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Record Information
Version2.0
Creation Date2009-06-02 22:20:30 UTC
Update Date2014-12-24 20:22:50 UTC
Accession NumberT3D0803
Identification
Common Name2,4,5-Trichlorophenoxyacetic acid
ClassSmall Molecule
Description2,4,5-Trichlorophenoxyacetic acid (also known as 2,4,5-T), a synthetic auxin, is a chlorophenoxy acetic acid herbicide used to defoliate broad-leafed plants. It was developed in the late 1940s and was widely used in the agricultural industry until being phased out, starting in the late 1970s due to toxicity concerns. Human health effects from 2,4,5-T at low environmental doses or at biomonitored levels from low environmental exposures are unknown. Intentional overdoses and unintentional high dose occupational exposures to chlorophenoxy acid herbicides have resulted in weakness, headache, dizziness, nausea, abdominal pain, myotonia, hypotension, renal and hepatic injury, and delayed neuropathy. IARC considers the chlorophenoxyacetic acids group of chemicals as possibly carcinogenic to humans.
Compound Type
  • Aromatic Hydrocarbon
  • Ether
  • Industrial/Workplace Toxin
  • Organic Compound
  • Organochloride
  • Pesticide
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(2,4, 5-Trichlorophenoxy)acetic acid
(2,4,5-Trichlor-phenoxy)-essigsaeure
(2,4,5-Trichlorophenoxy)acetic acid
(2,4,5-Trichlorphenoxy)essigsaeure
2,4,5-(Trichlorophenoxy)acetic acid
2,4,5-T
2,4,5-T acid
2,4,5-Trichlorophenoxyacetate
2,4,5-Trichlorphenoxyessigsaeure
4,5-Trichlorophenoxyacetic acid
93-76-5 (FREE ACID)
Acide 2,4,5-trichloro phenoxyacetique
Acido (2,4,5-tricloro-fenossi)-acetico
Arbokan
BCF-bushkiller
Brush killer
Brush rhap
Brush tox
Brush-off 445 low volatile brush killer
Brushtox
Caswell No. 881
Crossbow
Debroussaillant concentre
Debroussaillant super concentre
Decamine 4T
Ded-weed
Ded-weed brush killer
Ded-weed lv-6 brush kil and t-5 brush kil
Dinoxol
Envert-t
Estercide t-2 and t-245
Esteron
Esteron 245
Esteron 245 be
Esteron brush killer
Farmco fence rider
Fence rider
Forron
Forst U 46
Fortex
Fruitone a
Inverton 245
Line rider
Lo-vol
Phortox
RCRA waste no. U232
Reddon
Reddox
Spontox
Super d weedone
T-nox
Tippon
Tippontormona
Tormona
Transamine
Tributon
Trinoxol
Trioxon
Trioxone
VEON
Verton 2-T
Verton 2T
Visko rhap
Visko rhap low volatile ester
Weedar
Weedone
Weedone 2,4,5-T
Chemical FormulaC8H5Cl3O3
Average Molecular Mass255.483 g/mol
Monoisotopic Mass253.930 g/mol
CAS Registry Number93-76-5
IUPAC Name2-(2,4,5-trichlorophenoxy)acetic acid
Traditional Namefortex
SMILESOC(=O)COC1=CC(Cl)=C(Cl)C=C1Cl
InChI IdentifierInChI=1S/C8H5Cl3O3/c9-4-1-6(11)7(2-5(4)10)14-3-8(12)13/h1-2H,3H2,(H,12,13)
InChI KeyInChIKey=SMYMJHWAQXWPDB-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as chlorophenoxyacetates. Chlorophenoxyacetates are compounds containing a phenoxyacetate that carries one or more chlorine atoms on the benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenoxyacetic acid derivatives
Direct ParentChlorophenoxyacetates
Alternative Parents
Substituents
  • Chlorophenoxyacetate
  • Phenoxy compound
  • Phenol ether
  • Alkyl aryl ether
  • Chlorobenzene
  • Halobenzene
  • Aryl chloride
  • Aryl halide
  • Carboxylic acid derivative
  • Carboxylic acid
  • Ether
  • Monocarboxylic acid or derivatives
  • Organooxygen compound
  • Organic oxygen compound
  • Carbonyl group
  • Organic oxide
  • Organochloride
  • Hydrocarbon derivative
  • 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
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point153°C
Boiling PointNot Available
Solubility0.278 mg/mL at 25°C [HARTLEY,D & KIDD,H (1983)]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.073 g/LALOGPS
logP3.44ALOGPS
logP3.11ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)2.56ChemAxon
pKa (Strongest Basic)-5ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area46.53 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity53.02 m³·mol⁻¹ChemAxon
Polarizability21.51 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0090000000-022bb350e5597754eaddJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udr-0090000000-fab7dcfce398fcd73aeaJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-4980000000-e3bbb539bae44c823682JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0090000000-ea3c32f50b94ea7ce51eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-0090000000-497e12d49508588a6bbeJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a7i-0390000000-321b1df17ed37a468342JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0002-2940000000-9383d1cf77861ad29badJSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityCDDs cause their toxic effects by binding to the aryl hydrocarbon receptor and subsequently altering the trascription of certain genes. The affinity for the Ah receptor depends on the structure of the specific CDD. The change in gene expression may result from the direct interaction of the Ah receptor and its heterodimer-forming partner, the aryl hydrocarbon receptor nuclear translocator, with gene regulatory elements or the initiation of a phosphorylation/dephosphorylation cascade that subsequently activates other transcription factors. The affected genes include several oncogenes, growth factors, receptors, hormones, and drug-metabolizing enzymes. The change in transcription/translation of these genes is believed to be the cause of most of the toxic effects of CDDs. This includes 2,3,7,8-tetrachlorodibenzo-p-dioxin's carcinogenicity is thought to be the result of its ability to alter the capacity of both exogenous and endogenous substances to damage the DNA by inducing CYP1A1- and CYP1A2-dependent drug-metabolizing enzymes. (1)
MetabolismCDDs are absorbed through oral, inhalation, and dermal routes of exposure. CDDs are carried in the plasma by serum lipids and lipoproteins, distributing mainly to the liver and adipose tissue. CDDs are very slowly metabolized by the microsomal monooxygenase system to polar metabolites that can undergo conjugation with glucuronic acid and glutathione. They may increase the rate of their own metabolism by inducing CDDs induce both phase I and phase II enzymes. The major routes of excretion of CDDs are the bile and the feces, though smaller amounts are excreted in the urine and via lactation. (1)
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (4)
Uses/SourcesDioxins occur as by-products from the manufacture of organochlorides, the bleaching of paper, chlorination by waste and drinking water treatment plants, municipal solid waste and industrial incinerators, and natural sources such as volcanoes and forest fires. (1, 2)
Minimum Risk LevelNot Available
Health EffectsExposure to large amounts of CDDs causes chloracne, a severe skin disease with acne-like lesions that occur mainly on the face and upper body. CDDs may also cause liver damage and induce long-term alterations in glucose metabolism and subtle changes in hormonal levels. In addition, studies have shown that CDDs may disrupt the endocrine system and weaken the immune system, as well as cause reproductive damage and birth defects, central and peripheral nervous system pathology, thyroid disorders, endometriosis, and diabetes. 2,3,7,8-Tetrachlorodibenzo-p-dioxin is also a known human carcinogen. (1, 2)
SymptomsIn addition to chloracne, CDD exposure causes skin rashes, discoloration, and excessive body hair. (1)
TreatmentTreatment may include washing any areas of contact, GI decontamination if swallowed, administering an IV and forced alkaline diuresis. (3)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID1480
ChEMBL IDCHEMBL194458
ChemSpider ID1435
KEGG IDC07100
UniProt IDNot Available
OMIM ID
ChEBI ID27903
BioCyc IDCPD-121
CTD IDD015085
Stitch ID2,4,5-Trichlorophenoxyacetic acid
PDB IDNot Available
ACToR ID1419
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D0803.pdf
General References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (1998). Toxicological profile for chlorinated dibenzo-p-dioxins (CDDs). U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  2. Wikipedia. Polychlorinated dibenzodioxins. Last Updated 19 May 2009. [Link]
  3. US Environmental Protection Agency (2009). Recognition and Management of Pesticide Poisonings. [Link]
  4. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
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. Lemaire G, Mnif W, Mauvais P, Balaguer P, Rahmani R: Activation of alpha- and beta-estrogen receptors by persistent pesticides in reporter cell lines. Life Sci. 2006 Aug 15;79(12):1160-9. Epub 2006 Mar 27. [16626760 ]
  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
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:
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
  1. ATSDR - Agency for Toxic Substances and Disease Registry (1998). Toxicological profile for chlorinated dibenzo-p-dioxins (CDDs). U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]