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Record Information
Version2.0
Creation Date2014-09-11 05:18:34 UTC
Update Date2014-12-24 20:26:58 UTC
Accession NumberT3D4836
Identification
Common Name4-Nonylphenol
ClassSmall Molecule
DescriptionEnvironmental pollutant arising from the degradation of nonionic surfactants in sewage Nonoxynol-9, one of the APEs, is used as a surfactant in cleaning and cosmetic products, and as a spermicide in contraceptives. Nonylphenol is an organic compound of the wider family of alkylphenols. It is a product of industrial synthesis formed during the alkylation process of phenols, particularly in the synthesis of polyethoxylate detergents. Because of their man-made origins, nonylphenols are classified as xenobiotics. In nonylphenols, a hydrocarbon chain of nine carbon atoms is attached to the phenol ring in either the ortho (2), meta (3), or para (4) position, with the most common ring isomers being ortho or para (e.g. figure 1 para-nonylphenol). Moreover, the alkyl chains can exist as either linear n-alkyl chains, or complex branched chains. Nonylphenol is commonly obtained as a mixture of isomers, and is thus usually found as a pale yellow liquid at room temperature with a freezing point of -10°C and a boiling point of 295-320°C. However, pure isomers of nonylphenol crystallize readily at room temperatures and for example, para-n-nonylphenol, forms white crystals at room temperature. Nonylphenol, and a related compound tert-octylphenol, were first detected as an air pollutant in New York City and New Jersey, probably due to its evaporation from the Hudson river and other smaller rivers in the region that routinely receive municipal wastewaters. It is possible that the atmosphere is a destructive sink for nonylphenol as it is probably reactive with atmospheric radicals and/or is photoactive.
Compound Type
  • Cosmetic Toxin
  • Food Toxin
  • Household Toxin
  • Industrial/Workplace Toxin
  • Metabolite
  • Organic Compound
  • Pollutant
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
4-N-Nonyl phenol
4-N-Nonylphenol
4-Nonyl-Phenol
4-Tert-nonylphenol
Nonyl-Phenol
Nonylphenol
Nonylphenol (mixed)
P -N -Nonylphenol
P-N-Nonylphenol
p-Nonyl-Phenol
P-Nonylphenol
P-Nonylphenol (endocrine disrupter)
Para nonyl phenol
Para-nonylphenol
Phenol, nonyl derivs.
PPT
Chemical FormulaC15H24O
Average Molecular Mass220.351 g/mol
Monoisotopic Mass220.183 g/mol
CAS Registry Number104-40-5
IUPAC Name4-nonylphenol
Traditional Name4-nonylphenol
SMILESCCCCCCCCCC1=CC=C(O)C=C1
InChI IdentifierInChI=1S/C15H24O/c1-2-3-4-5-6-7-8-9-14-10-12-15(16)13-11-14/h10-13,16H,2-9H2,1H3
InChI KeyInChIKey=IGFHQQFPSIBGKE-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as 1-hydroxy-2-unsubstituted benzenoids. These are phenols that are unsubstituted at the 2-position.
KingdomOrganic compounds
Super ClassBenzenoids
ClassPhenols
Sub Class1-hydroxy-2-unsubstituted benzenoids
Direct Parent1-hydroxy-2-unsubstituted benzenoids
Alternative Parents
Substituents
  • 1-hydroxy-2-unsubstituted benzenoid
  • Monocyclic benzene moiety
  • Organic oxygen compound
  • 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
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point41 - 42.5 °C
Boiling Point180-181°C
Solubility0.007 mg/mL at 25 °C
LogP5.76
Predicted Properties
PropertyValueSource
Water Solubility0.0011 g/LALOGPS
logP6.09ALOGPS
logP5.74ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)10.31ChemAxon
pKa (Strongest Basic)-5.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area20.23 ŲChemAxon
Rotatable Bond Count8ChemAxon
Refractivity69.89 m³·mol⁻¹ChemAxon
Polarizability28.58 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)splash10-000i-2900000000-20e92b9b8f11cb8548c0JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-000i-2900000000-7a162fc7755b07f777e5JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-000i-2900000000-20e92b9b8f11cb8548c0JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-000i-2900000000-7a162fc7755b07f777e5JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4l-9700000000-fe61e00c002a2c662478JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-05i3-9340000000-6ce055b46c7aed006da8JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-014i-0090000000-12014c03fa338ffb5aa7JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 45V, Negativesplash10-014i-0090000000-f719b8dd054b6c059a5aJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0190000000-1088749f8c1369b2a470JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-7940000000-07de75334bf5f62511d9JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-052f-9200000000-ce735aee103f15b85e14JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0090000000-39c2fa3f29590455b87aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-0090000000-16076e327a7f5affad33JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-100c-5930000000-d3a16d7fd9d653998a31JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-9280000000-977825d44a9757c52a0eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a59-9100000000-3adc01f7ad81dc62e6edJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0apl-9200000000-3004aa4985fb6258b4e6JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0090000000-4af4c4ee1c4acef7e18bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-0090000000-4af4c4ee1c4acef7e18bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05mo-7900000000-61a13c97ec4075e97e9bJSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0a4i-0910000000-6dc5d11f43433e2b7f59JSpectraViewer | MoNA
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB38982
PubChem Compound ID1752
ChEMBL IDCHEMBL153062
ChemSpider ID1688
KEGG IDC14550
UniProt IDNot Available
OMIM ID
ChEBI ID34440
BioCyc IDNot Available
CTD IDC041594
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia Link4-Nonylphenol
References
Synthesis ReferenceNot Available
MSDST3D4836.pdf
General References
  1. Hao CJ, Cheng XJ, Xia HF, Ma X: The endocrine disruptor 4-nonylphenol promotes adipocyte differentiation and induces obesity in mice. Cell Physiol Biochem. 2012;30(2):382-94. doi: 10.1159/000339032. Epub 2012 Jul 3. [22739433 ]
  2. Palumbo AJ, Koivunen M, Tjeerdema RS: Optimization and validation of a California halibut environmental estrogen bioassay using a heterologous ELISA. Sci Total Environ. 2009 Jan 1;407(2):953-61. doi: 10.1016/j.scitotenv.2008.09.046. Epub 2008 Nov 11. [19004476 ]
  3. Okai Y, Sato EF, Higashi-Okai K, Inoue M: Potentiating effect of an endocrine disruptor, paranonylphenol, on the generation of reactive oxygen species (ROS) in human venous blood -- association with the activation of signal transduction pathway. J UOEH. 2007 Sep 1;29(3):221-33. [17900002 ]
  4. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.92 uMATG_ERa_TRANSAttagene
AC504.66 uMTox21_ERa_LUC_BG1_AgonistTox21/NCGC
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 ]
  2. Yoon K, Pallaroni L, Stoner M, Gaido K, Safe S: Differential activation of wild-type and variant forms of estrogen receptor alpha by synthetic and natural estrogenic compounds using a promoter containing three estrogen-responsive elements. J Steroid Biochem Mol Biol. 2001 Jul;78(1):25-32. [11530281 ]
  3. Wober J, Weisswange I, Vollmer G: Stimulation of alkaline phosphatase activity in Ishikawa cells induced by various phytoestrogens and synthetic estrogens. J Steroid Biochem Mol Biol. 2002 Dec;83(1-5):227-33. [12650720 ]
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. Gutendorf B, Westendorf J: Comparison of an array of in vitro assays for the assessment of the estrogenic potential of natural and synthetic estrogens, phytoestrogens and xenoestrogens. Toxicology. 2001 Sep 14;166(1-2):79-89. [11518614 ]
  2. Han DH, Denison MS, Tachibana H, Yamada K: Relationship between estrogen receptor-binding and estrogenic activities of environmental estrogens and suppression by flavonoids. Biosci Biotechnol Biochem. 2002 Jul;66(7):1479-87. [12224631 ]
  3. Dang Z: Comparison of relative binding affinities to fish and mammalian estrogen receptors: the regulatory implications. Toxicol Lett. 2010 Feb 15;192(3):298-315. doi: 10.1016/j.toxlet.2009.11.004. Epub 2009 Nov 12. [19913605 ]
  4. Vivacqua A, Recchia AG, Fasanella G, Gabriele S, Carpino A, Rago V, Di Gioia ML, Leggio A, Bonofiglio D, Liguori A, Maggiolini M: The food contaminants bisphenol A and 4-nonylphenol act as agonists for estrogen receptor alpha in MCF7 breast cancer cells. Endocrine. 2003 Dec;22(3):275-84. [14709801 ]
  5. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA: Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology. 1998 Oct;139(10):4252-63. [9751507 ]
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. Dring AM, Anderson LE, Qamar S, Stoner MA: Rational quantitative structure-activity relationship (RQSAR) screen for PXR and CAR isoform-specific nuclear receptor ligands. Chem Biol Interact. 2010 Dec 5;188(3):512-25. doi: 10.1016/j.cbi.2010.09.018. Epub 2010 Oct 20. [20869355 ]
  2. Kretschmer XC, Baldwin WS: CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005 Aug 15;155(3):111-28. [16054614 ]
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. Wang H, Li J, Gao Y, Xu Y, Pan Y, Tsuji I, Sun ZJ, Li XM: Xeno-oestrogens and phyto-oestrogens are alternative ligands for the androgen receptor. Asian J Androl. 2010 Jul;12(4):535-47. doi: 10.1038/aja.2010.14. Epub 2010 May 3. [20436506 ]
General Function:
Steroid hormone binding
Specific Function:
G-protein coupled estrogen receptor that binds to 17-beta-estradiol (E2) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. Stimulates cAMP production, calcium mobilization and tyrosine kinase Src inducing the release of heparin-bound epidermal growth factor (HB-EGF) and subsequent transactivation of the epidermal growth factor receptor (EGFR), activating downstream signaling pathways such as PI3K/Akt and ERK/MAPK. Mediates pleiotropic functions among others in the cardiovascular, endocrine, reproductive, immune and central nervous systems. Has a role in cardioprotection by reducing cardiac hypertrophy and perivascular fibrosis in a RAMP3-dependent manner. Regulates arterial blood pressure by stimulating vasodilation and reducing vascular smooth muscle and microvascular endothelial cell proliferation. Plays a role in blood glucose homeostasis contributing to the insulin secretion response by pancreatic beta cells. Triggers mitochondrial apoptosis during pachytene spermatocyte differentiation. Stimulates uterine epithelial cell proliferation. Enhances uterine contractility in response to oxytocin. Contributes to thymic atrophy by inducing apoptosis. Attenuates TNF-mediated endothelial expression of leukocyte adhesion molecules. Promotes neuritogenesis in developing hippocampal neurons. Plays a role in acute neuroprotection against NMDA-induced excitotoxic neuronal death. Increases firing activity and intracellular calcium oscillations in luteinizing hormone-releasing hormone (LHRH) neurons. Inhibits early osteoblast proliferation at growth plate during skeletal development. Inhibits mature adipocyte differentiation and lipid accumulation. Involved in the recruitment of beta-arrestin 2 ARRB2 at the plasma membrane in epithelial cells. Functions also as a receptor for aldosterone mediating rapid regulation of vascular contractibility through the PI3K/ERK signaling pathway. Involved in cancer progression regulation. Stimulates cancer-associated fibroblast (CAF) proliferation by a rapid genomic response through the EGFR/ERK transduction pathway. Associated with EGFR, may act as a transcription factor activating growth regulatory genes (c-fos, cyclin D1). Promotes integrin alpha-5/beta-1 and fibronectin (FN) matrix assembly in breast cancer cells.
Gene Name:
GPER1
Uniprot ID:
Q99527
Molecular Weight:
42247.12 Da
References
  1. Thomas P, Dong J: Binding and activation of the seven-transmembrane estrogen receptor GPR30 by environmental estrogens: a potential novel mechanism of endocrine disruption. J Steroid Biochem Mol Biol. 2006 Dec;102(1-5):175-9. Epub 2006 Nov 7. [17088055 ]
General Function:
Zinc ion binding
Specific Function:
Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital responsive element module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element.
Gene Name:
NR1I3
Uniprot ID:
Q14994
Molecular Weight:
39942.145 Da
References
  1. Hernandez JP, Huang W, Chapman LM, Chua S, Moore DD, Baldwin WS: The environmental estrogen, nonylphenol, activates the constitutive androstane receptor. Toxicol Sci. 2007 Aug;98(2):416-26. Epub 2007 May 5. [17483497 ]
General Function:
Zinc ion binding
Specific Function:
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
Gene Name:
PGR
Uniprot ID:
P06401
Molecular Weight:
98979.96 Da
References
  1. Scippo ML, Argiris C, Van De Weerdt C, Muller M, Willemsen P, Martial J, Maghuin-Rogister G: Recombinant human estrogen, androgen and progesterone receptors for detection of potential endocrine disruptors. Anal Bioanal Chem. 2004 Feb;378(3):664-9. Epub 2003 Oct 25. [14579009 ]