4-Nonylphenol
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Basic Info
| Common Name | 4-Nonylphenol(F05538) |
| 2D Structure | |
| Description | Environmental 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. |
| FRCD ID | F05538 |
| CAS Number | 104-40-5 |
| PubChem CID | 1752 |
| Formula | C15H24O |
| IUPAC Name | 4-nonylphenol |
| InChI Key | IGFHQQFPSIBGKE-UHFFFAOYSA-N |
| InChI | InChI=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 |
| Canonical SMILES | CCCCCCCCCC1=CC=C(C=C1)O |
| Isomeric SMILES | CCCCCCCCCC1=CC=C(C=C1)O |
| Wikipedia | 4-Nonylphenol |
| Synonyms |
p-Nonylphenol
4-nonylphenol
4-n-Nonylphenol
104-40-5
Phenol, 4-nonyl-
para-Nonylphenol
p-n-Nonylphenol
Phenol, nonyl-
Phenol, p-nonyl-
Nonylphenol (mixed)
|
| Classifies |
Pollutant
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Benzenoids |
| Class | Phenols |
| Subclass | 1-hydroxy-2-unsubstituted benzenoids |
| Intermediate Tree Nodes | Not available |
| Direct Parent | 1-hydroxy-2-unsubstituted benzenoids |
| Alternative Parents | |
| Molecular Framework | Aromatic homomonocyclic compounds |
| Substituents | 1-hydroxy-2-unsubstituted benzenoid - Monocyclic benzene moiety - Organic oxygen compound - Hydrocarbon derivative - Organooxygen compound - Aromatic homomonocyclic compound |
| Description | This compound belongs to the class of organic compounds known as 1-hydroxy-2-unsubstituted benzenoids. These are phenols that a unsubstituted at the 2-position. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 220.356 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 1 |
| Rotatable Bond Count | 8 |
| Complexity | 148 |
| Monoisotopic Mass | 220.183 |
| Exact Mass | 220.183 |
| XLogP | 5.9 |
| Formal Charge | 0 |
| Heavy Atom Count | 16 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9160 |
| Human Intestinal Absorption | HIA+ | 0.9974 |
| Caco-2 Permeability | Caco2+ | 0.8689 |
| P-glycoprotein Substrate | Non-substrate | 0.5544 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9560 |
| Non-inhibitor | 0.9000 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8177 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.6118 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7566 |
| CYP450 2D6 Substrate | Non-substrate | 0.8040 |
| CYP450 3A4 Substrate | Non-substrate | 0.6319 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.6205 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.8374 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.8981 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.7490 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8309 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.6925 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.5413 |
| Non-inhibitor | 0.7265 | |
| AMES Toxicity | Non AMES toxic | 0.9637 |
| Carcinogens | Non-carcinogens | 0.7809 |
| Fish Toxicity | High FHMT | 0.9787 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9911 |
| Honey Bee Toxicity | High HBT | 0.7439 |
| Biodegradation | Not ready biodegradable | 0.6972 |
| Acute Oral Toxicity | III | 0.9253 |
| Carcinogenicity (Three-class) | Non-required | 0.6492 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -2.8706 | LogS |
| Caco-2 Permeability | 1.4674 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.1654 | LD50, mol/kg |
| Fish Toxicity | -0.7285 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 2.3448 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Dietary intake of 4-nonylphenol and bisphenol A in Taiwanese population: Integrated risk assessment based on probabilistic and sensitive approach. | Environ Pollut | 2018 Oct 10 | 30326386 |
| Adverse stimulation of 4-nonylphenol in abnormal reproductive organs of femalechickens. | Oncotarget | 2017 Oct 16 | 29299127 |
| Determination of the priority substances regulated by 2000/60/EC and 2008/105/EC Directives in the surface waters supplying water treatment plants of Athens, Greece. | J Environ Sci Health A Tox Hazard Subst Environ Eng | 2017 Mar 21 | 27973987 |
| Green synthesis of CuO nanoparticles loaded on the seashell surface using Rumexcrispus seeds extract and its catalytic applications for reduction of dyes. | IET Nanobiotechnol | 2017 Jun | 28530181 |
| Dispersive liquid-liquid microextraction of phenolic compounds from vegetableoils using a magnetic ionic liquid. | J Sep Sci | 2017 Aug | 28581630 |
| Magnetic solid phase extraction with CoFe2O4/oleic acid nanoparticles coupled to gas chromatography-mass spectrometry for the determination of alkylphenols inbaby foods. | Food Chem | 2017 Apr 15 | 27979269 |
| Antioxidant and catalytic applications of silver nanoparticles using Dimocarpuslongan seed extract as a reducing and stabilizing agent. | J Photochem Photobiol B | 2016 Nov | 27723492 |
| 4-Nonylphenol reduces cell viability and induces apoptosis and ER-stress in a human epithelial intestinal cell line. | Toxicol In Vitro | 2015 Oct | 25998160 |
| An electrochemical DNA-sensor developed with the use of methylene blue as a redoxindicator for the detection of DNA damage induced by endocrine-disruptingcompounds. | Anal Chim Acta | 2015 Mar 31 | 25813025 |
| Migration of plasticisers from Tritan™ and polycarbonate bottles andtoxicological evaluation. | Food Chem | 2013 Nov 1 | 23768370 |
| Binding of the endocrine disruptors 4-tert-octylphenol and 4-nonylphenol to human serum albumin. | J Hazard Mater | 2013 Mar 15 | 23416871 |
| Analysis of bisphenol A, nonylphenol, and natural estrogens in vegetables andfruits using gas chromatography-tandem mass spectrometry. | J Agric Food Chem | 2013 Jan 9 | 23215552 |
| Determination of nonylphenol ethoxylate metabolites in vegetables and crops byhigh performance liquid chromatography-tandem mass spectrometry. | Food Chem | 2012 May 1 | 26434323 |
| Alkylphenols--potential modulators of the allergic response. | Kaohsiung J Med Sci | 2012 Jul | 22871601 |
| Occurrence of nonylphenol and nonylphenol monoethoxylate in soil and vegetablesfrom vegetable farms in the Pearl River Delta, South China. | Arch Environ Contam Toxicol | 2012 Jul | 22203462 |
| Migration of plasticizers phthalates, bisphenol A and alkylphenols from plasticcontainers and evaluation of risk. | Food Addit Contam Part A Chem Anal Control Expo Risk Assess | 2011May | 21400322 |
| Effects of 4-nonylphenol on proliferation of AGS gastric cells. | Cell Prolif | 2011 Oct | 21951290 |
| Analysis of phenolic xenoestrogens by pressurized CEC with amperometricdetection. | Electrophoresis | 2010 Mar | 20155739 |
| Scents and scents-ability: pollution disrupts chemical social recognition andshoaling in fish. | Proc Biol Sci | 2008 Jan 7 | 17956844 |
| Mixture effects of estrogenic compounds on proliferation and pS2 expression ofMCF-7 human breast cancer cells. | Food Chem Toxicol | 2007 Nov | 17651883 |
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
- 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 ]
- 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
- 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 ]
- 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
- 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
- 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:
- 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
- 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
- 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 ]
- 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
- 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 ]