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Record Information
Version2.0
Creation Date2014-08-12 17:44:32 UTC
Update Date2014-12-24 20:26:34 UTC
Accession NumberT3D3948
Identification
Common NameTetrachlorobisphenol A
ClassSmall Molecule
DescriptionTetrachlorobisphenol A is estrogen receptor(ER) alpha agonists, antagonists for androgen receptor(AR), progesterone receptor(PR) antagonists. It exhibits the ability to reverse the ERR inhibition induced by 4-hydroxytamoxifen.
Compound Type
  • Industrial/Workplace Toxin
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
2,2-Bis(4-hydroxy-3,5-dichlorophenyl)propane
3,3',5,5'-Tetrachlorobisphenol a
Tetrachlorobisphenol a
Tetrachlorodian
Chemical FormulaC15H12Cl4O2
Average Molecular Mass366.067 g/mol
Monoisotopic Mass363.959 g/mol
CAS Registry Number79-95-8
IUPAC Name2,6-dichloro-4-[2-(3,5-dichloro-4-hydroxyphenyl)propan-2-yl]phenol
Traditional Nametetrachlorobisphenol A
SMILESCC(C)(C1=CC(Cl)=C(O)C(Cl)=C1)C1=CC(Cl)=C(O)C(Cl)=C1
InChI IdentifierInChI=1S/C15H12Cl4O2/c1-15(2,7-3-9(16)13(20)10(17)4-7)8-5-11(18)14(21)12(19)6-8/h3-6,20-21H,1-2H3
InChI KeyInChIKey=KYPYTERUKNKOLP-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as bisphenols. These are methylenediphenols, HOC6H4CH2C6H4OH, commonly p,p-methylenediphenol, and their substitution products (generally derived from condensation of two equivalent amounts of a phenol with an aldehyde or ketone).
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentBisphenols
Alternative Parents
Substituents
  • Bisphenol
  • Phenylpropane
  • 1,3-dichlorobenzene
  • 2-halophenol
  • 2-chlorophenol
  • Chlorobenzene
  • Halobenzene
  • Phenol
  • Aryl halide
  • Aryl chloride
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Organooxygen compound
  • Organohalogen compound
  • Organochloride
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceSolid.
Experimental Properties
PropertyValue
Melting Point130-132°C (lit.)
Boiling PointNot Available
SolubilityDMSO and Methanol
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0005 g/LALOGPS
logP7.22ALOGPS
logP6.46ChemAxon
logS-5.9ALOGPS
pKa (Strongest Acidic)6.27ChemAxon
pKa (Strongest Basic)-7.5ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity98.49 m³·mol⁻¹ChemAxon
Polarizability34.18 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0udi-0129000000-d11faa3074c258e0bb4e2021-09-24View 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 (TMS_1_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Negativesplash10-0w29-0092000000-17853fe903a3975e5f902021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-0002-0090000000-2772dcd617aaa92b1f6c2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-03di-0019000000-ba2de1df5989b335615e2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Negativesplash10-03di-0009000000-f35b14b05fa85968fee82021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-001j-0190000000-04aba6d56eb8a7f850722021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-001i-1190000000-700b9d5cef5b6b06d83e2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-0w29-0092000000-51a18251a74cd74306452021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0009000000-05964ea61258d00fd8ab2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-0009000000-6ac1db351cc0fded92812016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0hha-0439000000-94f5c9202b1187d29d992016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0009000000-94363d558a1a5e2576b02016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-0009000000-caeb72dcd7861497e33d2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-03di-0719000000-05ef1cc3f3e40642b2ef2016-08-03View Spectrum
MSMass Spectrum (Electron Ionization)splash10-0udi-2419000000-f720422fd1ffc745c38f2014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 90 MHz, CDCl3, experimental)Not Available2014-09-20View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID6619
ChEMBL IDCHEMBL1738928
ChemSpider ID6367
KEGG IDC14528
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D3948.pdf
General References
  1. Li J, Ma M, Wang Z: In vitro profiling of endocrine disrupting effects of phenols. Toxicol In Vitro. 2010 Feb;24(1):201-7. doi: 10.1016/j.tiv.2009.09.008. Epub 2009 Sep 16. [19765641 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Zinc ion binding
Specific Function:
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
Gene Name:
PGR
Uniprot ID:
P06401
Molecular Weight:
98979.96 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.19 uMNVS_NR_hPRNovascreen
References
  1. Li J, Ma M, Wang Z: In vitro profiling of endocrine disrupting effects of phenols. Toxicol In Vitro. 2010 Feb;24(1):201-7. doi: 10.1016/j.tiv.2009.09.008. Epub 2009 Sep 16. [19765641 ]
  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 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
Gene Name:
PPARG
Uniprot ID:
P37231
Molecular Weight:
57619.58 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.27 uMNVS_NR_hPPARgNovascreen
References
  1. Riu A, Grimaldi M, le Maire A, Bey G, Phillips K, Boulahtouf A, Perdu E, Zalko D, Bourguet W, Balaguer P: Peroxisome proliferator-activated receptor gamma is a target for halogenated analogs of bisphenol A. Environ Health Perspect. 2011 Sep;119(9):1227-32. doi: 10.1289/ehp.1003328. Epub 2011 May 11. [21561829 ]
  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 ]
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
AC507.31 uMATG_ERa_TRANSAttagene
AC505.23 uMATG_ERE_CISAttagene
AC501.42 uMNVS_NR_hERNovascreen
References
  1. Li J, Ma M, Wang Z: In vitro profiling of endocrine disrupting effects of phenols. Toxicol In Vitro. 2010 Feb;24(1):201-7. doi: 10.1016/j.tiv.2009.09.008. Epub 2009 Sep 16. [19765641 ]
  2. Riu A, le Maire A, Grimaldi M, Audebert M, Hillenweck A, Bourguet W, Balaguer P, Zalko D: Characterization of novel ligands of ERalpha, Erbeta, and PPARgamma: the case of halogenated bisphenol A and their conjugated metabolites. Toxicol Sci. 2011 Aug;122(2):372-82. doi: 10.1093/toxsci/kfr132. Epub 2011 May 27. [21622942 ]
  3. Molina-Molina JM, Amaya E, Grimaldi M, Saenz JM, Real M, Fernandez MF, Balaguer P, Olea N: In vitro study on the agonistic and antagonistic activities of bisphenol-S and other bisphenol-A congeners and derivatives via nuclear receptors. Toxicol Appl Pharmacol. 2013 Oct 1;272(1):127-36. doi: 10.1016/j.taap.2013.05.015. Epub 2013 May 25. [23714657 ]
  4. 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 receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.68 uMATG_PXR_TRANSAttagene
AC503.54 uMATG_PXRE_CISAttagene
AC505.25 uMNVS_NR_hPXRNovascreen
References
  1. Molina-Molina JM, Amaya E, Grimaldi M, Saenz JM, Real M, Fernandez MF, Balaguer P, Olea N: In vitro study on the agonistic and antagonistic activities of bisphenol-S and other bisphenol-A congeners and derivatives via nuclear receptors. Toxicol Appl Pharmacol. 2013 Oct 1;272(1):127-36. doi: 10.1016/j.taap.2013.05.015. Epub 2013 May 25. [23714657 ]
  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 ]
General Function:
Zinc ion binding
Specific Function:
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:
AR
Uniprot ID:
P10275
Molecular Weight:
98987.9 Da
References
  1. Li J, Ma M, Wang Z: In vitro profiling of endocrine disrupting effects of phenols. Toxicol In Vitro. 2010 Feb;24(1):201-7. doi: 10.1016/j.tiv.2009.09.008. Epub 2009 Sep 16. [19765641 ]
  2. Sun H, Xu LC, Chen JF, Song L, Wang XR: Effect of bisphenol A, tetrachlorobisphenol A and pentachlorophenol on the transcriptional activities of androgen receptor-mediated reporter gene. Food Chem Toxicol. 2006 Nov;44(11):1916-21. Epub 2006 Jul 4. [16893599 ]
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. Riu A, le Maire A, Grimaldi M, Audebert M, Hillenweck A, Bourguet W, Balaguer P, Zalko D: Characterization of novel ligands of ERalpha, Erbeta, and PPARgamma: the case of halogenated bisphenol A and their conjugated metabolites. Toxicol Sci. 2011 Aug;122(2):372-82. doi: 10.1093/toxsci/kfr132. Epub 2011 May 27. [21622942 ]
General Function:
Zinc ion binding
Specific Function:
Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity). Induces the expression of PERM1 in the skeletal muscle.
Gene Name:
ESRRG
Uniprot ID:
P62508
Molecular Weight:
51305.485 Da
References
  1. Li J, Ma M, Wang Z: In vitro profiling of endocrine disrupting effects of phenols. Toxicol In Vitro. 2010 Feb;24(1):201-7. doi: 10.1016/j.tiv.2009.09.008. Epub 2009 Sep 16. [19765641 ]
General Function:
Identical protein binding
Specific Function:
Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.
Gene Name:
TTR
Uniprot ID:
P02766
Molecular Weight:
15886.88 Da
References
  1. Meerts IA, van Zanden JJ, Luijks EA, van Leeuwen-Bol I, Marsh G, Jakobsson E, Bergman A, Brouwer A: Potent competitive interactions of some brominated flame retardants and related compounds with human transthyretin in vitro. Toxicol Sci. 2000 Jul;56(1):95-104. [10869457 ]
General Function:
Zinc ion binding
Specific Function:
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic genes expression.
Gene Name:
NR3C1
Uniprot ID:
P04150
Molecular Weight:
85658.57 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC505.16 uMTox21_GR_BLA_Antagonist_ratioTox21/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 ]