Tmic
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Record Information
Version2.0
Creation Date2009-03-06 18:58:41 UTC
Update Date2014-12-24 20:21:46 UTC
Accession NumberT3D0389
Identification
Common NameBiphenyl
ClassSmall Molecule
DescriptionBiphenyl is found in alcoholic beverages. Fungistat, especially for citrus fruits. Biphenyl is used as food preservative and flavouring agent. Biphenyl is detected in bilberry, wine grape, carrot, peas, rum, potato, bell pepper, tomato, butter, milk, smoked fatty fish, cocoa, coffee, roast peanuts, olive, buckwheat and tamarind. Generally, the fruit packaging is impregnated with biphenyl, which evaporates into the air space surrounding the fruit. Some biphenyl is absorbed by the fruit skins Biphenyl has been shown to exhibit anti-coagulant and catabolic functions (5, 6). Biphenyl belongs to the family of Biphenyls and Derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond.
Compound Type
  • Aromatic Hydrocarbon
  • Coolant
  • Food Toxin
  • Industrial/Workplace Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Organochloride
  • Plasticizer
  • Pollutant
  • Polychlorinated Biphenyl
Chemical Structure
Thumb
Synonyms
Synonym
1, 1'-Diphenyl
1,1'-Biphenyl
Bibenzene
Diphenyl
FEMA 3129
Lemonene
Phenador-X
Phenylbenzene
PHPH
Tetrosin LY
Xenene
Chemical FormulaC12H10
Average Molecular Mass154.208 g/mol
Monoisotopic Mass154.078 g/mol
CAS Registry Number92-52-4
IUPAC Name1,1'-biphenyl
Traditional Namediphenyl
SMILESC1=CC=C(C=C1)C1=CC=CC=C1
InChI IdentifierInChI=1S/C12H10/c1-3-7-11(8-4-1)12-9-5-2-6-10-12/h1-10H
InChI KeyInChIKey=ZUOUZKKEUPVFJK-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as biphenyls and derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBiphenyls and derivatives
Direct ParentBiphenyls and derivatives
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite scales (2).
Experimental Properties
PropertyValue
Melting Point71°C
Boiling Point254.5°C (490.1°F)
Solubility0.00748 mg/mL at 25°C
LogP4.01
Predicted Properties
PropertyValueSource
Water Solubility0.015 g/LALOGPS
logP4.02ALOGPS
logP3.62ChemAxon
logS-4ALOGPS
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity51.19 m³·mol⁻¹ChemAxon
Polarizability17.96 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-8900000000-e5b4f289ac40ae7f058dView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-3900000000-11fa850b6e97cb680eddView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-2900000000-59a470228d72016ea76fView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-0900000000-01b08aa1cb97e4f8749aView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-1900000000-4ed186df67a09ce0650fView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-3900000000-b083707713188a3b56afView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-2900000000-931304319dd9f132e118View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-6900000000-f9f4bb759b70237cae7bView in MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0a4i-0900000000-5043f3793673c0f94d67View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0udi-0900000000-77f5c79fcaa35c93a5b8View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-8900000000-e5b4f289ac40ae7f058dView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-3900000000-11fa850b6e97cb680eddView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-2900000000-59a470228d72016ea76fView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-0900000000-01b08aa1cb97e4f8749aView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-1900000000-4ed186df67a09ce0650fView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-3900000000-b083707713188a3b56afView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-2900000000-931304319dd9f132e118View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-6900000000-f9f4bb759b70237cae7bView in MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0a4i-0900000000-5043f3793673c0f94d67View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0udi-0900000000-77f5c79fcaa35c93a5b8View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0udi-1900000000-56e5bf47be0405d6836bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0900000000-edde0dcdd8d1f5866932View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-0900000000-e45b080cc4494ae7ace3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0pdr-3900000000-eeea5f59ba3188214b77View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0900000000-f405b638fff04b7f3ea6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-0900000000-f405b638fff04b7f3ea6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0udi-0900000000-5347e97776fd82473263View in MoNA
MSMass Spectrum (Electron Ionization)splash10-0udi-3900000000-92b73f1f35424a0fd73dView in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureInhalation (3) ; dermal (3) ; eye contact (3)
Mechanism of ToxicityBiphenyl alters the permeability properties of mitochondrial membranes (1).
MetabolismDiphenyl is well absorbed through the gastrointestinal tract. It is rapidly metabolized to 4-hydroxybiphenyl, 4-phenyl-catechol and 4,4'-dihydroxyphenyl, which are excreted in urine and bile as glucuronide and mercapturic conjugates. The metabolites of diphenyl, mainly 4-hydroxybiphenyl, are excreted rapidly and almost exclusively in the urine. Acute oral toxicity is moderate. (9, 4).
Toxicity ValuesLD50: 3280 mg/kg (Oral, Rat) (11) LD50: 2400 mg/kg (Oral, Rabbit) (7) LD50: 2500 mg/kg (Dermal, Rabbit) (10)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity (not listed by IARC). (17)
Uses/SourcesOrganic synthesis; heat transfer agent; fungistat in packaging of citrus fruit; plant disease control; manufacture of benzidine; dyeing assistant for polyesters (2).
Minimum Risk LevelNot Available
Health EffectsExposure to diphenyl can cause necrosis in the liver and kidney, with regions of cirrhosis in liver; also, degenerative changes in heart muscle, damage to the central and peripheral nervous systems, as well as death can result from diphenyl poisoning (9).
SymptomsSymptoms of diphenyl poisoning include headache, fatigue, abdominal pain with nausea or diarrhea and various symptoms, vomiting and bronchitis (9).
TreatmentConsider gastric lavage, after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion. In case of inhalation exposure, move patient to fresh air and monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. In case of eye exposure, irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. I f the exposure occurred through dermal contact, remove contaminated clothing and wash exposed area thoroughly with soap and water. (8)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB34437
PubChem Compound ID7095
ChEMBL IDCHEMBL14092
ChemSpider ID6828
KEGG IDC06588
UniProt IDNot Available
OMIM ID
ChEBI ID17097
BioCyc IDCPD-945
CTD IDC010574
Stitch IDDiphenyl
PDB IDBNL
ACToR ID162
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Nishihara Y: Comparative study of the effects of biphenyl and Kanechlor-400 on the respiratory and energy linked activities of rat liver mitochondria. Br J Ind Med. 1985 Feb;42(2):128-32. [3918562 ]
  2. Maeda A, Maeda T, Imanishi Y, Golczak M, Moise AR, Palczewski K: Aberrant metabolites in mouse models of congenital blinding diseases: formation and storage of retinyl esters. Biochemistry. 2006 Apr 4;45(13):4210-9. [16566595 ]
  3. Wigg SJ, Tare M, Forbes J, Cooper ME, Thomas MC, Coleman HA, Parkington HC, O'Brien RC: Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-beta in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats. Diabetologia. 2004 Jun;47(6):1038-46. Epub 2004 Jun 8. [15184978 ]
  4. Huang Y, Ishizuka T, Miura A, Kajita K, Ishizawa M, Kimura M, Yamamoto Y, Kawai Y, Morita H, Uno Y, Yasuda K: Effect of 1 alpha,25-dihydroxy vitamin D3 and vitamin E on insulin-induced glucose uptake in rat adipocytes. Diabetes Res Clin Pract. 2002 Mar;55(3):175-83. [11850093 ]
  5. Jia ZJ, Wu Y, Huang W, Zhang P, Clizbe LA, Goldman EA, Sinha U, Arfsten AE, Edwards ST, Alphonso M, Hutchaleelaha A, Scarborough RM, Zhu BY: 1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides as potent factor Xa inhibitors. Part 2: A survey of P4 motifs. Bioorg Med Chem Lett. 2004 Mar 8;14(5):1221-7. [14980670 ]
  6. Kosono S, Maeda M, Fuji F, Arai H, Kudo T: Three of the seven bphC genes of Rhodococcus erythropolis TA421, isolated from a termite ecosystem, are located on an indigenous plasmid associated with biphenyl degradation. Appl Environ Microbiol. 1997 Aug;63(8):3282-5. [9251216 ]
  7. American Conference of Governmental Industrial Hygienists (2001). Documentation of Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2001. Cincinnati, OH: American Conference of Governmental Industrial Hygienists.
  8. Rumack BH (2009). POISINDEX(R) Information System. Englewood, CO: Micromedex, Inc. CCIS Volume 141, edition expires Aug, 2009.
  9. Gosselin RE, Smith RP, and Hodge HC (1984). Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins.
  10. Kirk-Othmer Encyclopedia of Chemical Technology (1978-1984). 3rd ed. Volumes 1-26. New York, NY: John Wiley and Sons.
  11. O'Neil MJ (ed) (2001). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th ed. Whitehouse Station, NJ: Merck and Co., Inc.
  12. Lewis RJ Sr. (ed) (1997). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: Van Nostrand Rheinhold Co.
  13. NIOSH: The National Institute for Occupational Safety and Health (1983). National Occupational Exposure Survey (NOES).
  14. World Health Organization/International Programme on Chemical Safety (1999). Concise International Chemical Assessment Document No. 6. Biphenyl.
  15. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
  16. ATSDR - Agency for Toxic Substances and Disease Registry (2000). Toxicological profile for polychlorinated biphenyls. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  17. 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:
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
AC503.29 uMATG_ERa_TRANSAttagene
References
  1. Taccone-Gallucci M, Manca-di-Villahermosa S, Battistini L, Stuffler RG, Tedesco M, Maccarrone M: N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity. Kidney Int. 2006 Apr;69(8):1450-4. [16531984 ]
  2. 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 ]
  3. Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors α and β: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
Gene Name:
ESR2
Uniprot ID:
Q92731
Molecular Weight:
59215.765 Da
References
  1. Taccone-Gallucci M, Manca-di-Villahermosa S, Battistini L, Stuffler RG, Tedesco M, Maccarrone M: N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity. Kidney Int. 2006 Apr;69(8):1450-4. [16531984 ]
  2. Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors α and β: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50160 uMNot AvailableBindingDB 50168002
References
  1. Korhonen LE, Rahnasto M, Mahonen NJ, Wittekindt C, Poso A, Juvonen RO, Raunio H: Predictive three-dimensional quantitative structure-activity relationship of cytochrome P450 1A2 inhibitors. J Med Chem. 2005 Jun 2;48(11):3808-15. [15916432 ]
General Function:
Oxygen binding
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, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compounds to their activated forms, including polycyclic aromatic hydrocarbons. Promotes angiogenesis by removing cellular oxygenation products, thereby decreasing oxidative stress, release of antiangiogenic factor THBS2, then allowing endothelial cells migration, cell adhesion and capillary morphogenesis. These changes are concommitant with the endothelial nitric oxide synthase activity and nitric oxide synthesis. Plays an important role in the regulation of perivascular cell proliferation, migration, and survival through modulation of the intracellular oxidative state and NF-kappa-B expression and/or activity, during angiogenesis. Contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression.
Gene Name:
CYP1B1
Uniprot ID:
Q16678
Molecular Weight:
60845.33 Da
References
  1. Shimada T, Tanaka K, Takenaka S, Foroozesh MK, Murayama N, Yamazaki H, Guengerich FP, Komori M: Reverse type I binding spectra of human cytochrome P450 1B1 induced by flavonoid, stilbene, pyrene, naphthalene, phenanthrene, and biphenyl derivatives that inhibit catalytic activity: a structure-function relationship study. Chem Res Toxicol. 2009 Jul;22(7):1325-33. doi: 10.1021/tx900127s. [19563207 ]
General Function:
Zinc ion binding
Specific Function:
Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism. Induces the expression of PERM1 in the skeletal muscle.
Gene Name:
ESRRA
Uniprot ID:
P11474
Molecular Weight:
45509.11 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.72 uMATG_ERRa_TRANSAttagene
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 ]