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Butylhydroxytoluene, also known as dibutylhydroxytoluene, is a lipophilic organic compound, chemically a derivative of phenol, that is useful for its antioxidant properties.
Butylhydroxytoluene is widely used to prevent free radical-mediated oxidation in fluids (e.g. fuels, oils) and other materials, and the regulations overseen by the U.S. F.D.A.—which considers
CAS Number: 128-37-0
EC Number: 204-881-4
IUPAC Name: 2,6-Di-tert-butyl-4-methylphenol
Chemical Formula: C15H24O
Other names: 2,6-Di-tert-butyl-4-methylphenol, 128-37-0, Butylhydroxytoluene, 2,6-Di-tert-butyl-p-cresol, 2,6-Di-t-butyl-4-methylphenol, Ionol, BHT, DBPC, Dibunol, Stavox, Ionol CP, Phenol, 2,6-bis(1,1-dimethylethyl)-4-methyl-, Impruvol, Kerabit, Topanol, Dalpac, Deenax, Ionole, Vianol, Antioxidant KB, 3,5-Di-tert-butyl-4-hydroxytoluene, 2,6-ditert-butyl-4-methylphenol, Antioxidant 4K, Sumilizer BHT, Topanol O, Topanol OC, Vanlube PC, Antioxidant DBPC, Sustane BHT, Tenamene 3, Vanlube PCX, Antioxidant 29, Antioxidant 30, Nonox TBC, Tenox BHT, Chemanox 11, Ionol 1, Agidol, Catalin CAO-3, Advastab 401, Ionol (antioxidant), BUKS, Parabar 441, Paranox 441, 2,6-Di-tert-butyl-4-cresol, Catalin antioxydant 1, Antrancine 8, Vulkanox KB, Di-tert-butyl-p-cresol, 2,6-Bis(1,1-dimethylethyl)-4-methylphenol, Ional, AO 4K, CAO 1, CAO 3, Di-tert-butyl-p-methylpheno, FEMA No. 2184, o-Di-tert-butyl-p-methylphenol, 4-Methyl-2,6-tert-butylphenol, 2,6-Di-tert-butyl-1-hydroxy-4-methylbenzene, 2,6-Di-tert-butyl-p-methylphenol, AO 29, NCI-C03598, 2,6-ditert-butyl-4-methyl-phenol, 2,6-DI-T-BUTYL-P-CRESOL, 4-Methyl-2,6-di-tert-butylphenol, Butyl hydroxy toluene, 2,6-Di-terc.butyl-p-kresol, 4-Hydroxy-3,5-di-tert-butyltoluene, P 21, Bht(food grade), 4-Methyl-2,6-di-terc. butylfenol, 2,6-Di-tert-butyl-4-methyl-phenol, 1-Hydroxy-4-methyl-2,6-di-tert-butylbenzene, Di-tert-butylcresol, Dbpc(technical grade), E321, p-Cresol, 2,6-di-tert-butyl-, NSC-6347, CHEMBL146, 2,6-ditertiary-butyl-p-cresol, INS NO.321, CHEBI:34247, INS-321, 1P9D0Z171K, 2,6-di-tert-butyl-4-methyl phenol, NCGC00091761-03, Tonarol, DSSTox_CID_216, Antioxidant MPJ, E-321, Antioxidant 4, Toxolan P, Alkofen BP, Swanox BHT, Tenamen 3, Antox QT, Antioxidant 264, DSSTox_RID_75440, Agidol 1, DSSTox_GSID_20216, Bht (food grade), Antioxidant T 501, Nocrac 200, Caswell No. 291A, Dbpc (technical grade), Annulex BHT, AOX 4K, AOX 4, Butylhydroxytoluenum, MFCD00011644, CAS-128-37-0, Butylohydroksytoluenu, CCRIS 103, Butylohydroksytoluenu [Polish], Ionol CP-antioxidant, Di-tert-butyl-p-cresol (VAN), HSDB 1147, BHT 264, NSC 6347, EINECS 204-881-4, 2,6-Di-terc.butyl-p-kresol [Czech], EPA Pesticide Chemical Code 022105, 2,6-Di-tert-butyl-4-methylhydroxybenzene, Popol, UNII-1P9D0Z171K, AI3-19683, 4-Methyl-2,6-di-terc. butylfenol [Czech], Lowinox BHT, Nipanox BHT, BHT Swanox, BHT, food grade, 4-Methyl-2,6-di-t-butyl-phenol, Ionol BHT, Ralox BHT, 2, food grade, 3IM, Dibutyl-para-cresol, 2,6-bis(tert-butyl)-4-methylphenol, Spectrum_001790, BHT FCC/NF, SpecPlus_000768, Methyldi-tert-butylphenol, Spectrum3_001849, Spectrum5_001612, BHT [INCI], Hydagen DEO (Salt/Mix), BHT [FCC], EC 204-881-4, 2,6-di-Butyl-para-cresol, 2.6-di-t-butyl-p-cresol, SCHEMBL3950, 2,6-ditert-butyl-p-cresol, p-Cresol,6-di-tert-butyl-, Di-tert-Butylparamethylphenol, BSPBio_003238, KBioSS_002281, 2,6-di-tert.butyl-p-cresol, Di-tert-Butyl-4-methylphenol, MLS000069425, BIDD:ER0031, DivK1c_006864, SPECTRUM1600716, 2,6-bis-tert-butyl-p-cresol, 2,6-di-tert-butyl-paracresol, 2,6-di-tert. butyl-p-cresol, 2,6-di-tert.-butyl-p-cresol, 2,6-di-tert-butyl-para-cresol, 2,6-di-tert-Butyl-methylphenol, 2,6-ditertbutyl-4-methylphenol, DTXSID2020216, 2,6-di-t butyl-4-methylphenol,
Butylhydroxytoluene to be "generally recognized as safe"—allow small amounts to be added to foods.
Despite this, and the earlier determination by the National Cancer Institute that Butylhydroxytoluene was noncarcinogenic in an animal model, societal concerns over its broad use have been expressed.
Butylhydroxytoluene has also been postulated as an antiviral drug, but as of December 2022 , use of Butylhydroxytoluene as a drug is not supported by the scientific literature and it has not been approved by any drug regulatory agency for use as an antiviral.
Phytoplankton, including the green algae Botryococcus braunii, as well as three different cyanobacteria (Cylindrospermopsis raciborskii, Microcystis aeruginosa and Oscillatoria sp.) are capable of producing Butylhydroxytoluene as a natural product.
The fruit lychee also produces Butylhydroxytoluene in its pericarp.
Several fungi (for example Aspergillus conicus) living in olives produce Butylhydroxytoluene.
Butylhydroxytoluene is a synthetic phenolic compound mainly used as an antioxidant and preservative in the food industry.
Butylhydroxytoluene is used to prevent the lipid oxidation in oils and fat-containing foods.
Butylated Hydroxytoluene toxicity is generally considered as being low.
Since Butylhydroxytoluene is used in many near consumer products population wide exposure is expected.
The antioxidant butylated hydroxytoluene is contained in food, adhesive glues, industrial oils and greases, including cutting fluids.
Sensitization seems very rare.
Butylhydroxytoluene is a synthetic antioxidant.
Butylhydroxytoluene scavenges peroxide, 2,2-diphenyl-1-picrylhydrazyl (DPPH; ), superoxide, and ABTS radicals in cell-free assays, as well as inhibits lipid peroxidation of linoleic acid (Item Nos. 90150 | 90150.1 | 21909) in vitro when used at a concentration of 45 μg/ml.
Butylhydroxytoluene (0.025-3.2 mM) reduces freeze-thaw-induced malondialdehyde (MDA) production and increases sperm viability in boar spermatozoa preparations.
Formulations containing Butylhydroxytoluene have been used as antioxidant cosmetic and food additives.
A member of the class of phenols that is 4-methylphenol substituted by tert-butyl groups at positions 2 and 6.
Butylhydroxytoluene Chemical Properties
Melting point: 69-73 °C(lit.)
Boiling point: 265 °C(lit.)
Density: 1.048
Vapor density: 7.6 (vs air)
Vapor pressure: <0.01 mm Hg ( 20 °C)
Refractive index: 1.4859
FEMA: 2184 | BUTYLATED HYDROXYTOLUENE
Fp: 127 °C
Storage temp.: 2-8°C
Solubility methanol: 0.1 g/mL, clear, colorless
Form: Crystals
pka: pKa 14(H2O t = 25 c = 0.002 to 0.01) (Uncertain)
Color: white
Odor: faint characteristic odor
Water Solubility: insoluble
Merck: 14,1548
BRN: 1911640
Exposure limits: ACGIH: TWA 2 mg/m3
NIOSH: TWA 10 mg/m3
Stability: Stable, but light-sensitive. Incompatible with acid chlorides, acid anhydrides, brass, copper, copper alloys, steel, bases, oxidizing agents. Combustible.
InChIKey: NLZUEZXRPGMBCV-UHFFFAOYSA-N
LogP: 5.2
CAS DataBase Reference: 128-37-0(CAS DataBase Reference)
NIST Chemistry Reference: Butylated hydroxytoluene(128-37-0)
IARC: 3 (Vol. 40, Sup 7) 1987
EPA Substance Registry System: Butylhydroxytoluene (128-37-0)
Butylhydroxytoluene is white or light yellow crystal.
Butylhydroxytoluene has a melting point of 71°C, a boiling point of 265°C, a relative density of 1.048 (20/4°C), and a refractive index of 1.4859 (75°C).
Solubility of Butylhydroxytoluene at normal temperature: methanol 25, ethanol 25-26, isopropanol 30, mineral oil 30, acetone 40, petroleum ether 50, benzene 40, lard (40-50°C ) 40-50, corn oil and soybean oil 40-50.
Butylhydroxytoluene is insoluble in water, 10NaOH solution, glycerol, and propylene glycol. Butylhydroxytoluene is odorless, odorless with good thermal stability.
BHA and Butylhydroxytoluene are monohydric phenolic antioxidants that, prior to their introduction and acceptance in the food industry, were used to protect petroleum against oxidative degumming.
Butylhydroxytoluene has a very faint, musty, occasional cresylictype odor.
BHA and Butylhydroxytoluene are extensively used in foods as antioxidants.
Most fats, oils and fat-containing foods are naturally susceptible to rapid rancification and other oxidative reactions that produce compounds having objectionable taste and odor, making foods containing them unpalatable.
Lipid oxidation is autocatalytic and proceeds as a complex of chain reactions, the nature and speed of which vary with the substrate, temperature, light, availability of oxygen and presence or absence of oxidation catalysts.
Antioxidants like Butylhydroxytoluene act as “chain breaks” in the autooxidation processes under the usual conditions of processing, storage and use of fat-containing foods (Burdock, 1997).
Butylhydroxytoluene is a white to pale yellow crystalline solid or powder.
Butylhydroxytoluene occurs as a white or pale yellow crystalline solid or powder with a faint characteristic phenolic odor.
Butylhydroxytoluene is a phenolic antioxidant. Butylated Hydroxytoluene can inhibit lipid peroxidation and cause lung injury in mice and promote tumor growth, which may be due to the metabolites of Butylhydroxytoluene, 6-tert-butyl-2-[2′-(2′-hydroxymethyl)-propyl]-4-Methylphenol.
Butylhydroxytoluene metabolites have also been reported to cause DNA strand breaks in cultured cells and DNA breaks between nucleosomes (a typical feature of apoptosis).
A single intraperitoneal injection of Butylhydroxytoluene (60mg/kg body weight) into rats caused a significant increase in nuclear DNA methyltransferase activity in the liver, kidney, heart, spleen, brain, and lung.
Butylhydroxytoluene is an organic chemical composed of 4-methylphenol modified with tert-butyl groups at positions 2 and 6.
Butylhydroxytoluene inhibits autoxidation of unsaturated organic compounds.
Butylhydroxytoluene is used in food, cosmetics and industrial fluids to prevent oxidation and free radical formation.
Uses
Butylhydroxytoluene has wide application, such as flavors, fragrances, biochemical reagents-other chemical reagents, chemical raw materials, organic chemical raw materials, biochemical, inorganic salts, antioxidants, food additives, feed additives, feed storage additives, aromatic hydrocarbons, bulk drugs and so on.
As a phenolic antioxidant, Butylhydroxytoluene can inhibit lipid peroxidation and exhibit electrophilic quinone methyl ether toxicity mediated by oxidative metabolism.
The Butylhydroxytoluene metabolites, 6-tert-butyl-2- [2 ′-(2′-hydroxymethyl) -propyl] -4-methylphenol, may cause lung damage in mice and promote tumor growth.
The applications of Butylhydroxytoluene have been reported as following :
Butylhydroxytoluene metabolites causing DNA strand breaks in cultured cells and DNA breaks between nucleosomes (a typical feature of apoptosis), which result in relieving inflammation.
Inhibiting secretion, aggregation, and protein phosphorylation caused by protein kinase C activators at the process of the pre-incubation of aspirin-treated platelets.
Inhibiting liver cancer formation induced by aflatoxin B1.
As Michael receptor, butylated hydroxytoluene can react with uninucleophiles and proteins.
Reaction of 2, 6-di-tert-butyl-4-methylphenol with fluorine (II) - benzophenone dianion complex.
Food additive 2, 6-di-tert-butyl-4-methylphenol can promote acute lung toxicity and tumor growth in mice.
Butylhydroxytoluene can be used to prepare organoaluminum compound methylaluminum bis (2, 6-di-tert-butyl-4-alkylphenol oxide).
Because they prevent rancidity, antioxidants are of great interest to the food industry.
For example, Butylhydroxytoluene, butylated hydroxyanisole (BHA), and EDTA are frequently used to preserve various foods, such as cheese or fried products.
Butylhydroxytoluene is a powerful inhibitor of lipid peroxidation, yet large doses of it can induce oxidative DNA damage and cancer development in the rat forestomach.
Butylhydroxytoluene is also known as butylated hydroxy toluene.
Butylhydroxytoluene is an anti-oxidant that also has preservative and masking capabilities.
Butylhydroxytoluene is an antioxidant that functions similarly to butylated hydroxyanisole (BHA) but is less stable at high temperatures.
Butylhydroxytoluene is also termed 2,6-di-tert-butyl-para-cresol.
Butylhydroxytoluene as general antioxidants is used widely in polymer materials, petroleum products and food processing industries.
Butylhydroxytoluene is commonly used rubber antioxidant, heat, oxygen aging have some protective effect, but also can inhibit copper harm.
Butylhydroxytoluene does not change color, not pollution.
Butylhydroxytoluene high solubility in oil, no precipitation, less volatile, non-toxic and non-corrosive.
Butylhydroxytoluene for food, animal feed, petroleum products, synthetic rubbers, plastics, animal and vegetable oils, soaps.
Antiskinning agent in paints and inks.
Butylhydroxytoluene is used as an antioxidant in cosmetics, foods, and pharmaceuticals.
Butylhydroxytoluene is mainly used to delay or prevent the oxidative rancidity of fats and oils and to prevent loss of activity of oil-soluble vitamins.
Butylhydroxytoluene is also used at 0.5–1.0% w/w concentration in natural or synthetic rubber to provide enhanced color stability.
Butylhydroxytoluene has some antiviral activity and has been used therapeutically to treat herpes simplex labialis.
Butylhydroxytoluene is a phenolic antioxidant.
Butylhydroxytoluene has been shown to inhibit lipid peroxidation.
Butylhydroxytoluene causes lung injury and promotes tumors in mice, but this may be due to a metabolite of Butylated Hydroxytoluene, 6-tert-butyl-2-[2′-(2′-hydroxymethyl)-propyl]-4-methylphenol.
Metabolites of Butylhydroxytoluene have also been reported to induce DNA strand breaks and internucleosomal DNA fragmentation (a characteristic of apoptosis) in cultured cells.
In rats, a single intraperitoneal injection of Butylhydroxytoluene (60 mg/kg body mass) results in a significant increase in nuclear DNA methyl transferase activity in the liver, kidneys, heart, spleen, brain and lungs.
Incubation of alveolar macrophages with Butylhydroxytoluene significantly reduced the level of TNF-α which may explain the mechanism by which this antioxidant reduces inflammation. Preincubation of aspirin-treated platelets with Butylhydroxytoluene inhibits the secretion, aggregation, and protein phosphorylation induced by protein kinase C activators.
Butylhydroxytoluene was also found to inhibit the initiation of hepatocarcinogenesis by aflatoxin B1.
Butylhydroxytoluene is listed by the NIH Hazardous Substances Data Bank under several categories in catalogues and databases, such as food additive, household product ingredient, industrial additive, personal care product/cosmetic ingredient, pesticide ingredient, plastic/rubber ingredient and medical/veterinary/research.
Food additive
Butylhydroxytoluene is primarily used as an antioxidant food additive.
In the United States, Butylhydroxytoluene is classified as generally recognized as safe (GRAS) based on a National Cancer Institute study from 1979 in rats and mice.
Butylhydroxytoluene is approved for use in the U.S. by the Food and Drug Administration: For example, 21 CFR § 137.350(a)(4) allows Butylhydroxytoluene up to 0.0033% by weight in "enriched rice", while 9 CFR § 381.147](f)(1) allows up to 0.01% in poultry "by fat content".
Butylhydroxytoluene is permitted in the European Union under E321.
Butylhydroxytoluene is used as a preservative ingredient in some foods.
With this usage Butylhydroxytoluene maintains freshness or prevents spoilage; Butylhydroxytoluene may be used to decrease the rate at which the texture, color, or flavor of food changes.
Some food companies have voluntarily eliminated Butylhydroxytoluene from their products or have announced that they were going to phase Butylhydroxytoluene out.
Antioxidant
Butylhydroxytoluene is also used as an antioxidant in products such as metalworking fluids, cosmetics, pharmaceuticals, rubber, transformer oils, and embalming fluid.
In the petroleum industry, where Butylhydroxytoluene is known as the fuel additive AO-29, it is used in hydraulic fluids, turbine and gear oils, and jet fuels.
Butylhydroxytoluene is also used to prevent peroxide formation in organic ethers and other solvents and laboratory chemicals.
Butylhydroxytoluene is added to certain monomers as a polymerisation inhibitor to facilitate their safe storage.
Some additive products contain Butylhydroxytoluene as their primary ingredient, while others contain the chemical merely as a component of their formulation, sometimes alongside butylated hydroxyanisole (BHA).
Health effects
Like many closely related phenol antioxidants, Butylhydroxytoluene has low acute toxicity (e.g., the desmethyl analog of BHT, 2,6-di-tert-butylphenol, has an LD50 of >9 g/kg).
The US Food and Drug Administration classifies Butylhydroxytoluene as generally recognized as safe (GRAS) as a food preservative when used according in an approved manner.
In 1979, the National Cancer Institute determined that Butylhydroxytoluene was noncarcinogenic in a mouse model.
Nevertheless, the World Health Organization discussed a possible link between Butylhydroxytoluene and cancer risk in 1986, and some primary research studies in the 1970s–1990s reported both potential for increased risk and potential for decreased risk in the area of oncology.
Because of this uncertainty, the Center for Science in the Public Interest puts Butylhydroxytoluene in its "caution" column and recommends avoiding it.
Based on various, disparate primary research reports, Butylhydroxytoluene has been suggested to have anti-viral activity, and the reports divide into various study types.
First, there are studies that describe virus inactivation—where treatment with the chemical results in disrupted or otherwise inactivated virus particles.
The action of Butylhydroxytoluene in these is akin to the action of many other organic compounds, e.g., quaternary ammonium compounds, phenolics, and detergents, which disrupt viruses by insertion of the chemical into the virus membrane, coat, or other structure, which are established methods of viral disinfection secondary to methods of chemical oxidation and UV irradiation.
In addition, there is a report of Butylhydroxytoluene use, topically against genital herpes lesions, a report of inhibitory activity in vitro against pseudorabies (in cell culture), and two studies, in veterinary contexts, of use of Butylhydroxytoluene to attempt to protect against virus exposure (pseudorabies in mouse and swine, and Newcastle in chickens).
The relevance of other reports, regarding influenza in mice, is not easily discerned.
Notably, this series of primary research reports does not support a general conclusion of independent confirmation of the original research results, nor are there critical reviews appearing thereafter, in secondary sources, for the various host-virus systems studied with Butylhydroxytoluene.
Hence, at present, the results do not present a scientific consensus in favour of the conclusion of the general antiviral potential of Butylhydroxytoluene when dosed in humans.
Moreover, as of March 2020, no guidance from any of the internationally recognized associations of infectious disease specialists had advocated use of Butylhydroxytoluene products as an antiviral therapy or prophylactic.
Reactivity Profile
Phenols, such as 2,6-Di-tert-butyl-4-methylphenol, do not behave as organic alcohols, as one might guess from the presence of a hydroxyl (-OH) group in their structure.
Instead, they react as weak organic acids.
Phenols and cresols are much weaker as acids than common carboxylic acids (phenol has Ka = 1.3 x 10^).
These materials are incompatible with strong reducing substances such as hydrides, nitrides, alkali metals, and sulfides.
Flammable gas (H2) is often generated, and the heat of the reaction may ignite the gas.
Heat is also generated by the acid-base reaction between phenols and bases.
Such heating may initiate polymerization of the organic compound.
Phenols are sulfonated very readily (for example, by concentrated sulfuric acid at room temperature).
The reactions generate heat.
Phenols are also nitrated very rapidly, even by dilute nitric acid.
Nitrated phenols often explode when heated.
Many of them form metal salts that tend toward detonation by rather mild shock.
May react with oxidizing materials.
Preparation
Butylhydroxytoluene is produced commercially by the alkylation of para-cresol with isobutylene. Butylhydroxytoluene is also produced by several western European manufacturers, production/processing plants in Germany, France, the Netherlands, United Kingdom and Spain.
