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p-Aminophenol

PubChem CID
403
Structure
p-Aminophenol_small.png
p-Aminophenol_3D_Structure.png
Molecular Formula
Synonyms
  • 4-aminophenol
  • p-aminophenol
  • 123-30-8
  • 4-hydroxyaniline
  • p-hydroxyaniline
Molecular Weight
109.13 g/mol
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Dates
  • Create:
    2004-09-16
  • Modify:
    2025-01-18
Description
P-aminophenol appears as white or reddish-yellow crystals or light brown powder. Turns violet when exposed to light. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
4-aminophenol is an amino phenol (one of the three possible isomers) which has the single amino substituent located para to the phenolic -OH group. It has a role as a metabolite and an allergen.
4-Aminophenol has been reported in Camellia oleifera with data available.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
p-Aminophenol.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

4-aminophenol
Computed by Lexichem TK 2.7.0 (PubChem release 2024.11.20)

2.1.2 InChI

InChI=1S/C6H7NO/c7-5-1-3-6(8)4-2-5/h1-4,8H,7H2
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.3 InChIKey

PLIKAWJENQZMHA-UHFFFAOYSA-N
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.4 SMILES

C1=CC(=CC=C1N)O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C6H7NO
Computed by PubChem 2.2 (PubChem release 2024.11.20)

2.3 Other Identifiers

2.3.1 CAS

123-30-8

2.3.3 Deprecated CAS

1309774-68-2, 52985-09-8

2.3.4 European Community (EC) Number

2.3.5 UNII

2.3.6 UN Number

2.3.7 ChEBI ID

2.3.8 ChEMBL ID

2.3.9 DrugBank ID

2.3.10 DSSTox Substance ID

2.3.11 HMDB ID

2.3.12 KEGG ID

2.3.13 Metabolomics Workbench ID

2.3.14 Nikkaji Number

2.3.15 NSC Number

2.3.16 RXCUI

2.3.17 Wikidata

2.3.18 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 4-aminophenol
  • 4-aminophenol conjugate monoacid
  • 4-aminophenol hydrochloride
  • 4-aminophenol monopotassium salt
  • 4-aminophenol monosodium salt
  • 4-aminophenol sulfate
  • 4-aminophenol sulfate (2:1)
  • 4-aminophenol, 18O-labeled
  • 4-aminophenol, 3H-labeled
  • 4-aminophenol, ion(1+)
  • 4-hydroxyaniline
  • p-aminophenol
  • p-aminophenol phosphate
  • para-aminophenol

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
109.13 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
XLogP3
Property Value
0
Reference
Computed by XLogP3 3.0 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Donor Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Acceptor Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Rotatable Bond Count
Property Value
0
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Exact Mass
Property Value
109.052763847 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Monoisotopic Mass
Property Value
109.052763847 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Topological Polar Surface Area
Property Value
46.3 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Heavy Atom Count
Property Value
8
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
66.9
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
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

P-aminophenol appears as white or reddish-yellow crystals or light brown powder. Turns violet when exposed to light. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
Dry Powder
White or reddish-yellow crystals or light-brown powder that turns violet when exposed to light; [CAMEO]
Solid

3.2.2 Color / Form

Orthorhombic plates from water
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 78
White plates from water
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-22
Colorless crystals
Sax, N.I. Dangerous Properties of Industrial Materials. Vol 1-3 7th ed. New York, NY: Van Nostrand Reinhold, 1989., p. 209
White or reddish yellow crystals turn violet on exposure to light
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 62

3.2.3 Boiling Point

543 °F at 760 mmHg (Decomposes) (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
284 °C at 760 mm Hg, decomposes; 167 °C at 8.0 mm Hg; 150 °C at 3.0 mm Hg; 130.2 °C at 0.3 mm Hg
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 78
BP: Can be sublimed at 0.3 mm Hg and 110 °C without decomposition ... forms salts with acids and bases ... Deteriorates under the influence of air and light ... Commercial product usually pink ... MP of commercial product 186 °C
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 78
187.5 °C

3.2.4 Melting Point

367 to 369 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
367-369 °F
187.5 °C
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-22
187.50 °C. @ 760.00 mm Hg
The Good Scents Company Information System

3.2.5 Flash Point

195 °C (383 °F) - closed cup
Sigma-Aldrich Corp; Safety Data Sheet for 4-Aminophenol (Product Number: A71328) Version 3.0 (August 21, 2009). Available from, as of June 15, 2010: https://www.sigmaaldrich.com

3.2.6 Solubility

less than 1 mg/mL at 73 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
Solubility in water: 0.39% at 0 °C; 0.65% at 24 °C; 0.80% at 30 °C; in ethyl methyl ketone: 9.3% at 58.5 °C; in absolute ethanol: 4.5% at 0 °C; practically insoluble in benzene and chloroform
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 78
Slightly soluble in toluene, diethyl ether, ethanol, cold water; soluble in acetonitrile, ethyl acetate, acetone, hot water; very soluble in dimethylsulfoxide.
Mitchel CS et al; Kirk-Othmer Encyclopedia of Chemical Technology. (2001). New York, NY: John Wiley & Sons; Aminophenols. Online Posting Date: Jun 20, 2003.
Very soluble in ethanol; insoluble in benzene, chloroform; slightly soluble in trifluoroacetic acid; soluble in alkalies
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. V4: 3990
In water, 1.6X10+3 mg/L at 20 °C
Yalkowsky, S.H., He, Yan., Handbook of Aqueous Solubility Data: An Extensive Compilation of Aqueous Solubility Data for Organic Compounds Extracted from the AQUASOL dATAbASE. CRC Press LLC, Boca Raton, FL. 2003., p. 263
16.0 mg/mL

3.2.7 Density

4-Aminophenol crystals exist in two forms. The alpha form (from alcohol, water, or ethyl acetate) is the more stable and has an orthorhombic pyramidal structure, density 1.290 g/cu cm /alpha-4-Aminophenol/
Mitchell SC, Waring RH; Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (2008). New York, NY: John Wiley & Sons; Aminophenols. Online Posting Date: Sept 15, 2000.

3.2.8 Vapor Pressure

0.00004 [mmHg]
4.0X10-5 mm Hg at 25 °C
Dunn SA; J Amer Chem Soc 76: 6191-2 (1954)

3.2.9 LogP

log Kow = 0.04 at pH 7.4
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 20
0.04
HANSCH,C ET AL. (1995)

3.2.10 Stability / Shelf Life

Deteriorates under influence of air and light
The Merck Index. 9th ed. Rahway, New Jersey: Merck & Co., Inc., 1976., p. 64

3.2.11 Decomposition

When heated to decomposition it emits toxic fumes of /nitric oxides/.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 208

3.2.12 Ionization Efficiency

1 of 2
Ionization mode
Positive
logIE
2.56
pH
2.7
Instrument
Agilent XCT
Ion source
Electrospray ionization
Additive
formic acid (5.3nM)
Organic modifier
MeCN (80%)
2 of 2
Ionization mode
Negative
logIE
-1.47
pH
10.5
Instrument
Agilent XCT
Ion source
Electrospray ionization
Additive
ammonia (10nM)
Organic modifier
MeCN (80%)

3.2.13 Dissociation Constants

pK1 = 5.48 at 25 °C (conjugate acid)
Perrin DD; Dissociation Constants of Organic Bases in aqueous Solution. IUPAC Chemical Data Series: Supplement 1972. Buttersworth, London (1972)
pK2 = 10.46
Serjeant, E.P., Dempsey B.; Ionisation Constants of Organic Acids in Aqueous Solution. International Union of Pure and Applied Chemistry (IUPAC). IUPAC Chemical Data Series No. 23, 1979. New York, New York: Pergamon Press, Inc., p. 216

3.2.14 Kovats Retention Index

Standard non-polar
1265 , 1265 , 1314 , 1314 , 1314 , 1265

3.2.15 Other Experimental Properties

Heat of formation = -190.6 kJ/mol
Mitchel CS et al; Kirk-Othmer Encyclopedia of Chemical Technology. (2001). New York, NY: John Wiley & Sons; Aminophenols. Online Posting Date: Jun 20, 2003.
4-Aminophenol crystals exist in two forms. The less stable beta form (from acetone) exists as acicular crystals that turn into the alpha form on standing; they are orthorhombic bipyramidal or pyramidal /beta-4-Aminophenol/
Mitchell SC, Waring RH; Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (2008). New York, NY: John Wiley & Sons; Aminophenols. Online Posting Date: Sept 15, 2000.
Crystalline powder; gradually becomes darker. Decomposes about 306 °C. Very soluble in water; soluble in alcohol /p-Aminophenol hydrochloride/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 78

3.3 SpringerMaterials Properties

3.4 Chemical Classes

Nitrogen Compounds -> Amino Phenols
Dye
S120 | DUSTCT2024 | Substances from Second NORMAN Collaborative Dust Trial | DOI:10.5281/zenodo.13835254

3.4.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749

3.4.2 Cosmetics

Cosmetic ingredients (p-Aminophenol) -> CIR (Cosmetic Ingredient Review)
Hair dyeing
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118

3.4.3 Endocrine Disruptors

Potential endocrine disrupting compound
S109 | PARCEDC | List of 7074 potential endocrine disrupting compounds (EDCs) by PARC T4.2 | DOI:10.5281/zenodo.10944198

3.4.4 Pesticides

Environmental transformation -> Pesticide transformation products (metabolite, successor)
S60 | SWISSPEST19 | Swiss Pesticides and Metabolites from Kiefer et al 2019 | DOI:10.5281/zenodo.3544759

4 Spectral Information

4.1 1D NMR Spectra

1 of 2
1D NMR Spectra
1H NMR: 717 (Sadtler Research Laboratories Spectral Collection)
2 of 2
1D NMR Spectra

4.1.1 1H NMR Spectra

1 of 4
View All
Spectra ID
Instrument Type
Varian
Frequency
500 MHz
Solvent
CDCl3
pH
7.00
Shifts [ppm]:Intensity
6.60:56.91, 6.67:86.27, 6.62:100.00, 6.69:59.28
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2 of 4
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Spectra ID
Instrument Type
JEOL
Frequency
400 MHz
Solvent
DMSO-d6
Shifts [ppm]:Intensity
6.41:493.00, 6.47:160.00, 6.49:217.00, 8.36:78.00, 6.51:65.00, 6.48:1000.00, 6.48:305.00, 6.44:162.00, 6.43:993.00, 6.50:516.00, 6.41:67.00, 6.42:227.00, 4.36:194.00, 6.43:286.00
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4.1.2 13C NMR Spectra

1 of 3
View All
Spectra ID
Instrument Type
JEOL
Frequency
22.53 MHz
Solvent
DMSO-d6
Shifts [ppm]:Intensity
115.51:951.00, 148.25:354.00, 115.26:1000.00, 140.46:299.00
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2 of 3
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Source of Sample
MCB Manufacturing Chemists, Norwood, Ohio
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. 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 2D NMR Spectra

4.2.1 1H-13C NMR Spectra

2D NMR Spectra Type
1H-13C HSQC
Spectra ID
Instrument Type
Bruker
Frequency
600 MHz
Solvent
Water
pH
7.00
Shifts [ppm] (F2:F1):Intensity
6.82:118.90:0.84, 6.87:121.79:1.00
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4.3 Mass Spectrometry

4.3.1 GC-MS

1 of 14
View All
Spectra ID
Instrument Type
EI-B
Ionization Mode
positive
Top 5 Peaks

109.0 99.99

80.0 24.14

108.0 13.80

53.0 10.13

52.0 8.56

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Notes
instrument=JEOL JMS-D-3000
2 of 14
View All
Spectra ID
Instrument Type
EI-B
Ionization Mode
positive
Top 5 Peaks

109.0 99.99

80.0 58.40

53.0 28.90

52.0 22.42

29.0 18.64

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Notes
instrument=HITACHI M-80A

4.3.2 MS-MS

1 of 7
View All
Spectra ID
Instrument Type
Quattro_QQQ
Ionization Mode
Positive
Top 5 Peaks

110.0 100

92.0 13.59

93.0 12.69

65.0 7.43

82.0 2.95

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Notes
delivery=Flow_Injectionanalyzer=Triple_Quad
2 of 7
View All
Spectra ID
Instrument Type
Quattro_QQQ
Ionization Mode
Positive
Top 5 Peaks

65.0 100

93.0 18.63

109.0 4.99

110.0 3.50

80.0 3.11

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Notes
delivery=Flow_Injectionanalyzer=Triple_Quad

4.3.3 LC-MS

1 of 7
View All
Authors
Krauss M, Schymanski EL, Weidauer C, Schupke H, UFZ and Eawag
Instrument
Q Exactive Plus Orbitrap Thermo Scientific
Instrument Type
LC-ESI-QFT
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
35 (nominal)
Fragmentation Mode
HCD
Column Name
Kinetex C18 EVO 2.6 um, 2.1x50 mm, precolumn 2.1x5 mm, Phenomenex
Retention Time
0.482 min
Precursor m/z
110.06
Precursor Adduct
[M+H]+
Top 5 Peaks

110.06 999

92.0494 83

65.0386 77

93.0334 76

82.0651 35

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License
CC BY
Reference
Schymanski, E. L.; Ruttkies, C.; Krauss, M.; Brouard, C.; Kind, T.; Dührkop, K.; Allen, F.; Vaniya, A.; Verdegem, D.; Böcker, S.; et al. Critical Assessment of Small Molecule Identification 2016: Automated Methods. Journal of Cheminformatics 2017, 9 (1). DOI:10.1186/s13321-017-0207-1
2 of 7
View All
Authors
Sawada Y, Matsuda F, and Hirai MY. Plant Science Center, RIKEN
Instrument
TQD, Waters
Instrument Type
LC-ESI-QQ
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
10
Precursor m/z
110.05
Top 5 Peaks

110 999

89 548

69 154

68 64

109 45

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License
CC BY-NC
Reference
Sawada, Y.; Akiyama, K.; Sakata, A.; Kuwahara, A.; Otsuki, H.; Sakurai, T.; Saito, K.; Hirai, M. Y. Widely Targeted Metabolomics Based on Large-Scale MS/MS Data for Elucidating Metabolite Accumulation Patterns in Plants. Plant and Cell Physiology 2008, 50 (1), 37-47. DOI:10.1093/pcp/pcn183

4.3.4 Other MS

1 of 5
View All
Other MS
MASS: 1446 (NIST/EPA/MSDC Mass Spectral Database, 1990 version)
2 of 5
View All
Authors
FUJISE Y, HAMAMATSU UNIV. SCHOOL OF MEDICINE
Instrument
JEOL JMS-D-3000
Instrument Type
EI-B
MS Level
MS
Ionization Mode
POSITIVE
Ionization
ENERGY 70 eV
Top 5 Peaks

109 999

80 241

108 138

53 101

52 86

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License
CC BY-NC-SA

4.4 UV Spectra

Max absorption (water): 229 nm (log e = 3.78); 294 nm (log e = 3.30)
Weast, R.C. (ed.). Handbook of Chemistry and Physics. 57th ed. Cleveland: CRC Press Inc., 1976., p. C-428
UV: 236 (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. V4: 3990

4.4.1 UV-VIS Spectra

1 of 2
Copyright
Copyright © 2008-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Copyright
Copyright © 2008-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.5 IR Spectra

IR Spectra
IR: 712 (Sadtler Research Laboratories Prism Collection)

4.5.1 FTIR Spectra

1 of 2
Instrument Name
Bio-Rad FTS
Technique
KBr0
Source of Spectrum
Forensic Spectral Research
Copyright
Copyright © 2012-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Instrument Name
Bruker IFS 85
Technique
KBr-Pellet
Source of Sample
E. Merck AG, Darmstadt
Copyright
Copyright © 1989, 1990-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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4.5.2 ATR-IR Spectra

1 of 2
Instrument Name
PerkinElmer SpectrumTwo
Technique
ATR-IR
Copyright
Copyright © 2013-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Source of Sample
Aldrich
Catalog Number
245992
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.5.3 Vapor Phase IR Spectra

Instrument Name
DIGILAB FTS-14
Technique
Vapor Phase
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.6 Raman Spectra

Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Copyright
Copyright © 2015-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.7 Other Spectra

Sadtler reference number: 158 (IR, grating)
Weast, R.C. (ed.). Handbook of Chemistry and Physics. 57th ed. Cleveland: CRC Press Inc., 1976., p. C-428
Intense mass spectral peaks: 52 m/z, 80 m/z, 109 m/z
Pfleger, K., H. Maurer and A. Weber. Mass Spectral and GC Data of Drugs, Poisons and their Metabolites. Parts I and II. Mass Spectra Indexes. Weinheim, Federal Republic of Germany. 1985., p. 131

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Labels

Drug and label
Active ingredient and drug

7.2 Reported Fatal Dose

4.4 = very toxic: probable oral lethal dose (human) 50-500 mg/kg, between 1 teaspoon & 1 oz for 70 kg person (150 lb). ... causes methemoglobinemia, but less toxic than aniline in animals. ... diln used in photography do not have significant percutaneous toxicity in most cases.
Gosselin, R.E., H.C. Hodge, R.P. Smith, and M.N. Gleason. Clinical Toxicology of Commercial Products. 4th ed. Baltimore: Williams and Wilkins, 1976., p. II-141

8 Food Additives and Ingredients

8.1 Associated Foods

9 Agrochemical Information

9.1 Agrochemical Transformations

4-hydroxy benzonitrile is a known environmental transformation product of Bromoxynil.

Buprofezin metabolite BF22 is a known environmental transformation product of Buprofezin.

S60 | SWISSPEST19 | Swiss Pesticides and Metabolites from Kiefer et al 2019 | DOI:10.5281/zenodo.3544759

10 Pharmacology and Biochemistry

10.1 MeSH Pharmacological Classification

Mutagens
Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. (See all compounds classified as Mutagens.)

10.2 Absorption, Distribution and Excretion

An absorption and excretion study of permanent hair dye intermediates containing 14-C was conducted in hairless Wistar rats under conditions of oxidation hair dyeing (ie, intermediates were mixed with H202 immediately before application). The cutaneous penetration of 14C-4-aminophenol (PAP) alone and in admixture with a nonradioactive coupler (3-amino-6-methylphenol, a 3-aminophenol (MAP) derivative) and that of the resultant 14C-indamine (N-[4-hydroxyphenyl}-3-amino-6-methyl benzoquinone imine) was determined. Hair dye solutions containing uniformly labeled PAP (0.75% or 70 nM) in a simple vehicle were applied to a 10 sq cm dorsal surface of up to 5 rats. Doses of PAP of 0.14 uM/sq cm, 0.69 uM/sq cm, and 3.44/ uM/sq cm yielded respective concentrations of 15.9 +/- 4.76 nM/sq cm, 52.04 +/- 6.73 nM/sq cm, and 58.4 +/- 11.5 nM/sq cm, which penetrated the skin and were detected in the excreta, the viscera, and the skin (excluding PAP found at the site of application) of the treated rats after 4 days. At the highest 14C-PAP concentration applied, the total quantity of 14C-PAP detected per sq cm of skin was approximately the same for PAP alone as for PAP mixed with nonradioactive MAP coupler (56.8 +/- 4.0 nM/sq cm). Penetration of the 14C-indamine was approximately 17 times less (3.6 +/- 0.46 nM) than that of PAP or of the mixture of PAP with the nonradioactive coupler..
Cosmetic Ingredient Expert Review Panel; Final Report on the Safety Assessment of p-Aminophenol, m-Aminophenol, and o-Aminophenol; Journal of the American College of Toxicology 7 (3): 279-333 (1988).

10.3 Metabolism / Metabolites

... Hepatocytes prepared from male Sprague-Dawley rats ... converted para-aminophenol (PAP) to two major metabolites (PAP-GSH conjugates and PAP-N-acetylcysteine conjugates) and several minor metabolites [PAP-O-glucuronide, acetaminophen (APAP), APAP-O-glucuronide, APAP-GSH conjugates, and 4-hydroxyformanilide]. Preincubating hepatoyctes with 1-aminobenzotriazole, an inhibitor of cytochromes P450, did not alter the pattern of PAP metabolism. In conclusion, we found that PAP was metabolized in hepatocytes predominantly to PAP-GSH conjugates and PAP-N-acetylcysteine conjugates in sufficient quantities to account for the nephrotoxicity of PAP.
Yan Z et al; Drug Metab Dispos 28 (8): 880-6 (2000)
... The hepatic metabolism of p-aminophenol in Wistar rats and the cytotoxicity of formed glutathione S-conjugates in rat renal epithelial cells /were examined/. After ip application of p-aminophenol (100 mg/kg), the following metabolites were identified in rat bile: 4-amino-2-(glutathion-S-yl)phenol, 4-amino-3-(glutathion-S-yl)-phenol, 4-amino-2,5-bis(glutathion-S-yl)phenol, 4-amino-2,3,5(or 6)-tris(glutathion-S-yl)phenol, an aminophenol conjugate (likely a sulfate or glucuronide), acetaminophen glucuronide, and 3-(glutathion-S-yl)acetaminophen. 4-Amino-3-(glutathion-S-yl)phenol, 4-amino-2,5-bis(glutathion-S-yl)phenol, and 4-amino-2,3,5(or 6)-tris(glutathion-S-yl)phenol induced a dose- and time-dependent loss of cell viability in rat kidney cortical cells. Cell killing was significantly reduced by inhibition of gamma-glutamyl transpeptidase with Acivicin. p-Aminophenol was also toxic to renal epithelial cells. Coincubation of p-aminophenol with tetraethylammonium bromide, a competitive inhibitor of the organic cation transporter, and with SKF-525A, an inhibitor of cytochrome P450, protected cells from p-aminophenol-induced toxicity. p-Aminophenol would thus be accumulated in the kidney mainly by organic cation transport systems, which are concentrated in the S-1 segment of the proximal tubule. However, p-aminophenol toxicity in vivo is directed toward the S-2 and S-3 segments, which are rich in gamma-glutamyl transpeptidase. These results and the observation that biliary cannulation and glutathione depletion reduce p-aminophenol nephrotoxicity suggest that the biosynthesis of toxic glutathione conjugates is responsible for p-aminophenol nephrotoxicity in vivo. The aminophenol glutathione S-conjugates formed induce p-aminophenol nephrotoxicity by a pathway dependent on gamma-glutamyl transpeptidase.
Klos C et al; Toxicol Appl Pharmacol 115 (1): 98-106 (1992)
4-Aminophenol in the presence of oxyhemoglobin forms numerous adducts with glutathione (GSH). Using (14)C-4-aminophenol and (3)H-glutathione, ten different thioethers were isolated, by HPLC, with isotope ratios of 1:1, 1:2, 1:3, respectively ... In erythrocytes of humans and dogs, and in dog blood, in vivo, the same pattern of 4-aminophenol conjugates with GSH was found. In vivo, 5% of administered 4-aminophenol is converted into thioethers within erythrocytes, accompanied by a 60% decrease in the cellular GSH, indicating the role of erythrocytes in the biotransformation of xenobiotics.
Eckert KG; Xenobiotica 18 (11): 1319-26 (1988)
p-Aminophenol yields p-acetamidophenol, p-aminophenyl-beta-d-glucuronide, p-aminophenyl sulfate, 4-aminoresorcinol, and p-methylaminophenol in rabbit.
European Commission, ESIS; IUCLID Dataset, 4-Aminophenol (123-30-8) p.15 (2000 CD-ROM edition). Available from, as of May 17, 2010: https://esis.jrc.ec.europa.eu/
For more Metabolism/Metabolites (Complete) data for 4-Aminophenol (12 total), please visit the HSDB record page.
4-aminophenol is a known human metabolite of aniline.
S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560

10.4 Mechanism of Action

... Markers of ER stress (XBP1 messenger RNA processing and protein expression; GRP78 and GRP94 upregulation) and ER-mediated cell death (caspase-12 and calpain activation) were examined in kidney tissue of rats exposed to nephrotoxic doses of cisplatin (CIS), gentamicin (GEN), and p-aminophenol (PAP), a nephrotoxic metabolite of acetaminophen. XBP1 signaling was observed with all three drugs and was associated with increased expression of GRP94 and GRP78 in GEN- and PAP-treated animals, but not after CIS exposure. m-Calpain expression was increased after 7 days of CIS treatment, whereas it was decreased in PAP-treated rats. Caspase-12 cleavage products were increased after CIS, GEN, and PAP administration. The results of this study demonstrate that three clinically relevant nephrotoxic drugs are all associated with changes in markers of ER stress and ER-mediated cell death in vivo ...
Peyrou M et al; Toxicol Sci 99 (1): 346-53 (2007)
4-Aminophenol (4-AP), D-serine, and cisplatin are established rodent nephrotoxins that damage proximal tubules within the renal cortex ... High throughput 2D gel proteomics to profile protein changes in the plasma of compound-treated animals, ... /demonstrated/ several markers of kidney toxicity. Male F344 and Alpk rats were treated with increasing doses of 4-AP, D-serine, or cisplatin, and plasma samples were collected over time ... Several isoforms of the rat-specific T-kininogen protein were identified in each study. T-kininogen was elevated in the plasma of 4-AP-, D-serine-, and cisplatin-treated animals at early time points, returning to baseline levels 3 weeks after treatment. The protein was not elevated in the plasma of control animals or those treated with nontoxic compounds. /It was proposed/ that T-kininogen may be required to counteract apoptosis in proximal tubular cells in order to minimize tissue damage following a toxic insult. In addition, T-kininogen may be required to stimulate localized inflammation to aid tissue repair ... Several isoforms of the inter-alpha inhibitor H4P heavy chain /were identified/ in the 4-AP and D-serine studies. In each case, the protein expression levels in the blood samples paralleled the extent of kidney toxicity, highlighting the correlation between protein alterations and clinical chemistry endpoints. A further set of proteins correlating with kidney damage was found to be a component of the complement cascade and other blood clotting factors, indicating a contribution of the immune system to the observed toxicity. These observations underscore the value of proteomics in identifying new biomarkers and in the elucidation of mechanisms of toxicity.
Bandara LR et al; Toxicol Sci 73 (1): 195-206 (2003)
One of the primary effects found from exposure to p-aminophenol is the formation of methemoglobin. This effect has been found in many species with a wide degree of susceptibility. The oxidation of hemoglobin to methemoglobin interferes with normal oxygen transport functions of hemoglobin and can result in a chemical asphyxia (usually at levels of 60% or more). It is believed that p-aminophenol forms a covalent bond with the reactive -SH groups of hemoglobin and transfers electrons to oxygen to created methemoglobin.
European Commission, ESIS; IUCLID Dataset, 4-Aminophenol (123-30-8) p.43 (2000 CD-ROM edition). Available from, as of May 17, 2010: https://esis.jrc.ec.europa.eu/
p-Aminophenol is a significantly toxic chemical and one mechanism associated with its cytotoxicity has been attributed to its activity as a tissue respiratory (oxidative phosphorylation) inhibitor ... .
Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 973

10.5 Human Metabolite Information

10.5.1 Tissue Locations

  • Epidermis
  • Spleen

10.6 Biochemical Reactions

10.7 Transformations

11 Use and Manufacturing

11.1 Uses

Cosmetic Ingredient Review Link
CIR ingredient: p-Aminophenol
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 as a dye for textiles, hair, furs, and feathers; also used as a photographic developer and chemical intermediate for pharmaceuticals and dyes; [HSDB]
Industrial Processes with risk of exposure

Photographic Processing [Category: Other]

Fur Dressing and Dyeing [Category: Industry]

Textiles (Printing, Dyeing, or Finishing) [Category: Industry]

Dressing Hair [Category: Other]

Dyeing textiles, hair, furs, feathers; photographic developer; pharmaceuticals; antioxidants, oil additives
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 62
Intermediate in the manufacture of sulfur and azo dyes
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 78
CHEM INT FOR THE ANALGESIC, PHENACETIN, AND FOR OTHER ANALGESICS & ANTIPYRETICS; CHEM INT FOR THE DYES, DISPERSE YELLOW 1, ACID YELLOW 40, AND ACID YELLOW 76
SRI
4-Aminophenol is a strong reducing agent ... it also acts as a corrosion inhibitor in paints and as an anticorrosion-lubricating agent in 2-cycle engine fuels. 4-Aminophenol is also used as a wood stain, imparting a roselike color to timber
Mitchel CS et al; Kirk-Othmer Encyclopedia of Chemical Technology. (2001). New York, NY: John Wiley & Sons; Aminophenols. Online Posting Date: Jun 20, 2003.
Used as a chemical intermediate for the synthesis of Acid Yellow 40; Acid Yellow 76; N-benzyl-p-aminophenol hydrochloride; N-butyryl-p-aminophenol; N-(4-hydroxyphenyl)glycine; N-lauroyl-p-aminophenol; N-methyl-p-aminophenol; paracetamol; N-pelagonoyl-p-aminophenol; N-stearoyl-p-aminophenol; Sulphur Black 11; Sulphur Green 1; Sulphur Green 9; Sulphur Green 11; Sulphur Red 10; triglycidyl-p-aminophenol
Ashford, R.D. Ashford's Dictionary of Industrial Chemicals. London, England: Wavelength Publications Ltd., 1994., p. 73
4-Aminophenol is commonly used as a developer in black and white film, marketed under the name Rodinal. Aminophenols are also intermediates in the synthesis of dyes and can thus be found in numerous cosmetics products, particularly hair dyes. (L1882, L1883)
L1882: Wikipedia. 2-Aminophenol. Last Updated 12 June 2009. http://en.wikipedia.org/wiki/2-Aminophenol
L1883: Wikipedia. 4-Aminophenol. Last Updated 3 July 2009. http://en.wikipedia.org/wiki/4-aminophenol

11.1.1 Use Classification

Cosmetics -> Hair dyeing
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118
Environmental transformation -> Pesticide transformation products (metabolite, successor)
S60 | SWISSPEST19 | Swiss Pesticides and Metabolites from Kiefer et al 2019 | DOI:10.5281/zenodo.3544759

11.1.2 Industry Uses

Not Known or Reasonably Ascertainable

11.1.3 Household Products

Household & Commercial/Institutional Products

Information on 242 consumer products that contain p-Aminophenol in the following categories is provided:

• Inside the Home

• Personal Care

11.2 Methods of Manufacturing

REDUCTION OF NITROBENZENE WITH IRON FILINGS IN ACID OR BY CATALYTIC HYDROGENATION
SRI
Usually prepared by the reduction of p-nitrophenol
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 78
(1) By reduction of p-nitrophenol with iron filings and hydrochloric acid; (2) by electrolytic reduction of nitrobenzene in concentrated sulfuric acid and treatment with an alkali to free the base.
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 62

11.3 Formulations / Preparations

Grades: Technical; photographic
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 78

11.4 U.S. Production

Aggregated Product Volume

2019: 171,299 lb

2018: 851,248 lb

2017: 2,019,478 lb

2016: 757,530 lb

(1972) GREATER THAN 4.54X10+6 GRAMS
SRI
(1975) GREATER THAN 9.08X10+5 GRAMS
SRI
Production figures for the aminophenols are scarce, the compounds usually being classified along with many other aniline derivatives. Most production of the technical grade materials (95% purity) occurs on-site as they are chiefly used as intermediate reactants in continuous chemical syntheses. World production of the fine chemicals (99% purity) is probably no more than a few hundred metric tons yearly... /Aminophenols/
Mitchel CS et al; Kirk-Othmer Encyclopedia of Chemical Technology. (2001). New York, NY: John Wiley & Sons; Aminophenols. Online Posting Date: Jun 20, 2003.
Phenol, 4-amino- 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. Phenol, 4-amino- (123-30-8). Available from, as of June 7, 2010: https://www.epa.gov/hpv/pubs/general/opptsrch.htm
For more U.S. Production (Complete) data for 4-Aminophenol (6 total), please visit the HSDB record page.

11.5 U.S. Imports

(1972) 2.61x10+6 grams (princpl custms dists)
SRI
(1975) 1.27X10+6 GRAMS (PRINCPL CUSTMS DISTS)
SRI

11.6 General Manufacturing Information

Industry Processing Sectors
  • All Other Basic Organic Chemical Manufacturing
  • Cyclic Crude and Intermediate Manufacturing
  • Plastics Material and Resin Manufacturing
EPA TSCA Commercial Activity Status
Phenol, 4-amino-: ACTIVE
EPA TSCA Regulatory Flag
TP - indicates a substance that is the subject of a proposed TSCA section 4 test rule.

12 Identification

12.1 Analytic Laboratory Methods

Choice of TLC systems for routine screening for acidic drugs during toxicological analyses.
Owen P et al; J Chromatogr 161: 195-203 (1978)
Nitrogen flame ionization detector/flame ionization detector ratio as aid for identification of forensically relevant cmpd.
Kijewski H, Poehlmann K; Beitr Gerichtl Med 36: 463-70 (1978)
Hair dyes acting by oxidation. Their identification & estimation by high-performance liq phase chromatography.
Midler O, Karleskind A; Parfums Cosmet Aromes 23: 77-80 & 83-5 (1978)
Chloramin "fahlberg"--a new detection reagent for identification & semiquantitative determination of nitro- & aminophenols in polluted water. A TLC determination.
Thielemann H; Acta Hydrochim Hydrobiol 7 (1): 123-4 (979.)
Methods for analysis of arylamines & their N- & C-hydroxylated metabolites, including high-pressure liq chromatography & spectrophotometric methods.
Sternson LA, Dewitte WJ; Biol Oxid Nitrogen Proc Int Symp 2nd 257-62 (1978)

13 Safety and Hazards

13.1 Hazards Identification

13.1.1 GHS Classification

1 of 6
View All
Pictogram(s)
Irritant
Health Hazard
Environmental Hazard
Signal
Warning
GHS Hazard Statements

H302+H332 (31.7%): Harmful if swallowed or if inhaled [Warning Acute toxicity, oral; acute toxicity, inhalation]

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

H317 (28.6%): May cause an allergic skin reaction [Warning Sensitization, Skin]

H332 (99.5%): Harmful if inhaled [Warning Acute toxicity, inhalation]

H341 (100%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]

H373 (28.6%): May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

H400 (98.7%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

H410 (100%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

Precautionary Statement Codes

P203, P260, P261, P264, P270, P271, P272, P273, P280, P301+P317, P302+P352, P304+P340, P317, P318, P319, P321, P330, P333+P317, P362+P364, P391, 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 378 reports by companies from 22 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

13.1.2 Hazard Classes and Categories

Acute Tox. 4 (100%)

Skin Sens. 1 (28.6%)

Acute Tox. 4 (99.5%)

Muta. 2 (100%)

STOT RE 2 (28.6%)

Aquatic Acute 1 (98.7%)

Aquatic Chronic 1 (100%)

Acute toxicity - category 4

Acute toxicity - category 4

Germ cell mutagenicity - category 2

Specific target organ toxicity (repeated exposure) - category 2

Skin sensitisation - category 1

Hazardous to the aquatic environment (acute) - category 1

Hazardous to the aquatic environment (chronic) - category 1

13.1.3 NFPA Hazard Classification

NFPA 704 Diamond
4-1-0
NFPA Health Rating
4 - Materials that, under emergency conditions, can be lethal.
NFPA Fire Rating
1 - Materials that must be preheated before ignition can occur. Materials require considerable preheating, under all ambient temperature conditions, before ignition and combustion can occur.
NFPA Instability Rating
0 - Materials that in themselves are normally stable, even under fire conditions.

13.1.4 Health Hazards

SYMPTOMS: Symptoms of exposure to this chemical may include asthma, irritation of the skin and eyes, dermatitis and methemoglobinemia with cyanosis.

ACUTE/CHRONIC HAZARDS: This compound is a skin and eye irritant and an allergen. When heated to decomposition it emits toxic fumes. (NTP, 1992)

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

13.1.5 Fire Hazards

Flash point data are not available for this chemical. It is probably combustible. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

13.1.6 Hazards Summary

The lethal oral dose in humans is in the range of 50-500 mg/kg. p-Aminiophenol induces methemoglobinemia in experimental animals, but it is not as potent as aniline. It is a potential sensitizer of the skin and respiratory tract. [HSDB] Symptoms of exposure to this chemical may include asthma, irritation of the skin and eyes, dermatitis and methemoglobinemia with cyanosis; This compound is a skin and eye irritant and an allergen. [CAMEO] Danger of skin sensitization; [MAK]

13.1.7 Skin, Eye, and Respiratory Irritations

... skin and eye irritant.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 208

13.2 First Aid Measures

13.2.1 First Aid

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.

INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.

INGESTION: DO NOT INDUCE VOMITING. Phenols are very toxic poisons AND corrosive and irritating, so that inducing vomiting may make medical problems worse. IMMEDIATELY call a hospital or poison control center and locate activated charcoal, egg whites, or milk in case the medical advisor recommends administering one of them. If advice from a physician is not readily available and the victim is conscious and not convulsing, give the victim a glass of activated charcoal slurry in water or, if this is not available, a glass of milk, or beaten egg whites and IMMEDIATELY transport victim to a hospital. If the victim is convulsing or unconscious, do not give anything by mouth, assure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

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

13.3 Fire Fighting

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

13.3.1 Fire Fighting Procedures

Use dry chemical, carbon dioxide, or alcohol foam extinguishers. Vapors are heavier than air and will collect in low areas. Vapors may travel long distances to ignition sources and flashback. Vapors in confined areas may explode when exposed to fire. Storage containers and parts of containers may rocket great distances, in many directions. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire officials and pollution control agencies. From a secure, explosion-proof location, use water spray to cool exposed containers. If cooling streams are ineffective (venting sound increases in volume and pitch, tank discolors or shows any signs of deforming), withdraw immediately to a secure position ... The only respirators recommended for fire fighting are self-contained breathing apparatuses that have full facepieces and are operated in a pressure-demand or other positive-pressure mode. /Anisidines/
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 5th Edition Volume 1: A-H,Volume 2: I-Z. William Andrew, Norwich, NY 2008, p. 220
If material on fire or involved in fire: Extinguish fire using agent suitable for type of surrounding fire. (Material itself does not burn or burns with difficulty.) Use water in flooding quantities as fog. Use foam, dry chemical, or carbon dioxide. Keep run-off water out of sewers and water sources. /Aminophenols/
Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 53

13.4 Accidental Release Measures

13.4.1 Isolation and Evacuation

Excerpt from ERG Guide 152 [Substances - Toxic (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)

13.4.2 Cleanup Methods

Spill handling: keep dust under control. Use a vacuum or wet method to reduce dust during clean-up. Do not sweep. Evacuate persons not wearing protective equipment from area of spill or leak until clean-up is complete. Remove all ignition sources. Collect powdered material in the most convenient and safe manner and deposit in sealed containers. Ventilate area after clean-up is complete. It may be necessary to contain and dispose of this chemical as a hazardous waste. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Contact your Department of Environmental Protection of your regional office of the federal EPA for specific recommendations. /Aminophenols/
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 5th Edition Volume 1: A-H,Volume 2: I-Z. William Andrew, Norwich, NY 2008, p. 138

13.4.3 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.
Incineration. /Aminophenols/
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 5th Edition Volume 1: A-H,Volume 2: I-Z. William Andrew, Norwich, NY 2008, p. 138

13.4.4 Preventive Measures

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.
... Disposable natural rubber latex gloves and disposable PVC gloves should not be used repeatedly for handling the hair dye products /p-aminophenol, m-aminophenol, o-aminophenol, and p-phenylenediamine/.
Lee HS, Lin YW; Ann Occup Hyg 53 (3): 289-96 (2009)
If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. /Aminophenols/
Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 53
Personnel protection: Avoid breathing dusts, and fumes from burning material. Keep upwind ... Avoid bodily contact with the material ... Do not handle broken packages unless wearing appropriate personal protective equipment. /Aminophenols/
Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 53

13.5 Handling and Storage

13.5.1 Nonfire Spill Response

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

STORAGE PRECAUTIONS: You should protect this chemical from exposure to light. Keep the container tightly closed under an inert atmosphere, and store under refrigerated temperatures. (NTP, 1992)

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

13.5.2 Storage Conditions

Store in tightly closed containers in a cool, well-ventilated area. Aminophenols must be stored to avoid contact with strong oxidizers (such as chlorine, bromine, and fluorine), since violent reactions occur. /Aminophenols/
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 5th Edition Volume 1: A-H,Volume 2: I-Z. William Andrew, Norwich, NY 2008, p. 138

13.6 Exposure Control and Personal Protection

13.6.1 Personal Protective Equipment (PPE)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
Wear protective gloves and clothing to prevent any reasonable probability of skin contact ... Wear dust-proof chemical goggles and face shield unless full facepiece respiratory protection is worn. /Aminophenols/
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 5th Edition Volume 1: A-H,Volume 2: I-Z. William Andrew, Norwich, NY 2008, p. 138

13.7 Stability and Reactivity

13.7.1 Air and Water Reactions

Insoluble in water.

13.7.2 Reactive Group

Phenols and Cresols

Amines, Aromatic

13.7.3 Reactivity Profile

P-AMINOPHENOL is sensitive to: Heat (decomposition forming HCN, nitrous vapors, CO); water (CO2); reacts violently with acids, bases, alcohols and amines causing fire and explosion hazards [Handling Chemicals Safely 1980 p. 647].

13.7.4 Hazardous Reactivities and Incompatibilities

Strong oxidants. /Aminophenols/
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 5th Edition Volume 1: A-H,Volume 2: I-Z. William Andrew, Norwich, NY 2008, p. 137

13.8 Transport Information

13.8.1 DOT Emergency Guidelines

/GUIDE 152: SUBSTANCES - TOXIC (COMBUSTIBLE)/ Health: Highly toxic, may be fatal if inhaled, swallowed or absorbed through skin. Contact with molten substance may cause severe burns to skin and eyes. Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution. /Aminophenols/
U.S. Department of Transportation. 2008 Emergency Response Guidebook. Washington, D.C. 2008
/GUIDE 152: SUBSTANCES - TOXIC (COMBUSTIBLE)/ Fire or Explosion: Combustible material: may burn but does not ignite readily. Containers may explode when heated. Runoff may pollute waterways. Substance may be transported in a molten form. /Aminophenols/
U.S. Department of Transportation. 2008 Emergency Response Guidebook. Washington, D.C. 2008
/GUIDE 152: SUBSTANCES - TOXIC (COMBUSTIBLE)/ Public Safety: CALL Emergency Response Telephone Number ... As an 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. Keep unauthorized personnel away. Stay upwind. Keep out of low areas. /Aminophenols/
U.S. Department of Transportation. 2008 Emergency Response Guidebook. Washington, D.C. 2008
/GUIDE 152: SUBSTANCES - TOXIC (COMBUSTIBLE)/ Protective Clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible. /Aminophenols/
U.S. Department of Transportation. 2008 Emergency Response Guidebook. Washington, D.C. 2008
For more DOT Emergency Guidelines (Complete) data for 4-Aminophenol (8 total), please visit the HSDB record page.

13.8.2 Shipping Name / Number DOT/UN/NA/IMO

UN 2512; Aminophenols (o-,m-,p-).
IMO 6.1; Aminophenols (o-, m-, p-)

13.8.3 Shipment Methods and Regulations

No person may /transport,/ offer or accept a hazardous material for transportation in commerce unless that person is registered in conformance ... and the hazardous material is properly classed, described, packaged, marked, labeled, and in condition for shipment as required or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./
49 CFR 171.2 (7/1/2000)
The International Air Transport Association (IATA) Dangerous Goods Regulations are published by the IATA Dangerous Goods Board pursuant to IATA Resolutions 618 and 619 and constitute a manual of industry carrier regulations to be followed by all IATA Member airlines when transporting hazardous materials.
IATA. Dangerous Goods Regulations. 41st Ed.Montreal, Canada and Geneva, Switzerland: International Air Transport Association, Dangerous Goods Regulations, 2000., p. 110
The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals. Detailed recommendations for individual substances and a number of recommendations for good practice are included in the classes dealing with such substances. A general index of technical names has also been compiled. This index should always be consulted when attempting to locate the appropriate procedures to be used when shipping any substance or article.
IMDG; International Maritime Dangerous Goods Code; International Maritime Organization p.6063 (1998)

13.8.4 DOT Label

Poison

13.9 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: Phenol, 4-amino-
REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
4-Aminophenol: Does not have an individual approval but may be used under an appropriate group standard

13.9.1 Atmospheric Standards

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. p-Aminophenol is produced, as an intermediate or a final product, by process units covered under this subpart.
40 CFR 60.489 (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 2, 2010: https://www.ecfr.gov

13.10 Other Safety Information

Chemical Assessment
IMAP assessments - Phenol, 4-amino-: Human health tier II assessment

13.10.1 Toxic Combustion Products

Poisonous gases are produced in fire, including nitrogen oxides. /Aminophenols/
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 5th Edition Volume 1: A-H,Volume 2: I-Z. William Andrew, Norwich, NY 2008, p. 138

14 Toxicity

14.1 Toxicological Information

14.1.1 Toxicity Summary

4-Aminobiphenyl requires metabolic activation in order to exert its toxicity. This is catalyzed by N-hydroxylation via cytochrome P450 1A2, then followed by O-sulfation and O-acetylation by sulfotransferase 1A1 and arylamine N-acetyltransferase 2. The metabolites of 4-aminobiphenyl then form adducts with DNA, inducing mutations. 4-Aminobiphenyl and its metabolites may also cross the placenta and have fetal effects. (1, 2, 3, 4). It is also though that the mode of action involves metabolic activation by N-hydroxylation, followed by N-esterification leading to the formation of a reactive electrophile, which binds covalently to DNA, principally to deoxyguanosine, leading to an increased rate of DNA mutations and ultimately to the development of cancer. In humans and dogs, the urinary bladder urothelium is the target organ, whereas in mice it is the bladder and liver; in other species, other tissues can be involved. Differences in organ specificity are thought to be due to differences in metabolic activation versus inactivation (A15085).
A15085: Cohen SM1, Boobis AR, Meek ME, Preston RJ, McGregor DB. "4-Aminobiphenyl and DNA reactivity: case study within the context of the 2006 IPCS Human Relevance Framework for Analysis of a cancer mode of action for humans.". Crit Rev Toxicol. 2006 Nov-Dec;36(10):803-19. PMID:17118730

14.1.2 EPA Provisional Peer-Reviewed Toxicity Values

Chemical Substance
Reference Dose (RfD), Chronic
2 x 10^-2 mg/kg-day
Reference Dose (RfD), Subchronic
2 x 10^-1 mg/kg-day
PPRTV Assessment
Last Revision
2005

14.1.3 RAIS Toxicity Values

Oral Chronic Reference Dose (RfDoc) (mg/kg-day)
0.02
Oral Chronic Reference Dose Reference
PPRTV Current
Oral Subchronic Chronic Reference Dose (RfDos) (mg/kg-day)
0.2
Oral Subchronic Chronic Reference Dose Reference
PPRTV Current

14.1.4 Carcinogen Classification

Carcinogen Classification
Not listed by IARC.

14.1.5 Health Effects

4-Aminophenol may act as a skin sensitizer and cause contact dermatitis. In addition, inhalation of large amounts can cause methemoglobinemia and bronchial asthma. (T21)
T21: Clayton GD and Clayton FE (eds) (1993-1994). Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc.

14.1.6 Exposure Routes

Oral (L138) ; inhalation (L138)
L138: HSDB: Hazardous Substances Data Bank. National Library of Medicine (2001). http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB

14.1.7 Symptoms

4-Aminophenol may cause contact dermatitis. Signs and symptoms of methemoglobinemia may include shortness of breath, cyanosis, mental status changes, headache, fatigue, exercise intolerance, dizziness and loss of consciousness. Severe methemoglobinemia can result in dysrhythmias, seizures, coma, and death. (T21, L1613)
L1613: Wikipedia. Methemoglobinemia. Last Updated 22 July 2009. http://en.wikipedia.org/wiki/Methemoglobinemia
T21: Clayton GD and Clayton FE (eds) (1993-1994). Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc.

14.1.8 Adverse Effects

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

Skin Sensitizer - An agent that can induce an allergic reaction in the skin.

Asthma - Reversible bronchoconstriction (narrowing of bronchioles) initiated by the inhalation of irritating or allergenic agents.

14.1.9 Acute Effects

14.1.10 Toxicity Data

LC50 (rat) =>5 mg/m3/1H
LD50: 375 mg/kg (Oral, Rat) (T14)
T14: Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.

14.1.11 Treatment

Methemoglobinemia can be treated with supplemental oxygen and methylene blue 1% solution administered intravenously slowly over five minutes followed by IV flush with normal saline. Methylene blue restores the iron in hemoglobin to its normal (reduced) oxygen-carrying state. (L1613)
L1613: Wikipedia. Methemoglobinemia. Last Updated 22 July 2009. http://en.wikipedia.org/wiki/Methemoglobinemia

14.1.12 Interactions

p-Aminophenol (pAP, 225 mg/kg) administration to rats induced renal failure and has been associated with markers of endoplasmic reticulum (ER) stress, as well as calpain and caspase-12 activation in kidneys. To determine the importance of ER stress and calpain during pAP-induced nephrotoxicity, rats were pretreated with low, nontoxic, doses of ER stress inducers or with the selective calpain inhibitor PD150606 (3 mg/kg). Prior ER stress induced by tunicamycin and oxidized dithiothreitol did not result in protection against renal failure, but PD150606 administration was protective and decreased significantly the rise in creatinine and blood urea nitrogen observed after 24-hr post-pAP administration. pAP-induced XBP1 upregulation was not modified by calpain inhibition, but a trend to lower GRP94 induction was determined, suggesting that pAP-induced ER stress was mostly calpain independent. In contrast, pAP-induced caspase-12 cleavage products were significantly decreased with PD150606 pretreatment, demonstrating that caspase-12 activation was calpain dependent ...
Peyrou M et al; Toxicol Sci 99 (1): 338-45 (2007)
The effects of a glutathione depletor, buthionine sulfoximine (BSO) and biliary cannulation on the nephrotoxicity of p-aminophenol (PAP) have been investigated in the F344 rat. Pretreatment with BSO completely protected against the nephrotoxicity of a 50 mg/kg dose of PAP, assessed by clinical chemistry, renal histopathology, and (1)H-NMR urinalysis. Biliary cannulation partially protects against nephrotoxicity induced by 100 mg/kg PAP. These data suggest that the nephrotoxicity of PAP may be due in part to the formation of a proximate toxic metabolite in the liver which is excreted in the bile, subsequently reabsorbed and transported via the systemic circulation to the kidney where the toxic effects occur.
Gartland KP et al; Arch Toxicol 64 (1): 14-25 (1990)
Screening tests revealed that aniline increased urine trimethoprim (TMP) excretion in rat. The study attempted to investigate the effect of aniline under conditions of repeated exposure on the course of TMP excretion with urine. ... Three groups of rats (10 rats each) were used. Group I was exposed for 12 days (6 hr a day) to aniline vapour. Group II received TMP only. Group III was exposed both to aniline & TMP. Concns of TMP & p-aminophenol (an aniline metabolite) were determined in the 24 hr urine samples after 1, 6, & 12 days. The exposure to aniline vapors was found to cause almost 3-fold incr of TMP removal. No effect of TMP on p-aminophenol excretion was observed.
Jodynis-Liebert J; Bromatologia I Chemia Toksykologiczna 30 (3): 277-281 (1997)
An investigation was carried out of the effects of ortho-aminophenol (95556) (o-AP), meta-aminophenol (591275) (m-AP), para-aminophenol (123308) (p-AP) & acetaminophen (103902) (AAP) on the induction of preneoplastic lesions in the liver & kidney of male Fischer-344-rats by N-ethyl-N-hydroxyethylnitrosamine (13147256) (EHEN). The rats in this 52 wk investigation included those give 0.1% EHEN in their drinking water for 2 wk & then, beginning 1 wk later, given 0.8% of either o-AP, m-AP, p-AP or AAP in the basal diet for 49 wk; those given EHEN & thereafter only the basal diet; & those given one of the test cmpds without prior EHEN admin. Body, liver & kidney weights were determined for sacrificed rats, & liver sections were subjected to immunohistochemical exam of glutathione-S-transferase placental type (GSTP) positive foci. The numbers of GSTP positive foci in the liver were significantly decreased in rats given o-AP, m-AP, p-AP or AAP after EHEN as compared to values for rats given EHEN alone. However, lowered incidences of GSTP positive foci were observed only in rats given o-AP or AAP after EHEN. Only p-AP & AAP gave significantly higher incidences of microadenoma & adenoma in the kidney.
Kurata Y et al; Carcinogenesis 8 (9): 1281-1285 (1987)

14.1.13 Antidote and Emergency Treatment

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. /Aniline and related compounds/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 238
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 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 patent can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Aniline and related compounds/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 239
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. Monitor cardiac rhythm and treat arrhythmias as 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. Consider vasopressors if hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen. ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Aniline and related compounds/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 239

14.1.14 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ An examination of 31 employees from a chemical factory producing 4-aminophenol (PAP) and other aromatic compounds was conducted using single 48-hr occlusive patches with five of the suspected chemicaIs. Ten of the 31 employees reacted positively to PAP in petrolatum at one or more of the applied doses. Generally dose related, these responses ranged from 1+ at 0.1% PAP (1/31) to 2+ (3/31) and 3+ (1/31) at 1% PAP, with 6/10 employees having 1+ reactions at 0.5% PAP. PAP did not induce primary irritant contact dermatitis in any of the 5 controls, and none of the 31 sensitized subjects who were tested with PAP had cross sensitization when later challenged with dinitrochlorobenzene.
Cosmetic Ingredient Expert Review Panel; Final Report on the Safety Assessment of p-Aminophenol, m-Aminophenol, and o-Aminophenol; Journal of the American College of Toxicology 7 (3): 279-333 (1988).
/HUMAN EXPOSURE STUDIES/ Aqueous solutions of 1.0% 3-aminopheol (MAP) and 0.5% 4-aminophenol (PAP) were tested for depigmentation and discoloration after repeated topical application to the skin on one of the forearms of 26 volunteers (20 black and 6 white). The subjects were separated into 2 groups of 13; 1 group received 0.1 5 mL applications of the PAP solution, and the other group received 0.1 5 mL of the MAP solution. Sites were washed by the subjects 1 hr after application of the solutions. The solutions were applied to the same sites for 3 consecutive days the first week and for 4 consecutive days the second and third weeks. Three days after the 11th application, the subjects' arms were evaluated for "circumscribed areas on either forearm in which the skin color appeared different from that of the surrounding area." Subjects were asked to comment on the test procedure or any adverse effects experienced during the study. There was no evidence of skin color changes, lightening or darkening, in any of the 6 white subjects. No lightening of skin color was observed in any of the black subjects. A slight darkening of the skin of 2 black subjects treated with the PAP solution was noted. Slight to moderate primary skin irritation was found in I subject after three to seven applications of the PAP solution.
Cosmetic Ingredient Expert Review Panel; Final Report on the Safety Assessment of p-Aminophenol, m-Aminophenol, and o-Aminophenol; Journal of the American College of Toxicology 7 (3): 279-333 (1988).
/HUMAN EXPOSURE STUDIES/ In 80 patients, positive to at least one hapten of the para group (para-phenylenediamine, diaminodiphenylmethane, benzocaine, PPD mix), patch tests were carried out with freshly prepared solutions of para-phenylenediamine (PPD) and of 3 selected aromatic compounds related structurally to PPD (para-aminophenol, ortho-aminophenol, hydroquinone). The number of positive reactions correlated with the rate of decomposition of the substances as evaluated by high-pressure liquid chromatography. PPD, which was almost decomposed after 24 hr, gave the highest number of positive reactions, followed by ortho-aminophenol and by para-aminophenol, while hydroquinone, which was oxidized to the extent of 35%, did not give any reactions ... The results suggest that the rate of decomposition and therefore the amount of quinone(s) generated, might be the key to eliciting patch test responses to oxidizable aromatic haptens.
Picardo M et al; Dermatologica 181 (2): 104-8 (1990)
/SIGNS AND SYMPTOMS/ Short term exposure: Aminophenols can be absorbed through the skin, thereby increasing exposure. Can cause lung irritation. Poisonous if swallowed. These chemicals lower the blood's ability to carry oxygen (methemoglobinemia). This condition causes a bluish color to the skin and lips, headaches, dizziness; higher exposures can result in unconsciousness and death. Irritates eyes, skin, and respiratory tract. Skin contact can cause burning sensation and rash ... May produce dermatitis, methemoglobinemia, bronchial asthma, and restlessness. Long term exposure: prolonged or repeated contact can cause blood damage, skin disorders, liver, kidney, and brain damage. Aminophenols may cause mutations, and there is limited teratogenic evidence. Skin allergy or asthma may develop; future exposures, even in low doses, can cause symptoms to occur. /Aminophenols/
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 5th Edition Volume 1: A-H,Volume 2: I-Z. William Andrew, Norwich, NY 2008, p. 137
For more Human Toxicity Excerpts (Complete) data for 4-Aminophenol (16 total), please visit the HSDB record page.

14.1.15 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ 10 albino rats (five male and five female, COX-SD strain) weighing 216 - 314 g were exposed by inhalation to undiluted sample at a delivery rate of approx 5.91 mg/L of air at a flow rate of 3.0 L/min for a period of 60 min plus 19 min for equilibration. All of the animals survived the 60 min exposure and the 14 day observation period which followed.
European Commission, ESIS; IUCLID Dataset, 4-Aminophenol (123-30-8) p.17 (2000 CD-ROM edition). Available from, as of May 17, 2010: https://esis.jrc.ec.europa.eu/
/LABORATORY ANIMALS: Acute Exposure/ The acute dermal LD50 of a sample when applied as a 50% w/w suspension in a 1% aqueous gum tragacanth to the intact and abraded skin of male and female New Zealand albino rabbits weighing 2.35 - 3.07 kg, was found to be > 8,000 mg/kg bw. No mortality. This was the largest practicable dose under the conditions of the test.
European Commission, ESIS; IUCLID Dataset, 4-Aminophenol (123-30-8) p.18 (2000 CD-ROM edition). Available from, as of May 17, 2010: https://esis.jrc.ec.europa.eu/
/LABORATORY ANIMALS: Acute Exposure/ Using clipped New Zealand rabbits with occlusive patches with doses of 0.5 g which remained in contact with the skin for 4 or 23 hr, no cutaneous effects were observed.
European Commission, ESIS; IUCLID Dataset, 4-Aminophenol (123-30-8) p.21 (2000 CD-ROM edition). Available from, as of May 17, 2010: https://esis.jrc.ec.europa.eu/
/LABORATORY ANIMALS: Acute Exposure/ In rabbits, a 2.5% (w/v) preparation failed to produce any toxic effects /in the eye/.
European Commission, ESIS; IUCLID Dataset, 4-Aminophenol (123-30-8) p.25 (2000 CD-ROM edition). Available from, as of May 17, 2010: https://esis.jrc.ec.europa.eu/
For more Non-Human Toxicity Excerpts (Complete) data for 4-Aminophenol (85 total), please visit the HSDB record page.

14.1.16 Non-Human Toxicity Values

LD50 Rat oral 375 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. 207
LD50 Rat oral 671 mg/kg
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 5th Edition Volume 1: A-H,Volume 2: I-Z. William Andrew, Norwich, NY 2008, p. 137
LD50 Rat oral 1270 mg/kg
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 5th Edition Volume 1: A-H,Volume 2: I-Z. William Andrew, Norwich, NY 2008, p. 137
LD50 Mouse oral 420 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. 207
For more Non-Human Toxicity Values (Complete) data for 4-Aminophenol (6 total), please visit the HSDB record page.

14.2 Ecological Information

14.2.1 Ecotoxicity Values

LC50; Species: Oncorhynchus mykiss (rainbow trout); Concentration: 1.2 mg/L for 96 hr /Conditions of bioassay not specified/
Sigma-Aldrich Corp; Safety Data Sheet for 4-Aminophenol (Product Number: A71328) Version 3.0 (August 21, 2009). Available from, as of June 15, 2010: https://www.sigmaaldrich.com
EC50; Species: Tetrahymena thermophila (ciliate protozoa, B-III); Conditions: freshwater; Concentration: 16.4 mg/L (16400 ug/L) for 90 minutes; Effect: Behavioral changes, general
Pauli W et al; FU-Berlin, Institut fur Biochemie und Molekularbiologie, UFO-Plan, F+E-Vorhaben 106 03 083, 62 pp. (1993) as cited in the ECOTOX database. Available from, as of June 18, 2010
EC50; Species: Tetrahymena thermophila (ciliate protozoa, B-III); Conditions: freshwater; Concentration: 0.31 mg/L (310 ug/L) for 48 hr; Effect: Population growth rate
Pauli W et al; FU-Berlin, Institut fur Biochemie und Molekularbiologie, UFO-Plan, F+E-Vorhaben 106 03 083, 62 pp. (1993) as cited in the ECOTOX database. Available from, as of June 18, 2010
EC50; Species: Tetrahymena thermophila (ciliate protozoa, B-III); Conditions: freshwater; Concentration: 0.44 mg/L (440 ug/L) for 48 hr; Effect: Population growth rate
Pauli W et al; FU-Berlin, Institut fur Biochemie und Molekularbiologie, UFO-Plan, F+E-Vorhaben 106 03 083, 62 pp. (1993) as cited in the ECOTOX database. Available from, as of June 18, 2010
For more Ecotoxicity Values (Complete) data for 4-Aminophenol (6 total), please visit the HSDB record page.

14.2.2 US EPA Regional Screening Levels for Chemical Contaminants

Resident Soil (mg/kg)
1.30e+03
Industrial Soil (mg/kg)
1.60e+04
Tapwater (ug/L)
4.00e+02
MCL (ug/L)
4.00e+00
Risk-based SSL (mg/kg)
1.50e-01
Chronic Oral Reference Dose (mg/kg-day)
2.00e-02
Volatile
Volatile
Mutagen
Mutagen
Fraction of Contaminant Absorbed in Gastrointestinal Tract
1
Fraction of Contaminant Absorbed Dermally from Soil
0.1

14.2.3 US EPA Regional Removal Management Levels for Chemical Contaminants

Resident Soil (mg/kg)
3.80e+03
Industrial Soil (mg/kg)
4.90e+04
Tapwater (ug/L)
1.20e+03
MCL (ug/L)
4.00e+00
Chronic Oral Reference Dose (mg/kg-day)
2.00e-02
Volatile
Volatile
Mutagen
Mutagen
Fraction of Contaminant Absorbed in Gastrointestinal Tract
1
Fraction of Contaminant Absorbed Dermally from Soil
0.1

14.2.4 Environmental Fate / Exposure Summary

4-Aminophenol's production and use as a photographic developer; as a dyeing agent for textiles, fur, feathers, hair; in pharmaceuticals; as an antioxidant; as an oil additive and as a chemical intermediate may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 4X10-5 mm Hg at 25 °C indicates 4-aminophenol will exist in both the vapor and particulate phases in the atmosphere. Vapor-phase 4-aminophenol 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 5 hours. Particulate-phase 4-aminophenol will be removed from the atmosphere by wet or dry deposition. 4-Aminophenol absorbs light at wavelengths of 294 nm and, therefore, may be susceptible to direct photolysis by sunlight. If released to soil, 4-aminophenol is expected to have high mobility based upon an estimated Koc of 90. However, anilines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group, suggesting that mobility may be much lower in some soils. Measured pKa values are 5.48 and 10.46, for the amine and hydroxy functional groups, respectively. 4-Aminophenol is amphoteric and behaves either as a weak acid or weak base; the basic character usually predominates. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 3.6X10-10 atm-cu m/mole. Biodegradation results are mixed. Utilizing the Japanese MITI test, 6% of the Theoretical BOD was reached in 4 weeks; using acclimated activated sludge, an 87% COD was noyed in 5 days. If released into water, 4-aminophenol is expected to adsorb to suspended solids and sediment based upon the estimated Koc. 4-Aminophenol, under aerobic conditions, seems to biodegrade as shown by studies where 85 and 100% of 10 mg/L 4-aminophenol was degraded in river and seawater, respectively, however at 50 mg/L no biodegradation was observed. Under denitrifying and methanogenic conditions in sediment, 4-aminophenol was mineralized following a long lag phase at a rate of 15.7 and 20 umol/L/day, respectively. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. BCFs of 10-39 and 15-46 in carp (Cyprinus carpio) suggest bioconcentration in aquatic organisms is low to moderate. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. Occupational exposure to 4-aminophenol may occur through inhalation and dermal contact with this compound at workplaces where 4-aminophenol is produced or used. Use data indicate that the general population may be exposed to 4-aminophenol via dermal contact with consumer products, particularly hair dye products, containing 4-aminophenol. (SRC)

14.2.5 Artificial Pollution Sources

4-Aminophenol's production and use as a photographic developer; as a dyeing agent for textiles, fur, feathers, hair; in pharmaceuticals; as an antioxidant; as an oil additive(1) and as a chemical intermediate(2) may result in its release to the environment through various waste streams(SRC).
(1) Lewis RJ Sr; Hawley's Condensed Chemical Dictionary 15th ed., New York, NY: John Wiley & Sons p. 62 (2007)
(2) O'Neil MJ, ed; The Merck Index.14th ed., Whitehouse Station, NJ: Merck and Co, p. 78 (2006)

14.2.6 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 90(SRC), determined from a structure estimation method(2), indicates that 4-aminophenol is expected to have high mobility in soil(SRC). However, anilines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(3,4), suggesting that mobility may be much lower in some soils(SRC). Measured pKa values are 5.48(5) and 10.46(6), for the amine and hydroxy functional groups, respectively(7). 4-Aminophenol is amphoteric and behaves either as a weak acid or weak base; the basic character usually predominates(8). Volatilization of 4-aminophenol from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.6X10-10 atm-cu m/mole(SRC), based upon its vapor pressure, 4X10-5 mm Hg(9), and water solubility, 16,000 mg/L(10). 4-Aminophenol is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(9). A 6% of theoretical BOD using activated sludge in the Japanese MITI test(11) suggests that biodegradation may not be important environmental fate process in soil(SRC). However, 87% chemical oxygen demand removal was reached in 5 days in a screening test using acclimated activated sludge at 100 mg/L and 4-aminophenol at 200 mg/L chemical oxygen demand(12).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. Available from, as of April 27, 2010: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Adrian P et al; Toxicol Environ Chem 20-21: 109-120 (1989)
(4) Bollag JM et al; J Agric Food Chem 26: 1302-6 (1978)
(5) Perrin DD; Dissociation Constants of Organic Bases in Aqueous Solution. IUPAC Chemical Data Series: Supplement 1972. Buttersworth, London (1972)
(6) Serjeant EP, Dempsey B; Ionisation Constants of Organic Acids in Aqueous Solution. IUPAC Chemical Data Series No. 23. NY, NY: Pergamon Press p. 216 (1979)
(7) SPARC; pKa/property server. Ver 3. Jan, 2006. Available from, as of April 27, 2010: https://ibmlc2.chem.uga.edu/sparc/
(8) Mitchel CS et al; Kirk-Othmer Encyclopedia of Chemical Technology. (2001). New York, NY: John Wiley & Sons; Aminophenols. Online Posting Date: Jun 20, 2003.
(9) Dunn SA; J Amer Chem Soc 76: 6191-2 (1954)
(10) Yalkowsky SH, Dannenfelser RM Aquasol Database of Aqueous Solubility. Version 5. College of Pharmacy, University of Arizona - Tucson, AZ. PC Version (1992)
(11) NITE; Chemical Risk Information Platform (CHRIP). Biodegradation and Bioconcentration. Tokyo, Japan: Natl Inst Tech Eval. Available from, as of April 27, 2010: https://www.safe.nite.go.jp/english/db.html.
(12) Pitter P; Wat Res 10: 231-35 (1976)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 90(SRC), determined from a structure estimation method(2), indicates that 4-aminophenol is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.6X10-10 atm-cu m/mole(SRC), derived from its vapor pressure, 4X10-5 mm Hg(4), and water solubility, 16,000 mg/L(5). According to a classification scheme(6), BCFs of 10-39 and 15-46 in carp (Cyprinus carpio)(7) suggest bioconcentration in aquatic organisms is low to moderate(SRC). 4-Aminophenol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). 4-Aminophenol, under aerobic conditions, seems to biodegrade as shown by studies where 85 and 100% of 10 mg/L 4-aminophenol was degraded in river and seawater, respectively, however at 50 mg/L no biodegradation was observed(8). Under denitrifying and methanogenic conditions in sediment, 4-aminophenol was mineralized following a long lag phase at a rate of 15.7 and 20 umol/L/day, respectively(9).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. Available from, as of April 27, 2010: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 15-1 to 15-29 (1990)
(4) Dunn SA; J Amer Chem Soc 76: 6191-2 (1954)
(5) Yalkowsky SH, Dannenfelser RM Aquasol Database of Aqueous Solubility. Version 5. College of Pharmacy, University of Arizona - Tucson, AZ. PC Version (1992)
(6) Franke C et al; Chemosphere 29: 1501-14 (1994)
(7) NITE; Chemical Risk Information Platform (CHRIP). Biodegradation and Bioconcentration. Tokyo, Japan: Natl Inst Tech Eval. Available from, as of April 27, 2010: https://www.safe.nite.go.jp/english/db.html.
(8) Kondo M et al; Eisei Kagaku 34: 188-95 (1988)
(9) O'Connor OA, Young LY; Environ Sci Technol 30: 1419-28 (1996)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 4-aminophenol, which has a vapor pressure of 4X10-5 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 4-aminophenol 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 5 hours(SRC), calculated from its rate constant of 7.4X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase 4-aminophenol may be removed from the air by wet or dry deposition(SRC). 4-Aminophenol absorbs light at wavelengths of 294 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) Dunn SA; J Amer Chem Soc 76:6191-2 (1954)
(3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(4) Mitchel CS et al; Kirk-Othmer Encyclopedia of Chemical Technology. (2001). New York, NY: John Wiley & Sons; Aminophenols. Online Posting Date: Jun 20, 2003.

14.2.7 Environmental Biodegradation

AEROBIC: 4-Aminophenol, present at 100 mg/L, reached 6% of its theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/L in the Japanese MITI test(1). Total loss of UV absorbancy due to cleavage of the benzene ring was reported in 16 days in a screening study using a soil inoculum and 4-aminophenol at 5 ppm(2). 4-Aminophenol, present at 100 mg/L, in an electrolytic respirometry screening test using an activated sludge inoculum, was not biodegraded over a 10-day period as measured by BOD(3). 4-Aminophenol, at 200 mg/L chemical oxygen demand reached 87% removal in 5 days in a screening test using acclimated activated sludge at 100 mg/L(4). 4-Aminophenol, present at 50 and 10 mg/L was degraded by 0 and 85%, respectively, in river water and 0 and 100% in seawater, respectively(5).
(1) NITE; Chemical Risk Information Platform (CHRIP). Biodegradation and Bioconcentration. Tokyo, Japan: Natl Inst Tech Eval. Available from, as of April 27, 2010: https://www.safe.nite.go.jp/english/db.html
(2) Alexander M, Lustigman BK; J Agric Food 14: 410 (1966)
(3) Urano K, Kato Z; J Hazard Mat 13: 147-159 (1986)
(4) Pitter P; Wat Res 10: 231-35 (1976)
(5) Kondo M et al; Eisei Kagaku 34: 188-95 (1988)
ANAEROBIC: 20% of the theoretical gas production was reached over 60 days in a screening study using methanogenic primary digesting sludge when 4-aminophenol was present; a lag phase of 57 days was noted(1). 4-Aminophenol at 30 mg-C/L was not degraded over a 28-day period, measured by removal of dissolved organic carbon, in an anaerobic screening study using 100 mg-C/L sewage(2). 4-Aminophenol, incubated in sediment under denitrifying conditions, showed an initial lag phase of 2.7 to 4.7 weeks followed by mineralization at a rate of 15.7 umol/L/day; 89% of theoretical N2 was recovered over the 30-week study(3). 4-Aminophenol was mineralized at a rate of 20 umol/L/day following a lag phase of 6.5 to 9 weeks under methanogenic conditions in a 26-week sediment grab sample study(3). 15% of the theoretical methane production was reached in 150 days with a 70-day lag period in an anaerobic screening study using 2-nitrophenol-adapted sludge; the study was run under methanogenic conditions with 1000 mg/L 4-aminophenol(4). No mineralization of 4-aminophenol was reported for the same study repeated using non-adapted sludge(4). 45.5% of the theoretical methane production was reached in 220 days with a 70-day lag period when 4-aminophenol was supplied to 2-nitrophenol-adapted granular sludge as the sole carbon source(5). 4-Aminophenol was not degraded over a 29-week period in anaerobic freshwater lake sediment or over an 8-week period when incubated with 2 different anaerobic municipal digested sludge samples(6). 4-Aminophenol was not degraded in 10% anaerobic sludge over 8 weeks(7).
(1) Battersby NS, Wilson V; Appl Environ Microbiol 55: 433-39 (1989)
(2) Kameya T et al; Sci Total Environ 170: 43-51 (1995)
(3) O'Connor OA, Young LY; Environ Sci Technol 30: 1419-28 (1996)
(4) Razo-Flores E et al; Wat Sci Tech 33: 47-57 (1996)
(5) Razo-Flores E et al; FEMS Microbiol Rev 20: 525-38 (1997)
(6) Horowitz A et al; Dev Ind Microbiol 23: 435-44 (1982)
(7) Shelton DR, Tiedje JM; Development of Tests for determining Anaerobic Biodegradation Potential. East Lansing, MI: Mich State Univ., Dept Crop Soil Sci, USEPA560/5-81-013 (NTIS PB84-166495) (1981)

14.2.8 Environmental Abiotic Degradation

The rate constant for the vapor-phase reaction of 4-aminophenol with photochemically-produced hydroxyl radicals has been estimated as 7.4X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 5 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). 4-Aminophenol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). 4-Aminophenol is expected to undergo fairly rapid oxidation in the presence of air(3) and may be susceptible to direct photolysis due to its absorption in the environmental UV spectrum (UV max = 294 nm)(3). Measured pKa values are 5.48(4) and 10.46(5), for the amine and hydroxy functional groups, respectively(6). 4-Aminophenol is amphoteric and behaves either as a weak acid or weak base; the basic character usually predominates(3).
(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 (1990)
(3) Mitchel CS et al; Kirk-Othmer Encyclopedia of Chemical Technology. (2001). New York, NY: John Wiley & Sons; Aminophenols. Online Posting Date: Jun 20, 2003.
(4) Perrin DD; Dissociation Constants of Organic Bases in Aqueous Solution. IUPAC Chemical Data Series: Supplement 1972. Buttersworth, London (1972)
(5) Serjeant EP, Dempsey B; Ionisation Constants of Organic Acids in Aqueous Solution. IUPAC Chemical Data Series No. 23. NY, NY: Pergamon Press p. 216 (1979)
(6) SPARC; pKa/property server. Ver 3. Jan, 2006. Available at https://ibmlc2.chem.uga.edu/sparc/ as of April 27, 2010.

14.2.9 Environmental Bioconcentration

BCFs of 10-39 and 15-46 in carp (Cyprinus carpio) were reported for a 8 week study using 1.5 and 0.15 mg/L 4-aminophenol, respectively(1). According to a classification scheme(2), these BCFs suggest the potential for bioconcentration in aquatic organisms is low to moderate(SRC).
(1) NITE; Chemical Risk Information Platform (CHRIP). Biodegradation and Bioconcentration. Tokyo, Japan: Natl Inst Tech Eval. Available from, as of April 27, 2010: https://www.safe.nite.go.jp/english/db.html
(2) Franke C et al; Chemosphere 29: 1501-14 (1994)

14.2.10 Soil Adsorption / Mobility

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 4-aminophenol can be estimated to be 90(SRC). According to a classification scheme(2), this estimated Koc value suggests that 4-aminophenol is expected to have high mobility in soil. However, anilines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(3-4), suggesting that mobility may be much lower in some soils(SRC). Measured pKa values are 5.48(5) and 10.46(6), for the amine and hydroxy functional groups, respectively(7). 4-Aminophenol is amphoteric and behaves either as a weak acid or weak base; the basic character usually predominates(8).
(1) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. Available from, as of April 27, 2010: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(2) Swann RL et al; Res Rev 85: 17-28 (1983)
(3) Adrian P et al; Toxicol Environ Chem 20-21: 109-120 (1989)
(4) Bollag JM et al; J Agric Food Chem 26: 1302-6 (1978)
(5) Perrin DD; Dissociation Constants of Organic Bases in Aqueous Solution. IUPAC Chemical Data Series: Supplement 1972. Buttersworth, London (1972)
(6) Serjeant EP, Dempsey B; Ionisation Constants of Organic Acids in Aqueous Solution. IUPAC Chemical Data Series No. 23. NY, NY: Pergamon Press p. 216 (1979)
(7) SPARC; pKa/property server. Ver 3. Jan, 2006. Available from, as of April 27, 2010: https://ibmlc2.chem.uga.edu/sparc/
(8) Mitchel CS et al; Kirk-Othmer Encyclopedia of Chemical Technology. (2001). New York, NY: John Wiley & Sons; Aminophenols. Online Posting Date: Jun 20, 2003.

14.2.11 Volatilization from Water / Soil

The Henry's Law constant for 4-aminophenol is estimated as 3.6X10-10 atm-cu m/mole(SRC) derived from its vapor pressure, 4X10-5 mm Hg(1), and water solubility, 16,000 mg/L(2). This Henry's Law constant indicates that 4-aminophenol is expected to be essentially nonvolatile from water surfaces(3). 4-Aminophenol is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).
(1) Dunn SA; J Amer Chem Soc 76: 6191-2 (1954)
(2) Yalkowsky SH, Dannenfelser RM Aquasol Database of Aqueous Solubility. Version 5. College of Pharmacy, University of Arizona - Tucson, AZ. PC Version (1992)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)

14.2.12 Probable Routes of Human Exposure

According to the 2006 TSCA Inventory Update Report, the number of persons reasonably likely to be exposed in the industrial manufacturing, processing, and use of 4-aminophenol 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 April 28, 2010: https://cfpub.epa.gov/iursearch/index.cfm
NIOSH (NOES Survey 1981-1983) has statistically estimated that 49,882 workers (37,110 of these were female) were potentially exposed to 4-aminophenol in the US(1). Occupational exposure to 4-aminophenol may occur through dermal contact with this compound at workplaces where 4-aminophenol is produced or used(SRC). Use data indicate that the general population may be exposed to 4-aminophenol via dermal contact with consumer products, particularly hair dye products, containing 4-aminophenol(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 April 27, 2010: https://www.cdc.gov/noes/

15 Associated Disorders and Diseases

Associated Occupational Diseases with Exposure to the Compound

Asthma, occupational [Category: Airway Disease]

Contact dermatitis, allergic [Category: Skin Disease]

16 Literature

16.1 Consolidated References

16.2 NLM Curated PubMed Citations

16.3 Springer Nature References

16.4 Thieme References

16.5 Wiley References

16.6 Nature Journal References

16.7 Chemical Co-Occurrences in Literature

16.8 Chemical-Gene Co-Occurrences in Literature

16.9 Chemical-Disease Co-Occurrences in Literature

17 Patents

17.1 Depositor-Supplied Patent Identifiers

17.2 WIPO PATENTSCOPE

17.3 Chemical Co-Occurrences in Patents

17.4 Chemical-Disease Co-Occurrences in Patents

17.5 Chemical-Gene Co-Occurrences in Patents

18 Interactions and Pathways

18.1 Protein Bound 3D Structures

18.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Conformer

18.2 Chemical-Target Interactions

18.3 Pathways

19 Biological Test Results

19.1 BioAssay Results

20 Taxonomy

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

21 Classification

21.1 MeSH Tree

21.2 ChEBI Ontology

21.3 ChemIDplus

21.4 CAMEO Chemicals

21.5 ChEMBL Target Tree

21.6 UN GHS Classification

21.7 EPA CPDat Classification

21.8 NORMAN Suspect List Exchange Classification

21.9 EPA DSSTox Classification

21.10 Consumer Product Information Database Classification

21.11 EPA TSCA and CDR Classification

21.12 LOTUS Tree

21.13 EPA Substance Registry Services Tree

21.14 MolGenie Organic Chemistry Ontology

22 Information Sources

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    https://www.epa.gov/tsca-inventory
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    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  10. EPA Provisional Peer-Reviewed Toxicity Values (PPRTVs)
  11. European Chemicals Agency (ECHA)
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    https://www.whatsinproducts.com/contents/view/1/6
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    https://www.norman-network.com/nds/SLE/
  30. DailyMed
  31. EPA Regional Screening Levels for Chemical Contaminants at Superfund Sites
  32. Hazardous Chemical Information System (HCIS), Safe Work Australia
  33. NITE-CMC
    p-Aminophenol - FY2006 (New/original classication)
    https://www.chem-info.nite.go.jp/chem/english/ghs/06-imcg-0508e.html
    p-Aminophenol - FY2017 (Revised classification)
    https://www.chem-info.nite.go.jp/chem/english/ghs/17-mhlw-2012e.html
    p-Aminophenol - FY2016 (Revised classification)
    https://www.chem-info.nite.go.jp/chem/english/ghs/16-meti-0011e.html
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    https://foodb.ca/about
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  44. Kruve Lab, Ionization & Mass Spectrometry, Stockholm University
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  47. Nature Chemical Biology
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  52. Rhea - Annotated Reactions Database
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    Rhea has chosen to apply the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). This means that you are free to copy, distribute, display and make commercial use of the database in all legislations, provided you credit (cite) Rhea.
    https://www.rhea-db.org/help/license-disclaimer
  53. Springer Nature
  54. SpringerMaterials
  55. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
  56. Wikidata
  57. Wikipedia
  58. Wiley
  59. PubChem
  60. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
  61. GHS Classification (UNECE)
  62. EPA Substance Registry Services
  63. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  64. PATENTSCOPE (WIPO)
  65. NCBI
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