T3DB: Tetrabromodiphenyl ethers

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (6)XML

Targets (6)

Record Information

Version

2.0

Creation Date

2009-06-24 17:25:21 UTC

Update Date

2014-12-24 20:25:06 UTC

Accession Number

T3D2039

Identification

Common Name

Tetrabromodiphenyl ethers

Class

Small Molecule

Description

Persistent environmental pollutants, detected in fish and human breast milk. Tetrabromodiphenyl ethers is present in land-applied sewage sludge.

Compound Type

Aromatic Hydrocarbon
Bromide Compound
Ether
Food Toxin
Metabolite
Organic Compound
Organobromide
Pollutant
Polybrominated Biphenyl
Synthetic Compound

Chemical Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

Synonym
Benzene, 1,1'-oxybis-, tetrabromo deriv
Benzene, 1,1'-oxybis-, tetrabromo deriv.
Diphenyl ether, tetrabromo derivative
Tetrabromobiphenyl ether
Tetrabromodiphenyl ether
Tetrabromodiphenyl oxide
Toluene, dibromo derivative

Chemical Formula

C₁₂H₆Br₄O

Average Molecular Mass

485.791 g/mol

Monoisotopic Mass

481.715 g/mol

CAS Registry Number

40088-47-9

IUPAC Name

1,2,3-tribromo-4-(3-bromophenoxy)benzene

Traditional Name

1,2,3-tribromo-4-(3-bromophenoxy)benzene

SMILES

BrC1=CC(OC2=C(Br)C(Br)=C(Br)C=C2)=CC=C1

InChI Identifier

InChI=1S/C12H6Br4O/c13-7-2-1-3-8(6-7)17-10-5-4-9(14)11(15)12(10)16/h1-6H

InChI Key

InChIKey=VIHUMJGEWQPWOT-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as bromodiphenyl ethers. Bromodiphenyl ethers are compounds that contain two benzene groups linked to each other via an ether bond, and where at least one ring is substituted with a bromo group.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Diphenylethers

Direct Parent

Bromodiphenyl ethers

Alternative Parents

Substituents

Bromodiphenyl ether
Diaryl ether
Phenoxy compound
Phenol ether
Halobenzene
Bromobenzene
Aryl halide
Aryl bromide
Ether
Organic oxygen compound
Hydrocarbon derivative
Organooxygen compound
Organobromide
Organohalogen compound
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

Not Available

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	Not Available
LogP	6.05

Predicted Properties

Property	Value	Source
Water Solubility	0.00018 g/L	ALOGPS
logP	6.38	ALOGPS
logP	6.55	ChemAxon
logS	-6.4	ALOGPS
pKa (Strongest Basic)	-3.7	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	0	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	9.23 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	82.79 m³·mol⁻¹	ChemAxon
Polarizability	31.56 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-001i-0000900000-8cdb5f72db684973ea8d	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-001i-0000900000-e035323fe6cd6984da2b	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-001i-1103900000-f966a6ca870fc7abdda7	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-001i-0000900000-57ed240262b403867f45	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-001i-0000900000-3a78ad9d8a76b44af69c	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0fc0-1419800000-7713b917d4f071476fc5	2016-08-03	View Spectrum

Toxicity Profile

Route of Exposure

Oral (4) ; inhalation (4) ; dermal (4)

Mechanism of Toxicity

Like other halogenated aromatic hydrocarbons, polybrominated diphenyl ethers bind to the cellular aryl hydrocarbon receptor (AhR), which regulates the synthesis of a variety of proteins. Activation of the AhR induces a number of enzymes, including cytochrome P-450-dependent monooxygenases of the CYP1A and CYP2B families, UDP-glucuronosyltransferase, and ethoxyresorufin-o-deethylase. PBDEs are also believed to disrupt the production, transport, and disposition of thyroid hormones. One mechanism of this involves metabolites ot PDBEs 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. Certain PDBEs and their metabolites are also endocrine disruptors and may act as agonists at the estrogen receptors or antagonists at the androgen and progesterone receptors. (4, 1)

Metabolism

Polybrominated biphenyls can be absorbed through oral, inhalation, and dermal routes. Once in the body they distribute throughout and bioaccumulate in the blood, breast milk, and adipose tissue. The extent of PBDE metabolism depends on the degree of bromination. Metabolism is believed to involve debromination and methylation, resulting in phenolic metabolites. Metabolized and unmetabolized PDBE compounds are excreted mainly in the faeces. (4, 5)

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Polybrominated diphenyl ethers (PBDEs) are flame-retardant chemicals found in plastics used in a variety of consumer products to make them difficult to burn. Because they are mixed into plastics and foams rather than bound to them, PBDEs can leave the products that contain them and enter the environment. (4)

Minimum Risk Level

Intermediate Inhalation: 0.006 mg/m3 (3) Acute Oral: 0.03 mg/kg/day (3) Intermediate Oral: 0.007 mg/kg/day (3)

Health Effects

Polybrominated diphenyl ethers may affect the thyroid gland and liver. Animals studies have also shown that PDBEs can cause neurobehavioral alterations and affect the immune system. (4)

Symptoms

Not Available

Treatment

EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. INHALATION: supply fresh air. If required provide artificial respiration.

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

HMDB37520

PubChem Compound ID

38386

ChEMBL ID

Not Available

ChemSpider ID

35182

KEGG ID

Not Available

UniProt ID

Not Available

OMIM ID

ChEBI ID

Not Available

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Tetrabromobiphenyl Ether

PDB ID

Not Available

ACToR ID

6540

Wikipedia Link

Not Available

References

Synthesis Reference

Not Available

MSDS

Not Available

General References

Hamers T, Kamstra JH, Sonneveld E, Murk AJ, Kester MH, Andersson PL, Legler J, Brouwer A: In vitro profiling of the endocrine-disrupting potency of brominated flame retardants. Toxicol Sci. 2006 Jul;92(1):157-73. Epub 2006 Apr 6. [16601080 ]
Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
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]
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]
Wikipedia. Polybrominated diphenyl ether. Last Updated 19 June 2009. [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Androgen receptor

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

Hamers T, Kamstra JH, Sonneveld E, Murk AJ, Kester MH, Andersson PL, Legler J, Brouwer A: In vitro profiling of the endocrine-disrupting potency of brominated flame retardants. Toxicol Sci. 2006 Jul;92(1):157-73. Epub 2006 Apr 6. [16601080 ]

Target Details

2. 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

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]

Target Details

3. 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

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]

Target Details

4. 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

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]

Target Details

5. Progesterone receptor

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

References

Hamers T, Kamstra JH, Sonneveld E, Murk AJ, Kester MH, Andersson PL, Legler J, Brouwer A: In vitro profiling of the endocrine-disrupting potency of brominated flame retardants. Toxicol Sci. 2006 Jul;92(1):157-73. Epub 2006 Apr 6. [16601080 ]

Target Details

6. Transthyretin

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

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]

Tetrabromodiphenyl ethers (T3D2039)

Structure for T3D2039: Tetrabromodiphenyl ethers

Targets

References

References

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