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N,N-Dimethyl-p-toluidine

PubChem CID
7471
Structure
N,N-Dimethyl-p-toluidine_small.png
N,N-Dimethyl-p-toluidine_3D_Structure.png
Molecular Formula
Synonyms
  • N,N-Dimethyl-p-toluidine
  • 99-97-8
  • N,N,4-TRIMETHYLANILINE
  • Dimethyl-p-toluidine
  • Benzenamine, N,N,4-trimethyl-
Molecular Weight
135.21 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-03-26
  • Modify:
    2024-12-27
Description
N,N-Dimethyl-p-toluidine can cause cancer according to The National Toxicology Program.
N,n-dimethyl-p-toluidine appears as a clear colorless liquid with an aromatic odor. Density 0.937 g / cm3 (Lancaster) and insoluble in water. Hence floats on water. Toxic by skin absorption and inhalation. May release toxic vapors when burned.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
N,N-Dimethyl-p-toluidine.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

N,N,4-trimethylaniline
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C9H13N/c1-8-4-6-9(7-5-8)10(2)3/h4-7H,1-3H3
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

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

2.1.4 SMILES

CC1=CC=C(C=C1)N(C)C
Computed by OEChem 2.3.0 (PubChem release 2021.10.14)

2.2 Molecular Formula

C9H13N
Computed by PubChem 2.2 (PubChem release 2021.10.14)

C9H13N

CH3C6H4N(CH3)2

2.3 Other Identifiers

2.3.1 CAS

99-97-8

2.3.2 Deprecated CAS

129899-34-9

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 UN Number

2.3.6 ChEMBL ID

2.3.7 DSSTox Substance ID

2.3.8 HMDB ID

2.3.9 ICSC Number

2.3.10 NCI Thesaurus Code

2.3.11 Nikkaji Number

2.3.12 NSC Number

2.3.13 Wikidata

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • dimethyl-4-toluidine
  • dimethyl-p-toluidine
  • dimethyl-para-toluidine
  • N,N-dimethyl-p-toluidine

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
135.21 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
2.8
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
0
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
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
135.104799419 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
135.104799419 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
3.2Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
10
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
90.9
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,n-dimethyl-p-toluidine appears as a clear colorless liquid with an aromatic odor. Density 0.937 g / cm3 (Lancaster) and insoluble in water. Hence floats on water. Toxic by skin absorption and inhalation. May release toxic vapors when burned.
Liquid
Clear colorless liquid with an aromatic odor. [CAMEO]
YELLOW-BROWN VISCOUS (TECHNICAL-GRADE PRODUCT) LIQUID WITH CHARACTERISTIC ODOUR.

3.2.2 Color / Form

Clear colorless liquid
NOAA; CAMEO Chemicals. Database of Hazardous Materials. N,N-Dimethyl-p-toluidine (99-97-8). Natl Ocean Atmos Admin, Off Resp Rest; NOAA Ocean Serv. Available from, as of Jul 3, 2014: https://cameochemicals.noaa.gov/
Colorless to brown oil
Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New York, NY. 2001, p. V1: 944

3.2.3 Odor

Aromatic
NOAA; CAMEO Chemicals. Database of Hazardous Materials. N,N-Dimethyl-p-toluidine (99-97-8). Natl Ocean Atmos Admin, Off Resp Rest; NOAA Ocean Serv. Available from, as of Jul 3, 2014: https://cameochemicals.noaa.gov/

3.2.4 Boiling Point

211 °C
Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 94th Edition. CRC Press LLC, Boca Raton: FL 2013-2014, p. 3-368
215 °C

3.2.5 Flash Point

76 °C (closed cup)
ALS Environmental; N,N-dimethyl-p-toluidine (99-97-8). Available from, as of September 11, 2014: https://www.caslab.com/N-N-dimethyl-p-toluidine_CAS_99-97-8/
83 °C

3.2.6 Solubility

In water, 455 mg/L
Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New York, NY. 2001, p. V1: 944
In water, 650 mg/L at 37 °C
US EPA; High Production Volume Information System (HPVIS). HPV Chemical Hazard Characterizations. Monocyclic Aromatic Amines Category. Sept 2009. Available from, as of Jul 16, 2014: https://iaspub.epa.gov/oppthpv/hpv_hc_characterization.get_report?doctype=2
Miscible with ethanol, ethyl ether; soluble in carbon tetrachloride
Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 94th Edition. CRC Press LLC, Boca Raton: FL 2013-2014, p. 3-368
Solubility in water, g/l at 37 °C: 0.65 (very slightly soluble)

3.2.7 Density

0.9366 g/cu cm at 20 °C
Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 94th Edition. CRC Press LLC, Boca Raton: FL 2013-2014, p. 3-368
Relative density (water = 1): 0.9

3.2.8 Vapor Density

Relative vapor density (air = 1): 4.7

3.2.9 Vapor Pressure

0.17 [mmHg]
0.178 mm Hg at 25 °C
Chao J et al; J Chem Phys Ref Data 12: 1033-63 (1983)

3.2.10 LogP

log Kow = 2.81
Sangster J; LOGKOW Database. A databank of evaluated octanol-water partition coefficients (Log P). Available from, as of Jul 3, 2014: https://logkow.cisti.nrc.ca/logkow/search.html
2.61

3.2.11 Stability / Shelf Life

Stable under recommended storage conditions.
Sigma-Aldrich Corp; Safety Data Sheet for 4,N,N-Trimethylaniline (Product Number: D189006) Version 4.6 (March 18, 2014). Available from, as of June 18, 2014: https://www.sigmaaldrich.com/safety-center.html

3.2.12 Decomposition

When heated to decomposition ir emits toxic vapors of NOx
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3579

3.2.13 Refractive Index

Index of refraction: 1.5366 at 20 °C/D
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. V1: 573

3.2.14 Dissociation Constants

pKa = 5.63 at 25 °C (conjugate acid)
Perrin DD; Dissociation Constants of Organic Bases in Aqueous Solution. IUPAC Chem Data Ser, Buttersworth, London (1965)

3.2.15 Kovats Retention Index

Standard non-polar
1160.4, 1162, 1163
Standard polar
1642.6, 1673.9, 1673.9

3.3 SpringerMaterials Properties

3.4 Chemical Classes

Nitrogen Compounds -> Amines, Aromatic

3.4.1 Cosmetics

Cosmetics ingredient -> Other (Specify); Solvent

4 Spectral Information

4.1 1D NMR Spectra

1 of 2
1D NMR Spectra
1H NMR: 3171 (Sadtler Research Laboratories spectral collection)
2 of 2
1D NMR Spectra

4.1.1 1H NMR Spectra

1 of 2
Instrument Name
Varian A-60
Source of Sample
The Matheson Company, Inc., East Rutherford, New Jersey
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
D189006
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
Source of Sample
MCB Manufacturing Chemists, Norwood, Ohio
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. 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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4.2 Mass Spectrometry

4.2.1 GC-MS

1 of 7
View All
MoNA ID
MS Category
Experimental
MS Type
GC-MS
MS Level
MS1
Instrument
HITACHI RMU-6M
Instrument Type
EI-B
Ionization Mode
positive
Top 5 Peaks

134 99.99

91 19.20

119 13.50

118 12.10

65 10.10

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License
CC BY-NC-SA
2 of 7
View All
MoNA ID
MS Category
Experimental
MS Type
GC-MS
MS Level
MS1
Instrument
HITACHI RMU-6M
Instrument Type
EI-B
Ionization Mode
positive
Top 5 Peaks

135 99.99

134 96.60

136 10.20

119 9.40

91 8.40

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License
CC BY-NC-SA

4.2.2 Other MS

1 of 3
View All
Other MS
MASS: 70906 (NIST/EPA/MSDC Mass Spectral Database, 1990 version)
2 of 3
View All
Authors
YAMAMOTO M, DEP. CHEMISTRY, FAC. SCIENCE, NARA WOMEN'S UNIV.
Instrument
HITACHI RMU-6M
Instrument Type
EI-B
MS Level
MS
Ionization Mode
POSITIVE
Ionization
ENERGY 70 eV
Top 5 Peaks

134 999

91 192

119 135

118 121

65 101

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License
CC BY-NC-SA

4.3 UV Spectra

UV: 1119 (Sadtler Research Laboratories spectral collection)
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. V1: 573

4.4 IR Spectra

IR Spectra
IR: 3171 (Sadtler Research Laboratories IR grating collection)

4.4.1 FTIR Spectra

1 of 2
Technique
CAPILLARY CELL: NEAT
Source of Sample
The Matheson Company, Inc., East Rutherford, New Jersey
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
Cell
Source of Sample
Fluka Feinchemikalien GmbH Neu-Ulm
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
D189006
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
BRUKER IFS 88
Technique
NIR
Source of Spectrum
Prof. Buback, University of Goettingen, Germany
Copyright
Copyright © 1989, 1990-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
Thumbnail
Thumbnail
2 of 2
Instrument Name
BRUKER IFS 88
Technique
NIR
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.
Thumbnail
Thumbnail
2 of 2
Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Sigma-Aldrich Co. LLC.
Catalog Number
D189006
Copyright
Copyright © 2021-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2021 John Wiley & Sons, Inc. All Rights Reserved.
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4.5 Raman Spectra

Catalog Number
D189006
Copyright
Copyright © 2017-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2017-2024 John Wiley & Sons, Inc. All Rights Reserved.
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6 Chemical Vendors

7 Pharmacology and Biochemistry

7.1 Absorption, Distribution and Excretion

DMPT is used as a polymerization accelerator in the manufacture of bone cements and dental materials, in industrial glues, and as an intermediate in dye and pesticide synthesis. Thus, there is potential for human exposure to DMPT, an aromatic amine with a structural alert for potential DNA reactivity. The National Toxicology Program (NTP) is evaluating the toxicity and carcinogenicity of DMPT in male and female Fischer 344 rats and B6C3F1 mice. To aid in the design and interpretation of those studies, we have investigated the excretion and tissue distribution of oral and intravenous (IV) doses of radiolabeled DMPT in these strains of rodents. A single low (2.5 mg/kg), mid (25 mg/kg) or high (250 mg/kg) dose of carbon-14 labeled DMPT was administered. Excreta collected for up to 72 hr after dosing and tissues collected at sacrifice were analyzed for total radioactivity. Early studies were terminated at 72 hr. After a low IV dose to male rats ~100% of the dose was excreted and <2% was recovered in tissues at 72 hr. The high oral dose was acutely toxic to male mice. The same oral dose was not overtly toxic to male rats, and by 72 hr 86% of the dose was excreted and 2% remained in tissues. Subsequent studies were terminated at 24 hr to better understand the tissue distribution of radioactivity at earlier time points, which are more relevant to the interpretation of repeated dose toxicity studies. After the high oral dose to male rats ~18% of the dose was recovered in tissues and ~72% was excreted by 24 hr. In contrast, at the low and mid doses most of the radioactivity (~83-100%) was excreted by 24 hr and <5% remained in tissues. In summary, DMPT derived radioactivity was rapidly excreted by rats and mice after a single oral or IV dose and no striking sex differences in DMPT disposition were observed within a species. However, dose dependent differences in toxicity and disposition were observed. These data will be used to aid in the interpretation of safety/toxicity studies of DMPT conducted by the NTP.
Dix KJ et al; Toxicol Sci 90 (1-S): 116 (2006)
DMPT is a high-production-volume chemical used in the manufacture of bone cements and dental materials, is found in industrial glues and artifical fingernail preparations, and is used as an intermediate in dye and pesticide synthesis. Human exposure to DMPT has resulted in methemoglobinemia and allergic responses; suspected from the formation of a toxic metabolite, p methylphenylhydroxylamine, an analog of the aniline metabolite phenylhydroxlyamine (thought to be responsible for methemoglobinemia from aniline exposure). ...results of disposition studies of DMPT in Fisher 344 (F344) rats and B6C3F1 mice after oral administration of [(14)C]DMPT /were previously reported/. The majority of [(14)C]DMPT-derived radioactivity was excreted in urine by 24 hours. /This study/ report on the metabolism of orally administered DMPT. The profile of radiolabeled metabolites was determined by liquid chromatography (HPLC) using a C18 stationary phase and a mobile phase that transitioned from mostly water (polar) to mostly organic (neutral). The same four radiolabeled chromatographic peaks were observed in both rats and mice. Due to the limited volume of mouse urine, further work to elucidate the DMPT metabolite structures was performed with rat urine only. All four peaks have been isolated and preliminary structural elucidation by gas chromatography/mass spectrometry (GC/MS) and comparison to authentic standards confirmed excretion of the parent compound. We have tentatively identified a second peak by GC/MS as N-methyl-p-toluidine. A third peak had different HPLC and GC retention times than DMPT but an identical electron impact mass spectrum. Attempts at preliminary identification of the most polar metabolite have been unsuccessful. Further purification coupled with infrared and nuclear magenetic resonance spectroscopy will be employed along with incubation of isolated metabolites with glucuronidase and sulfatase enzymes (to assess conjugation) to complete structural elucidation/confirmation
Ghanbari K et al; Toxicologist 78 (1-S): 299 (2004)

7.2 Metabolism / Metabolites

The metabolism of orally administered N,N-dimethyl-p-toluidine (DMPT) in male F344 rats was investigated. The rat urinary metabolite profile was determined by analytical reverse-phase high performance liquid chromatography (HPLC). Four radiolabeled peaks were observed, isolated, and purified by solid-phase extraction (SPE) and preparative HPLC methods. The 4 peaks were identified as p-(N-acetylhydroxyamino)hippuric acid (M1), DMPT N-oxide (M2), N-methyl-p-toluidine (M3), and parent DMPT. Metabolites M1 and M2 were identified by spectrometric and spectroscopic methods, including mass fragmentation pattern identification from both liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry, and from chemical analysis of nuclear magnetic resonance spectra. Structural confirmation of metabolite M2 was accomplished by comparison with a synthetic standard. Peaks M3 and the peak suspected to be DMPT were identified by comparison of their HPLC retention times and mass fragmentation patterns with authentic standards of N-methyl-p-toluidine and DMPT, respectively. DMPT metabolism is similar to that reported for N,N-dimethylaniline.
Kim NC et al; J Toxicol Environ Health A 70 (10): 781-8 (2007)

8 Use and Manufacturing

8.1 Uses

EPA CPDat Chemical and Product Categories
The Chemical and Products Database, a resource for exposure-relevant data on chemicals in consumer products, Scientific Data, volume 5, Article number: 180125 (2018), DOI:10.1038/sdata.2018.125
Sources/Uses
Used to accelerate polymerization of ethyl methacrylate; Used in artificial nail application; [Olson, p. 702]
Olson - Olson KR (ed). Poisoning & Drug Overdose, 7th Ed. New York: Lange Medical Books/McGraw-Hill, 2018., p. 702
Industrial Processes with risk of exposure
N,N-Dimethyl-p-toluidine is an accelerator in the redox initiator-accelerator system used commercially to cure methyl methacrylate monomers. Polymerization is rarely complete
NTP; TOXICOLOGY AND CARCINOGENESIS STUDIES OF N,N-DIMETHYL-p-TOLUIDINE (CAS NO. 99-97-8) IN F344/N RATS AND B6C3F1/N MICE (GAVAGE STUDIES) NTP TR 579 NIH Publication No. 12-5921 (September 2012) https://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=99-97-
N,N-Dimethyl-p-toluidine is a high-production volume chemical with potential for widespread human exposure through its use in dental materials and bone cements
NTP; TOXICOLOGY AND CARCINOGENESIS STUDIES OF N,N-DIMETHYL-p-TOLUIDINE (CAS NO. 99-97-8) IN F344/N RATS AND B6C3F1/N MICE (GAVAGE STUDIES) NTP TR 579 NIH Publication No. 12-5921 (September 2012) https://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=99-97-
N,N-Dimethyl-p-toluidine has been used in the preparation of acrylic denture materials for the past 50 years. It is used as the accelerator for the cement in most of the hip and bone replacements to activate the polymerization reaction at concentrations ranging from 0.7% to 2.6% . N,N-Dimethyl-p-toluidine is found in industrial glues and artificial fingernail preparations and is used as an intermediate in dye and pesticide synthesis. It has a shorter setting time (11.5 minutes) than some alternative accelerators.
NTP; TOXICOLOGY AND CARCINOGENESIS STUDIES OF N,N-DIMETHYL-p-TOLUIDINE (CAS NO. 99-97-8) IN F344/N RATS AND B6C3F1/N MICE (GAVAGE STUDIES) NTP TR 579 NIH Publication No. 12-5921 (September 2012) https://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=99-97-

8.1.1 Industry Uses

  • Intermediates
  • Not Known or Reasonably Ascertainable
  • Paint additives and coating additives not described by other categories

8.1.2 Consumer Uses

Paint additives and coating additives not described by other categories

8.1.3 Household Products

California Safe Cosmetics Program (CSCP)

Cosmetics product ingredient: N,N-Dimethyl-p-toluidine (Dimethyltolylamine)

Reason for Listing:

- Known to cause cancer under Health and Safety Code section 25249.8 of the California Safe Drinking Water and Toxic Enforcement Act of 1986 (Prop 65).

- Group 2B carcinogen identified by the International Agency for Research on Cancer.

Potential Health Impacts: Carcinogenicity

Product count: 59

8.2 U.S. Production

Aggregated Product Volume

2019: 500,000 - <1,000,000 lb

2018: <1,000,000 lb

2017: <1,000,000 lb

2016: <1,000,000 lb

Benzenamine, N,N,4-trimethyl- is listed as a High Production Volume (HPV) chemical (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).
EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program. Benzenamine, N,N,4-trimethyl- (99-97-8). Available from, as of June 28, 2014: https://www.epa.gov/hpv/pubs/general/opptsrch.htm
Production volumes for non-confidential chemicals reported under the Inventory Update Rule.
Year
1986
Production Range (pounds)
10 thousand - 500 thousand
Year
1990
Production Range (pounds)
10 thousand - 500 thousand
Year
1994
Production Range (pounds)
>1 million - 10 million
Year
1998
Production Range (pounds)
>1 million - 10 million
Year
2002
Production Range (pounds)
>500 thousand - 1 million
US EPA; Non-confidential Production Volume Information Submitted by Companies for Chemicals Under the 1986-2002 Inventory Update Rule (IUR). Benzenamine, N,N,4-trimethyl- (99-97-8). Available from, as of June 28, 2014: https://epa.gov/cdr/tools/data/2002-vol.html
Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: Benzenamine, N,N,4-trimethyl-. Aggregated National Production Volume: 1 to < 10 million pounds.
US EPA; Non-Confidential 2006 Inventory Update Reporting. National Chemical Information. Benzenamine, N,N,4-trimethyl- (99-97-8). Available from, as of June 28, 2014: https://cfpub.epa.gov/iursearch/index.cfm
Non-confidential 2014 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Benzenamine, N,N,4-trimethyl-. National Production Volume: 1,000,000 - 10,000,000 lb/yr.
USEPA/Pollution Prevention and Toxics; 2014 Chemical Data Reporting Database. Benzenamine, N,N,4-trimethyl- (99-97-8). Available from, as of June 28, 2014: https://java.epa.gov/oppt_chemical_search/

8.3 General Manufacturing Information

Industry Processing Sectors
  • Plastics Material and Resin Manufacturing
  • Not Known or Reasonably Ascertainable
  • Miscellaneous Manufacturing
EPA TSCA Commercial Activity Status
Benzenamine, N,N,4-trimethyl-: ACTIVE
The residual amounts of N,N-dimethyl-p-toluidine in acrylic resins have been reported to be 0.6% after storage in water for up to 15 months. Others have detected up to 0.2% of N,N-dimethyl-p-toluidine in methyl methacrylates after long term implantation...
NTP; TOXICOLOGY AND CARCINOGENESIS STUDIES OF N,N-DIMETHYL-p-TOLUIDINE (CAS NO. 99-97-8) IN F344/N RATS AND B6C3F1/N MICE (GAVAGE STUDIES) NTP TR 579 NIH Publication No. 12-5921 (September 2012) https://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=99-97-
Acryl resins used in dental practice are blends of poly(methyl methacrylated) particles and methyl methacrylate monomer, or copolymers of methyl methacrylate with styrene or other acrylic monomers. This blend is a slurry of high viscosity that is hardened by the free radical polymerization of the monomeric components. The hardening process is initiated by the decomposition of a small quantity of organic peroxides (1% to 3%; usually benzoyl peroxide) activated by the redox reaction with the tertiary amine. The tertiary amine, most often N,N-dimethyl-p-toluidine, is the ingredient that induces the reaction giving rise to free radicals capable of initiating polymerization of the acrylic monomers. Polymerization is rarely complete.
NTP; TOXICOLOGY AND CARCINOGENESIS STUDIES OF N,N-DIMETHYL-p-TOLUIDINE (CAS NO. 99-97-8) IN F344/N RATS AND B6C3F1/N MICE (GAVAGE STUDIES) NTP TR 579 NIH Publication No. 12-5921 (September 2012) https://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=99-97-

9 Identification

9.1 Analytic Laboratory Methods

Method: NIOSH 2002, Issue 2; Procedure: gas chromatography with flame ionization detection; Analyte: N,N-dimethyl-p-toluidine; Matrix: air; Detection Limit: 0.01 mg/sample.
CDC; NIOSH Manual of Analytical Methods, 4th ed. N,N-Dimethyl-p-toluidine (99-97-8). Available from, as of July 21, 2014: https://www.cdc.gov/niosh/docs/2003-154/
Methyl methacrylate polymer (PolyMMA) is widely used as the composite resin for the dental plate. During the fabrication process of PolyMMA for the polymerization reaction, benzoylperoxide (BPO) and N,N-dimethyl p-toluidine (DMPT) are added as the initiator and the stimulator, respectively. Because these compounds exhibit toxicity as well as a residue potential, their use raises concerns regarding human safety. The degree of dissolution into serum was determined to evaluate risk to the user. Analysis was by HPLC combined with solid-phase extraction using a C-18 column. The eluted compounds were found to be in the order of 10 to 100 ppm.
Shintani H et al; J Anal Toxicol 17 (2): 73-8 (1993)
Five commercially available bone cements were analysed by high-performance liquid chromatography for detecting the residual content of an accelerator, the amine N,N-dimethyl-p-toluidine (DMPT), after curing. It was found that the concentration of DMPT in aqueous extracts decreases with time, being almost absent 7 days after curing. Differences were noticed among the cements; residual DMPT is higher in cements prepared with higher content of the amine. It is verified that DMPT's toxic effect on cell cultures is dose-related; a delay in the cell replication cycle is induced in vitro. Damage is reversible, thus justifying the low bone cement toxicity that is clinically ascertained.
Stea S et al; Biomaterials 18 (3): 243-6 (1997)
The use of solid phase extraction (SPE) and high performance liquid chromatography (HPLC) for the analysis of toxic components eluted from methyl-methacrylate polymer (pMMA) dental materials was described. Two pMMA composite resins, Yunifast and Acron, were analyzed. Yunifast was polymerized at room temperature, and Acron at 100 degrees-C. Each sample was then placed in equine serum at room temperature, and serum was replaced daily. The serum extract was subjected to SPE and HPLC, for methyl-methacrylate, N,N-dimethyl-p-toluidine (DMPT), and benzoylperoxide (BPO) (initiator and stimulator for the polymerization) analysis. Results showed that the MMA and DMPT eluted was in the order of 10 to 100 parts per million. Almost negligible amounts of BPO and benzoic-acid were also eluted. A greater amount of these compounds was eluted from Yunifast, a more pliant material. DMPT showed greater elution than MMA. The hydrophilic portion of Yunifast was more cytotoxic than the hydrophobic portion, and contained BA and p-toluidine as major and minor components. The /study/ conclude that the rigidity of the material is critical to the extractable quantity, and recommend that both Yunifast and Acron be immersed in hot water before use in order to remove hydrophilic toxic compounds from these pMMA dental materials.
Shintani H et al; Journal of Analytical Toxicology 17(2): 73-78(1993)

9.2 NIOSH Analytical Methods

10 Safety and Hazards

10.1 Hazards Identification

10.1.1 GHS Classification

1 of 7
View All
Note
Pictograms displayed are for 99.8% (545 of 546) of reports that indicate hazard statements. This chemical does not meet GHS hazard criteria for 0.2% (1 of 546) of reports.
Pictogram(s)
Acute Toxic
Health Hazard
Environmental Hazard
Signal
Danger
GHS Hazard Statements

H301+H311+H331 (19.2%): Toxic if swallowed, in contact with skin or if inhaled [Danger Acute toxicity, oral; acute toxicity, dermal; acute toxicity, inhalation]

H301 (99.6%): Toxic if swallowed [Danger Acute toxicity, oral]

H311 (97.3%): Toxic in contact with skin [Danger Acute toxicity, dermal]

H331 (94.9%): Toxic if inhaled [Danger Acute toxicity, inhalation]

H373 (99.6%): May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

H410 (13%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

H412 (86.8%): Harmful to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

Precautionary Statement Codes

P260, P261, P262, P264, P270, P271, P273, P280, P301+P316, P302+P352, P304+P340, P316, P319, P321, P330, P361+P364, P391, P403+P233, 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 546 reports by companies from 29 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 1 of 546 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 28 notifications provided by 545 of 546 reports by companies with hazard statement code(s).

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.

10.1.2 Hazard Classes and Categories

Acute Tox. 3 (99.6%)

Acute Tox. 3 (97.3%)

Acute Tox. 3 (94.9%)

STOT RE 2 (99.6%)

Aquatic Chronic 1 (13%)

Aquatic Chronic 3 (86.8%)

Acute toxicity (ingestion) - category 3

Acute toxicity (dermal) - category 3

Acute toxicity (inhalation) - category 3

Carcinogenicity - category 2

Specific target organ toxicity (repeated exposure) - category 2

Skin sensitisation - category 1

Hazardous to the aquatic environment (chronic) - category 3

10.1.3 Health Hazards

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

TOXIC and/or CORROSIVE; inhalation, ingestion or skin contact with material may cause severe injury or death. Methyl bromoacetate (UN2643) is an eye irritant/lachrymator (causes flow of tears). Contact with molten substance may cause severe burns to skin and eyes. Avoid any skin contact. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause environmental contamination. (ERG, 2024)

10.1.4 Fire Hazards

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

Combustible material: may burn but does not ignite readily. When heated, vapors may form explosive mixtures with air: indoors, outdoors and sewers explosion hazards. Those substances designated with a (P) may polymerize explosively when heated or involved in a fire. Corrosives in contact with metals may evolve flammable hydrogen gas. Containers may explode when heated. Runoff may pollute waterways. Substance may be transported in a molten form. (ERG, 2024)

Combustible. Above 83 °C explosive vapour/air mixtures may be formed.

10.1.5 Hazards Summary

Can induce methemoglobinemia; [ICSC] See Carcinogenicity of some industrial chemicals, Volume 115. [IARC, News Release, 23 February 2016]

10.2 Safety and Hazard Properties

10.2.1 Explosive Limits and Potential

Upper explosion limit: 7 %(V); Lower explosion limit: 1.2 %(V)
Sigma-Aldrich; Material Safety Data Sheet for 4,N,N-Trimethylaniline. Product Number: D189006, Version 4.7 (Revision Date 06/26/2014). Available from, as of September 12, 2014: https://www.sigmaaldrich.com/safety-center.html

10.3 First Aid Measures

Inhalation First Aid
Fresh air, rest. Refer for medical attention.
Skin First Aid
Remove contaminated clothes. Rinse and then wash skin with water and soap. Refer for medical attention .
Eye First Aid
Rinse with plenty of water (remove contact lenses if easily possible).
Ingestion First Aid
Rinse mouth. Give nothing to drink. Refer for medical attention .

10.3.1 First Aid

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

Refer to the "General First Aid" section. Specific First Aid: For corrosives, in case of contact, immediately flush skin or eyes with running water for at least 30 minutes. Additional flushing may be required. Removal of solidified molten material from skin requires medical assistance. (ERG, 2024)

10.4 Fire Fighting

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

SMALL FIRE: Dry chemical, CO2 or water spray.

LARGE FIRE: Dry chemical, CO2, alcohol-resistant foam or water spray. If it can be done safely, move undamaged containers away from the area around the fire. Dike runoff from fire control for later disposal.

FIRE INVOLVING TANKS, RAIL TANK CARS OR HIGHWAY TANKS: Fight fire from maximum distance or use unmanned master stream devices or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks in direct contact with flames. (ERG, 2024)

Use powder, AFFF, foam, carbon dioxide.

10.4.1 Fire Fighting Procedures

Wear self contained breathing apparatus for fire fighting if necessary.
Sigma-Aldrich Corp; Safety Data Sheet for 4,N,N-Trimethylaniline (Product Number: D189006) Version 4.6 (March 18, 2014). Available from, as of June 18, 2014: https://www.sigmaaldrich.com/safety-center.html
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Sigma-Aldrich Corp; Safety Data Sheet for 4,N,N-Trimethylaniline (Product Number: D189006) Version 4.6 (March 18, 2014). Available from, as of June 18, 2014: https://www.sigmaaldrich.com/safety-center.html
Use water spray to cool unopened containers.
Sigma-Aldrich Corp; Safety Data Sheet for 4,N,N-Trimethylaniline (Product Number: D189006) Version 4.6 (March 18, 2014). Available from, as of June 18, 2014: https://www.sigmaaldrich.com/safety-center.html

10.5 Accidental Release Measures

10.5.1 Isolation and Evacuation

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids.

SPILL: Increase the immediate precautionary measure distance, in the downwind direction, as necessary.

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

10.5.2 Spillage Disposal

Personal protection: complete protective clothing including self-contained breathing apparatus. Collect leaking and spilled liquid in sealable containers as far as possible. Absorb remaining liquid in sand or inert absorbent. Then store and dispose of according to local regulations.

10.5.3 Cleanup Methods

Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and place in container for disposal according to local regulations. Keep in suitable, closed containers for disposal.
Sigma-Aldrich Corp; Safety Data Sheet for 4,N,N-Trimethylaniline (Product Number: D189006) Version 4.6 (March 18, 2014). Available from, as of June 18, 2014: https://www.sigmaaldrich.com/safety-center.html

10.5.4 Disposal Methods

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.
Product: This combustible material may be burned in a chemical incinerator equipped with an afterburner and scrubber. Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product.
Sigma-Aldrich Corp; Safety Data Sheet for 4,N,N-Trimethylaniline (Product Number: D189006) Version 4.6 (March 18, 2014). Available from, as of June 18, 2014: https://www.sigmaaldrich.com/safety-center.html

10.5.5 Preventive Measures

Avoid contact with skin and eyes. Avoid inhalation of vapour or mist. Keep away from sources of ignition - No smoking.Take measures to prevent the build up of electrostatic charge.
Sigma-Aldrich Corp; Safety Data Sheet for 4,N,N-Trimethylaniline (Product Number: D189006) Version 4.6 (March 18, 2014). Available from, as of June 18, 2014: https://www.sigmaaldrich.com/safety-center.html

10.6 Handling and Storage

10.6.1 Nonfire Spill Response

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

ELIMINATE all ignition sources (no smoking, flares, sparks or flames) from immediate area. Do not touch damaged containers or spilled material unless wearing appropriate protective clothing. Stop leak if you can do it without risk. Prevent entry into waterways, sewers, basements or confined areas. Absorb or cover with dry earth, sand or other non-combustible material and transfer to containers. DO NOT GET WATER INSIDE CONTAINERS. (ERG, 2024)

10.6.2 Safe Storage

Separated from oxidants and food and feedstuffs.

10.6.3 Storage Conditions

Empty containers retain product residue, (liquid and/or vapor), and can be dangerous. Keep container tightly closed.
Chemcas; MSDS for N,N-Dimethyl-p-toluidine, 99% (99-97-8) Revision #4 Date: 10/20/2005. Avialable from, as of September 11, 2014: https://www.chemcas.org/drug/analytical/cas/99-97-8.asp
Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage.
Sigma-Aldrich Corp; Safety Data Sheet for 4,N,N-Trimethylaniline (Product Number: D189006) Version 4.6 (March 18, 2014). Available from, as of June 18, 2014: https://www.sigmaaldrich.com/safety-center.html

10.7 Exposure Control and Personal Protection

10.7.1 Other Standards Regulations and Guidelines

Workplace Environmental Exposure Level (WEEL): 8-hr Time-weighted Average (TWA) 0.5 ppm.
2013 Emergency Response Planning Guidelines (ERPG) & Workplace Exposure Level (WEEL). American Industrial Hygiene Association, Falls Church, VA 2013, p. 45

10.7.2 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.

10.7.3 Effects of Short Term Exposure

The substance may cause effects on the red blood cells. This may result in the formation of methaemoglobin. The effects may be delayed.

10.7.4 Effects of Long Term Exposure

The substance may have effects on the kidneys and liver. This substance is possibly carcinogenic to humans.

10.7.5 Personal Protective Equipment (PPE)

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer when there is NO RISK OF FIRE. Structural firefighters' protective clothing provides thermal protection but only limited chemical protection. (ERG, 2024)

Skin protection: Handle with gloves.
Sigma-Aldrich Corp; Safety Data Sheet for 4,N,N-Trimethylaniline (Product Number: D189006) Version 4.6 (March 18, 2014). Available from, as of June 18, 2014: https://www.sigmaaldrich.com/safety-center.html
Eye/face protection: Face shield and safety glasses Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Sigma-Aldrich Corp; Safety Data Sheet for 4,N,N-Trimethylaniline (Product Number: D189006) Version 4.6 (March 18, 2014). Available from, as of June 18, 2014: https://www.sigmaaldrich.com/safety-center.html
Body Protection: Complete suit protecting against chemicals, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.
Sigma-Aldrich Corp; Safety Data Sheet for 4,N,N-Trimethylaniline (Product Number: D189006) Version 4.6 (March 18, 2014). Available from, as of June 18, 2014: https://www.sigmaaldrich.com/safety-center.html
Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Sigma-Aldrich Corp; Safety Data Sheet for 4,N,N-Trimethylaniline (Product Number: D189006) Version 4.6 (March 18, 2014). Available from, as of June 18, 2014: https://www.sigmaaldrich.com/safety-center.html

10.7.6 Preventions

Fire Prevention
NO open flames. Above 83 °C use a closed system and ventilation.
Exposure Prevention
PREVENT GENERATION OF MISTS! STRICT HYGIENE!
Inhalation Prevention
Use ventilation. Use local exhaust or breathing protection.
Skin Prevention
Protective gloves. Protective clothing.
Eye Prevention
Wear safety goggles or eye protection in combination with breathing protection.
Ingestion Prevention
Do not eat, drink, or smoke during work.

10.8 Stability and Reactivity

10.8.1 Air and Water Reactions

Tends to darken upon exposure to air. Insoluble in water.

10.8.2 Reactive Group

Amines, Aromatic

10.8.3 Reactivity Profile

N,N-DIMETHYL-P-TOLUIDINE neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. May generate hydrogen, a flammable gas, in combination with strong reducing agents such as hydrides.

10.8.4 Hazardous Reactivities and Incompatibilities

Incompatible materials acids, Acid chlorides, Acid anhydrides, Strong oxidizing agents
Sigma-Aldrich Corp; Safety Data Sheet for 4,N,N-Trimethylaniline (Product Number: D189006) Version 4.6 (March 18, 2014). Available from, as of June 18, 2014: https://www.sigmaaldrich.com/safety-center.html
Conditions to avoid Heat, flames and sparks.
Sigma-Aldrich Corp; Safety Data Sheet for 4,N,N-Trimethylaniline (Product Number: D189006) Version 4.6 (March 18, 2014). Available from, as of June 18, 2014: https://www.sigmaaldrich.com/safety-center.html

10.9 Transport Information

10.9.1 DOT Label

Poison

10.9.2 Packaging and Labelling

Do not transport with food and feedstuffs.

10.9.3 EC Classification

H301; H311; H331; H373; H412

10.9.4 UN Classification

UN Hazard Class: 6.1

10.10 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: Benzenamine, N,N,4-trimethyl-
California Safe Cosmetics Program (CSCP) Reportable Ingredient

Hazard Traits - Carcinogenicity

Authoritative List - IARC Carcinogens - 2B; Prop 65

Report - regardless of intended function of ingredient in the product

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

10.11 Other Safety Information

Chemical Assessment
IMAP assessments - Benzenamine, N,N,4-trimethyl-: Human health tier II assessment

10.11.1 History and Incidents

The National Occupational Exposure Survey, which was conducted by the National Institute for Occupational Safety and Health (NIOSH) between 1981 and 1983, estimated that 62,720 workers were potentially exposed to N,N-dimethyl-p-toluidine in the workplace (NIOSH, 1990). There is potential for widespread human exposure to N,N-dimethyl-p-toluidine in occupational settings where bone cements, dental prostheses, industrial glues, and artificial fingernails are manufactured or used. Exposure to N,N-dimethyl-p-toluidine may be a concern because of the possible release of unreacted chemicals from polymeric composites...
NTP; TOXICOLOGY AND CARCINOGENESIS STUDIES OF N,N-DIMETHYL-p-TOLUIDINE (CAS NO. 99-97-8) IN F344/N RATS AND B6C3F1/N MICE (GAVAGE STUDIES) NTP TR 579 NIH Publication No. 12-5921 (September 2012) https://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=99-97-

11 Toxicity

11.1 Toxicological Information

11.1.1 Toxicity Summary

IDENTIFICATION AND USE: Dimethyl-4-toluidine is a clear to yellow liquid with an aromatic odor; insoluble in water. Dimethyl-4-toluidine is an accelerator in the redox initiator-accelerator system used commercially to cure methyl methacrylate monomers. It is a high-production volume chemical with potential for widespread human exposure through its use in dental materials and bone cements. Dimethyl-4-toluidine has been used in the preparation of acrylic denture materials for the past 50 years. It is used as the accelerator for the cement in most of the hip and bone replacements to activate the polymerization reaction. Dimethyl-4-toluidine is found in industrial glues and artificial fingernail preparations and is used as an intermediate in dye and pesticide synthesis. HUMAN EXPOSURE AND TOXICITY: Toxic by skin absorption and inhalation. Short-term exposure effects are mostly hematotoxic (methemoglobinemia causing cyanosis, brain damage and renal insufficiency) and may be delayed. Exposure to high concentrations may lead to death. An acute cyanotic episode due to methemoglobinemia occurred in a 16-month old girl following the ingestion of dimethyl-4-toluidine (6 mg/kg of body weight ) used in the production of artificial fingernails. Administration of methylene blue was effective in the reversal of the methemoglobinemia. In vitro studies suggest that the activity of the compound was probably due to its biochemical transformation to the toxic metabolite p-methylphenylhydroxylamine. There is potential for widespread human exposure to dimethyl-4-toluidine in occupational settings where bone cements, dental prostheses, industrial glues, and artificial fingernails are manufactured or used. Exposure to dimethyl-4-toluidine may be a concern because of the possible release of unreacted chemicals from polymeric composites. "Sniffing" glue is one possible means of exposure to dimethyl-4-toluidine. Contact allergy to dimethyl-4-toluidine was reported in 3 cases among 22 patients with the burning mouth syndrome who wore complete or partial dentures. ANIMAL STUDIES: Under the conditions of the NTP 2-year oral gavage studies, there was clear evidence of carcinogenic activity of dimethyl-4-toluidine in rats based on increased incidences of hepatocellular carcinoma, and hepatocellular adenoma or carcinoma (combined) in male and female rats, and increased incidences of nasal cavity neoplasms (primarily nasal cavity transitional epithelium adenoma) in male rats. There was clear evidence of carcinogenic activity of dimethyl-4-toluidine in mice based on increased incidences of hepatocellular adenoma (multiple), hepatocellular carcinoma, and hepatoblastoma in male and female mice, and increased incidences of alveolar/ bronchiolar neoplasms (primarily adenoma)in female mice. Administration of dimethyl-4-toluidine resulted in increased incidences of nonneoplastic lesions of the liver and nasal cavity in male and female rats and mice; the kidney in male and female rats; the spleen and bone marrow in male and female rats and female mice; the lung in male and female mice; the forestomach in male rats and female mice; the mesenteric lymph node in male rats and female mice; and the olfactory lobe in male and female mice. Dimethyl-4-toluidine also caused hematologic toxicity and increases in methemoglobin levels in male and female rats and mice (as measured at 3 months). Dimethyl-4-toluidine was tested in two independent bacterial gene mutation studies; both studies gave negative results in S. typhimurium or E. coli tester strains, with and without exogenous metabolic activation. No significant increases in the frequencies of micronucleated erythrocytes were observed in peripheral blood of male or female mice treated with dimethyl-4-toluidine by gavage for 3 months. Furthermore, no increases in micronucleated reticulocytes were observed in male mice treated with dimethyl-4-toluidine for 4 days. Results of DNA damage (comet) studies yielded mixed results. No increases in DNA damage (measured as percent tail DNA) were seen in liver cells or blood leukocytes of male mice administered dimethyl-4-toluidine by gavage once daily for 4 days. However, a small but significant increase in DNA damage was seen in liver cells of male rats administered 60 mg/kg dimethyl-4-toluidine once daily for 4 days. It was also tested for structural and numerical chromosome aberrations in hamster V79 cells (micronucleus test, matched with an immunofluorescent staining for kinetochore proteins), and in vivo DNA damage in mouse and rat liver (alkaline DNA elution test). The results essentially indicate that the chemical is a chromosome damaging agent.

11.1.2 Carcinogen Classification

IARC Carcinogenic Agent
N,N-Dimethyl-p-toluidine
IARC Carcinogenic Classes
Group 2B: Possibly carcinogenic to humans
IARC Monographs
Volume 115: (2018) Some Industrial Chemicals

11.1.3 Exposure Routes

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

11.1.4 Symptoms

Inhalation Exposure
Fatigue. Headache. Dizziness. Nausea. Blue lips, fingernails and skin. Convulsions. Unconsciousness.
Skin Exposure
MAY BE ABSORBED! See Inhalation.
Ingestion Exposure
See Inhalation.

11.1.5 Adverse Effects

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

IARC Carcinogen - Class 3: Chemicals are not classifiable by the International Agency for Research on Cancer.

11.1.6 Acute Effects

11.1.7 Toxicity Data

LC50 (rat) = 1400 mg/m3/4h

11.1.8 Interactions

Camphorquinone (CQ) is widely used as an initiator in modern visible-light (VL) cured resin systems. CQ is also characterized as a potential allergenic compound. To date, there is growing concern that CQ may produce genetic damage by inducing mutation. In this study, CQ in the presence of reducing agent N,N-dimethyl-p-toluidine (DMT) with or without VL irradiation was analyzed for the induction of chromosomal aberrations indicated by micronuclei (MN) induced in CHO cells. /The/ data demonstrated that an increase in the numbers of MN was observed with CQ/DMT with or without VL irradiation (p < 0.05). Significant prolongation of cell cycles was observed by the treatment with CQ/DMT with or without VL irradiation (p < 0.05). In addition, VL irradiated CQ/DMT was found to exhibit significantly genotoxic and cytotoxic effects as compared with CQ/DMT alone (p < 0.05). Furthermore, to determine whether oxidative stress could modulate the MN induced by CQ/DMT with or without VL irradiation in CHO cells, cells were pre-treated with various antioxidants 10 mM N-acetyl-L-cysteine (NAC), 2 mM ascorbic acid, and 2 mM alpha-tocopherol. The pre-treatment with antioxidants could antagonize not only the increased MN cells but also the prolonged cell cycle induced by CQ/DMT with or without VL irradiation in CHO cells (p < 0.05). /These/ findings provide the evidences for the induction of MN by CQ/DMT employing mammalian test system, indicating clastogenic activity of CQ/DMT with or without VL irradiation in vitro. In addition, VL irradiated CQ/DMT exhibits higher genotoxic and cytotoxic effects than CQ/DMT alone. Moreover, NAC, ascorbic acid, and alpha-tocopherol act as the antagonists against the genotoxicity and cytotoxicity of CQ/DMT with or without VL irradiation.
Li YC et al; J Biomed Mater Res B Appl Biomater 82 (1): 23-8 (2007)
9-Fluorenone (9F), the aromatic photosensitizer, is widely used as an initiator in visible-light (VL) cured resin systems. There is growing concern that 9F may produce genetic damage by inducing mutation. In this study, 9F in the presence or absence of reducing agent N,N-dimethyl-p-toluidine (DMT) with or without VL irradiation was analyzed for the induction of chromosomal aberrations indicated by micronuclei (MN) induced in CHO cells. /The/ data demonstrated that a dose-related increase in the frequency of MN and prolonged cell cycles in 9F with or without DMT in the presence or absence of VL irradiation (p < 0.05). The rank orders with respect to genotoxicity and cytotoxicity were found to be as follows: 9F/DMT +VL > 9F/DMT = 9F + VL > 9F. To determine whether oxidative stress could modulate MN induced by 9F/DMT with or without VL irradiation in CHO cells, cells were pretreated with N-acetyl-L-cysteine (NAC), ascorbic acid, and alpha-tocopherol. The pretreatment with antioxidants could diminish not only the prolonged cell cycle but also the decreased frequency of MN which is induced by 9F with or without DMT in the presence or absence of VL irradiation in CHO cells (p < 0.05). /These/ findings provide the evidences for the induction of MN by 9F in the presence or absence of DMT with or without VL irradiation in CHO cells, indicating clastogenic activity of 9F/DMT in vitro. These antioxidants act as the antagonists against the genotoxicity and cytotoxicity of 9F/DMT. Thus, leaching photoinitiator and reducing agent might be contributing the sources of oxidative stress.
Li YC et al; J Biomed Mater Res B Appl Biomater 84 (1): 58-63 (2008)
Resin composites are widely used in dentistry, and are polymerized in situ using a blue-light activated, free-radical polymerization mechanism. Blue light (400-500nm) is used to activate camphoroquinone (CQ), which decomposes to form free radicals that are stabilized by dimethyl-p-toludine (DMPT). CQ and DMPT are applied near tooth pulpal tissues and are irradiated during restorative procedures, suggesting that pulpal cells are exposed to free radicals. Because glutathione is a major component of the cellular redox management system, /the study/ tested the hypothesis that blue light irradiation would shift cellular glutathione redox balance of cells exposed to CQ and DMPT. /The study/ also measured NFkappaB activation, a redox-sensitive transcription factor that regulates inflammatory responses and glutathione synthetic enzyme levels. THP1 human monocytes were exposed to sublethal levels of CQ (0.4 mM) or DMPT (1.0 mM), with or without blue light exposure (25 J/sq cm) from a quartz-tungsten-halogen source. The ratio of reduced to oxidized glutathione was measured using as assay based on 5,5'-dithio-bis(2-nitrobenszoic acid). NFkappaB transactivation was measured by transfection of an NFkappaB-containing plasmid linked to a luciferase reporter. Our results showed that blue light, CQ, or DMPT alone had no significant effect on cellular glutathione redox balance, but that the combination of these agents induced a marked oxidative bias, and reduced total glutathione levels up to 50%. On the other hand, light, CQ, and DMPT alone or in combination suppressed NFkappaB transactivation by >70%. Our results suggest that CQ and DMPT pose risks to pulpal tissues with or without blue light irradiation, and that multiple, interacting mechanisms shape the response to these agents.
Noda M et al; J Biomed Mater Res A 83 (1): 123-9 (2007)

11.1.9 Antidote and Emergency Treatment

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Aromatic hydrocarbons and related compounds/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 209
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Aromatic hydrocarbons and related compounds/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 209-10
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Consider drug therapy for pulmonary edema ... . Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias if necessary ... Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... .Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Aromatic hydrocarbons and related compounds/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 210

11.1.10 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ Aseptic loosening is seen in a significant proportion of cemented total hip replacements (THR). In a small subgroup of patients who suffer early loosening polyethylene debris is unlikely to be responsible. ...one case of allergic contact dermatitis to N,N-dimethylparatoluidine (DMT), an accelerator used in bone cement /was recently reported/. /This study/ have therefore investigated this using skin-patch tests to a variety of substances including metals, polyethylene and the separated individual components of Simplex cement. /The study tested/ 70 patients, 15 with aseptic loosening less than two years after THR, 25 with satisfactory long-term cemented fixation, five with infected loosening of cemented THRs and 25 awaiting hip arthroplasty. /The study/ found seven positive reactions to DMT, all of them in patients with the rapid onset of aseptic loosening. Allergy to DMT is recognized in the dental profession in respect of the 'denture sore mouth' syndrome, and could also be an occupational hazard since some industrial glues contain DMT. /These/ results suggest the need for awareness of possible previous dental or occupational exposure of the constituents of bone cement. /The study/ recommend the use of skin-patch testing in high-risk cases.
Haddad FS et al; J Bone Joint Surg Br 78 (4): 546-9 (1996)
/HUMAN EXPOSURE STUDIES/ The pathogenesis of the burning mouth syndrome (BMS) is not yet understood. Apart from psychologic factors, several etiologic "somatic" factors have been reported. In 22 patients (19 women, 3 men, mean age 56 years) classified with BMS, clinical and laboratory investigations were performed, with particular emphasis on the role of contact hypersensitivity. Twenty of the 22 patients wore a complete or partial denture. Besides clinical and laboratory investigations patch testing was performed with a standard routine series and a standardized denture-dental (acrylate and metal) series. Folate, iron, pyridoxine deficiency, and Candida infections were found, but correction of the deficiency or treatment of the infection was of no benefit. Contact allergy to allergens used in the production of acrylate-based dentures was observed in six (27%) of the cases (all wore a denture); positive reactions were seen to N,N,-dimethyl-4-toluidine (3 cases), to 4-tolyldiethanolamine (2 cases), to benzoylperoxide (2 cases), and to oligotriacrylate (1 case). In six cases (27%) a possible relevant sensitization was seen to dental metals and in particular to gold chloride (four cases).
Dutree-Meulenberg RO et al; J Am Acad Dermatol 26 (6): 935-40 (1992)
/SIGNS AND SYMPTOMS/ Short-term exposure effects: skin absorption; delayed effects; hematotoxic effects (methemoglobinemia causing cyanosis, brain damage and renal insufficiency); exposure to high concentrations may lead to death.
Instituto Nacional de Seguridad e Higiene en el Trabajo, Ediciones y Publicaciones, correlaguna 73, 28027 Madrid, Spain, 1991. 2p.
/CASE REPORTS/ An acute cyanotic episode due to methemoglobinemia occurred in a 16-month old girl following the ingestion of N,N-dimethyl-p-toluidine, a commercially available component used in the production of artificial fingernails. The amount of the parent compound ingested was about 6 mg/kg of body weight. Administration of methylene blue was effective in the reversal of the methemoglobinemia. In vitro studies suggest that the activity of the compound was probably due to its biochemical transformation to the toxic metabolite p-methylphenylhydroxylamine. /The study/ expand the list of aromatic amino or nitro compounds and their derivatives capable of producing methemoglobinemia and call attention to the hazard of their ingestion.
Potter JL et al; Ann Emerg Med 17 (10): 1098-100 (1988)
For more Human Toxicity Excerpts (Complete) data for Dimethyl-4-toluidine (8 total), please visit the HSDB record page.

11.1.11 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ N,N-Dimethyl-p-toluidine (DMPT) is used as a polymerization accelerator, in industrial glues, and as an intermediate in dye and pesticide synthesis. There is potential for human exposure to DMPT. The disposition of oral and intravenous (i.v.) doses of [(14)C]DMPT in F344 rats and B6C3F1 mice was investigated. A single i.v. (2.5 mg/kg) or oral (2.5, 25, or 250 mg/kg) dose of [(14)C]DMPT (1-25 uCi) was administered in an aqueous vehicle to male rats and mice. The 25-mg/kg oral dose was administered to females to investigate possible gender differences in disposition. However, no striking gender differences were observed. Since toxicity studies conducted elsewhere used a corn oil vehicle, the 250-mg/kg oral dose also was administered in corn oil to male rats; disposition was not dependent on vehicle. Excreta (through 24 hr) and tissues collected at sacrifice were analyzed for total radioactivity. Dose-dependent differences in toxicity and disposition were observed. Toxicity at the 250-mg/kg oral dose to male mice was consistent with acute renal failure. At the same dose, male rats exhibited clinical signs of toxicity through 12 hr but were clinically normal by 24 hr. At lower oral doses, [(14)C]DMPT-derived radioactivity was well absorbed and rapidly excreted, primarily in urine.
Dix KJ et al; J Toxicol Environ Health A 70 (10): 789-98 (2007)
/LABORATORY ANIMALS: Acute Exposure/ The aim of the present investigation was to evaluate if a bone cement monomer with a high concentration of accelerator (N,N-dimethyl-p-toluidine) is more toxic than a methyl methacrylate (MMA) monomer, free from accelerator. Tissue reaction to 3 MMA monomers was studied by injecting the ears of 16 adult male rabbits; the material was studied by microangiograms. No difference in the acute local toxicity between CMW, Simplex-P and pure MMA monomer was seen. By gas chromatography, N,N-dimethyl-p-toluidine was shown to be water soluble to a small extent. Any bone cement monomer in current use can be fully dissolved in saline to a concentration of about 1%.
Linder L; Acta Orthop Scand 47 (1): 3-10 (1976)
/GENOTOXICITY/ In two in vivo alkaline elution assays, Sprague-dawley rats were administered N,N-dimethyl-p-toluidine via oral or intraperitoneal injection at up to 1080 mg/kg-bw for up to 24 hours. DNA fragmentation increased in liver cells to about 2.4 times the control at the highest dose only and suggested that N,N-dimethyl-p-toluidine was weakly positive in this assay. Negative results were obtained when N,N-dimethyl-p-toluidine was tested in Balb/c mice. N,N-Dimethyl-p-toluidine induced chromosomal effects in these assay.
USEPA; Hazard Characterization Document: SCREENING-LEVEL HAZARD CHARACTERIZATION Monocyclic Aromatic Amines Category; p. 23 (September, 2009)
/GENOTOXICITY/ In a cytogenetic assay, Chinese Hamster V79 cells were exposed to N,N-dimethyl-p-toluidine up to 1.2mM without metabolic activation. Cytotoxicity was observed at 1.2 mM, where > 10% survival was estimated by colony formation. It is not clear if positive controls were used. N,N-Dimethyl-p-toluidine induced chromosomal aberrations in this assay.
USEPA; Hazard Characterization Document: SCREENING-LEVEL HAZARD CHARACTERIZATION Monocyclic Aromatic Amines Category; p. 22 (September, 2009)
For more Non-Human Toxicity Excerpts (Complete) data for Dimethyl-4-toluidine (7 total), please visit the HSDB record page.

11.1.12 Non-Human Toxicity Values

LD50 Rats gavage 1650 mg/kg bw
USEPA; Hazard Characterization Document: SCREENING-LEVEL HAZARD CHARACTERIZATION Monocyclic Aromatic Amines Category; p. 12 (September, 2009)
LD50 Mice i.p. 212 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3579
LD50 Rabbit skin > 2000 mg/kg bw
USEPA; Hazard Characterization Document: SCREENING-LEVEL HAZARD CHARACTERIZATION Monocyclic Aromatic Amines Category; p.12 (September, 2009)
LC50 Rats inhal 1.4 mg/L 4 hr
USEPA; Hazard Characterization Document: SCREENING-LEVEL HAZARD CHARACTERIZATION Monocyclic Aromatic Amines Category; p. 13 (September, 2009)

11.1.13 Ongoing Test Status

EPA has released the first beta version (version 0.5) of the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The beta version of the iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays; Click on the "Chemical Explorer" button on the tool bar to see the data./[USEPA; ICSS Dashboard Application; Available from, as of June 27, 2014: http://actor.epa.gov/dashboard/]
The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from, as of June 30, 2014: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=99-97-8]

11.1.14 National Toxicology Program Studies

3-MONTH STUDY IN RATS Groups of 10 male and 10 female rats were administered 0, 62.5, 125, 250, 500, or 1,000 mg N,N-dimethyl-p-toluidine/kg body weight in corn oil by gavage, 5 days per week for 14 weeks. Additional groups of 10 male and 10 female rats (clinical pathology study) were administered the same doses, 5 days per week for 25 days. On day 88, blood was collected from core study rats for hemoglobin and methemoglobin analyses only. All 1,000 mg/kg male and female rats and one 500 mg/kg male rat died by study day 3. Mean body weights of all surviving dosed groups of males and females were significantly less than those of the vehicle controls. Clinical findings associated with exposure to N,N-dimethyl-p-toluidine included cyanosis, abnormal breathing, and lethargy in groups administered 250 mg/kg or greater. Methemoglobinemia appeared to be the primary hematologic toxic response, and many other lesions could be explained as secondary to methemoglobin formation including Heinz body formation; a macrocytic, hypochromic, responsive anemia; and increased hematopoietic cell proliferation in the spleen and bone marrow. In general, hematologic changes were dose-related and occurred at both evaluated timepoints in all dosed groups. Anemia was evidenced by decreases in hematocrit values, hemoglobin concentrations, and erythrocyte counts; erythrocyte macrocytosis was characterized by increases in mean cell volume and mean cell hemo-globin values; erythrocyte hypochromia was evidenced by decreases in mean cell hemoglobin concentration values; and an erythropoietic response to the anemia was characterized by substantially increased reticulocyte and nucleated erythrocyte counts. Liver weights of all surviving dosed groups of males and females were significantly greater than those of the vehicle controls. Kidney weights of all surviving dosed groups of females were significantly greater than those of the vehicle controls. There were significant decreases in left cauda epididymis and left epididymis weights in 250 mg/kg males. There was a dose-related decrease in the number of cycling females, with only four females in the 250 mg/kg group having regular cycles and females in the 125 and 250 mg/kg groups spending a significantly higher proportion of time in extended diestrus compared to the vehicle control group. In the surviving groups of rats, there were significantly increased incidences of pigmentation in the liver of all dosed groups, hepatocyte hypertrophy in groups administered 125 mg/kg or greater, and hepatocyte necrosis in 62.5, 250, and 500 mg/kg females. In the olfactory epithelium of the nose, there were dose-related increases in the incidences and severities of degeneration in all dosed groups and significantly increased incidences of metaplasia in the 250 and 500 mg/kg groups. In the respiratory epithelium of the nose, there were significantly increased incidences of hyperplasia and squamous metaplasia in all of the groups administered 125 mg/kg or greater. The incidences of glandular hyperplasia of the nose were significantly increased in males and females administered 125, 250, or 500 mg/kg. In the spleen, there were significantly increased incidences of capsule fibrosis, congestion, mesothelial hypertrophy, and lymphoid follicle atrophy primarily in groups administered 125 mg/kg or greater. Hematopoietic cell proliferation and pigmentation were increased in severity in treated groups. In the kidney, there were significantly increased incidences of nephropathy (females), pigmentation (males and females), papillary necrosis (males and females), and mineralization (males). Other treatment-related lesions included inflammation of the forestomach in males, mesenteric lymph node atrophy in females, and bone marrow hyperplasia in males and females.
DHHS/NTP; Toxicology and Carcinogenesis Studies of N,N-Dimethyl-P-Toluidine (Cas No. 99-97-8) in F344/N Rats and B6C3F1/N Mice (Gavage Studies) p.7 (2012) Technical Rpt Series No.579 NIH Pub No.12-5921. Available from, as September 11, 2014: https://ntp-server.niehs.nih.gov/
3-MONTH STUDY IN MICE Groups of 10 male and 10 female mice were administered 0, 15, 30, 60, 125, or 250 mg N,N-dimethyl-p-toluidine/kg body weight in corn oil by gavage, 5 days per week for 14 weeks. All 250 mg/kg male and female mice (except for one male mouse) died before day 10, and three males and two females administered 125 mg/kg died before the end of the study. The final mean body weight of 125 mg/kg males and the mean body weight gains of 125 mg/kg males and females were significantly less than those of the vehicle controls. Clinical findings associated with administration of N,N-dimethyl-p-toluidine included abnormal breath-ing, thinness, lethargy, cyanosis, and ruffled fur in 125 and 250 mg/kg males and females. Methemoglobinemia appeared to be the primary hematologic toxic response; however there were less severe erythron changes compared to the 3-month study in rats. In females, no erythron changes were detected up to 125 mg/kg. In males, inconsistent and minor decreases in hematocrit values, hemoglobin concentrations, and erythrocyte counts, and increased reticulocyte counts occurred in groups administered 60 mg/kg or greater. Methemoglobin values were minimally increased in males and females administered 30 mg/kg or greater. Heinz bodies were slightly increased in 60 mg/kg females, 125 mg/kg males and females, and the one surviving 250 mg/kg male; Heinz body formation was considered secondary to methemoglobin formation. Liver weights of all dosed groups of mice were significantly greater than those of the vehicle controls. In the surviving groups of mice, there were significantly increased incidences of bronchiolar epithelium degeneration, bronchiolar epithelium regeneration, and peribronchiolar chronic active inflammation in the lung of 125 mg/kg groups, and histiocytic infiltrates of the alveoli in 125 mg/kg females. In the nose, there were significantly increased incidences of glandular hyperplasia and olfactory epithelium metaplasia in the 125 mg/kg groups and olfactory epithelium degenera-tion in 60 mg/kg females and 125 mg/kg males and females. In the thymus, the incidences of thymocyte necrosis in the 125 mg/kg groups were significantly increased. In the liver, the severities of cytoplasmic vacuolization of the hepatocytes were increased in dosed groups of males and females.
DHHS/NTP; Toxicology and Carcinogenesis Studies of N,N-Dimethyl-P-Toluidine (Cas No. 99-97-8) in F344/N Rats and B6C3F1/N Mice (Gavage Studies) p.8 (2012) Technical Rpt Series No.579 NIH Pub No.12-5921. Available from, as September 11, 2014: https://ntp-server.niehs.nih.gov/
2-YEAR STUDY IN RATS Groups of 50 male and 50 female rats were administered 0, 6, 20, or 60 mg N,N-dimethyl-p-toluidine/kg body weight in corn oil by gavage, 5 days per week for 104 or 105 weeks. Additional groups of 10 male and 10 female rats (clinical pathology study) were administered the same doses for 86 days. Survival of 60 mg/kg males was significantly less than that of the vehicle controls. Mean body weights of 60 mg/kg males and females were more than 10% less than those of the vehicle controls after week 61 and week 33, respectively. Clinical findings included signs of pallor in 60 mg/kg females and hyperactivity and boxing behavior in 20 mg/kg females and 60 mg/kg males and females. The hematology findings at the 3-month timepoint were consistent with those in the 3-month study in rats which indicated that methemoglobinemia was the primary hematologic toxic response. In the 20 and 60 mg/kg groups, there were dose-related decreases in hematocrit values, hemoglobin concentrations, and erythrocyte counts. There were similar trends toward erythrocyte macrocytosis and hypochromia and increased erythropoiesis as seen in the 3-month study. While the magnitudes of the erythron decreases were not sufficient to classify the responses as anemias, the patterns of the erythron changes were identical to those in the 3-month study. In the liver of 60 mg/kg males and females, there were significantly increased incidences of hepatocellular car-cinoma and hepatocellular adenoma or hepatocellular carcinoma (combined). Numerous nonneoplastic liver lesions occurred in dosed males and females primarily in the 20 and 60 mg/kg groups. In the nose, there were significantly increased incidences of transitional epithelium adenoma and transi-tional epithelium adenoma or carcinoma (combined) in 60 mg/kg males; transitional epithelium adenoma also occurred in female rats administered 6 or 60 mg/kg. In the nose, there were significantly increased incidences of nonneoplastic lesions in the olfactory, respiratory, and transitional epithelia of dosed rats. These lesions occurred with the greatest incidence and severity in the 60 mg/kg groups. The incidences of inflammation and nerve atrophy were significantly increased in males and females administered 60 mg/kg. There were increased incidences of follicular cell ade-noma or carcinoma (combined) of the thyroid gland in all dosed groups of males, and an increased incidence of follicular cell adenoma in 20 mg/kg females. In the spleen, there were significantly increased incidences of hematopoietic cell proliferation in all dosed groups of males and females. The incidences of congestion and mesothelial hypertrophy of the capsule were significantly increased in 60 mg/kg males and all dosed groups of females. There were also significantly increased incidences of capsular fibrosis and atrophy of the lymphoid follicle in the 60 mg/kg groups. The incidences of pigmentation were significantly increased in all dosed groups of males and in 60 mg/kg females. In all dosed groups of female rats, there were signifi-cantly increased incidences of nephropathy. Although the incidences of this lesion were not significantly increased in dosed males, the severities increased with increasing dose in both males and females. The incidences of pigmentation of the kidney were significantly increased in all dosed groups of males and in 60 mg/kg females. In the forestomach of males, there were significantly increased incidences of hyperplasia and ulcer in the 20 and 60 mg/kg groups and inflammation in the 60 mg/kg group. In the bone marrow of 20 and 60 mg/kg males and 60 mg/kg females, there were significantly increased incidences of hyperplasia. In the mesenteric lymph node of 20 and 60 mg/kg males, there were significantly increased incidences of histiocytic cellular infiltrates.
DHHS/NTP; Toxicology and Carcinogenesis Studies of N,N-Dimethyl-P-Toluidine (Cas No. 99-97-8) in F344/N Rats and B6C3F1/N Mice (Gavage Studies) p.8 (2012) Technical Rpt Series No.579 NIH Pub No.12-5921. Available from, as September 11, 2014: https://ntp-server.niehs.nih.gov/
2-YEAR STUDY IN MICE Groups of 50 male and 50 female mice were adminis-tered 0, 6, 20, or 60 mg N,N-dimethyl-p-toluidine/kg body weight in corn oil by gavage, 5 days per week for 105 weeks. Survival of 60 mg/kg females was significantly less than that of the vehicle control group. Mean body weights of 60 mg/kg males and females were more than 10% less than those of the vehicle controls after week 89 and week 65, respectively. In the liver, there were significantly increased incidences of hepatocellular adenoma in 20 and 60 mg/kg females and hepatocellular carcinoma in 60 mg/kg males and all dosed female groups. The increased inci-dences of hepatocellular adenoma and carcinoma in the dosed groups were primarily due to increased incidences of animals with multiple hepatocellular neo-plasms. The incidences of hepatoblastoma were signifi-cantly increased in 20 mg/kg males and 60 mg/kg males and females. In all dosed groups of males and females, there were significantly increased incidences of hepatocyte hypertrophy, and the incidences of eosinophilic focus were significantly increased in the 20 and 60 mg/kg males and females. There were significantly increased incidences of fatty change and necrosis in 60 mg/kg females. In the lung of 20 and 60 mg/kg female mice, there were significantly increased incidences of alveolar/ bronchi-olar adenoma and alveolar/bronchiolar adenoma or car-cinoma (combined). There were also significantly increased incidences of alveolar epithelium hyperplasia in 20 mg/kg females; bronchiolar epithelium regenera-tion, bronchus epithelium regeneration, and bronchus necrosis in 60 mg/kg females; and alveolar infiltrates of histiocytes in 60 mg/kg males and females. In the forestomach of 20 and 60 mg/kg female mice, there were significantly increased incidences of squa-mous cell papilloma and squamous cell papilloma or carcinoma (combined). There were significantly increased incidences of epithelium hyperplasia in 20 and 60 mg/kg females, and inflammation and ulcer in 60 mg/kg females. In the nose, there were significantly increased incidences of nonneoplastic lesions of the olfactory and respiratory epithelia in 60 mg/kg males and 20 and 60 mg/kg females. There were significantly increased incidences of nerve atrophy in 60 mg/kg males and females and of inflammation in 60 mg/kg females. The incidences of atrophy of the olfactory lobe were significantly increased in 60 mg/kg males and females. In 60 mg/kg females, the incidences of regenerative hyper-plasia of the nasolacrimal duct and necrosis of the vomeronasal organ were significantly increased. In the spleen, there was a significantly increased incidence of atrophy in 60 mg/kg females. There were also significantly increased incidences of bone marrow hyperplasia in all dosed groups of females and mesenteric lymph node atrophy in 60 mg/kg females.
DHHS/NTP; Toxicology and Carcinogenesis Studies of N,N-Dimethyl-P-Toluidine (Cas No. 99-97-8) in F344/N Rats and B6C3F1/N Mice (Gavage Studies) p.9 (2012) Technical Rpt Series No.579 NIH Pub No.12-5921. Available from, as September 11, 2014: https://ntp-server.niehs.nih.gov/
For more National Toxicology Program Studies (Complete) data for Dimethyl-4-toluidine (6 total), please visit the HSDB record page.

11.2 Ecological Information

11.2.1 Ecotoxicity Values

LC50; Species: Oryzias latipes (Japanese Medaka) length 2 cm, weight 0.2 g; Conditions: freshwater, static, 25 °C; Concentration: 44000 ug/L for 24 hr
Tonogai Y et al; J Toxicol Sci 7 (3): 193-203 (1982) as cited in the ECOTOX database. Available from, as of June 19, 2014
LC50; Species: Oryzias latipes (Japanese Medaka) length 2 cm, weight 0.2 g; Conditions: freshwater, static, 25 °C; Concentration: 20000 ug/L for 48 hr
Tonogai Y et al; J Toxicol Sci 7 (3): 193-203 (1982) as cited in the ECOTOX database. Available from, as of June 19, 2014
LC50; Species: Pimephales promelas (Fathead minnow); Conditions: flow through; Concentration: 48.9 mg/L for 96 hr (geometric mean of studies)
USEPA; Hazard Characterization Document: SCREENING-LEVEL HAZARD CHARACTERIZATION Monocyclic Aromatic Amines Category; p. 30 (September 2009)
LC50; Species: Pimephales promelas (Fathead Minnow) age 32 days, length 24.5 mm, weight 0.242 g; Conditions: freshwater, flow through, 24.9 °C, pH 7.4, hardness 40.3 mg/L CaCO3, alkalinity 46.1 mg/L CaCO3, dissolved oxygen 5.0 mg/L; Concentration: 46000 ug/L for 96 hr (95% confidence interval: 42000-50500 ug/L) /99% purity/
Geiger DL et al; Univ of Wisconsin, Ctr for Lake Superior Environ Studies: 328 (1986) as cited in the ECOTOX database. Available from, as of June 19, 2014
For more Ecotoxicity Values (Complete) data for Dimethyl-4-toluidine (6 total), please visit the HSDB record page.

11.2.2 ICSC Environmental Data

The substance may cause long-term effects in the aquatic environment.

11.2.3 Environmental Fate / Exposure Summary

Dimethyl-4-toluidine's production and use as a polymerization accelerator in the manufacture of bone cements and dental materials, in industrial glues, and as an intermediate in dye and pesticide synthesis may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 0.178 mm Hg at 25 °C indicates dimethyl-4-toluidine will exist solely as a vapor in the atmosphere. Vapor-phase dimethyl-4-toluidine 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 2 hrs. Dimethyl-4-toluidine does not contains chromophores that absorb at wavelengths >290 nm and, therefore, is not expected to be susceptible to direct photolysis by sunlight. If released to soil, dimethyl-4-toluidine is expected to have moderate mobility based upon an estimated Koc of 260. The pKa of dimethyl-4-toluidine is 5.63, indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization of the neutral species from moist soil surfaces is expected to be an important fate process based upon an estimated Henry's Law constant of 7.0X10-5 atm-cu m/mole. Dimethyl-4-toluidine is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Biodegradation data in soil or water were not available. If released into water, dimethyl-4-toluidine is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is expected to be an important fate process based upon this compound's estimated Henry's Law constant. Estimated volatilization half-lives for a model river and model lake are 1 and 10 days, respectively. An estimated BCF of 33 suggests the potential for bioconcentration in aquatic organisms is moderate. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9). Occupational exposure to dimethyl-4-toluidine may occur through inhalation and dermal contact with this compound at workplaces where dimethyl-4-toluidine is produced or used. (SRC)

11.2.4 Artificial Pollution Sources

Dimethyl-4-toluidine's production and use as a polymerization accelerator in the manufacture of bone cements and dental materials, in industrial glues, and as an intermediate in dye and pesticide synthesis(1) may result in its release to the environment through various waste streams(SRC).
(1) Dix KJ et al; Toxicol Sci 90 (1-S): 116 (2006)

11.2.5 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 260(SRC), determined from a log Kow of 2.81(2) and a regression-derived equation(3), indicates that dimethyl-4-toluidine is expected to have moderate mobility in soil(SRC). The pKa of dimethyl-4-toluidine is 5.63(4), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization of the neutral species of dimethyl-4-toluidine from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.0X10-5 atm-cu m/mole(SRC), derived from its vapor pressure, 0.178 mm Hg(6), and water solubility, 455 mg/L(7). Dimethyl-4-toluidine is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(6). Biodegradation data in soil were not available(SRC, 2014).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Sangster J; LOGKOW Database. A databank of evaluated octanol-water partition coefficients (Log P). Available from, as of Jul 3, 2014: https://logkow.cisti.nrc.ca/logkow/search.html
(3) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Jul 3, 2014: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(4) Perrin DD; Dissociation Constants of Organic Bases in Aqueous Solution. IUPAC Chem Data Ser, Buttersworth, London (1965)
(5) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(6) Chao J et al; J Chem Phys Ref Data 12: 1033-63 (1983)
(7) Verschueren K; Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New York, NY. P. 944 (2001)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 260(SRC), determined from a log Kow of 2.81(2) and a regression-derived equation(3), indicates that dimethyl-4-toluidine is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(4) based upon an estimated Henry's Law constant of 7.0X10-5 atm-cu m/mole(SRC), derived from its vapor pressure, 0.178 mm Hg(5), and water solubility, 455 mg/L(6). Using this Henry's Law constant and an estimation method(4), volatilization half-lives for a model river and model lake are 1 and 10 days, respectively(SRC). According to a classification scheme(7), an estimated BCF of 33(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Biodegradation data in water were not available(SRC, 2014).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Sangster J; LOGKOW Database. A databank of evaluated octanol-water partition coefficients (Log P). Available from, as of Jul 3, 2014: https://logkow.cisti.nrc.ca/logkow/search.html
(3) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Jul 3, 2014: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(4) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)
(5) Chao J et al; J Chem Phys Ref Data 12: 1033-63 (1983)
(6) Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New York, NY. P. 944 (2001)
(7) Franke C et al; Chemosphere 29: 1501-14 (1994)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), dimethyl-4-toluidine, which has a vapor pressure of 0.178 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase dimethyl-4-toluidine 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 2 hrs(SRC), calculated from its rate constant of 2.0X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Dimethyl-4-toluidine does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) Chao J et al; J Chem Phys Ref Data 12: 1033-63 (1983)
(3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(4) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)

11.2.6 Environmental Abiotic Degradation

The rate constant for the vapor-phase reaction of dimethyl-4-toluidine with photochemically-produced hydroxyl radicals has been estimated as 2.0X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Dimethyl-4-toluidine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Dimethyl-4-toluidine does not contain chromophores that absorb at wavelengths >290 nm(2) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).
(1) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12 (1990)

11.2.7 Environmental Bioconcentration

An estimated BCF of 33 was calculated in fish for dimethyl-4-toluidine(SRC), using a log Kow of 2.81(1) and a regression-derived equation(2). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).
(1) Sangster J; LOGKOW Database. A databank of evaluated octanol-water partition coefficients (Log P). Available from, as of Jul 3, 2014: https://logkow.cisti.nrc.ca/logkow/search.html
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Jul 3, 2014: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm/
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

11.2.8 Soil Adsorption / Mobility

The Koc of dimethyl-4-toluidine is estimated as 260(SRC), using a log Kow of 2.81(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that dimethyl-4-toluidine is expected to have moderate mobility in soil. The pKa of dimethyl-4-toluidine is 5.63(4), indicating that this compound will exist partially in the cation form and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). A Kd value of 380 for sorption to monmorillonite has been reported(6).
(1) Sangster J; LOGKOW Database. A databank of evaluated octanol-water partition coefficients (Log P). Available from, as of Jul 3, 2014: https://logkow.cisti.nrc.ca/logkow/search.html
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Jul 3, 2014: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Swann RL et al; Res Rev 85: 17-28 (1983)
(4) Perrin DD; Dissociation Constants of Organic Bases in Aqueous Solution. IUPAC Chem Data Ser, Buttersworth, London (1965)
(5) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(6) Carrasquillo AJ, et al; Environ Sci Technol 42: 7634-7642 (2008)

11.2.9 Volatilization from Water / Soil

The Henry's Law constant for dimethyl-4-toluidine is estimated as 7.0X10-5 atm-cu m/mole(SRC) derived from its vapor pressure, 0.178 mm Hg(1), and water solubility, 455 mg/L(2). This Henry's Law constant indicates that dimethyl-4-toluidine is expected to volatilize from water surfaces(3). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(3) is estimated as 1 day(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(3) is estimated as 10 days(SRC). Dimethyl-4-toluidine's estimated Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Dimethyl-4-toluidine is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).
(1) Chao J et al; J Chem Phys Ref Data 12: 1033-63 (1983)
(2) Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New York, NY. P. 944 (2001)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)

11.2.10 Probable Routes of Human Exposure

According to the 2006 TSCA Inventory Update Reporting data, the number of persons reasonably likely to be exposed in the industrial manufacturing, processing, and use of dimethyl-4-toluidine is 100 to 999; the data may be greatly underestimated(1).
(1) US EPA; Inventory Update Reporting (IUR). Non-confidential 2006 IUR Records by Chemical, including Manufacturing, Processing and Use Information. Washington, DC: U.S. Environmental Protection Agency. Available from, as of Jul 3, 2014: https://cfpub.epa.gov/iursearch/index.cfm
NIOSH (NOES Survey 1981-1983) has statistically estimated that 67,720 workers (27,118 of these were female) were potentially exposed to dimethyl-4-toluidine in the US(1). Occupational exposure to dimethyl-4-toluidine may occur through inhalation and dermal contact with this compound at workplaces where dimethyl-4-toluidine is produced or used(SRC).
(1) NIOSH; NOES. National Occupational Exposure Survey conducted from 1981-1983. Estimated numbers of employees potentially exposed to specific agents by 2-digit standard industrial classification (SIC). Available from, as of Jul 3, 2014: https://www.cdc.gov/noes/

12 Associated Disorders and Diseases

13 Literature

13.1 Consolidated References

13.2 NLM Curated PubMed Citations

13.3 Springer Nature References

13.4 Thieme References

13.5 Wiley References

13.6 Chemical Co-Occurrences in Literature

13.7 Chemical-Gene Co-Occurrences in Literature

13.8 Chemical-Disease Co-Occurrences in Literature

14 Patents

14.1 Depositor-Supplied Patent Identifiers

14.2 WIPO PATENTSCOPE

14.3 Chemical Co-Occurrences in Patents

14.4 Chemical-Disease Co-Occurrences in Patents

14.5 Chemical-Gene Co-Occurrences in Patents

15 Interactions and Pathways

15.1 Chemical-Target Interactions

16 Biological Test Results

16.1 BioAssay Results

17 Classification

17.1 MeSH Tree

17.2 NCI Thesaurus Tree

17.3 ChemIDplus

17.4 CAMEO Chemicals

17.5 UN GHS Classification

17.6 EPA CPDat Classification

17.7 NORMAN Suspect List Exchange Classification

17.8 EPA DSSTox Classification

17.9 International Agency for Research on Cancer (IARC) Classification

17.10 EPA TSCA and CDR Classification

17.11 EPA Substance Registry Services Tree

17.12 MolGenie Organic Chemistry Ontology

18 Information Sources

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  7. EPA Chemicals under the TSCA
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  12. ILO-WHO International Chemical Safety Cards (ICSCs)
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  14. California Safe Cosmetics Program (CSCP) Product Database
    N,N-Dimethyl-p-toluidine (Dimethyltolylamine)
    https://cscpsearch.cdph.ca.gov/search/detailresult/1122
  15. California Office of Environmental Health Hazard Assessment (OEHHA)
  16. Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
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    https://haz-map.com/About
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    https://haz-map.com/Agents/2197
  17. ChEMBL
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  19. EPA Chemical and Products Database (CPDat)
  20. Hazardous Chemical Information System (HCIS), Safe Work Australia
  21. NITE-CMC
    N,N-Dimethyl-p-toluidine - FY2012 (New/original classication)
    https://www.chem-info.nite.go.jp/chem/english/ghs/12-mhlw-0047e.html
    N,N-Dimethyl-p-toluidine - FY2022 (Revised classification)
    https://www.chem-info.nite.go.jp/chem/english/ghs/22-jniosh-2091e.html
    N,N-Dimethyl-p-toluidine - FY2016 (Revised classification)
    https://www.chem-info.nite.go.jp/chem/english/ghs/16-mhlw-0114e.html
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    https://eur-lex.europa.eu/content/legal-notice/legal-notice.html
  23. IUPAC Digitized pKa Dataset
  24. MassBank Europe
  25. NMRShiftDB
  26. Human Metabolome Database (HMDB)
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    https://publications.iarc.fr/Terms-Of-Use
    IARC Classification
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  28. Japan Chemical Substance Dictionary (Nikkaji)
  29. MassBank of North America (MoNA)
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    http://www.nist.gov/srd/nist1a.cfm
  31. SpectraBase
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  37. Wikidata
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  40. Medical Subject Headings (MeSH)
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  42. NORMAN Suspect List Exchange
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    NORMAN Suspect List Exchange Classification
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  43. EPA Substance Registry Services
  44. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  45. PATENTSCOPE (WIPO)
CONTENTS