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Record Information
Version2.0
Creation Date2009-03-06 18:57:56 UTC
Update Date2014-12-24 20:20:55 UTC
Accession NumberT3D0026
Identification
Common NameBenzidine
ClassSmall Molecule
DescriptionBenzidine is the organic compound with the formula (C6H4NH2)2. it is an aromatic amine. It is prepared in a two step process from nitrobenzene. First, the nitrobenzene is converted to 1,2-diphenylhydrazine, usually using iron powder as the reducing agent. Treatment of this hydrazine with mineral acids induces a rearrangement reaction to 4,4'-benzidine. Smaller amounts of other isomers are also formed. The benzidine rearrangement, which proceeds intramolecularly, is a classic mechanistic puzzle in organic chemistry. This aromatic amine is a component of a test for cyanide and also in the production of dyes. Benzidine has been linked to bladder and pancreatic cancer. Since August 2010 benzidine dyes are included in the EPA's List of Chemicals of Concern.
Compound Type
  • Amine
  • Aromatic Hydrocarbon
  • Industrial/Workplace Toxin
  • Metabolite
  • Organic Compound
  • Pollutant
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
4'-Amino[1,1'-biphenyl]-4-ylamine
4, 4'-Biphenylenediamine
4,4'-Bianiline
4,4'-Biphenyldiamine
4,4'-Biphenylenediamine
4,4'-Diamino-1,1'-biphenyl
4,4'-Diaminobiphenyl
4,4'-Diaminodiphenyl
4,4'-Diphenylenediamine
Benzidin
Biphenyl -4,4'-ylenediamine
Fast Corinth Base B
p,p'-Bianiline
p,p'-Diaminobiphenyl
p,p'-Dianiline
p,p-Bianiline
p-Diaminodiphenyl
[1,1'-Biphenyl]-4,4'-diamine
{[1,} 1'-Biphenyl]-4,4'-diamine
Chemical FormulaC12H12N2
Average Molecular Mass184.237 g/mol
Monoisotopic Mass184.100 g/mol
CAS Registry Number92-87-5
IUPAC Name4-(4-aminophenyl)aniline
Traditional Namebenzidine
SMILESNC1=CC=C(C=C1)C1=CC=C(N)C=C1
InChI IdentifierInChI=1S/C12H12N2/c13-11-5-1-9(2-6-11)10-3-7-12(14)8-4-10/h1-8H,13-14H2
InChI KeyInChIKey=HFACYLZERDEVSX-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzidines. These are organic compounds containing the benzidine skeleton, made up of a biphenyl ring system substituted at the 4- and 4'-positions with a unsubstituted amine group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBiphenyls and derivatives
Direct ParentBenzidines
Alternative Parents
Substituents
  • Benzidine
  • Aniline or substituted anilines
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Primary amine
  • 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 LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point120°C
Boiling PointNot Available
Solubility0.322 mg/mL at 25°C
LogP1.34
Predicted Properties
PropertyValueSource
Water Solubility0.395 mg/mLALOGPS
logP1.59ALOGPS
logP1.96ChemAxon
logS-2.7ALOGPS
pKa (Strongest Basic)4.73ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area52.04 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity60.6 m3·mol-1ChemAxon
Polarizability21.05 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSsplash10-001i-1900000000-da909bc8739471b977a5View in MoNA
GC-MSGC-MS Spectrum - EI-Bsplash10-001i-1900000000-46465bd7171400dfc550View in MoNA
GC-MSGC-MS Spectrum - EI-Bsplash10-001i-1900000000-46465bd7171400dfc550View in MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-ITFT , positivesplash10-000i-0900000000-36d2368b345aadafe472View in MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-ITFT , positivesplash10-014i-0900000000-c5c1dcbf033fe4c60c26View in MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-ITFT , positivesplash10-014i-0900000000-d5e0ce902c65a7d945a1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-ITFT , positivesplash10-014i-0900000000-527aa9bf80b633185478View in MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-ITFT , positivesplash10-014i-0900000000-d455d086a3a2f8252f64View in MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-ITFT , positivesplash10-000i-0900000000-8a4d7fb696a251cf65f2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-ITFT , positivesplash10-000i-0900000000-9894faa005f0ae52dc53View in MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-ITFT , positivesplash10-014r-0900000000-0b8ab8dbf459dd778773View in MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-ITFT , positivesplash10-014i-0900000000-497ea7121bf277833bb6View in MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-ITFT , positivesplash10-014i-0900000000-6af8bfce4a24520cec00View in MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-ITFT , positivesplash10-014i-0900000000-91749c0c5e4ef529093eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-ITFT , positivesplash10-014i-0900000000-49669661b9cd83218acbView in MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-ITFT , positivesplash10-014i-0900000000-a61957b37aba01bd4ee0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-ITFT , positivesplash10-00kr-1900000000-c4a27064ec37d84f0355View in MoNA
LC-MS/MSLC-MS/MS Spectrum - APCI-ITFT , positivesplash10-014i-0900000000-5f242ea7ebce9e040adfView in MoNA
LC-MS/MSLC-MS/MS Spectrum - APCI-ITFT , positivesplash10-014i-0900000000-6ee5a8d18cf5b5e520e3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - APCI-ITFT , positivesplash10-014i-0900000000-bfa10df85ed8a268fafcView in MoNA
LC-MS/MSLC-MS/MS Spectrum - APCI-ITFT , positivesplash10-014i-0900000000-fccc4a1798517c633d70View in MoNA
LC-MS/MSLC-MS/MS Spectrum - APCI-ITFT , positivesplash10-014i-0900000000-df132eef993f855e82edView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0900000000-7e5627a8d5f62d9aa7e0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-0900000000-39f67531ed6e9de51adeView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-056r-1900000000-9a354370a58dd3accdf9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0900000000-9d1762ff8a90d7425837View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-0900000000-9d1762ff8a90d7425837View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001i-2900000000-caeb9b49b279ff5b605fView in MoNA
MSMass Spectrum (Electron Ionization)splash10-001i-2900000000-0c34c7cea9097e35e7e1View in MoNA
Toxicity Profile
Route of ExposureOral (7) ; inhalation (7) ; dermal (7)
Mechanism of ToxicityN-acetylated benzidine metabolites are believed to form adducts with nucleic acids. Carcinogenesis is initiated when they are activated by peroxidation by prostaglandin H synthetase, oxidation by cytochrome P-450, or O-esterification by O-acetyltransferase or N,O-acetyltransferase. Benzidine has also been shown to bind to RNA and hemoglobin. (7, 1)
MetabolismBenzidine is absorpted following inhalation, oral, and dermal routes of exposure. Metabolism involves multiple and complex enzymatic pathways, including cytochrome P-450 and flavin monooxygenase systems, peroxidation by prostaglandin H synthase, and oxidation by lipoxygenases. The main reactions involved are N-acetylation, N-oxidation, and N-glucuronidation. Benzidine and its metabolites are excreted in the urine and faeces. (7)
Toxicity ValuesLD50: 309 mg/kg (Oral, Rat) (6) LD50: 110 mg/kg (Intraperitoneal, Mouse) (6)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)1, carcinogenic to humans. (8)
Uses/SourcesBenzidine was used to produce dyes for cloth, paper, and leather. (7)
Minimum Risk LevelNot Available
Health EffectsBenzidine is a known human carcinogen, most often associated with cancer of the urinary bladder. If benzidine comes in contact with skin it may cause a skin allergy. Liver, kidney, immune, and neurological effects have also been observed in animals exposed to benzidine. (7)
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB41835
PubChem Compound ID7111
ChEMBL IDCHEMBL15901
ChemSpider ID6844
KEGG IDC16444
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDC029876
Stitch IDBenzidine
PDB IDNot Available
ACToR ID139
Wikipedia LinkBenzidine
References
Synthesis ReferenceNot Available
MSDST3D0026.pdf
General References
  1. Birner G, Albrecht W, Neumann HG: Biomonitoring of aromatic amines. III: Hemoglobin binding of benzidine and some benzidine congeners. Arch Toxicol. 1990;64(2):97-102. [2350241 ]
  2. Zenser TV, Lakshmi VM, Rustan TD, Doll MA, Deitz AC, Davis BB, Hein DW: Human N-acetylation of benzidine: role of NAT1 and NAT2. Cancer Res. 1996 Sep 1;56(17):3941-7. [8752161 ]
  3. Lakshmi VM, Zenser NT, Hsu FF, Mattammal MB, Zenser TV, Davis BB: NADPH-dependent oxidation of benzidine by rat liver. Carcinogenesis. 1996 Sep;17(9):1941-7. [8824518 ]
  4. Arlt M, Scheffler A, Suske I, Eschner M, Saragi TP, Salbeck J, Fuhrmann-Lieker T: Bipolar redox behaviour, field-effect mobility and transistor switching of the low-molecular azo glass AZOPD. Phys Chem Chem Phys. 2010 Nov 7;12(41):13828-34. doi: 10.1039/c0cp00643b. Epub 2010 Sep 20. [20852800 ]
  5. Lardo MM, Diaz NB, Artaza JR, Carbia CD, Nazer R, Valdez R: [Vitamin E as protective agent against hemolysis in leprosy patients under dapsone treatment]. Medicina (B Aires). 1997;57(2):150-4. [9532824 ]
  6. Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.
  7. ATSDR - Agency for Toxic Substances and Disease Registry (2001). Toxicological profile for benzidine. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  8. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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. Birner G, Albrecht W, Neumann HG: Biomonitoring of aromatic amines. III: Hemoglobin binding of benzidine and some benzidine congeners. Arch Toxicol. 1990;64(2):97-102. [2350241 ]
2. 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. ATSDR - Agency for Toxic Substances and Disease Registry (2001). Toxicological profile for benzidine. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
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. Birner G, Albrecht W, Neumann HG: Biomonitoring of aromatic amines. III: Hemoglobin binding of benzidine and some benzidine congeners. Arch Toxicol. 1990;64(2):97-102. [2350241 ]
General Function:
Oxygen transporter activity
Specific Function:
Involved in oxygen transport from the lung to the various peripheral tissues.
Gene Name:
HBD
Uniprot ID:
P02042
Molecular Weight:
16055.41 Da
References
  1. Birner G, Albrecht W, Neumann HG: Biomonitoring of aromatic amines. III: Hemoglobin binding of benzidine and some benzidine congeners. Arch Toxicol. 1990;64(2):97-102. [2350241 ]
General Function:
Oxygen transporter activity
Specific Function:
The epsilon chain is a beta-type chain of early mammalian embryonic hemoglobin.
Gene Name:
HBE1
Uniprot ID:
P02100
Molecular Weight:
16202.71 Da
References
  1. Birner G, Albrecht W, Neumann HG: Biomonitoring of aromatic amines. III: Hemoglobin binding of benzidine and some benzidine congeners. Arch Toxicol. 1990;64(2):97-102. [2350241 ]
General Function:
Oxygen transporter activity
Specific Function:
Gamma chains make up the fetal hemoglobin F, in combination with alpha chains.
Gene Name:
HBG1
Uniprot ID:
P69891
Molecular Weight:
16140.37 Da
References
  1. Birner G, Albrecht W, Neumann HG: Biomonitoring of aromatic amines. III: Hemoglobin binding of benzidine and some benzidine congeners. Arch Toxicol. 1990;64(2):97-102. [2350241 ]
General Function:
Gamma chains make up the fetal hemoglobin F, in combination with alpha chains.
Specific Function:
Heme binding
Gene Name:
HBG2
Uniprot ID:
P69892
Molecular Weight:
16126.35 Da
References
  1. Birner G, Albrecht W, Neumann HG: Biomonitoring of aromatic amines. III: Hemoglobin binding of benzidine and some benzidine congeners. Arch Toxicol. 1990;64(2):97-102. [2350241 ]
General Function:
Oxygen transporter activity
Specific Function:
Not Available
Gene Name:
HBM
Uniprot ID:
Q6B0K9
Molecular Weight:
15617.97 Da
References
  1. Birner G, Albrecht W, Neumann HG: Biomonitoring of aromatic amines. III: Hemoglobin binding of benzidine and some benzidine congeners. Arch Toxicol. 1990;64(2):97-102. [2350241 ]
General Function:
Oxygen transporter activity
Specific Function:
Not Available
Gene Name:
HBQ1
Uniprot ID:
P09105
Molecular Weight:
15507.575 Da
References
  1. Birner G, Albrecht W, Neumann HG: Biomonitoring of aromatic amines. III: Hemoglobin binding of benzidine and some benzidine congeners. Arch Toxicol. 1990;64(2):97-102. [2350241 ]
General Function:
Oxygen transporter activity
Specific Function:
The zeta chain is an alpha-type chain of mammalian embryonic hemoglobin.
Gene Name:
HBZ
Uniprot ID:
P02008
Molecular Weight:
15636.845 Da
References
  1. Birner G, Albrecht W, Neumann HG: Biomonitoring of aromatic amines. III: Hemoglobin binding of benzidine and some benzidine congeners. Arch Toxicol. 1990;64(2):97-102. [2350241 ]
General Function:
Steroid hydroxylase activity
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. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.45 uMNVS_ADME_hCYP2C9Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.89 uMNVS_ADME_hCYP2C19Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC509.40 uMTox21_ERa_LUC_BG1_AgonistTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]