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Record Information
Version2.0
Creation Date2009-06-15 17:16:04 UTC
Update Date2014-12-24 20:22:54 UTC
Accession NumberT3D0868
Identification
Common Name4-Chlorophenol
ClassSmall Molecule
Description4-Chlorophenol or para-chlorophenol is a monochlorophenol isomer that has a chlorine atom in the para position. It is used as a disinfectant agent (3).
Compound Type
  • Aromatic Hydrocarbon
  • Household Toxin
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
P-Chlorophenol
Parachlorophenol
Chemical FormulaC6H5ClO
Average Molecular Mass128.556 g/mol
Monoisotopic Mass128.003 g/mol
CAS Registry Number106-48-9
IUPAC Name4-chlorophenol
Traditional Namechlorophenol
SMILESOC1=CC=C(Cl)C=C1
InChI IdentifierInChI=1S/C6H5ClO/c7-5-1-3-6(8)4-2-5/h1-4,8H
InChI KeyInChIKey=WXNZTHHGJRFXKQ-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as p-chlorophenols. These are chlorophenols carrying a iodine at the C4 position of the benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassPhenols
Sub ClassHalophenols
Direct ParentP-chlorophenols
Alternative Parents
Substituents
  • 4-chlorophenol
  • 1-hydroxy-2-unsubstituted benzenoid
  • Halobenzene
  • Chlorobenzene
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organochloride
  • Organohalogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic 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
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point42.8°C
Boiling PointNot Available
Solubility24 mg/mL at 25°C [ROBERTS,MS et al. (1977)]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility14 g/LALOGPS
logP2.37ALOGPS
logP2.27ChemAxon
logS-0.96ALOGPS
pKa (Strongest Acidic)8.96ChemAxon
pKa (Strongest Basic)-6.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area20.23 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity32.84 m³·mol⁻¹ChemAxon
Polarizability12.02 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-004i-8900000000-f5b8d40439248259fba62017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-004i-9800000000-3a8b74727039919cacc42017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-004i-5900000000-7c45de518d13780605c42017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-004i-5900000000-4855b919f4b9bab8519f2017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-004i-9800000000-32ffdbba762c4f0fc6092017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-004i-4900000000-34735a026ba083fa0b7f2021-09-24View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, PositiveNot Available2021-11-03View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-11-03View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-004i-0900000000-edd6b8e255429561226b2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-004i-0900000000-edd6b8e255429561226b2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-004i-0900000000-4f6d51ee33067bb474ab2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-004i-0900000000-099706b387a703bff1632017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-004i-1900000000-51fe6ac2fa9bed9bb10a2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-004i-2900000000-a2fb225f178a8a1f43452017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-004i-9600000000-ec3022a622bccb6ec3fb2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-05r0-9400000000-1debf82a3dd9a5d2c1172017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-05r3-9200000000-a2b07eb09c8d6ed52d742017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0690-9100000000-657bec677b116442fc422017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-014l-9000000000-ad1f7056f8d05e4051292017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0gbc-9000000000-c791cec8d419b63d8d592017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-0690-9100000000-657bec677b116442fc422021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-05r3-9200000000-a2b07eb09c8d6ed52d742021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-05r0-9400000000-1debf82a3dd9a5d2c1172021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-0gbc-9000000000-c791cec8d419b63d8d592021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-014l-9000000000-ad1f7056f8d05e4051292021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-004i-0900000000-edd6b8e255429561226b2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Negativesplash10-004i-0900000000-4f6d51ee33067bb474ab2021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0900000000-48f80a2ed99c319f28ee2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-0900000000-a9a4905ea5907e3041292016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-002b-9400000000-bf69c6609bd6a3690b0f2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0900000000-f67531a18d328dd396022016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-0900000000-f67531a18d328dd396022016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9800000000-244eb0ef00d140eea0ab2016-08-03View Spectrum
MSMass Spectrum (Electron Ionization)splash10-004i-9600000000-55d86628a011109663e22014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
Toxicity Profile
Route of ExposureInhalation (3) ; oral (3) ; dermal (3)
Mechanism of Toxicity4-chlorophenol works as a weak uncoupler of oxidative phosphorylation and inhibitors of cellular respiration. The ability of chlorophenols to uncouple oxidative phosphorylation increases with increasing chlorination. In fact, studies indicate a concentration-dependent triphasic effect of chlorophenols on phosphorylation and cellular respiration. At low concentrations, uncoupling produces stimulation of the resting state respiration as a result of increased adenosine triphosphatase (ATPase) activity in the absence of a phosphate acceptor.Inhibition of active respiration is also observed. At moderate concentrations, resting respiration is neither stimulated nor inhibited. Significant inhibition of respiration, associated with a breakdown of the electron transport process and decreased ATPase activity, occurs at very high concentrations. Uncoupling activity has been attributed to a protonophoric effect (a disruption of the energy gradient across the mitochondrial membrane resulting from distribution of chlorophenols in the phospholipid bilayer of the membrane), whereas inhibition of cellular respiration has been attributed to a direct action on intracellular proteins (3).
MetabolismAbsorption of 4-chlorophenol is favored in the stomach and the intestine. Absorption through the gastrointestinal tract is by simple diffusion and is expected to be both rapid and virtually complete. It is proposed that 4-CP is metabolized by P-450 enzymes to intermediates that react with glutathione to form glutathionyl adducts.The metabolism of the 4-chlorophenol is principally via conjugation. The principal metabolite ecreted is the glucuronide. Other metabolites are sulfate conjugates such as the ethereal sulfate. The metabobites are excreted in urine (3).
Toxicity ValuesLD50: 670 mg/kg (Oral, Rat) (4) LC50: 11 mg/m3 (Inhalation, Rat) (4)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity (not listed by IARC). (2)
Uses/SourcesBreathing in contaminated air; drinking contaminated water; dermal and eye exposure (3).
Minimum Risk LevelAcute Oral: 0.01 mg/kg/day (Rat) (3)
Health Effects4-chlorophenol is corrosive to epithelial tissue. It produce effects ranging from slight hyperemia to severe corrosion when applied to the corneas. Acute inhalation exposure may lead to hemorrhage in the lungs and tachypnea. Oral exposure to 2-chlorophenol can produce a variety of neurological effects, including tremors, myoclonic convulsions, a hunched posture, dyspnea, collapse, and coma (3).
SymptomsCough, shortness of breath and sore throat can result from inhalation of 2-chlorophenol. These symptoms may be delayed. Abdominal pain, drowsiness, weakness, and convulsions can result from ingestion as well as inhalation. moreover, ingestion of 2-chlorophenol can cause restlessness, tremors, or central nervous system depression to occur. Eye exposure to 2-chlorophenol can lead to redness, pain, and blurred vision, while dermal contact can lead to redness and pain of the skin. Moreover, the substance can be rapidily absorbed after derma exposure (3).
TreatmentAvoid dilution following oral exposure; instead, administer charcoal as a slurry. Following inhalation, move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. If the exposure occurs through eye contact, irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. Following dermal exposure, remove phenol with undiluted polyethylene glycol 300 to 400 or isopropyl alcohol prior to washing, if readily available. Wash exposed areas twice or for at least 10 minutes with large quantities of soapy water. Water alone may be harmful. (1)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound IDNot Available
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch ID4-Chlorophenol
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D0868.pdf
General References
  1. Rumack BH (2009). POISINDEX(R) Information System. Englewood, CO: Micromedex, Inc. CCIS Volume 141, edition expires Aug, 2009.
  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 (1999). Toxicological profile for chlorophenols. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  4. The Physical and Theoretical Chemistry Laboratory of Oxford University (2005). Material Safety Data Sheet (MSDS) for 4-chlorophenol. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.13 uMNVS_NR_hERNovascreen
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. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
  3. 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.
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.37 uMOT_ER_ERbERb_1440Odyssey Thera
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. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
  3. 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.
General Function:
Voltage-gated sodium channel activity
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. This sodium channel may be present in both denervated and innervated skeletal muscle.
Gene Name:
SCN4A
Uniprot ID:
P35499
Molecular Weight:
208059.175 Da
References
  1. Leuwer M, Haeseler G, Hecker H, Bufler J, Dengler R, Aronson JK: An improved model for the binding of lidocaine and structurally related local anaesthetics to fast-inactivated voltage-operated sodium channels, showing evidence of cooperativity. Br J Pharmacol. 2004 Jan;141(1):47-54. Epub 2003 Dec 8. [14662728 ]