Dicyclohexyl phthalate (T3D3643)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (6)XML
Targets (6)
Record Information
Version2.0
Creation Date2009-12-03 20:13:26 UTC
Update Date2014-12-24 20:26:16 UTC
Accession NumberT3D3643
Identification
Common NameDicyclohexyl phthalate
ClassSmall Molecule
DescriptionDicyclohexyl phthalate is a phthalate ester. Phthalate esters are esters of phthalic acid and are mainly used as plasticizers, primarily used to soften polyvinyl chloride. They are found in a number of products, including glues, building materials, personal care products, detergents and surfactants, packaging, children's toys, paints, pharmaceuticals, food products, and textiles. Phthalates are hazardous due to their ability to act as endocrine disruptors. They are being phased out of many products in the United States and European Union due to these health concerns. (5)
Compound Type
  • Aromatic Hydrocarbon
  • Cosmetic Toxin
  • Ester
  • Ether
  • Food Toxin
  • Household Toxin
  • Industrial/Workplace Toxin
  • Organic Compound
  • Phthalate
  • Plasticizer
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
1, 2-Benzenedicarboxylic acid, dicyclohexyl ester
1,2-Benzenedicarboxylic acid, 1,2-dicyclohexyl ester
Diclohexyl 1,2-benzenedicarboxylate
Dicyclohexyl benzene-1,2-dicarboxylate
Dicyclohexyl phthalic acid
Ergoplast FDC
Ergoplast.FDC
Phthalic acid, dicyclohexyl ester
Chemical FormulaC20H26O4
Average Molecular Mass330.418 g/mol
Monoisotopic Mass330.183 g/mol
CAS Registry Number84-61-7
IUPAC Name1,2-dicyclohexyl benzene-1,2-dicarboxylate
Traditional Namedicyclohexyl phthalate
SMILESO=C(OC1CCCCC1)C1=CC=CC=C1C(=O)OC1CCCCC1
InChI IdentifierInChI=1S/C20H26O4/c21-19(23-15-9-3-1-4-10-15)17-13-7-8-14-18(17)20(22)24-16-11-5-2-6-12-16/h7-8,13-16H,1-6,9-12H2
InChI KeyInChIKey=VOWAEIGWURALJQ-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzoic acid esters. These are ester derivatives of benzoic acid.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzoic acids and derivatives
Direct ParentBenzoic acid esters
Alternative Parents
Substituents
  • Benzoate ester
  • Benzoyl
  • Dicarboxylic acid or derivatives
  • Carboxylic acid ester
  • Carboxylic acid derivative
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen 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
AppearanceColorless liquid.
Experimental Properties
PropertyValue
Melting Point66°C
Boiling PointNot Available
Solubility0.004 mg/mL at 24°C
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0011 g/LALOGPS
logP5.01ALOGPS
logP5.58ChemAxon
logS-5.5ALOGPS
pKa (Strongest Basic)-6.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area52.6 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity92.14 m³·mol⁻¹ChemAxon
Polarizability36.74 ųChemAxon
Number of Rings3ChemAxon
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, Positivesplash10-001i-9130000000-bf0948298eaf003c4b852021-09-23View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-0002-0900000000-6292662bbf9b60a81a1f2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-0002-0900000000-2cfad1f4af158b70d42b2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-0002-0900000000-b282160570c579fdfe292021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Positivesplash10-014j-0900000000-485433678a4139d43b452021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-00kb-0900000000-1571f7fd0d316e936cd12021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-00kb-0961000000-c88d62b294acffd6dcb12021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-0002-0900000000-2efae9c6305335252bfa2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-0002-0900000000-1a9c5667074c58fd3aea2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Negativesplash10-000i-0900000000-dc2329b6e9627b0ab41e2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-000i-0900000000-0e9e05d84dece9c4fcf42021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-0592-1900000000-5dde58db5f1d07da79582021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Negativesplash10-004i-0009000000-d6f710e95c96144c92932021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-004r-0908000000-2feeaa694888a4f85bc62021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-059b-1900000000-1bcdee72e6811fa5577a2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-006t-2900000000-7fd656f0fb35208fe09e2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-0002-0900000000-65d03365935b622d1c5a2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-0002-0900000000-7d99b84ee48e55ce76c72021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-0002-0900000000-5b09efcb9bfbcd7037432021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-4049000000-19a242cdddec79ba89d42016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-9252000000-827bb993f2bceb843e282016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0536-9200000000-85eeb6af0b4b3ace20c32016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-2019000000-b1267d2f456e3940f8d82016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004j-6289000000-9268ea958926bcb137a82016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0002-9210000000-911ce1d58439498b52212016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-1295000000-0cb0458e63126d3c03d42021-10-12View Spectrum
MSMass Spectrum (Electron Ionization)splash10-0002-4900000000-a0f78df766b297c292602014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 90 MHz, CDCl3, experimental)Not Available2014-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 15.09 MHz, CDCl3, experimental)Not Available2014-09-23View Spectrum
Toxicity Profile
Route of ExposureOral (5) ; inhalation (5) ; dermal (5)
Mechanism of ToxicityPhthalate esters are endocrine disruptors. They decrease foetal testis testosterone production and reduce the expression of steroidogenic genes by decreasing mRNA expression. Some phthalates have also been shown to reduce the expression of insulin-like peptide 3 (insl3), an important hormone secreted by the Leydig cell necessary for development of the gubernacular ligament. Animal studies have shown that these effects disrupt reproductive development and can cause a number of malformations in affected young. (1)
MetabolismPhthalate esters are first hydrolyzed to their monoester derivative. Once formed, the monoester derivative can be further hydrolyzed in vivo to phthalic acid or conjugated to glucuronide, both of which can then be excreted. The terminal or next-to-last carbon atom in the monoester can also be oxidized to an alcohol, which can be excreted as is or first oxidized to an aldehyde, ketone, or carboxylic acid. The monoester and oxidative metabolites are excreted in the urine and faeces. (2)
Toxicity ValuesLD50: >3200 mg/kg (Oral, Mouse) (3) LD50: 1600 mg/kg (Intraperitoneal, Mouse) (3)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesPhthalate esters are mainly used as plasticizers, primarily used to soften polyvinyl chloride. They are found in a number of products, including glues, building materials, personal care products, detergents and surfactants, packaging, children's toys, paints, pharmaceuticals, food products, and textiles. Phthalates are used in a variety of household applications such as shower curtains, vinyl upholstery, adhesives, floor tiles, food containers and wrappers, and cleaning materials. Personal care items containing phthalates include perfume, eye shadow, moisturizer, nail polish, liquid soap, and hair spray. (5)
Minimum Risk LevelNot Available
Health EffectsPhthalate esters are endocrine disruptors. Animal studies have shown that they disrupt reproductive development and can cause a number of malformations in affected young, such as reduced anogenital distance (AGD), cryptorchidism, hypospadias, and reduced fertility. The combination of effects associated with phthalates is called 'phthalate syndrome’. (1)
SymptomsPhthalate esters are endocrine disruptors and can cause a number of developmental malformations termed 'phthalate syndrome'. (1)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID6777
ChEMBL IDNot Available
ChemSpider ID6519
KEGG IDC14529
UniProt IDNot Available
OMIM ID
ChEBI ID33308
BioCyc IDO-ACETYLCARNITINE
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D3643.pdf
General References
  1. Wilson VS, Blystone CR, Hotchkiss AK, Rider CV, Gray LE Jr: Diverse mechanisms of anti-androgen action: impact on male rat reproductive tract development. Int J Androl. 2008 Apr;31(2):178-87. doi: 10.1111/j.1365-2605.2007.00861.x. [18315717 ]
  2. Wittassek M, Angerer J: Phthalates: metabolism and exposure. Int J Androl. 2008 Apr;31(2):131-8. Epub 2007 Dec 7. [18070048 ]
  3. Quadros EV, Jacobsen DW: The dynamics of cobalamin utilization in L-1210 mouse leukemia cells: a model of cellular cobalamin metabolism. Biochim Biophys Acta. 1995 Jun 9;1244(2-3):395-403. [7599160 ]
  4. European Chemicals Bureau (2000). IUCLID Dataset, Dicyclohexyl Phthalate (84-61-7).
  5. Wikipedia. Phthalate. Last Updated 22 November 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot 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
TypeValueAssay TypeAssay Source
AC503.34 uMATG_ERa_TRANSAttagene
References
  1. Takeuchi S, Iida M, Kobayashi S, Jin K, Matsuda T, Kojima H: Differential effects of phthalate esters on transcriptional activities via human estrogen receptors alpha and beta, and androgen receptor. Toxicology. 2005 Jun 1;210(2-3):223-33. [15840436 ]
  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 ]
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
References
  1. Takeuchi S, Iida M, Kobayashi S, Jin K, Matsuda T, Kojima H: Differential effects of phthalate esters on transcriptional activities via human estrogen receptors alpha and beta, and androgen receptor. Toxicology. 2005 Jun 1;210(2-3):223-33. [15840436 ]
Target Details
3. 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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.24 uMATG_PXR_TRANSAttagene
AC500.90 uMATG_PXRE_CISAttagene
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
4. Vitamin D3 receptor
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Recruited to promoters via its interaction with BAZ1B/WSTF which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.
Gene Name:
VDR
Uniprot ID:
P11473
Molecular Weight:
48288.64 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.68 uMATG_VDRE_CISAttagene
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
5. Translocator protein
General Function:
Cholesterol binding
Specific Function:
Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:24814875), but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides (PubMed:1847678).
Gene Name:
TSPO
Uniprot ID:
P30536
Molecular Weight:
18827.81 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.12 uMNVS_MP_hPBRNovascreen
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
6. Retinoic acid receptor RXR-beta
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Specifically binds 9-cis retinoic acid (9C-RA).
Gene Name:
RXRB
Uniprot ID:
P28702
Molecular Weight:
56921.38 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.81 uMATG_RXRb_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 ]