4-Aminophenol (T3D3600)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (6)XML
Targets (6)
Record Information
Version2.0
Creation Date2009-11-11 22:18:18 UTC
Update Date2014-12-24 20:26:12 UTC
Accession NumberT3D3600
Identification
Common Name4-Aminophenol
ClassSmall Molecule
Description4-Aminophenol is an amphoteric molecule and a reducing agent. Aminophenols are intermediates in the synthesis of dyes and can thus be found in numerous cosmetics products, particularly hair dyes. 4-aminophenol is considered a minor nephrotoxic metabolite of phenacetin and acetaminophen (paracetamol) in man. 4-Aminophenol can undergo autoxidations and metal-catalyzed and enzymatic oxidations in man to produce reactive oxygen species. (2) (17)
Compound Type
  • Amine
  • Aromatic Hydrocarbon
  • Cosmetic Toxin
  • Food Toxin
  • Household Toxin
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
1-Amino-4-hydroxybenzene
4-Amino-1-hydroxybenzene
4-Aminobenzenol
4-Hydroxyaniline
Activol
Aminophenol
Energol
Fouramine P
p-Aminophenol
p-Hydroxyaniline
p-Hydroxyphenylamine
Paramidophenol
Paranol
Chemical FormulaC6H7NO
Average Molecular Mass109.126 g/mol
Monoisotopic Mass109.053 g/mol
CAS Registry Number123-30-8
IUPAC Name4-aminophenol
Traditional Nameaminophenol
SMILESNC1=CC=C(O)C=C1
InChI IdentifierInChI=1S/C6H7NO/c7-5-1-3-6(8)4-2-5/h1-4,8H,7H2
InChI KeyInChIKey=PLIKAWJENQZMHA-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as aniline and substituted anilines. These are organic compounds containing an aminobenzene moiety.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassAniline and substituted anilines
Direct ParentAniline and substituted anilines
Alternative Parents
Substituents
  • P-aminophenol
  • Aniline or substituted anilines
  • Aminophenol
  • 1-hydroxy-2-unsubstituted benzenoid
  • Phenol
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Epidermis
  • Spleen
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceWhite powder. (18)
Experimental Properties
PropertyValue
Melting Point187.5°C
Boiling Point187.5°C
Solubility16 mg/mL at 20°C
LogP0.04
Predicted Properties
PropertyValueSource
Water Solubility121 g/LALOGPS
logP0.47ALOGPS
logP0.84ChemAxon
logS0.04ALOGPS
pKa (Strongest Acidic)10.4ChemAxon
pKa (Strongest Basic)5.43ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area46.25 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity32.74 m³·mol⁻¹ChemAxon
Polarizability11.23 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0a4i-6900000000-9c5bfea7a6ff3c8450012017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0pe9-9300000000-8ff47e2157f6fbfe67542017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0f79-1890000000-c8247060f46131c693d12017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-03di-1927000000-b873199d9ac85605a4df2017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0a4i-6900000000-9c5bfea7a6ff3c8450012018-05-18View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0pe9-9300000000-8ff47e2157f6fbfe67542018-05-18View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0f79-1890000000-c8247060f46131c693d12018-05-18View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-03di-1927000000-b873199d9ac85605a4df2018-05-18View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-5900000000-e64da39e73e3c0ea696c2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-060r-6900000000-2c6cd652b49e26ce3fce2017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-03di-3900000000-906f96b14dfdad2310de2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-014i-9000000000-d56be0077647bc66e9622012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-014i-9000000000-937794addf5b73c988e92012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-03di-2900000000-1d20b6ad92e8fe4dcb552017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-03di-2900000000-5950ca2352822bea4a012021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-02tc-9300000000-3524fecaa931f284564b2021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0900000000-da3b2114d9298a0363e72017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-1900000000-b43943b1e137b2912b0f2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00lr-9000000000-8ca8655366b90d8f42df2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0900000000-28f35dbe83fee57d4a702017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0900000000-6aa4cd1a9d2a859fa70b2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a7i-9300000000-177dcaf10b9e95cb409c2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0900000000-c89e2460dc3caf4abe052021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-9100000000-b0a8e0715ece78a9716d2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0159-9000000000-aed714f11873786e9c3a2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0900000000-875d8abd6f6773a406342021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0900000000-875d8abd6f6773a406342021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0f6x-9200000000-17afc5bcee8bb56bc9e82021-09-24View Spectrum
MSMass Spectrum (Electron Ionization)splash10-0a4i-9700000000-00bffb48fd955696bccc2014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, CDCl3, experimental)Not Available2012-12-04View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, DMSO-d6, experimental)Not Available2014-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 22.53 MHz, DMSO-d6, experimental)Not Available2014-09-23View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Not Available2012-12-05View Spectrum
Toxicity Profile
Route of ExposureOral (15) ; inhalation (15)
Mechanism of Toxicity4-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 (12).
MetabolismNot Available
Toxicity ValuesLD50: 375 mg/kg (Oral, Rat) (13)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not listed by IARC.
Uses/Sources4-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. (17, 18)
Minimum Risk LevelNot Available
Health Effects4-Aminophenol may act as a skin sensitizer and cause contact dermatitis. In addition, inhalation of large amounts can cause methemoglobinemia and bronchial asthma. (14)
Symptoms4-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. (14, 16)
TreatmentMethemoglobinemia 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. (16)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB01169
PubChem Compound ID403
ChEMBL IDCHEMBL1142
ChemSpider ID392
KEGG IDC02372
UniProt IDNot Available
OMIM ID237900
ChEBI ID17602
BioCyc IDCPD-259
CTD IDC026729
Stitch IDp-aminophenol
PDB ID4NL
ACToR ID27285
Wikipedia Link4-Aminophenol
References
Synthesis ReferenceZhu, Jianliang; Yang, Ying; Xu, Jinlai; Gu, Zhiqiang; Zhang, Xiaowei; Zheng, Zhigang; Li, Jianlin; Hao, Xiangyang. Method for preparation of p-aminophenol. Faming Zhuanli Shenqing Gongkai Shuomingshu (2005), 6 pp.
MSDSLink
General References
  1. Wind M, Stern A: Comparison of human adult and fetal hemoglobin: aminophenol-induced methemoglobin formation. Experientia. 1977 Nov 15;33(11):1500-1. [923727 ]
  2. Hegedus ZL, Nayak U: Para-aminophenol and structurally related compounds as intermediates in lipofuscin formation and in renal and other tissue toxicities. Arch Int Physiol Biochim Biophys. 1991 Feb;99(1):99-105. [1713494 ]
  3. Lampinen M, Bondesson U, Fredriksson E, Hedeland M: Validation of a method for quantification of ketobemidone in human plasma with liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jun 15;789(2):347-54. [12742125 ]
  4. Clark PM, Clark JD, Wheatley T: Urine discoloration after acetaminophen overdose. Clin Chem. 1986 Sep;32(9):1777-8. [3742803 ]
  5. Kanishchev PA, Bereza NM, Seniuk VF, Perevziaka AV: [Quantitative determination of blood loss from the gastrointestinal tract using Metol in chronic diseases of the digestive organs]. Lab Delo. 1989;(3):36-8. [2469837 ]
  6. Xu Y, Halsall B, Heineman WR: Heterogeneous enzyme immunoassay of alpha-fetoprotein in maternal serum by flow-injection amperometric detection of 4-aminophenol. Clin Chem. 1990 Nov;36(11):1941-4. [1700742 ]
  7. Bomhard EM, Herbold BA: Genotoxic activities of aniline and its metabolites and their relationship to the carcinogenicity of aniline in the spleen of rats. Crit Rev Toxicol. 2005 Dec;35(10):783-835. [16468500 ]
  8. Nohynek GJ, Duche D, Garrigues A, Meunier PA, Toutain H, Leclaire J: Under the skin: Biotransformation of para-aminophenol and para-phenylenediamine in reconstructed human epidermis and human hepatocytes. Toxicol Lett. 2005 Sep 15;158(3):196-212. [15890478 ]
  9. Van Bocxlaer JF, Clauwaert KM, Lambert WE, De Leenheer AP: Quantitative colorimetric determination of urinary p-aminophenol with an automated analyzer. Clin Chem. 1997 Apr;43(4):627-34. [9105264 ]
  10. Gil EP, Tang HT, Halsall HB, Heineman WR, Misiego AS: Competitive heterogeneous enzyme immunoassay for theophylline by flow-injection analysis with electrochemical detection of p-aminophenol. Clin Chem. 1990 Apr;36(4):662-5. [2138937 ]
  11. Arndt CA, Colvin OM, Balis FM, Lester CM, Johnson G, Poplack DG: Intrathecal administration of 4-hydroperoxycyclophosphamide in rhesus monkeys. Cancer Res. 1987 Nov 15;47(22):5932-4. [3664493 ]
  12. 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. [17118730 ]
  13. Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.
  14. 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.
  15. HSDB: Hazardous Substances Data Bank. National Library of Medicine (2001). [Link]
  16. Wikipedia. Methemoglobinemia. Last Updated 22 July 2009. [Link]
  17. Wikipedia. 2-Aminophenol. Last Updated 12 June 2009. [Link]
  18. Wikipedia. 4-Aminophenol. Last Updated 3 July 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Hemoglobin subunit alpha
General Function:
Oxygen transporter activity
Specific Function:
Involved in oxygen transport from the lung to the various peripheral tissues.
Gene Name:
HBA1
Uniprot ID:
P69905
Molecular Weight:
15257.405 Da
References
  1. Wind M, Stern A: Comparison of human adult and fetal hemoglobin: aminophenol-induced methemoglobin formation. Experientia. 1977 Nov 15;33(11):1500-1. [923727 ]
  2. Coghlin J, Gann PH, Hammond SK, Skipper PL, Taghizadeh K, Paul M, Tannenbaum SR: 4-Aminobiphenyl hemoglobin adducts in fetuses exposed to the tobacco smoke carcinogen in utero. J Natl Cancer Inst. 1991 Feb 20;83(4):274-80. [1994056 ]
  3. Wikipedia. Methemoglobinemia. Last Updated 22 July 2009. [Link]
Target Details
2. Hemoglobin subunit beta
General Function:
Oxygen transporter activity
Specific Function:
Involved in oxygen transport from the lung to the various peripheral tissues.LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure.Spinorphin: functions as an endogenous inhibitor of enkephalin-degrading enzymes such as DPP3, and as a selective antagonist of the P2RX3 receptor which is involved in pain signaling, these properties implicate it as a regulator of pain and inflammation.
Gene Name:
HBB
Uniprot ID:
P68871
Molecular Weight:
15998.34 Da
References
  1. Wind M, Stern A: Comparison of human adult and fetal hemoglobin: aminophenol-induced methemoglobin formation. Experientia. 1977 Nov 15;33(11):1500-1. [923727 ]
  2. Coghlin J, Gann PH, Hammond SK, Skipper PL, Taghizadeh K, Paul M, Tannenbaum SR: 4-Aminobiphenyl hemoglobin adducts in fetuses exposed to the tobacco smoke carcinogen in utero. J Natl Cancer Inst. 1991 Feb 20;83(4):274-80. [1994056 ]
  3. Wikipedia. Methemoglobinemia. Last Updated 22 July 2009. [Link]
Target Details
3. Arylamine N-acetyltransferase 2
General Function:
Arylamine n-acetyltransferase activity
Specific Function:
Participates in the detoxification of a plethora of hydrazine and arylamine drugs. Catalyzes the N- or O-acetylation of various arylamine and heterocyclic amine substrates and is able to bioactivate several known carcinogens.
Gene Name:
NAT2
Uniprot ID:
P11245
Molecular Weight:
33542.235 Da
References
  1. 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. [17118730 ]
  2. Jiang X, Yuan JM, Skipper PL, Tannenbaum SR, Yu MC: Environmental tobacco smoke and bladder cancer risk in never smokers of Los Angeles County. Cancer Res. 2007 Aug 1;67(15):7540-5. [17671226 ]
Target Details
4. Cytochrome P450 1A2
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. 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. [17118730 ]
  2. Landi MT, Zocchetti C, Bernucci I, Kadlubar FF, Tannenbaum S, Skipper P, Bartsch H, Malaveille C, Shields P, Caporaso NE, Vineis P: Cytochrome P4501A2: enzyme induction and genetic control in determining 4-aminobiphenyl-hemoglobin adduct levels. Cancer Epidemiol Biomarkers Prev. 1996 Sep;5(9):693-8. [8877060 ]
Target Details
5. Sulfotransferase 1A1
General Function:
Sulfotransferase activity
Specific Function:
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of catecholamines, phenolic drugs and neurotransmitters. Has also estrogen sulfotransferase activity. responsible for the sulfonation and activation of minoxidil. Is Mediates the metabolic activation of carcinogenic N-hydroxyarylamines to DNA binding products and could so participate as modulating factor of cancer risk.
Gene Name:
SULT1A1
Uniprot ID:
P50225
Molecular Weight:
34165.13 Da
References
  1. 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. [17118730 ]
  2. Ozawa S, Katoh T, Inatomi H, Imai H, Kuroda Y, Ichiba M, Ohno Y: Association of genotypes of carcinogen-activating enzymes, phenol sulfotransferase SULT1A1 (ST1A3) and arylamine N-acetyltransferase NAT2, with urothelial cancer in a Japanese population. Int J Cancer. 2002 Dec 1;102(4):418-21. [12402313 ]
6. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. 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. [17118730 ]