4th ed. NY, NY: John Wiley and Sons 14: 907 (1995)
(3) Schumacher JN et al; J Agric Food Chem 25: 310-20 (1977)
(4) Pitts JN et al; Environ Sci Technol 12: 946-53 (1978)
(5) Saunders DG; J Agric Food Chem 31: 237-41 (1983)

13.2.3 Environmental Fate

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).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 4 (1995)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9 (1990)
(4) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals: Data Compilation. Design Inst Phys Prop Data, Amer Inst Chem Eng New York, NY: Hemisphere Pub Corp 5 Vol (1989)
(5) Howard PH, Meylan WM; Handbook of Physical Properties of Organic Chemicals. Boca Raton, FL: CRC Lewis Publishers, p. 245 (1997)
(6) Doxtader KG, Alexander M; Soil Sci Soc Amer Proc 30: 351-6 (1966)
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).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 4 (1995)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9, 15-1 to 15-29 (1990)
(4) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals: Data Compilation. Design Inst Phys Prop Data, Amer Inst Chem Eng NY, NY: Hemisphere Pub Corp 5 Vol (1989)
(5) Howard PH, Meylan WM; Handbook of Physical Properties of Organic Chemicals. Boca Raton, FL: CRC Lewis Publishers, p. 245 (1997)
(6) Franke C et al; Chemosphere 29: 1501-14 (1994)
(7) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
(8) Verschueren K; Handbook of Environmental Data on Organic Chemicals. 4th ed. NY, NY: John Wiley and Sons 2: 1495 (2001)
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).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals: Data Compilation. Design Inst Phys Prop Data, Amer Inst Chem Eng NY, NY: Hemisphere Pub Corp 5 Vol (1989)
(3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)

13.2.4 Environmental Biodegradation

AEROBIC: 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(1). Using the BOD test, N-methylformamide achieved 2% of its theoretical BOD after 5 days(1). N-Methylformamide has also been shown to biodegrade by microorgansism obtained through soil enrichment(2). Therefore, N-methylformamide may biodegrade in the environment(SRC).
(1) Verschueren K; Handbook of Environmental Data on Organic Chemicals. 4th ed. NY, NY: John Wiley and Sons, 2: 1495 (2001)
(2) Doxtader KG, Alexander M; Soil Sci Soc Amer Proc 30: 351-6 (1966)

13.2.5 Environmental Abiotic Degradation

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).
(1) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(2) Mabey W, Mill T; J Phys Chem Ref Data 7:383-415 (1978)

13.2.6 Environmental Bioconcentration

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).
(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 4 (1995)
(2) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

13.2.7 Soil Adsorption / Mobility

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).
(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 4 (1995)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9 (1990)
(3) Swann RL et al; Res Rev 85: 17-28 (1983)

13.2.8 Volatilization from Water / Soil

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).
(1) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals: Data Compilation. Design Inst Phys Prop Data, Amer Inst Chem Eng NY, NY: Hemisphere Pub Corp 5 Vol (1989)
(2) Riddick JA et al; Organic Solvents: Physical Properties and Methods of Purification. Techniques of Chemistry. 4th Ed. NY, NY: Wiley-Interscience p. 655 (1986)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)

13.2.9 Fish / Seafood Concentrations

N-Methylformamide has been detected at concns of 0.09 and 4.06 ug/g in two samples of mussel collected at the Oarai Coast in Ibaraki, Japan on July 31, 1985 and July 31, 1986, respectively(1).
(1) Yasuhara A, Morita M; Chemosphere 16: 2559-65 (1987)

13.2.10 Other Environmental Concentrations

N-Methylformamide has been detected in cigarette smoke(1).
(1) Schumacher JN et al; J Agric Food Chem 25: 310-20 (1977)

13.2.11 Probable Routes of Human Exposure

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).
(1) Casal Lareo A, Perbellini L; Int Arch Occup Environ Health 67: 47-52 (1995)

13.2.12 Body Burden

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).
(1) Casal Lareo A, Perbellini L; Int Arch Occup Environ Health 67:47-52 (1995)

14 Associated Disorders and Diseases

Associated Occupational Diseases with Exposure to the Compound
Solvents, acute toxic effect [Category: Acute Poisoning]

15 Literature

15.1 Consolidated References

15.2 NLM Curated PubMed Citations

15.3 Springer Nature References

15.4 Thieme References

15.5 Nature Journal References

15.6 Chemical Co-Occurrences in Literature

15.7 Chemical-Gene Co-Occurrences in Literature

15.8 Chemical-Disease Co-Occurrences in Literature

16 Patents

16.1 Depositor-Supplied Patent Identifiers

16.2 WIPO PATENTSCOPE

16.3 Chemical Co-Occurrences in Patents

16.4 Chemical-Disease Co-Occurrences in Patents

16.5 Chemical-Gene Co-Occurrences in Patents

17 Interactions and Pathways

17.1 Chemical-Target Interactions

18 Biological Test Results

18.1 BioAssay Results

19 Taxonomy

The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106

20 Classification

20.1 MeSH Tree

20.2 NCI Thesaurus Tree

20.3 ChEBI Ontology

20.4 ChemIDplus

20.5 CAMEO Chemicals

20.6 UN GHS Classification

20.7 NORMAN Suspect List Exchange Classification

20.8 EPA DSSTox Classification

20.9 EPA TSCA and CDR Classification

20.10 LOTUS Tree

20.11 EPA Substance Registry Services Tree

20.12 MolGenie Organic Chemistry Ontology

21 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
  2. CAMEO Chemicals
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    https://cameochemicals.noaa.gov/help/reference/terms_and_conditions.htm?d_f=false
    CAMEO Chemical Reactivity Classification
    https://cameochemicals.noaa.gov/browse/react
  3. CAS Common Chemistry
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    https://creativecommons.org/licenses/by-nc/4.0/
  4. ChemIDplus
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    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
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  6. EPA Chemicals under the TSCA
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    https://www.epa.gov/tsca-inventory
  7. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  8. European Chemicals Agency (ECHA)
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    https://echa.europa.eu/web/guest/legal-notice
  9. FDA Global Substance Registration System (GSRS)
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  10. Hazardous Substances Data Bank (HSDB)
  11. Human Metabolome Database (HMDB)
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    http://www.hmdb.ca/citing
  12. ILO-WHO International Chemical Safety Cards (ICSCs)
  13. New Zealand Environmental Protection Authority (EPA)
    LICENSE
    This work is licensed under the Creative Commons Attribution-ShareAlike 4.0 International licence.
    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
  14. California Safe Cosmetics Program (CSCP) Product Database
  15. Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
    LICENSE
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    https://haz-map.com/About
  16. ChEBI
  17. LOTUS - the natural products occurrence database
    LICENSE
    The code for LOTUS is released under the GNU General Public License v3.0.
    https://lotus.nprod.net/
  18. NCI Thesaurus (NCIt)
    LICENSE
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    https://www.cancer.gov/policies/copyright-reuse
  19. NCI Investigational Drugs
  20. ChEMBL
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    http://www.ebi.ac.uk/Information/termsofuse.html
  21. Comparative Toxicogenomics Database (CTD)
    LICENSE
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    http://ctdbase.org/about/legal.jsp
  22. Drug Gene Interaction database (DGIdb)
    LICENSE
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    http://www.dgidb.org/downloads
  23. Crystallography Open Database (COD)
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    https://creativecommons.org/publicdomain/zero/1.0/
  24. Hazardous Chemical Information System (HCIS), Safe Work Australia
  25. NITE-CMC
    N-methylformamide - FY2018 (Revised classification)
    https://www.chem-info.nite.go.jp/chem/english/ghs/18-mhlw-2014e.html
    N-methylformamide - FY2007 (New/original classication)
    https://www.chem-info.nite.go.jp/chem/english/ghs/07-meti-0018e.html
  26. Regulation (EC) No 1272/2008 of the European Parliament and of the Council
    LICENSE
    The copyright for the editorial content of this source, the summaries of EU legislation and the consolidated texts, which is owned by the EU, is licensed under the Creative Commons Attribution 4.0 International licence.
    https://eur-lex.europa.eu/content/legal-notice/legal-notice.html
  27. FooDB
    LICENSE
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    https://foodb.ca/about
  28. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    n-methylformamide
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  29. NMRShiftDB
  30. MassBank Europe
  31. MassBank of North America (MoNA)
    LICENSE
    The content of the MoNA database is licensed under CC BY 4.0.
    https://mona.fiehnlab.ucdavis.edu/documentation/license
  32. NIST Mass Spectrometry Data Center
    LICENSE
    Data covered by the Standard Reference Data Act of 1968 as amended.
    https://www.nist.gov/srd/public-law
  33. SpectraBase
  34. Japan Chemical Substance Dictionary (Nikkaji)
  35. KEGG
    LICENSE
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    https://www.kegg.jp/kegg/legal.html
  36. Natural Product Activity and Species Source (NPASS)
  37. Metabolomics Workbench
  38. Nature Chemistry
  39. Springer Nature
  40. The Cambridge Structural Database
  41. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
  42. Wikidata
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  44. PubChem
  45. Medical Subject Headings (MeSH)
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    https://www.nlm.nih.gov/copyright.html
    Radiation-Sensitizing Agents
    https://www.ncbi.nlm.nih.gov/mesh/68011838
  46. GHS Classification (UNECE)
  47. EPA Substance Registry Services
  48. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  49. PATENTSCOPE (WIPO)
  50. NCBI
CONTENTS