2,4-Dichlorophenoxyacetic acid (T3D0248)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (9)XML
Targets (9)
Record Information
Version2.0
Creation Date2009-03-06 18:58:22 UTC
Update Date2014-12-24 20:21:24 UTC
Accession NumberT3D0248
Identification
Common Name2,4-Dichlorophenoxyacetic acid
ClassSmall Molecule
Description2,4-Dichlorophenoxyacetic acid (2,4-D) is a common systemic herbicide used in the control of broadleaf weeds. It is the most widely used herbicide in the world, and the third most commonly used in North America. 2,4-D is also an important synthetic auxin, often used in laboratories for plant research and as a supplement in plant cell culture media such as MS medium. (S685). 2,4-D can be formulated as emulsifiable concentrates, granules, soluble concentrate and solids, water-dispersible granules, and wettable powders. 2,4-D is used alone, but is commonly formulated with dicamba, mecoprop, mecoprop-p, MCPA, and clopyralid. 2,4-D was one of the ingredients in Agent Orange, the herbicide widely used during the Vietnam War. Though 2,4-D composed 50% of Agent Orange, the health effects of Agent Orange are related to dioxin contaminants generated during the production of Agent Orange – not 2,4-D itself. On August 8, 2007, the U.S. Environmental Protection Agency issued a ruling that stated that existing data do not support a link between human cancer and 2,4-D exposure.
Compound Type
  • Aromatic Hydrocarbon
  • Ether
  • Household Toxin
  • Industrial/Workplace Toxin
  • Metabolite
  • Organic Compound
  • Organochloride
  • Pesticide
  • Pollutant
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(2, 4-Dichlorophenoxy)acetic acid
(2,4-dichlorophenoxy)-Acetic acid
(2,4-Dichlorophenoxy)acetic acid
(2,4-Dichlorophenyloxy)acetic acid
(2,4-Dichlorphenoxy)acetic acid
(Dichlorophenoxy)acetic acid
2,4-D
2,4-D Mecoprop
2,4-Dichlorophenoxyacetate
2,4-Dichlorophenoxyethanoic acid
Agrotect
Amidox
Aminopielik 50SL
Amoxone
Aqua-Kleen
Atlas D
B-Selektonon
Barrage HF
Brush-rhap
Chipco turf herbicide D
Chipco turf herbicide quot DQuot
Chloroxone
Crop rider
Crotilin
Dacamine
Debroussaillant 600
Decamine
Ded-Weed
Ded-Weed LV-69
Desormone
Dezormon
Diclordon
Dicopur
Dicotox
Dinoxol
DMA-4
Dormone
Emulsamine bk
Emulsamine E-3
Envert 171
Envert dt
Esteron
Esteron 44 weed killer
Esteron 76 BE
Esteron 99
Esteron 99 concentrate
Esteron brush killer
Esterone
Esterone four
Estone
Farmco
Fernesta
Fernimine
Fernoxone
Ferxone
Foredex 75
Formula 40
Hedonal
Herbidal
Huragan
Ipaner
Krotiline
Lawn-keep
Macrondray
Miracle
Monosan
Mota Maskros
Moxone
Netagrone
Netagrone 600
Pennamine
Pennamine D
Phenox
Pielik
Planotox
Plantgard
Rhodia
Salvo
Spontox
Spritz-hormin/2,4-D
Spritz-hormit/2,4-D
Super D weedone
Superormone concentre
Tiller S
Transamine
Tributon
Trinoxol
Uniso
Vergemaster
Verton
Verton 2-D
Verton 2D
Verton D
Vertron 2D
Vidon 638
Visko-rhap
Weed tox
Weed-ag-bar
Weed-B-gon
Weed-Rhap
Weedar
Weedar-64
Weedatul
Weedez wonder bar
Weedone
Weedone LV4
Weedtrol
Chemical FormulaC8H6Cl2O3
Average Molecular Mass221.037 g/mol
Monoisotopic Mass219.969 g/mol
CAS Registry Number94-75-7
IUPAC Name2-(2,4-dichlorophenoxy)acetic acid
Traditional Namerhodia
SMILESOC(=O)COC1=C(Cl)C=C(Cl)C=C1
InChI IdentifierInChI=1S/C8H6Cl2O3/c9-5-1-2-7(6(10)3-5)13-4-8(11)12/h1-3H,4H2,(H,11,12)
InChI KeyInChIKey=OVSKIKFHRZPJSS-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
  • 1,3-dichlorobenzene
  • Phenol ether
  • Alkyl aryl ether
  • Chlorobenzene
  • Halobenzene
  • Aryl chloride
  • Aryl halide
  • Monocarboxylic acid or derivatives
  • Ether
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organochloride
  • Organohalogen compound
  • Organic oxygen compound
  • Carbonyl group
  • Organooxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • 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 Roles
Physical Properties
StateSolid
AppearanceWhite to yellow powder. (12)
Experimental Properties
PropertyValue
Melting Point140.5°C
Boiling Point160 °C (0.4 mm Hg)
Solubility0.677 mg/mL at 25°C
LogP2.81
Predicted Properties
PropertyValueSource
Water Solubility0.55 g/LALOGPS
logP2.82ALOGPS
logP2.5ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)2.81ChemAxon
pKa (Strongest Basic)-4.9ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area46.53 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity48.22 m³·mol⁻¹ChemAxon
Polarizability19.28 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-008c-5930000000-9e18343a9f7af8f4a0e72017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00di-9220000000-a032ac9bac05d35c02632017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0900000000-c5992eb4929bea0caa6f2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0920000000-3876fd4c2b58b792ae172017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0900000000-f62223c14a643777c1062017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0900000000-d29595def934a65b45422017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0900000000-d18ea65f7c9d27efe5a02017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0900000000-12b2f23aca41aae72df52017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03k9-1900000000-a0b74f1e7d9731547b092017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0910000000-43f63558efefe96b63ae2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0900000000-be8426feb3ff30050b902017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0900000000-8d1371b31d25aec0cee02017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0900000000-1256ac189274e190c88c2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0900000000-47d5448d947385bed9c72017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03k9-1900000000-4ec7a7637e246c888d262017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0900000000-c301b58f9c0c131183b22017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-03di-0900000000-6e3b873d7e2075a6278c2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-03k9-1900000000-4ec7a7637e246c888d262021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-03di-0900000000-918b0eab0ce642175a9f2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Negativesplash10-03di-0910000000-929b2d2c324a765328bd2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-03di-0900000000-47d5448d947385bed9c72021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0090000000-65c3456a76900ddcdf952016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0fk9-0090000000-a8795ac49517985dafc32016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0002-3930000000-16586343387743da8ed42016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0190000000-fb5ffe9f68edbfbd545d2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-0390000000-c164f3f3990c2d027cdf2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0fkc-3930000000-173e8bfc603e92ae9c832016-08-03View Spectrum
MSMass Spectrum (Electron Ionization)splash10-03di-2920000000-124d727a3888770108bf2014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, DMSO-d6, experimental)Not Available2014-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 15.09 MHz, DMSO-d6, experimental)Not Available2014-09-23View Spectrum
Toxicity Profile
Route of ExposureOral (13); inhalation (13); dermal (13)
Mechanism of Toxicity2,4-Dichlorophenoxyacetic acid is a strong oxidant and is known to cause lipid peroxidation and the generation of free radicals that can modify lipids and proteins. It is also known to inhibit glutathione S transferase which leads to a depletion of ATP, NADPH and glutathione (5, 6). These actions can cause cell toxicity and apopotosis among metabolically active cells. Some of the endocrine effects of 2,4-D may be mediated by the 2,4-D mediated displacement of sex hormones from the sex hormone binding globulin or the 2,4-D mediated blocking or OAT6 transport proteins that are needed for the transport of functional organic ions and dicarboxylates (including estrone sulfate).
MetabolismMetabolism of 2,4-D is minimal in humans, with nearly all of it excreted unchanged as the parent compound. In particular, 2,4-D is rapidly excreted from the body, primarily in the urine. Much of the compound appears to be eliminated unchanged, although some 2,4-D is eliminated from the body as a conjugate. 2,4-D is metabolized to 2,4-dichlorophenol (2,4-DCP) by cytochrome P450 3A4 (CYP 3A4), the major form of monooxygenase enzyme in the human liver.
Toxicity ValuesLD50: 1400 mg/kg (Dermal, Rabbit) (11) LD50: 469 mg/kg (Oral, Guinea pig) LD50: 639 mg/kg (Oral, Rat) (14) LD50: 138 mg/kg (Oral, Mouse) (14)
Lethal Dose80-800 mg/kg (Oral) (8)
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (15)
Uses/Sources2,4-D is is an agrochemical - a substance that is used in agriculture or horticulture. It is a broadleaf herbicide, which when sprayed or dusted on plants causes its leaves to fall off, and functions as a synthetic auxin. 2,4-D is commonly found in lawn care products; wheat, corn, and other grass family herbicides; forestry products; treatments for roadside weeds; and aquatic weed control products.
Minimum Risk LevelNot Available
Health EffectsAll forms of 2,4-D are considered low in toxicity when absorbed via skin or via inhalation. The acid and salt forms of 2,4-D are highly toxic to eye tissue. Long term chronic exposure to 2,4-D has been linked to non-Hodgkins lymphoma and Parkinson’s disease but these are epidemiological associations only. 2,4-D is also reported to have negative effects on the endocrine system (specifically the thyroid and gonads) and immune system. 2,4-D displaces sex hormones from the protein (sex hormone binding globulin) that normally transports these hormones in the blood. 2,4-D reduces the activity of several proteins important to immune system function. Researchers at NIOSH have demonstrated a decreased production of cells responsible for making antibodies in mice bone marrow, in addition to decreased T-cells, produced in the thymus.
SymptomsSymptoms of acute oral exposure include vomiting, diarrhea, headache, confusion, aggressive or bizarre behavior, hypotension and muscle twitching. Skeletal muscle injury and renal failure may also occur. Prolonged dermal exposure may include skin irritation, whereas prolonged inhalation exposure may lead to coughing and burning sensations in the upper respiratory tract and chest.
TreatmentThe general treatment of acute chlorophenoxy herbicide poisoning consists of decontamination of the gastrointestinal tract, resuscitation and supportive care. For severe, acute oral poisoning by 2,4-D forced alkaline diuresis appears to be most effective (9). Forced alkaline diuresis is often used to increase the excretion of acidic drugs like salicylates and phenobarbitone. For forced alkaline diuresis, a diuretic like furosemide is given intravenously and sodium bicarbonate is added to the infusion fluid to make blood and, in turn, urine alkaline. Potassium replacement becomes of utmost importance during the process because potassium is usually lost in urine. If blood levels of potassium are depleted below normal levels, then hypokalemia occurs, which promotes bicarbonate ion retention and prevents bicarbonate excretion, thus interfering with the alkalinization of the urine.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB41797
PubChem Compound ID1486
ChEMBL IDCHEMBL367623
ChemSpider ID1441
KEGG IDC03664
UniProt IDNot Available
OMIM ID
ChEBI ID28854
BioCyc IDCPD-9009
CTD IDD015084
Stitch ID2,4-Dichlorophenoxyacetic acid
PDB IDCFA
ACToR ID447
Wikipedia Link2,4-dichlorophenoxyacetic_acid
References
Synthesis ReferenceRobert Pokorny New Compounds. Some Chlorophenoxyacetic Acids J. Am. Chem. Soc., 1941, 63 (6), pp 1768–1768
MSDSLink
General References
  1. Aylward LL, Morgan MK, Arbuckle TE, Barr DB, Burns CJ, Alexander BH, Hays SM: Biomonitoring data for 2,4-dichlorophenoxyacetic acid in the United States and Canada: interpretation in a public health risk assessment context using Biomonitoring Equivalents. Environ Health Perspect. 2010 Feb;118(2):177-81. doi: 10.1289/ehp.0900970. [20123603 ]
  2. Amer SM, Aly FA: Genotoxic effect of 2,4-dichlorophenoxy acetic acid and its metabolite 2,4-dichlorophenol in mouse. Mutat Res. 2001 Jul 25;494(1-2):1-12. [11423340 ]
  3. Reuber MD: Carcinogenicity and toxicity of 2,4-dichlorophenoxy-acetic acid. Sci Total Environ. 1983 Dec 1;31(3):203-18. [6362003 ]
  4. Coady KK, Kan HL, Schisler MR, Gollapudi BB, Neal B, Williams A, LeBaron MJ: Evaluation of potential endocrine activity of 2,4-dichlorophenoxyacetic acid using in vitro assays. Toxicol In Vitro. 2014 Aug;28(5):1018-25. doi: 10.1016/j.tiv.2014.04.006. Epub 2014 May 6. [24815817 ]
  5. Vessey DA, Boyer TD: Differential activation and inhibition of different forms of rat liver glutathione S-transferase by the herbicides 2,4-dichlorophenoxyacetate (2,4-D) and 2,4,5-trichlorophenoxyacetate (2,4,5-T). Toxicol Appl Pharmacol. 1984 May;73(3):492-9. [6719464 ]
  6. Singh SV, Awasthi YC: Inhibition of human glutathione S-transferases by 2,4-dichlorophenoxyacetate (2,4-D) and 2,4,5-trichlorophenoxyacetate (2,4,5-T). Toxicol Appl Pharmacol. 1985 Nov;81(2):328-36. [4060158 ]
  7. Schnabolk GW, Youngblood GL, Sweet DH: Transport of estrone sulfate by the novel organic anion transporter Oat6 (Slc22a20). Am J Physiol Renal Physiol. 2006 Aug;291(2):F314-21. Epub 2006 Feb 14. [16478971 ]
  8. Dudley AW Jr, Thapar NT: Fatal human ingestion of 2,4-D, a common herbicide. Arch Pathol. 1972 Sep;94(3):270-5. [5051650 ]
  9. Wells WD, Wright N, Yeoman WB: Clinical features and management of poisoning with 2,4-D and mecoprop. Clin Toxicol. 1981 Mar;18(3):273-6. [7237959 ]
  10. Toxicity of 2,4-Dichlorophenoxyacetic Acid – Molecular Mechanisms. Polish Journal of Environmental Studies;2006, Vol. 15 Issue 3, p365
  11. Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.
  12. Wikipedia. 2,4-Dichlorophenoxyacetic acid. Last Updated 22 June 2009. [Link]
  13. 2,4-Dichlorophenoxyacetic Acid (2,4-D). U.S. EPA, Toxicity and Exposure Assessment for Children’s Health. [Link]
  14. 2,4-D Technical Fact Sheet [Link]
  15. 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 Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

Target Details
1. Glutathione S-transferase P
General Function:
S-nitrosoglutathione binding
Specific Function:
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.
Gene Name:
GSTP1
Uniprot ID:
P09211
Molecular Weight:
23355.625 Da
References
  1. Aylward LL, Morgan MK, Arbuckle TE, Barr DB, Burns CJ, Alexander BH, Hays SM: Biomonitoring data for 2,4-dichlorophenoxyacetic acid in the United States and Canada: interpretation in a public health risk assessment context using Biomonitoring Equivalents. Environ Health Perspect. 2010 Feb;118(2):177-81. doi: 10.1289/ehp.0900970. [20123603 ]
  2. Amer SM, Aly FA: Genotoxic effect of 2,4-dichlorophenoxy acetic acid and its metabolite 2,4-dichlorophenol in mouse. Mutat Res. 2001 Jul 25;494(1-2):1-12. [11423340 ]
  3. Reuber MD: Carcinogenicity and toxicity of 2,4-dichlorophenoxy-acetic acid. Sci Total Environ. 1983 Dec 1;31(3):203-18. [6362003 ]
  4. Coady KK, Kan HL, Schisler MR, Gollapudi BB, Neal B, Williams A, LeBaron MJ: Evaluation of potential endocrine activity of 2,4-dichlorophenoxyacetic acid using in vitro assays. Toxicol In Vitro. 2014 Aug;28(5):1018-25. doi: 10.1016/j.tiv.2014.04.006. Epub 2014 May 6. [24815817 ]
  5. Vessey DA, Boyer TD: Differential activation and inhibition of different forms of rat liver glutathione S-transferase by the herbicides 2,4-dichlorophenoxyacetate (2,4-D) and 2,4,5-trichlorophenoxyacetate (2,4,5-T). Toxicol Appl Pharmacol. 1984 May;73(3):492-9. [6719464 ]
  6. Singh SV, Awasthi YC: Inhibition of human glutathione S-transferases by 2,4-dichlorophenoxyacetate (2,4-D) and 2,4,5-trichlorophenoxyacetate (2,4,5-T). Toxicol Appl Pharmacol. 1985 Nov;81(2):328-36. [4060158 ]
  7. Schnabolk GW, Youngblood GL, Sweet DH: Transport of estrone sulfate by the novel organic anion transporter Oat6 (Slc22a20). Am J Physiol Renal Physiol. 2006 Aug;291(2):F314-21. Epub 2006 Feb 14. [16478971 ]
  8. 2,4-D Technical Fact Sheet [Link]
Target Details
2. Glutathione peroxidase 2
General Function:
Glutathione peroxidase activity
Specific Function:
Could play a major role in protecting mammals from the toxicity of ingested organic hydroperoxides. Tert-butyl hydroperoxide, cumene hydroperoxide and linoleic acid hydroperoxide but not phosphatidycholine hydroperoxide, can act as acceptors.
Gene Name:
GPX2
Uniprot ID:
P18283
Molecular Weight:
21953.835 Da
References
  1. Aylward LL, Morgan MK, Arbuckle TE, Barr DB, Burns CJ, Alexander BH, Hays SM: Biomonitoring data for 2,4-dichlorophenoxyacetic acid in the United States and Canada: interpretation in a public health risk assessment context using Biomonitoring Equivalents. Environ Health Perspect. 2010 Feb;118(2):177-81. doi: 10.1289/ehp.0900970. [20123603 ]
  2. Amer SM, Aly FA: Genotoxic effect of 2,4-dichlorophenoxy acetic acid and its metabolite 2,4-dichlorophenol in mouse. Mutat Res. 2001 Jul 25;494(1-2):1-12. [11423340 ]
  3. Reuber MD: Carcinogenicity and toxicity of 2,4-dichlorophenoxy-acetic acid. Sci Total Environ. 1983 Dec 1;31(3):203-18. [6362003 ]
  4. Coady KK, Kan HL, Schisler MR, Gollapudi BB, Neal B, Williams A, LeBaron MJ: Evaluation of potential endocrine activity of 2,4-dichlorophenoxyacetic acid using in vitro assays. Toxicol In Vitro. 2014 Aug;28(5):1018-25. doi: 10.1016/j.tiv.2014.04.006. Epub 2014 May 6. [24815817 ]
  5. Vessey DA, Boyer TD: Differential activation and inhibition of different forms of rat liver glutathione S-transferase by the herbicides 2,4-dichlorophenoxyacetate (2,4-D) and 2,4,5-trichlorophenoxyacetate (2,4,5-T). Toxicol Appl Pharmacol. 1984 May;73(3):492-9. [6719464 ]
  6. Singh SV, Awasthi YC: Inhibition of human glutathione S-transferases by 2,4-dichlorophenoxyacetate (2,4-D) and 2,4,5-trichlorophenoxyacetate (2,4,5-T). Toxicol Appl Pharmacol. 1985 Nov;81(2):328-36. [4060158 ]
  7. Schnabolk GW, Youngblood GL, Sweet DH: Transport of estrone sulfate by the novel organic anion transporter Oat6 (Slc22a20). Am J Physiol Renal Physiol. 2006 Aug;291(2):F314-21. Epub 2006 Feb 14. [16478971 ]
  8. 2,4-D Technical Fact Sheet [Link]
Target Details
3. Solute carrier family 22 member 20
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Organic anion transporter that mediates the uptake of estrone sulfate. Inhibited by probenecid, propionate, 2-methylbutyrate, 3-methylbutyrate, benzoate, heptanoate and 2-ethylhaxanoate. May act as an odorant transporter (By similarity).
Gene Name:
SLC22A20
Uniprot ID:
A6NK97
Molecular Weight:
60458.14 Da
References
  1. Aylward LL, Morgan MK, Arbuckle TE, Barr DB, Burns CJ, Alexander BH, Hays SM: Biomonitoring data for 2,4-dichlorophenoxyacetic acid in the United States and Canada: interpretation in a public health risk assessment context using Biomonitoring Equivalents. Environ Health Perspect. 2010 Feb;118(2):177-81. doi: 10.1289/ehp.0900970. [20123603 ]
  2. Amer SM, Aly FA: Genotoxic effect of 2,4-dichlorophenoxy acetic acid and its metabolite 2,4-dichlorophenol in mouse. Mutat Res. 2001 Jul 25;494(1-2):1-12. [11423340 ]
  3. Reuber MD: Carcinogenicity and toxicity of 2,4-dichlorophenoxy-acetic acid. Sci Total Environ. 1983 Dec 1;31(3):203-18. [6362003 ]
  4. Coady KK, Kan HL, Schisler MR, Gollapudi BB, Neal B, Williams A, LeBaron MJ: Evaluation of potential endocrine activity of 2,4-dichlorophenoxyacetic acid using in vitro assays. Toxicol In Vitro. 2014 Aug;28(5):1018-25. doi: 10.1016/j.tiv.2014.04.006. Epub 2014 May 6. [24815817 ]
  5. Vessey DA, Boyer TD: Differential activation and inhibition of different forms of rat liver glutathione S-transferase by the herbicides 2,4-dichlorophenoxyacetate (2,4-D) and 2,4,5-trichlorophenoxyacetate (2,4,5-T). Toxicol Appl Pharmacol. 1984 May;73(3):492-9. [6719464 ]
  6. Singh SV, Awasthi YC: Inhibition of human glutathione S-transferases by 2,4-dichlorophenoxyacetate (2,4-D) and 2,4,5-trichlorophenoxyacetate (2,4,5-T). Toxicol Appl Pharmacol. 1985 Nov;81(2):328-36. [4060158 ]
  7. Schnabolk GW, Youngblood GL, Sweet DH: Transport of estrone sulfate by the novel organic anion transporter Oat6 (Slc22a20). Am J Physiol Renal Physiol. 2006 Aug;291(2):F314-21. Epub 2006 Feb 14. [16478971 ]
  8. 2,4-D Technical Fact Sheet [Link]
Target Details
4. Sex hormone-binding globulin
General Function:
Androgen binding
Specific Function:
Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration.
Gene Name:
SHBG
Uniprot ID:
P04278
Molecular Weight:
43778.755 Da
References
  1. Aylward LL, Morgan MK, Arbuckle TE, Barr DB, Burns CJ, Alexander BH, Hays SM: Biomonitoring data for 2,4-dichlorophenoxyacetic acid in the United States and Canada: interpretation in a public health risk assessment context using Biomonitoring Equivalents. Environ Health Perspect. 2010 Feb;118(2):177-81. doi: 10.1289/ehp.0900970. [20123603 ]
  2. Amer SM, Aly FA: Genotoxic effect of 2,4-dichlorophenoxy acetic acid and its metabolite 2,4-dichlorophenol in mouse. Mutat Res. 2001 Jul 25;494(1-2):1-12. [11423340 ]
  3. Reuber MD: Carcinogenicity and toxicity of 2,4-dichlorophenoxy-acetic acid. Sci Total Environ. 1983 Dec 1;31(3):203-18. [6362003 ]
  4. Coady KK, Kan HL, Schisler MR, Gollapudi BB, Neal B, Williams A, LeBaron MJ: Evaluation of potential endocrine activity of 2,4-dichlorophenoxyacetic acid using in vitro assays. Toxicol In Vitro. 2014 Aug;28(5):1018-25. doi: 10.1016/j.tiv.2014.04.006. Epub 2014 May 6. [24815817 ]
  5. Vessey DA, Boyer TD: Differential activation and inhibition of different forms of rat liver glutathione S-transferase by the herbicides 2,4-dichlorophenoxyacetate (2,4-D) and 2,4,5-trichlorophenoxyacetate (2,4,5-T). Toxicol Appl Pharmacol. 1984 May;73(3):492-9. [6719464 ]
  6. Singh SV, Awasthi YC: Inhibition of human glutathione S-transferases by 2,4-dichlorophenoxyacetate (2,4-D) and 2,4,5-trichlorophenoxyacetate (2,4,5-T). Toxicol Appl Pharmacol. 1985 Nov;81(2):328-36. [4060158 ]
  7. Schnabolk GW, Youngblood GL, Sweet DH: Transport of estrone sulfate by the novel organic anion transporter Oat6 (Slc22a20). Am J Physiol Renal Physiol. 2006 Aug;291(2):F314-21. Epub 2006 Feb 14. [16478971 ]
  8. 2,4-D Technical Fact Sheet [Link]
Target Details
5. Fas-binding factor 1
General Function:
Not Available
Specific Function:
Keratin-binding protein required for epithelial cell polarization. Involved in apical junction complex (AJC) assembly via its interaction with PARD3. Required for ciliogenesis.
Gene Name:
FBF1
Uniprot ID:
Q8TES7
Molecular Weight:
125445.19 Da
References
  1. Purcell M, Neault JF, Malonga H, Arakawa H, Carpentier R, Tajmir-Riahi HA: Interactions of atrazine and 2,4-D with human serum albumin studied by gel and capillary electrophoresis, and FTIR spectroscopy. Biochim Biophys Acta. 2001 Jul 9;1548(1):129-38. [11451446 ]
  2. Rosso SB, Gonzalez M, Bagatolli LA, Duffard RO, Fidelio GD: Evidence of a strong interaction of 2,4-dichlorophenoxyacetic acid herbicide with human serum albumin. Life Sci. 1998;63(26):2343-51. [9877224 ]
Target Details
6. Nuclear receptor subfamily 1 group I member 2
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
References
  1. Kojima H, Sata F, Takeuchi S, Sueyoshi T, Nagai T: Comparative study of human and mouse pregnane X receptor agonistic activity in 200 pesticides using in vitro reporter gene assays. Toxicology. 2011 Feb 27;280(3):77-87. doi: 10.1016/j.tox.2010.11.008. Epub 2010 Nov 27. [21115097 ]
Target Details
7. Cytochrome P450 2B6
General Function:
Steroid hydroxylase activity
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. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular Weight:
56277.81 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.25 uMCLZD_CYP2B6_6CellzDirect
AC500.25 uMCLZD_CYP2B6_6CellzDirect
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 ]
Target Details
8. Interleukin-1 alpha
General Function:
Cytokine activity
Specific Function:
Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.
Gene Name:
IL1A
Uniprot ID:
P01583
Molecular Weight:
30606.29 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_BE3C_IL1a_upBioSeek
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 ]
Target Details
9. Urokinase plasminogen activator surface receptor
General Function:
Urokinase plasminogen activator receptor activity
Specific Function:
Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form.
Gene Name:
PLAUR
Uniprot ID:
Q03405
Molecular Weight:
36977.62 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_BE3C_uPAR_upBioSeek
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 ]