Record Information
Version 1.0
Creation Date 2009-03-06 11:58:02 -0700
Update Date 2013-04-25 02:32:43 -0600
Accession Number T3D0073
Identification
Common Name 2,3,7,8-Tetrachlorodibenzo-p-dioxin
Description 2,3,7,8-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. (R346, R347)
Compound Type
  • Organic Compound
  • Organochloride
  • Aromatic Hydrocarbon
  • Industrial By-product/Pollutant
  • Chlorinated Dibenzo-p-dioxin
Chemical Structure
Thumb
Synonyms
  1. 2,3,6,7-Tetrachlorodibenzo-p-dioxin
  2. 2,3,7,8-:tetrachlorodibenzo-p-dioxin
  3. 2,3,7,8-Czterochlorodwubenzo-p-dwuoksyny [Polish]
  4. 2,3,7,8-Tetra polychlorinated dibenzo-p-dioxin
  5. 2,3,7,8-Tetrachloro(b,e)dibenzodioxin
  6. 2,3,7,8-Tetrachloro(b,f)dibenzodioxin
  7. 2,3,7,8-Tetrachlorodibenzo(b,e)(1,4)dioxan
  8. 2,3,7,8-Tetrachlorodibenzo(b,e)(1,4)dioxin
  9. 2,3,7,8-Tetrachlorodibenzo-1,4-Dioxin
  10. 2,3,7,8-Tetrachlorodibenzo[b,e][1,4]dioxin
  11. 2,3,7,8-Tetrachlorooxanthrene
  12. 2,3,7,8-tetrachlorodibenzodioxin
  13. 2,3,7,8-tetrachlorodibenzodioxine
  14. Dioksyny [polish]
  15. Dioxine
  16. Tef transgenics (TCDD)
  17. Tetrachlorodibenzo-1,4-dioxin
  18. Tetrachlorodibenzo-p-dioxin
  19. Tetrachlorodibenzodioxin
  20. Tetradioxin
  21. Dibenzo-dioxin, 2,3,7,8-tetrachlorinated
Chemical Formula Not Available
Average Molecular Weight Not Available
Monoisotopic Molecular Weight Not Available
Chemical IUPAC Name
Not Available
CAS Registry Number 1746-01-6
SMILES
Not Available
InChI Identifier
Not Available
InChI Key Not Available
Chemical Taxonomy
Kingdom Not Available
Super Class Not Available
Class Not Available
Sub Class Not Available
Direct Parent Not Available
Alternative Parents Not Available
Molecular Framework Not Available
Substituents Not Available
External Descriptors Not Available
DrugBank ID Not Available
PubChem Compound ID 15625
KEGG ID C07557
UniProt ID Not Available
OMIM ID Not Available
ChEBI ID 28119
BioCyc ID Not Available
CTD ID D013749
Stitch ID 2,3,7,8-Tetrachlorodibenzo-p-dioxin
PDB ID Not Available
ACToR ID 1346
Wikipedia Link Not Available
Physical Properties
Appearance Colorless solid.
Melting Point 305 C
Solubility 2e-07 mg/mL at 25 °C [SHIU,WY et al. (1988)]
Predicted LogP Not Available
Toxicity Profile
Route of Exposure Oral (R346) ; inhalation (R346) ; dermal (R346)
Mechanism of Action CDDs 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. (R346)
Metabolism CDDs 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. (R346)
Toxicity Values LD50: 201 ug/kg (Oral, Rat) (R293) LD50: 120 ug/kg (Intraperitoneal, Mouse) (R263)
Lethal Dose Not Available
Carcinogenicity (IARC Classification) 1, carcinogenic to humans. (R264)
Uses/Sources 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. (R346, R347)
Minimum Risk Level Acute Oral: 0.0002 ug/kg/day (R260) Intermediate Oral: 0.00002 ug/kg/day (R260) Chronic Oral: 0.000001 ug/kg/day (R260)
Health Effects Exposure 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. (R346, R347)
Symptoms In addition to chloracne, CDD exposure causes skin rashes, discoloration, and excessive body hair. (R346)
Treatment Treatment of CDD exposure may include washing the area of contact, different methods of gastrointestinal decontamination, administration of intravenous fluids, or forced alkaline diuresis. (R622)
References
General References
  • R346 — 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]
  • R347 — Wikipedia. Polychlorinated dibenzodioxins. Last Updated 19 May 2009. [Link]
  • R293 — National Institute for Occupational Safety and Health (2002). RTECS: Registry of Toxic Effects of Chemical Substances.
  • R263 — Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.
  • R264 — International Agency for Research on Cancer (2009). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  • R260 — 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]
  • R622 — US Environmental Protection Agency (2009). Recognition and Management of Pesticide Poisonings. [Link]

Targets

1. Aryl hydrocarbon receptor

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.

Chlorinated dibenzo-p-dioxins cause their toxic effects by binding to the aryl hydrocarbon receptor and subsequently altering the trascription 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. This includes 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. (R346)
UniProt ID: P35869
Gene: AHR
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:

2. Transthyretin

Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.

CDDs are believed to disrupt the production, transport, and disposition of thyroid hormones. One mechanism of this involves metabolites of CDDs competing with thyroxine to bind to transthyretin, decreasing serum thyroid hormone levels. This change in thyroid hormone levels has been linked to both thyroid toxicity and neurobehavioral alterations. (R994)
UniProt ID: P02766
Gene: TTR
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References: