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Record Information
Version2.0
Creation Date2009-03-06 18:58:19 UTC
Update Date2014-12-24 20:21:21 UTC
Accession NumberT3D0222
Identification
Common Name2,4,5-Trichlorophenol
ClassSmall Molecule
Description2,4,5-Trichlorophenol is a chlorinated phenol that has been used as a fungicide, herbicide, insecticide, antiseptic, defoliant, and glue preservative. The chemical 2,4,5-trichlorophenol serves as a raw material for making the herbicides Silvex and 2,4,5-T (2,4,5-trichlorophenoxyacetic acid) (4).
Compound Type
  • Aromatic Hydrocarbon
  • Organic Compound
  • Organochloride
  • Pesticide
  • Pollutant
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
2,4, 5-Trichlorophenol
2,4,5-TCP
Collunosol
Dowcide 2
Dowicide 2
Dowicide b
Nurelle
Preventol I
TCP
Chemical FormulaC6H3Cl3O
Average Molecular Mass197.446 g/mol
Monoisotopic Mass195.925 g/mol
CAS Registry Number95-95-4
IUPAC Name2,4,5-trichlorophenol
Traditional Name2,4,5-trichlorophenol
SMILESOC1=CC(Cl)=C(Cl)C=C1Cl
InChI IdentifierInChI=1S/C6H3Cl3O/c7-3-1-5(9)6(10)2-4(3)8/h1-2,10H
InChI KeyInChIKey=LHJGJYXLEPZJPM-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
  • 2-chlorophenol
  • 3-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 Point69°C
Boiling PointNot Available
Solubility1.2 mg/mL at 25 °C [LEUENBERGER,C et al. (1985A)]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.48 g/LALOGPS
logP3.79ALOGPS
logP3.48ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)6.83ChemAxon
pKa (Strongest Basic)-7.4ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area20.23 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity42.45 m³·mol⁻¹ChemAxon
Polarizability16.35 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0002-7900000000-1ad962df00ced72b9a73JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0002-0900000000-cc8322e7ceec03d71239JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0006-0900000000-17866a9095a4c68b6221JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0900000000-2d745e697dd9c1195f70JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-0900000000-7b0e92ef3db54655fdd7JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0002-0900000000-8df6991815fdfda9c82cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0900000000-7d20943e8109cbd9b2c7JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-0900000000-7d20943e8109cbd9b2c7JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-0900000000-61a3b9d68e72f45b8d35JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0002-5900000000-956600ea67d104e5c8f6JSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureOral (4) ; inhalation (4) ; dermal (4) ; eye (4)
Mechanism of Toxicity2,4,5-Trichlorophenol is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.
Metabolism2,4,5-TCP can be metabolized to 3,4,6-trichlorocatechol, 2,5-dichlorohydroquinone, and a dihydroxydichlorobenzene. Metabolites can also be dimerized to a dihydroxyhexachlorobiphenyl, a dihydroxypentachlorodiphenyl ether, two hydroxypentachlorodiphenyl ethers, a hydoxyhexachlorodiphenyl ether, and a hydroxyhexachlorodioxin or hydroxyhexachlorodiphenoquinone. The metabolites are excreted in urine (4).
Toxicity ValuesLD50: 820 mg/kg (Oral, Rat) (5)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (3)
Uses/SourcesExposure may occur from drinking water that has been disinfected with chlorine and breathing air contaminated by 2,4,5-trichlorophenol. Dermal and eye contact with the toxin are also sources of exposure (4).
Minimum Risk LevelIntermediate Oral: 0.003 mg/kg/day (1)
Health EffectsAcute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.
SymptomsInhalation of 2,4,5-trichlorophenol may cause coughing and sore throat. Eye or skin contact causes redness and pain at the site of contact. Convulsions, diarrhoea, dizziness, headache, shortness of breath, vomiting, weakness, and ataxia may occur after ingestion (4).
TreatmentIf the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID7271
ChEMBL IDCHEMBL109095
ChemSpider ID7001
KEGG IDC07101
UniProt IDNot Available
OMIM ID
ChEBI ID28520
BioCyc IDCPD-10489
CTD IDC009534
Stitch ID2,4,5-Trichlorophenol
PDB IDNot Available
ACToR ID6559
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D0222.pdf
General References
  1. Nichkova M, Galve R, Marco MP: Biological monitoring of 2,4,5-trichlorophenol (I): preparation of antibodies and development of an immunoassay using theoretical models. Chem Res Toxicol. 2002 Nov;15(11):1360-70. [12437326 ]
  2. Rumack BH (2009). POISINDEX(R) Information System. Englewood, CO: Micromedex, Inc. CCIS Volume 141, edition expires Aug, 2009.
  3. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  4. 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]
  5. The Physical and Theoretical Chemistry Laboratory of Oxford University (2005). Material Safety Data Sheet (MSDS) for 2,4,5-trichlorophenol. [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
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. 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
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. 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:
Serine hydrolase activity
Specific Function:
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name:
ACHE
Uniprot ID:
P22303
Molecular Weight:
67795.525 Da
References
  1. Matsumura H, Matsuoka M, Igisu H, Ikeda M: Cooperative inhibition of acetylcholinesterase activities by hexachlorophene in human erythrocytes. Arch Toxicol. 1997;71(3):151-6. [9049051 ]
General Function:
Leukotriene-b4 20-monooxygenase activity
Specific Function:
Catalyzes leukotriene B4 omega-hydroxylation and arachidonic acid omega-hydroxylation but with an activity much lower than that of CYP4F2. Catalyzes the hydroxylation of the antihistamine ebastine.
Gene Name:
CYP4F12
Uniprot ID:
Q9HCS2
Molecular Weight:
60269.165 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.56 uMNVS_ADME_hCYP4F12Novascreen
References
  1. 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 ]
General Function:
Zinc ion binding
Specific Function:
Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine.
Gene Name:
HNF4A
Uniprot ID:
P41235
Molecular Weight:
52784.205 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.85 uMATG_HNF4a_TRANSAttagene
References
  1. 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 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC509.39 uMATG_PXR_TRANSAttagene
References
  1. 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 ]