T3DB: 2-Chlorobiphenyl

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (8)XML

Targets (8)

Record Information

Version

2.0

Creation Date

2009-03-06 18:58:41 UTC

Update Date

2014-12-24 20:21:46 UTC

Accession Number

T3D0390

Identification

Common Name

2-Chlorobiphenyl

Class

Small Molecule

Description

2-Chlorobiphenyl is one of 209 polychlorinated biphenyls (PCBs). PCBs are a group of synthetic organic compounds with 1-10 chlorine atoms attached to biphenyl. They were manufactured as commercial mixtures but banned in the 1970's because they were found to bioaccumulate and cause harmful health effects. However, PCBs do not break down readily and are still found in the environment. (9)

Compound Type

Aromatic Hydrocarbon
Coolant
Industrial/Workplace Toxin
Organic Compound
Organochloride
Plasticizer
Pollutant
Polychlorinated Biphenyl
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
1-Chloro-2-phenylbenzene
2-Chlorbiphenyl
2-Chloro-1, 1'-biphenyl
2-Chloro-1,1'-biphenyl
2-Chlorodiphenyl
2-Monochlorobiphenyl
2-PCB
Arochlor-1254
Chloro-1,1'-biphenyl
Chlorobiphenyl
Chlorodiphenyl
Diphenylchloride
Monochlorobiphenyl
o-Chlorobiphenyl
o-Chlorodiphenyl
PCB 1

Chemical Formula

C₁₂H₉Cl

Average Molecular Mass

188.653 g/mol

Monoisotopic Mass

188.039 g/mol

CAS Registry Number

2051-60-7

IUPAC Name

1-chloro-2-phenylbenzene

Traditional Name

aroclor 1232

SMILES

ClC1=CC=CC=C1C1=CC=CC=C1

InChI Identifier

InChI=1S/C12H9Cl/c13-12-9-5-4-8-11(12)10-6-2-1-3-7-10/h1-9H

InChI Key

InChIKey=LAXBNTIAOJWAOP-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as chlorinated biphenyls. These are organic compounds containing at least one chlorine atom attached to either benzene ring of the biphenyl moiety.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Biphenyls and derivatives

Direct Parent

Chlorinated biphenyls

Alternative Parents

Substituents

Chlorinated biphenyl
Halobenzene
Chlorobenzene
Aryl halide
Aryl chloride
Hydrocarbon derivative
Organochloride
Organohalogen compound
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

monochlorobiphenyl (CHEBI:34269 )

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 or Liquid

Appearance

Oily liquids or solids that are colorless to light yellow.

Experimental Properties

Property	Value
Melting Point	34°C
Boiling Point	290–325 °C
Solubility	0.00483 mg/mL at 25°C [CHIOU,CT et al. (1983)]; 0.00145 mg/mL at 25 °C [MABEY,WR et al. (1981)]
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0027 g/L	ALOGPS
logP	4.59	ALOGPS
logP	4.22	ChemAxon
logS	-4.8	ALOGPS
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	0	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	0 Å²	ChemAxon
Rotatable Bond Count	1	ChemAxon
Refractivity	56 m³·mol⁻¹	ChemAxon
Polarizability	19.93 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 GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-000i-0900000000-e6b67081e921b887cadc	2021-09-24	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-000i-0900000000-f04d99edf81b6956b603	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-000i-0900000000-33d3265e5741d7a57134	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-01p9-3900000000-7f7fd716c13cbcf571bd	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-000i-0900000000-498df0ac48be086685ce	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-000i-0900000000-498df0ac48be086685ce	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-000i-0900000000-3f1f614760c1bbc0f714	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-000i-0900000000-11939ca1d475c7aef404	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-000i-0900000000-11939ca1d475c7aef404	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-000i-0900000000-6b5c63913e7fe48093c7	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-000i-0900000000-7e793e1a0ff1d221dc86	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-000i-0900000000-7e793e1a0ff1d221dc86	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0019-5900000000-d2c141929d2d04d4aeb5	2021-10-12	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0f79-4900000000-76d189b490f2f879e15b	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, CDCl₃, experimental)	Not Available	2014-09-20	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100.41 MHz, CDCl₃, experimental)	Not Available	2014-09-23	View Spectrum

Toxicity Profile

Route of Exposure

Oral (9) ; inhalation (9) ; dermal (9)

Mechanism of Toxicity

The mechanism of action varies with the specific PCB. Dioxin-like PCBs bind to the aryl hydrocarbon receptor, which disrupts cell function by altering the transcription of genes, mainly be inducing the expression of hepatic Phase I and Phase II enzymes, especially of the cytochrome P450 family. Most of the toxic effects of PCBs are believed to be results of Ah receptor binding. Other PBCs are believed to interfere with calcium channels and/or change brain dopamine levels. PCBs can also cause endocrine disurption by altering the production of thyroid hormones and binding to estrogen receptors, which can stimulate the growth of certain cancer cells and produce other estrogenic effects, such as reproductive dysfunction. They will bioaccumulate by binding to receptor proteins such as uteroglobin. (1, 2, 4, 5)

Metabolism

PCBs are absorbed via inhalation, oral, and dermal routes of exposure. They are transported in the blood, often bound to albumin. Due to their lipophilic nature they tend to accumulate in lipid-rich tissues, such as the liver, adipose tissue, and skin. Metabolism of PCBs is very slow and varies based on the degree and position of chlorination. PCBs are metabolized by the microsomal monooxygenase system catalyzed by cytochrome P-450 enzymes to polar metabolites that can undergo conjugation with glutathione and glucuronic acid. The major metabolites are hydroxylated products which are excreted in the bile and faeces. The slow metabolism of PCBs means they tend to accumulate in body tissues. (9, 7)

Toxicity Values

LD50: 1010 mg/kg (Oral, Rat) (8) LD50: 880 mg/kg (Intraperitoneal, Mouse) (8)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

1, carcinogenic to humans. (11)

Uses/Sources

PCBs were used as coolants and lubricants in transformers, capacitors, and other electrical devices (such as fluorescent lights and refridgerators) produced before 1977. PCBs may contaminate the air and water near hazardous waste sites. In addition, PCBs bioaccumulate in the environment and may be found in fish, meat, and dairy products. (9)

Minimum Risk Level

Intermediate Oral: 0.03 ug/kg/day (10)

Health Effects

The most common health effects of PCBs are skin conditions such as chloracne and rashes. Chronic PCB exposure has also been shown to cause liver, stomach and kidney, damage, jaundice, edema, anemia, changes in the immune system, behavioral alterations, and impaired reproduction. (9)

Symptoms

Chronic PCB exposure results in symptoms such as abdominal pain, nausea, vomiting, diarrhea, headache, dizziness, depression, nervousness, dermal and ocular lesions, fatigue, irregular menstrual cycles and a lowered immune response. (1)

Treatment

There are no specific treatments for PCB poisoning, since it is not usually recognized until after substantial chronic exposure. Only preventing further exposure and treating the observed symptoms can be done. Acute inhalation can be treated by administering oxygen. (9)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

Not Available

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

BioCyc ID

CTD ID

Stitch ID

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Not Available

References

Synthesis Reference

Not Available

MSDS

Not Available

General References

Aoki Y: Polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans as endocrine disrupters--what we have learned from Yusho disease. Environ Res. 2001 May;86(1):2-11. [11386736 ]
Safe S, Bandiera S, Sawyer T, Robertson L, Safe L, Parkinson A, Thomas PE, Ryan DE, Reik LM, Levin W, et al.: PCBs: structure-function relationships and mechanism of action. Environ Health Perspect. 1985 May;60:47-56. [2992927 ]
Horowitz Y, Greenberg D, Ling G, Lifshitz M: Acrodynia: a case report of two siblings. Arch Dis Child. 2002 Jun;86(6):453. [12023189 ]
Troisi GM, Haraguchi K, Kaydoo DS, Nyman M, Aguilar A, Borrell A, Siebert U, Mason CF: Bioaccumulation of polychlorinated biphenyls (PCBs) and dichlorodiphenylethane (DDE) methyl sulfones in tissues of seal and dolphin morbillivirus epizootic victims. J Toxicol Environ Health A. 2001 Jan 12;62(1):1-8. [11205532 ]
Kester MH, Bulduk S, Tibboel D, Meinl W, Glatt H, Falany CN, Coughtrie MW, Bergman A, Safe SH, Kuiper GG, Schuur AG, Brouwer A, Visser TJ: Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites: a novel pathway explaining the estrogenic activity of PCBs. Endocrinology. 2000 May;141(5):1897-900. [10803601 ]
Gill KD, Gupta V, Sandhir R: Ca2+/calmodulin-mediated neurotransmitter release and neurobehavioural deficits following lead exposure. Cell Biochem Funct. 2003 Dec;21(4):345-53. [14624473 ]
World Health Organization (1993). Environ Health Criteria 140: Polychlorniated Biphenyls and Terphenyls.
Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.
ATSDR - Agency for Toxic Substances and Disease Registry (2000). Toxicological profile for polychlorinated biphenyls. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
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]
International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not 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

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 ]
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

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 ]
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. Estrogen sulfotransferase

General Function:: Sulfotransferase activity
Specific Function:: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of estradiol and estrone. May play a role in the regulation of estrogen receptor activity by metabolizing free estradiol. Maximally sulfates beta-estradiol and estrone at concentrations of 20 nM. Also sulfates dehydroepiandrosterone, pregnenolone, ethinylestradiol, equalenin, diethylstilbesterol and 1-naphthol, at significantly higher concentrations; however, cortisol, testosterone and dopamine are not sulfated.
Gene Name:: SULT1E1
Uniprot ID:: P49888
Molecular Weight:: 35126.185 Da

References

Aoki Y: Polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans as endocrine disrupters--what we have learned from Yusho disease. Environ Res. 2001 May;86(1):2-11. [11386736 ]
Kester MH, Bulduk S, Tibboel D, Meinl W, Glatt H, Falany CN, Coughtrie MW, Bergman A, Safe SH, Kuiper GG, Schuur AG, Brouwer A, Visser TJ: Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites: a novel pathway explaining the estrogenic activity of PCBs. Endocrinology. 2000 May;141(5):1897-900. [10803601 ]

Target Details

4. Aromatic-L-amino-acid decarboxylase

General Function:: Pyridoxal phosphate binding
Specific Function:: Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.
Gene Name:: DDC
Uniprot ID:: P20711
Molecular Weight:: 53925.815 Da

References

ATSDR - Agency for Toxic Substances and Disease Registry (2000). Toxicological profile for polychlorinated biphenyls. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]

Target Details

5. 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

Safe S, Bandiera S, Sawyer T, Robertson L, Safe L, Parkinson A, Thomas PE, Ryan DE, Reik LM, Levin W, et al.: PCBs: structure-function relationships and mechanism of action. Environ Health Perspect. 1985 May;60:47-56. [2992927 ]

Target Details

6. Cytochrome P450 1A2

General Function:: Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:: CYP1A2
Uniprot ID:: P05177
Molecular Weight:: 58293.76 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	230 uM	Not Available	BindingDB 50159252

References

Korhonen LE, Rahnasto M, Mahonen NJ, Wittekindt C, Poso A, Juvonen RO, Raunio H: Predictive three-dimensional quantitative structure-activity relationship of cytochrome P450 1A2 inhibitors. J Med Chem. 2005 Jun 2;48(11):3808-15. [15916432 ]

Target Details

7. Tyrosine 3-monooxygenase

General Function:: Tyrosine 3-monooxygenase activity
Specific Function:: Plays an important role in the physiology of adrenergic neurons.
Gene Name:: TH
Uniprot ID:: P07101
Molecular Weight:: 58599.545 Da

References

ATSDR - Agency for Toxic Substances and Disease Registry (2000). Toxicological profile for polychlorinated biphenyls. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]

Target Details

8. Uteroglobin

General Function:: Polychlorinated biphenyl binding
Specific Function:: Binds phosphatidylcholine, phosphatidylinositol, polychlorinated biphenyls (PCB) and weakly progesterone, potent inhibitor of phospholipase A2.
Gene Name:: SCGB1A1
Uniprot ID:: P11684
Molecular Weight:: 9993.6 Da

References

Troisi GM, Haraguchi K, Kaydoo DS, Nyman M, Aguilar A, Borrell A, Siebert U, Mason CF: Bioaccumulation of polychlorinated biphenyls (PCBs) and dichlorodiphenylethane (DDE) methyl sulfones in tissues of seal and dolphin morbillivirus epizootic victims. J Toxicol Environ Health A. 2001 Jan 12;62(1):1-8. [11205532 ]

2-Chlorobiphenyl (T3D0390)

Structure for T3D0390: 2-Chlorobiphenyl

Targets

References

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Binding/Activity Constants

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