Record Information
Version2.0 (beta)
Creation Date2009-03-06 11:58:02 -0700
Update Date2014-10-20 10:24:25 -0600
Accession NumberT3D0073
Identification
Common Name2,3,7,8-Tetrachlorodibenzo-p-dioxin
ClassSmall Molecule
Description2,3,7,8-Tetrachlorodibenzo-p-dioxin is the most toxic of 75 chlorinated dibenzo-p-dioxin (CDD) congeners. CDDs are a class of manufactured chemicals that consist of dioxin skeletel 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. (5, 6)
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
Synonyms
Synonym
2,3,6,7-Tetrachlorodibenzo-p-dioxin
2,3,7,8-:tetrachlorodibenzo-p-dioxin
2,3,7,8-Tetra polychlorinated dibenzo-p-dioxin
2,3,7,8-Tetrachloro(b,e)dibenzodioxin
2,3,7,8-Tetrachloro(b,f)dibenzodioxin
2,3,7,8-Tetrachlorodibenzo(b,e)(1,4)dioxan
2,3,7,8-Tetrachlorodibenzo(b,e)(1,4)dioxin
2,3,7,8-Tetrachlorodibenzo-1,4-Dioxin
2,3,7,8-Tetrachlorodibenzo-P-dioxin
2,3,7,8-tetrachlorodibenzodioxin
2,3,7,8-tetrachlorodibenzodioxine
2,3,7,8-Tetrachlorodibenzo[b,e][1,4]dioxin
2,3,7,8-Tetrachlorooxanthrene
Dibenzo-dioxin, 2,3,7,8-tetrachlorinated
Tetrachlorodibenzo-1,4-dioxin
Tetrachlorodibenzo-p-dioxin
Tetrachlorodibenzodioxin
Tetradioxin
Chemical FormulaC12H4Cl4O2
Average Molecular Mass321.971 g/mol
Monoisotopic Mass319.897 g/mol
CAS Registry Number1746-01-6
IUPAC Name2,3,7,8-tetrachlorooxanthrene
Traditional Namedioxin
SMILESClC1=CC2=C(OC3=C(O2)C=C(Cl)C(Cl)=C3)C=C1Cl
InChI IdentifierInChI=1S/C12H4Cl4O2/c13-5-1-9-10(2-6(5)14)18-12-4-8(16)7(15)3-11(12)17-9/h1-4H
InChI KeyInChIKey=HGUFODBRKLSHSI-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassHeterocyclic Compounds
ClassBenzodioxins
Sub ClassBenzo-p-dioxins
Direct ParentChlorinated Dibenzo-p-dioxins
Alternative Parents
Substituents
  • Chlorobenzene
  • Aryl chloride
  • Organochloride
  • 1,2-dichlorobenzene
  • Benzenoid
  • Aromatic heteropolycyclic compound
  • Halobenzene
  • Aryl halide
  • Organohalogen compound
  • Diaryl ether
  • Chlorinated-dibenzo-p-dioxin
Molecular FrameworkAromatic Heteropolycyclic Compounds
External Descriptors
  • Polychlorinated Dibenzodioxine (chebi)
  • Pcdds (kegg)
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Actin Filament
  • Basolateral Membrane
  • Cell junction
  • Cell surface
  • Centrosome
  • Cytosol
  • Extracellular
  • Extracellular matrix
  • Focal adhesion
  • Lysosome
  • Membrane
  • Membrane Fraction
  • Microsome
  • Microtubule
  • Mitochondrion
  • Nuclear Matrix
  • Nuclear Membrane
  • Nucleolus
  • Peroxisome
  • Plasma Membrane
  • Sarcoplasmic Reticulum
  • Secretory Granule
  • Tubulin
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
ApoptosisNot Availablemap04210
Cell cycleNot Availablemap04110
Insulin secretionNot Availablemap04911
Arachidonic Acid MetabolismSMP00075 map00590
Wnt signaling pathwayNot Availablemap04310
Fatty acid MetabolismSMP00051 map00071
Ovarian SteroidogenesisNot AvailableNot Available
Insulin signaling pathwayNot Availablemap04910
ProteasomeNot AvailableNot Available
EicosanoidsNot AvailableNot Available
Rna polymeraseNot Availablemap03020
PhenothiazinesNot AvailableNot Available
Oxidative phosphorylationNot Availablemap00190
Nitrogen MetabolismNot AvailableNot Available
Long-term potentiationNot Availablemap04720
Inositol Phosphate MetabolismSMP00462 map00562
EndocytosisNot Availablemap04144
Circadian rhythmNot Availablemap04710
Axon guidanceNot Availablemap04360
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceColorless solid.
Experimental Properties
PropertyValue
Melting Point305°C
Boiling PointNot Available
Solubility2e-07 mg/mL at 25 °C [SHIU,WY et al. (1988)]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.000371ALOGPS
logP6.59ALOGPS
logP5.42ChemAxon
logS-5.9ALOGPS
pKa (Strongest Basic)-3.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area18.46 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity71.7 m3·mol-1ChemAxon
Polarizability28.72 Å3ChemAxon
Spectra
SpectraMS
Toxicity Profile
Route of ExposureOral (5) ; inhalation (5) ; dermal (5)
Mechanism of ToxicityCDDs bind to the aryl hydrocarbon (Ah) receptor and subsequently alter the transcription of several genes (oncogenes, growth factors, receptors, hormones, and drug-metabolizing enzymes). 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 change in transcription/translation of these genes is believed to be the cause of most of the toxic effects of CDDs. 2,3,7,8-tetrachlorodibenzo-p-dioxin's carcinogenicity is thought to be the result of its ability to alter the capacity of both exogenous and endogenous substances to damage the DNA by inducing CYP1A1- and CYP1A2-dependent drug-metabolizing enzymes. (5)
MetabolismCDDs are absorbed through oral, inhalation, and dermal routes of exposure. CDDs are carried in the plasma by serum lipids and lipoproteins, and mainly distributed in the liver and adipose tissue. CDDs are slowly metabolized to polar metabolites by the microsomal monooxygenase system. These metabolites 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. (5)
Toxicity ValuesLD50: 201 ug/kg (Oral, Rat) (2) LD50: 120 ug/kg (Intraperitoneal, Mouse) (1)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)1, carcinogenic to humans. (4)
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. (5, 6)
Minimum Risk LevelAcute Oral: 0.0002 ug/kg/day (3) Intermediate Oral: 0.00002 ug/kg/day (3) Chronic Oral: 0.000001 ug/kg/day (3)
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 pathologies, thyroid disorders, endometriosis, and diabetes. 2,3,7,8-Tetrachlorodibenzo-p-dioxin is also a known as a human carcinogen. (5, 6)
SymptomsIn addition to chloracne, CDD exposure causes skin rashes, discoloration, and excessive body hair. (5)
TreatmentTreatment of CDD exposure may include washing the area of contact, different methods of gastrointestinal decontamination, administration of intravenous fluids, or forced alkaline diuresis. (7)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID15625
ChEMBL IDNot Available
ChemSpider ID137967
KEGG IDC07557
UniProt IDNot Available
OMIM ID
ChEBI ID28119
BioCyc IDNot Available
CTD IDD013749
Stitch ID2,3,7,8-Tetrachlorodibenzo-p-dioxin
PDB IDNot Available
ACToR ID1346
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D0073.pdf
General References
  1. Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.
  2. National Institute for Occupational Safety and Health (2002). RTECS: Registry of Toxic Effects of Chemical Substances.
  3. 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]
  4. International Agency for Research on Cancer (2009). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  5. 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]
  6. Wikipedia. Polychlorinated dibenzodioxins. Last Updated 19 May 2009. [Link]
  7. US Environmental Protection Agency (2009). Recognition and Management of Pesticide Poisonings. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Involved in Hsp90 protein 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
Gene Name:
AHR
Uniprot ID:
P35869
Molecular Weight:
96146.7 Da
References
  1. Roberts EA, Golas CL, Okey AB: Ah receptor mediating induction of aryl hydrocarbon hydroxylase: detection in human lung by binding of 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin. Cancer Res. 1986 Jul;46(7):3739-43. [3011254 ]
  2. 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]
General Function:
Involved in steroid binding
Specific Function:
Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain
Gene Name:
TTR
Uniprot ID:
P02766
Molecular Weight:
15887.0 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2004). Toxicological profile for polybrominated biphenyls and polybrominated diphenyl ethers (PBBs and PBDEs). U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]