T3DB: 4-tert-Butylphenol

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (3)XML

Targets (3)

Record Information

Version

2.0

Creation Date

2014-09-11 05:20:39 UTC

Update Date

2014-12-24 20:26:58 UTC

Accession Number

T3D4881

Identification

Common Name

4-tert-Butylphenol

Class

Small Molecule

Description

4-tert-Butylphenol is found in herbs and spices. 4-tert-Butylphenol is found in oregano. 4-tert-Butylphenol is a flavour ingredient. 4-tert-Butylphenol belongs to the family of Cumenes. These are aromatic compounds containing a prop-2-ylbenzene moiety.

Compound Type

Food Toxin
Household Toxin
Metabolite
Natural Compound
Organic Compound
Plant Toxin

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
1-Hydroxy-4-tert-butylbenzene
2-(4-Hydroxyphenyl)-2-methylpropane
4-(1, 1-Dimethylethyl)phenol
4-(1,1-Dimethylethyl)-Phenol
4-(1,1-Dimethylethyl)phenol
4-(1,1-Dimethylethyl)phenol, 9CI
4-t-Butylphenol
4-Tert-butyl-Phenol
4-Tert-butylphenol
4-Tertiary-butylphenol
Butylphen
FEMA 3918
Lowinox 070
Lowinox PTBT
Lowinox TBMX
p-(Tert-butyl)-Phenol
P-Sec-butylphenol
P-t-Butyl phenol
P-t-Butylphenol
P-Terc.butylfenol
p-Tert-butyl-Phenol
P-Tert-butylphenol
Para-tertiary-butylphenol
PTBP
T-Butylphenol
Ucar butylphenol 4-T
Ucar butylphenol 4-T flake

Chemical Formula

C₁₀H₁₄O

Average Molecular Mass

150.218 g/mol

Monoisotopic Mass

150.104 g/mol

CAS Registry Number

98-54-4

IUPAC Name

4-tert-butylphenol

Traditional Name

4-tert-butylphenol

SMILES

CC(C)(C)C1=CC=C(O)C=C1

InChI Identifier

InChI=1S/C10H14O/c1-10(2,3)8-4-6-9(11)7-5-8/h4-7,11H,1-3H3

InChI Key

InChIKey=QHPQWRBYOIRBIT-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as phenylpropanes. These are organic compounds containing a phenylpropane moiety.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Phenylpropanes

Direct Parent

Phenylpropanes

Alternative Parents

Substituents

Phenylpropane
1-hydroxy-2-unsubstituted benzenoid
Phenol
Organic oxygen compound
Hydrocarbon derivative
Organooxygen compound
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

phenols (CHEBI:34444 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	99 °C
Boiling Point	Not Available
Solubility	0.58 mg/mL at 25 °C
LogP	3.31

Predicted Properties

Property	Value	Source
Water Solubility	0.65 g/L	ALOGPS
logP	3.47	ALOGPS
logP	3.21	ChemAxon
logS	-2.4	ALOGPS
pKa (Strongest Acidic)	10.24	ChemAxon
pKa (Strongest Basic)	-5.4	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	1	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	20.23 Å²	ChemAxon
Rotatable Bond Count	1	ChemAxon
Refractivity	46.7 m³·mol⁻¹	ChemAxon
Polarizability	17.64 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-000i-8900000000-fcc9d5515e40bf2ce9bf	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-000i-2900000000-4db3c9778d301443456d	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - CI-B (Non-derivatized)	splash10-0002-0910000000-5f1bfd35cf8deb78b98c	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-000i-8900000000-fcc9d5515e40bf2ce9bf	2018-05-18	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-000i-2900000000-4db3c9778d301443456d	2018-05-18	View Spectrum
GC-MS	GC-MS Spectrum - CI-B (Non-derivatized)	splash10-0002-0910000000-5f1bfd35cf8deb78b98c	2018-05-18	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0f7c-6900000000-e6bc03dc9e08a393382a	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-0ab9-7950000000-9a3eb623432cc113e7c1	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 5V, negative	splash10-0002-0900000000-1b438e2954f692bde21c	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 6V, negative	splash10-0002-0900000000-4869d097cbf53b54eac7	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 7V, negative	splash10-0002-0900000000-eb91984e2eee362605ea	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 8V, negative	splash10-001j-0900000000-6f41817f2d53326891f5	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 9V, negative	splash10-001i-0900000000-743d3c04ea258d8d65f4	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 11V, negative	splash10-001i-0900000000-5b6aa25385985d180564	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 12V, negative	splash10-001i-1900000000-fd9628d81ef8f4e18133	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 14V, negative	splash10-001i-2900000000-ccd8003868f8bdeccc5c	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - n/a 10V, negative	splash10-001i-0900000000-d8230f5f259df6fea000	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 7V, negative	splash10-001i-1900000000-cfab9ce208c524adf321	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 8V, negative	splash10-00lu-2900000000-b607a227fde521d76913	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 9V, negative	splash10-014i-3900000000-81462e4176534374f843	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 11V, negative	splash10-014i-2900000000-13838214504729aab127	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 12V, negative	splash10-014i-2900000000-c76ede2275038ed75b6d	2020-07-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0udi-0900000000-e180d190b00910efa382	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0udi-1900000000-57816f46479a4b16509f	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0kmi-4900000000-4d051f92232b77a4f222	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0002-0900000000-22731f94c93a65d86fa7	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0002-0900000000-af037d6638ec1135f64a	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0002-3900000000-c10592e6ba17dd98b6ba	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0udi-3900000000-fceeeeb8e46c4e45273b	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0a4i-9100000000-a55d19411e2dc8e43a3d	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-9100000000-b8f56188be6daa978d82	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0002-0900000000-22917433edc8ad9dbc2e	2021-09-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0002-0900000000-22917433edc8ad9dbc2e	2021-09-25	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-000i-5900000000-d83739407ea92534ecaf	2014-09-20	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 25.16 MHz, CDCl₃, experimental)	Not Available	2014-09-23	View Spectrum

Toxicity Profile

Route of Exposure

Dermal

Mechanism of Toxicity

4-Tert-butylphenol is structurally similar to the melanin precursor tyrosine, and acts as a substrate for tyrosinase. Tyrosinase oxidizes 4-tert-butylphenol to a quinone (4-tert-butylcyclohexa-3,5-diene-1,2-dione) which in turn rapidly reacts with glutathione (GSH). A depletion of the GSH defence system may allow the quinone to generate reactive oxygen species that damage melanocytes and induce apoptosis, leading to leukoderma/vitiligo. (1, 2)

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

4-Tert-butylphenol is also found in herbs and spices and in oregano. 4-tert-Butylphenol is a flavour ingredient.

Minimum Risk Level

Not Available

Health Effects

Leukoderma, vitiligo.

Symptoms

Loss of skin pigmentation.

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

34444

BioCyc ID

Not Available

CTD ID

C006862

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Not Available

References

Synthesis Reference

Not Available

MSDS

T3D4881.pdf

General References

Manga P, Sheyn D, Yang F, Sarangarajan R, Boissy RE: A role for tyrosinase-related protein 1 in 4-tert-butylphenol-induced toxicity in melanocytes: Implications for vitiligo. Am J Pathol. 2006 Nov;169(5):1652-62. [17071589 ]
Thorneby-Andersson K, Sterner O, Hansson C: Tyrosinase-mediated formation of a reactive quinone from the depigmenting agents, 4-tert-butylphenol and 4-tert-butylcatechol. Pigment Cell Res. 2000 Feb;13(1):33-8. [10761994 ]
Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not 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

Type	Value	Assay Type	Assay Source
AC50	7.66 uM	ATG_ERa_TRANS	Attagene
AC50	5.78 uM	ATG_ERE_CIS	Attagene

References

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 ]
Hu JY, Aizawa T: Quantitative structure-activity relationships for estrogen receptor binding affinity of phenolic chemicals. Water Res. 2003 Mar;37(6):1213-22. [12598185 ]
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 ]

Target Details

2. Tyrosinase

General Function:: Protein homodimerization activity
Specific Function:: This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the rate-limiting conversions of tyrosine to DOPA, DOPA to DOPA-quinone and possibly 5,6-dihydroxyindole to indole-5,6 quinone.
Gene Name:: TYR
Uniprot ID:: P14679
Molecular Weight:: 60392.69 Da

References

Thorneby-Andersson K, Sterner O, Hansson C: Tyrosinase-mediated formation of a reactive quinone from the depigmenting agents, 4-tert-butylphenol and 4-tert-butylcatechol. Pigment Cell Res. 2000 Feb;13(1):33-8. [10761994 ]

Target Details

3. Nuclear receptor subfamily 1 group I member 3

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

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 ]

4-tert-Butylphenol (T3D4881)

Structure for T3D4881: 4-tert-Butylphenol

Targets

Binding/Activity Constants

References

References

References