T3DB: 4-Chlorophenol

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (3)XML

Targets (3)

Record Information

Version

2.0

Creation Date

2009-06-15 17:16:04 UTC

Update Date

2014-12-24 20:22:54 UTC

Accession Number

T3D0868

Identification

Common Name

4-Chlorophenol

Class

Small Molecule

Description

4-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

MOL SDF PDB SMILES InChI

Synonyms

Synonym
P-Chlorophenol
Parachlorophenol

Chemical Formula

C₆H₅ClO

Average Molecular Mass

128.556 g/mol

Monoisotopic Mass

128.003 g/mol

CAS Registry Number

106-48-9

IUPAC Name

4-chlorophenol

Traditional Name

chlorophenol

SMILES

OC1=CC=C(Cl)C=C1

InChI Identifier

InChI=1S/C6H5ClO/c7-5-1-3-6(8)4-2-5/h1-4,8H

InChI Key

InChIKey=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.

Kingdom

Super Class

Class

Sub Class

Direct Parent

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 Framework

Aromatic homomonocyclic compounds

External Descriptors

monochlorophenol (CHEBI:28078 )
a chloroaromatic compound (CPD-10870 )

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	42.8°C
Boiling Point	Not Available
Solubility	24 mg/mL at 25°C [ROBERTS,MS et al. (1977)]
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	14 g/L	ALOGPS
logP	2.37	ALOGPS
logP	2.27	ChemAxon
logS	-0.96	ALOGPS
pKa (Strongest Acidic)	8.96	ChemAxon
pKa (Strongest Basic)	-6.3	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	1	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	20.23 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	32.84 m³·mol⁻¹	ChemAxon
Polarizability	12.02 Å³	ChemAxon
Number of Rings	1	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
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-004i-8900000000-f5b8d40439248259fba6	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-004i-9800000000-3a8b74727039919cacc4	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-004i-5900000000-7c45de518d13780605c4	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-004i-5900000000-4855b919f4b9bab8519f	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-004i-9800000000-32ffdbba762c4f0fc609	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-004i-4900000000-34735a026ba083fa0b7f	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 GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	2021-11-03	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	2021-11-03	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-004i-0900000000-edd6b8e255429561226b	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-004i-0900000000-edd6b8e255429561226b	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-004i-0900000000-4f6d51ee33067bb474ab	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-004i-0900000000-099706b387a703bff163	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-004i-1900000000-51fe6ac2fa9bed9bb10a	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-004i-2900000000-a2fb225f178a8a1f4345	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-004i-9600000000-ec3022a622bccb6ec3fb	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-05r0-9400000000-1debf82a3dd9a5d2c117	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-05r3-9200000000-a2b07eb09c8d6ed52d74	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0690-9100000000-657bec677b116442fc42	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-014l-9000000000-ad1f7056f8d05e405129	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0gbc-9000000000-c791cec8d419b63d8d59	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 60V, Positive	splash10-0690-9100000000-657bec677b116442fc42	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 45V, Positive	splash10-05r3-9200000000-a2b07eb09c8d6ed52d74	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-05r0-9400000000-1debf82a3dd9a5d2c117	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 90V, Positive	splash10-0gbc-9000000000-c791cec8d419b63d8d59	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 75V, Positive	splash10-014l-9000000000-ad1f7056f8d05e405129	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Negative	splash10-004i-0900000000-edd6b8e255429561226b	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 45V, Negative	splash10-004i-0900000000-4f6d51ee33067bb474ab	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-004i-0900000000-48f80a2ed99c319f28ee	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-004i-0900000000-a9a4905ea5907e304129	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-002b-9400000000-bf69c6609bd6a3690b0f	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-004i-0900000000-f67531a18d328dd39602	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-004i-0900000000-f67531a18d328dd39602	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-004i-9800000000-244eb0ef00d140eea0ab	2016-08-03	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-004i-9600000000-55d86628a011109663e2	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-10-13	View Spectrum

Toxicity Profile

Route of Exposure

Inhalation (3) ; oral (3) ; dermal (3)

Mechanism of Toxicity

4-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).

Metabolism

Absorption 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 Values

LD50: 670 mg/kg (Oral, Rat) (4) LC50: 11 mg/m3 (Inhalation, Rat) (4)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity (not listed by IARC). (2)

Uses/Sources

Breathing in contaminated air; drinking contaminated water; dermal and eye exposure (3).

Minimum Risk Level

Acute Oral: 0.01 mg/kg/day (Rat) (3)

Health Effects

4-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).

Symptoms

Cough, 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).

Treatment

Avoid 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

External Links

DrugBank ID

Not Available

HMDB ID

Not Available

PubChem Compound ID

Not Available

ChEMBL ID

Not Available

ChemSpider ID

Not Available

KEGG ID

Not Available

UniProt ID

Not Available

OMIM ID

ChEBI ID

Not Available

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

4-Chlorophenol

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Not Available

References

Synthesis Reference

Not Available

MSDS

T3D0868.pdf

General References

Rumack BH (2009). POISINDEX(R) Information System. Englewood, CO: Micromedex, Inc. CCIS Volume 141, edition expires Aug, 2009.
International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
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]
The Physical and Theoretical Chemistry Laboratory of Oxford University (2005). Material Safety Data Sheet (MSDS) for 4-chlorophenol. [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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	0.13 uM	NVS_NR_hER	Novascreen

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 ]
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 ]
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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	4.37 uM	OT_ER_ERbERb_1440	Odyssey Thera

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 ]
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 ]
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. Sodium channel protein type 4 subunit alpha

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

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 ]

4-Chlorophenol (T3D0868)

Structure for T3D0868: 4-Chlorophenol

Targets

Binding/Activity Constants

References

Binding/Activity Constants

References

References