1,2,3,7,8-Pentachlorodibenzo-p-dioxin (T3D2093)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (3)XML
Targets (3)
Record Information
Version2.0
Creation Date2009-06-24 17:37:26 UTC
Update Date2014-12-24 20:25:13 UTC
Accession NumberT3D2093
Identification
Common Name1,2,3,7,8-Pentachlorodibenzo-p-dioxin
ClassSmall Molecule
Description1,2,3,7,8-Pentachlorodibenzo-p-dioxin is a chlorinated dibenzo-p-dioxin (CDD) isomer. CDDs are a class of manufactured chemicals that consist of dioxin skeletal structures with chlorine substituents. They are also persistent organic pollutants (POPs), thus their production is regulated in most areas. Dioxins occur as by-products from the manufacture of organochlorides, the bleaching of paper, chlorination by waste and drinking water treatment plants, municipal solid waste and industrial incinerators, and natural sources such as volcanoes and forest fires. (3, 4)
Compound Type
  • Aromatic Hydrocarbon
  • Chlorinated Dibenzo-p-dioxin
  • Ether
  • Industrial By-product/Pollutant
  • Industrial/Workplace Toxin
  • Organic Compound
  • Organochloride
  • Pollutant
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
1,2,3,7,8-PeCDD
1,2,3,7,8-Penta polychlorinated dibenzo-p-dioxin
1,2,3,7,8-Pentachlorodibenzo(b,e)(1,4)dioxin
1,2,3,7,8-Pentachlorodibenzo-P-dioxin
1,2,3,7,8-Pentachlorooxanthrene
PCDD 54
Chemical FormulaC12H3Cl5O2
Average Molecular Mass356.416 g/mol
Monoisotopic Mass353.858 g/mol
CAS Registry Number40321-76-4
IUPAC Name1,2,3,7,8-pentachlorooxanthrene
Traditional Name1,2,3,7,8-pentachlorooxanthrene
SMILESClC1=CC2=C(OC3=C(Cl)C(Cl)=C(Cl)C=C3O2)C=C1Cl
InChI IdentifierInChI=1S/C12H3Cl5O2/c13-4-1-7-8(2-5(4)14)19-12-9(18-7)3-6(15)10(16)11(12)17/h1-3H
InChI KeyInChIKey=FSPZPQQWDODWAU-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as chlorinated dibenzo-p-dioxins. These are organic compounds containing a chlorine atom attached to a dibenzo-p-dioxin moiety.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzodioxins
Sub ClassBenzo-p-dioxins
Direct ParentChlorinated dibenzo-p-dioxins
Alternative Parents
Substituents
  • Chlorinated-dibenzo-p-dioxin
  • Diaryl ether
  • Benzenoid
  • Aryl halide
  • Aryl chloride
  • Oxacycle
  • Ether
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organochloride
  • Organohalogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic 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
AppearanceColorless solid.
Experimental Properties
PropertyValue
Melting Point240°C
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00014 g/LALOGPS
logP7.06ALOGPS
logP6.02ChemAxon
logS-6.4ALOGPS
pKa (Strongest Basic)-9.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area18.46 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity76.51 m³·mol⁻¹ChemAxon
Polarizability30.79 ųChemAxon
Number of Rings3ChemAxon
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, Positivesplash10-0a4i-3079000000-b5a30ae4fe361e5b341b2021-09-23View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0009000000-a979278bc1bad0d1a2bc2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-0009000000-a979278bc1bad0d1a2bc2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-0009000000-96b5ac506bd6457dfe772016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0009000000-484bbfdb53eeac513fb22016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-0009000000-1fe3613b59fce89942772016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0uec-6098000000-990c8a26f11d5f321cfc2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0009000000-01da1ec8e5faea7e4ef92021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-0009000000-01da1ec8e5faea7e4ef92021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-0009000000-01da1ec8e5faea7e4ef92021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0009000000-fa928a3b09ed103fb3d02021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-0009000000-fa928a3b09ed103fb3d02021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0f6x-0097000000-ec89fe3c358f5c2ae8562021-10-12View Spectrum
MSMass Spectrum (Electron Ionization)splash10-0a4i-0139000000-9561997a66bec5a473c72014-09-20View Spectrum
Toxicity Profile
Route of ExposureOral (3) ; inhalation(3) ; dermal (3)
Mechanism of ToxicityCDDs cause their toxic effects by binding to the aryl hydrocarbon receptor and subsequently altering the transcription of certain genes. The affinity for the Ah receptor depends on the structure of the specific CDD. The change in gene expression may result from the direct interaction of the Ah receptor and its heterodimer-forming partner, the aryl hydrocarbon receptor nuclear translocator, with gene regulatory elements or the initiation of a phosphorylation/dephosphorylation cascade that subsequently activates other transcription factors. The affected genes include several oncogenes, growth factors, receptors, hormones, and drug-metabolizing enzymes. The change in transcription/translation of these genes is believed to be the cause of most of the toxic effects of CDDs. (3)
MetabolismCDDs are absorbed through oral, inhalation, and dermal routes of exposure. CDDs are carried in the plasma by serum lipids and lipoproteins, distributing mainly to the liver and adipose tissue. CDDs are very slowly metabolized by the microsomal monooxygenase system to polar metabolites that can undergo conjugation with glucuronic acid and glutathione. They may increase the rate of their own metabolism by inducing both phase I and phase II enzymes. The major routes of excretion of CDDs are the bile and the faeces, though smaller amounts are excreted in the urine and via lactation. (3)
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (2)
Uses/SourcesDioxins occur as by-products from the manufacture of organochlorides, the bleaching of paper, chlorination by waste and drinking water treatment plants, municipal solid waste and industrial incinerators, and natural sources such as volcanoes and forest fires. (3, 4)
Minimum Risk LevelAcute Oral: 0.0002 ug/kg/day (1) Intermediate Oral: 0.00002 ug/kg/day (1) Chronic Oral: 0.000001 ug/kg/day (1)
Health EffectsExposure to large amounts of CDDs causes chloracne, a severe skin disease with acne-like lesions that occur mainly on the face and upper body. CDDs may also cause liver damage and induce long-term alterations in glucose metabolism and subtle changes in hormonal levels. In addition, studies have shown that CDDs may disrupt the endocrine system and weaken the immune system, as well as cause reproductive damage and birth defects, central and peripheral nervous system pathology, thyroid disorders, endometriosis, and diabetes. (3, 4)
SymptomsIn addition to chloracne, CDD exposure causes skin rashes, discoloration, and excessive body hair. (3)
TreatmentTreatment of CDD exposure may include washing the area of contact, GI decontamination, administering an IV, or forced alkaline diuresis. (5)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID38439
ChEMBL IDCHEMBL137220
ChemSpider ID35228
KEGG IDC18099
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDDIHYDRO-DIOH-BENZOATE
CTD IDC051452
Stitch ID1,2,3,7,8-Pentachlorodibenzo-p-dioxin
PDB IDNot Available
ACToR ID7991
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2001). Minimal Risk Levels (MRLs) for Hazardous Substances. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  2. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  3. ATSDR - Agency for Toxic Substances and Disease Registry (1998). Toxicological profile for chlorinated dibenzo-p-dioxins (CDDs). U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  4. Wikipedia. Polychlorinated dibenzodioxins. Last Updated 19 May 2009. [Link]
  5. US Environmental Protection Agency (2009). Recognition and Management of Pesticide Poisonings. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

Target Details
1. Estrogen receptor
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
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.
Target Details
2. Estrogen receptor beta
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.
Target Details
3. Aryl hydrocarbon receptor
General Function:
Transcription regulatory region dna binding
Specific Function:
Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
Gene Name:
AHR
Uniprot ID:
P35869
Molecular Weight:
96146.705 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (1998). Toxicological profile for chlorinated dibenzo-p-dioxins (CDDs). U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]