BUTYLATED HYDROXYTOLUENE
Relevant Data
Food Additives Approved by WHO:
Food Additives Approved by European Union:
General Information
| Mainterm | BUTYLATED HYDROXYTOLUENE |
| Doc Type | ASP |
| CAS Reg.No.(or other ID) | 128-37-0 |
| Regnum |
175.105 175.300 178.2010 176.170 177.1010 175.380 175.390 177.1210 177.2260 177.2600 176.210 178.3570 166.110 175.125 179.45 177.1350 181.24 172.615 173.340 172.185 137.350 172.110 172.115 182.3173 |
From www.fda.gov
Computed Descriptors
Download SDF| 2D Structure | |
| CID | 31404 |
| IUPAC Name | 2,6-ditert-butyl-4-methylphenol |
| InChI | InChI=1S/C15H24O/c1-10-8-11(14(2,3)4)13(16)12(9-10)15(5,6)7/h8-9,16H,1-7H3 |
| InChI Key | NLZUEZXRPGMBCV-UHFFFAOYSA-N |
| Canonical SMILES | CC1=CC(=C(C(=C1)C(C)(C)C)O)C(C)(C)C |
| Molecular Formula | C15H24O |
| Wikipedia | butylated hydroxytoluene |
From Pubchem
Computed Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 220.356 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 1 |
| Rotatable Bond Count | 2 |
| Complexity | 207.0 |
| CACTVS Substructure Key Fingerprint | A A A D c e B w I A A A A A A A A A A A A A A A A A A A A A A A A A A w A A A A A A A A A A A B A A A A G g A A C A A A D g S A m A A y B o A A A g C A A i B C A A A C A A A g I A A A i A A E C I g I J i K C E R K A c A A k w B E I m A e A w O A P o A A C A A A I A A B A A A Q A A B A A A A A A A A A A A A = = |
| Topological Polar Surface Area | 20.2 |
| Monoisotopic Mass | 220.183 |
| Exact Mass | 220.183 |
| Compound Is Canonicalized | True |
| 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 |
From Pubchem
Food Additives Biosynthesis/Degradation
ADMET Predicted Profile --- Classification
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9502 |
| Human Intestinal Absorption | HIA+ | 0.9941 |
| Caco-2 Permeability | Caco2+ | 0.8876 |
| P-glycoprotein Substrate | Non-substrate | 0.6575 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9160 |
| Non-inhibitor | 0.9855 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9076 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.8267 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7402 |
| CYP450 2D6 Substrate | Substrate | 0.5915 |
| CYP450 3A4 Substrate | Substrate | 0.5169 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.8681 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.8477 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9368 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.8752 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8309 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.7477 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9482 |
| Non-inhibitor | 0.9156 | |
| AMES Toxicity | Non AMES toxic | 0.9494 |
| Carcinogens | Non-carcinogens | 0.7016 |
| Fish Toxicity | High FHMT | 0.7983 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.8900 |
| Honey Bee Toxicity | High HBT | 0.8332 |
| Biodegradation | Not ready biodegradable | 0.9458 |
| Acute Oral Toxicity | III | 0.8270 |
| Carcinogenicity (Three-class) | Non-required | 0.7295 |
From admetSAR
ADMET Predicted Profile --- Regression
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -2.3366 | LogS |
| Caco-2 Permeability | 1.7411 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.2064 | LD50, mol/kg |
| Fish Toxicity | -0.3153 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 1.2850 | pIGC50, ug/L |
From admetSAR
Toxicity Profile
| Route of Exposure | Ingestion; Inhalation |
|---|---|
| Mechanism of Toxicity | BHT is metabolized to quinone methides (QMs) which are responsible for promoting tumor formation in many animal models. One example of a QM is 2,6-di-tert-butyl-4-methylenecyclohexa-2,5-dienone (BHT-QM). QMs are strongly electrophilic and readily form adducts with proteins. Some of the QM targets include redox proteins such as glutathione S-transferase P1 (GST-P1), peroxiredoxin 6 (Prx6), Cu,Zn-superoxide dismutase (SOD1), carbonyl reductase, and selenium-binding protein 1, which have direct or indirect antioxidant functions. . The modification of these proteins leads to decreased cellular protection from electrophiles and oxidants. Alkylation also may interfere with GSTP1 regulation of stress kinases, thereby influencing phosphorylation and cell growth. BHT also binds to the retinoic acid receptor which can lead to changes in cell development. |
| Metabolism | Oxidative metabolism (phase 1 reactions) mediated by the microsomal monooxygenase system is the major route for BHT degradation. Oxidation of the tert-butyl groups is most common in man. Gallates and 2-tert-butylhydroquinone are mainly metabolized by non-oxidative pathways (methylation or conjugation with sulphate and glucuronic acid). . In particular BHT is frequently metabolized to quinone methides (QMs) which are thought to be responsible for promoting tumor formation. One example of a QM is 2,6-di-tert-butyl-4-methylenecyclohexa-2,5-dienone (BHT-QM). QMs are strongly electrophilic and readily form adducts with proteins. |
| Toxicity Values | |
| Lethal Dose | In rats, the oral LD50 was > 2930 mg/kg bw, the LD50 after dermal exposure was > 2000 mg/kg |
| Carcinogenicity (IARC Classification) | 3, not classifiable as to its carcinogenicity to humans. |
| Minimum Risk Level | 25 mg/kg/day for thyroid and liver damage. 100 mg/kg/day for cancer. |
| Health Effects | BHT is of low acute toxicity. Acute exposure to BHT can cause coughs and sore throat (inhalation), redness on the skin (via contact) and abdominal pain, confusion, dizziness and nausea (via ingestion). Long-term exposure to high doses of BHT is toxic in mice and rats, causing liver, thyroid and kidney problems and affecting lung function and blood coagulation. BHT can act as a tumour promoter in certain situations (A15353) although it is not a genotoxic carcinogen. Limited evidence suggests that high doses of BHT may mimic estrogen (A15354), the primary female sex hormone, and prevent expression of male sex hormones, resulting in adverse reproductive affects. On chronic oral exposure of rats, liver and thyroid are the main targets. Doses above 25 mg/kg bw/day BHT resulted in thyroid hyperactivity and enlargement of the liver. |
| Treatment | For acute exposure: EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. INHALATION: supply fresh air. If required provide artificial respiration. |
| Reference |
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From T3DB
Taxonomic Classification
| Kingdom | Organic compounds |
|---|---|
| Superclass | Benzenoids |
| Class | Benzene and substituted derivatives |
| Subclass | Phenylpropanes |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Phenylpropanes |
| Alternative Parents | |
| Molecular Framework | Aromatic homomonocyclic compounds |
| Substituents | Phenylpropane - P-cresol - Toluene - Phenol - Organic oxygen compound - Hydrocarbon derivative - Organooxygen compound - Aromatic homomonocyclic compound |
| Description | This compound belongs to the class of organic compounds known as phenylpropanes. These are organic compounds containing a phenylpropane moiety. |
From ClassyFire
Targets
- General Function:
- Prostaglandin-e2 9-reductase activity
- Specific Function:
- NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol. Can convert prostaglandin E2 to prostaglandin F2-alpha. Can bind glutathione, which explains its higher affinity for glutathione-conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione.
- Gene Name:
- CBR1
- Uniprot ID:
- P16152
- Molecular Weight:
- 30374.73 Da
References
- Meier BW, Gomez JD, Kirichenko OV, Thompson JA. "Mechanistic basis for inflammation and tumor promotion in lungs of 2,6-di-tert-butyl-4-methylphenol-treated mice: electrophilic metabolites alkylate and inactivate antioxidant enzymes.". Chem Res Toxicol. 2007 Feb;20(2):199-207. [17305404 ]
- General Function:
- Thioredoxin peroxidase activity
- Specific Function:
- Involved in redox regulation of the cell. Reduces peroxides with reducing equivalents provided through the thioredoxin system but not from glutaredoxin. May play an important role in eliminating peroxides generated during metabolism. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2). Reduces an intramolecular disulfide bond in GDPD5 that gates the ability to GDPD5 to drive postmitotic motor neuron differentiation (By similarity).
- Gene Name:
- PRDX1
- Uniprot ID:
- Q06830
- Molecular Weight:
- 22110.19 Da
References
- Meier BW, Gomez JD, Kirichenko OV, Thompson JA. "Mechanistic basis for inflammation and tumor promotion in lungs of 2,6-di-tert-butyl-4-methylphenol-treated mice: electrophilic metabolites alkylate and inactivate antioxidant enzymes.". Chem Res Toxicol. 2007 Feb;20(2):199-207. [17305404 ]
- General Function:
- Selenium binding
- Specific Function:
- Selenium-binding protein which may be involved in the sensing of reactive xenobiotics in the cytoplasm. May be involved in intra-Golgi protein transport (By similarity).
- Gene Name:
- SELENBP1
- Uniprot ID:
- Q13228
- Molecular Weight:
- 52390.575 Da
References
- Meier BW, Gomez JD, Kirichenko OV, Thompson JA. "Mechanistic basis for inflammation and tumor promotion in lungs of 2,6-di-tert-butyl-4-methylphenol-treated mice: electrophilic metabolites alkylate and inactivate antioxidant enzymes.". Chem Res Toxicol. 2007 Feb;20(2):199-207. [17305404 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
- Gene Name:
- SOD1
- Uniprot ID:
- P00441
- Molecular Weight:
- 15935.685 Da
References
- Meier BW, Gomez JD, Kirichenko OV, Thompson JA. "Mechanistic basis for inflammation and tumor promotion in lungs of 2,6-di-tert-butyl-4-methylphenol-treated mice: electrophilic metabolites alkylate and inactivate antioxidant enzymes.". Chem Res Toxicol. 2007 Feb;20(2):199-207. [17305404 ]
- 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 RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function.
- Gene Name:
- RARB
- Uniprot ID:
- P10826
- Molecular Weight:
- 50488.63 Da
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 ]
- 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 ]
- 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
- Meier BW, Gomez JD, Kirichenko OV, Thompson JA. "Mechanistic basis for inflammation and tumor promotion in lungs of 2,6-di-tert-butyl-4-methylphenol-treated mice: electrophilic metabolites alkylate and inactivate antioxidant enzymes.". Chem Res Toxicol. 2007 Feb;20(2):199-207. [17305404 ]
- 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
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 ]
From T3DB