2,6-Di-Tert-Butyl-4-Cresol is a synthetic phenolic compound mainly used as an antioxidant and preservative in the food industry.
2,6-Di-Tert-Butyl-4-Cresol is used to prevent the lipid oxidation in oils and fat-containing foods.
2,6-Di-Tert-Butyl-4-Cresol toxicity is generally considered as being low.
2,6-Di-Tert-Butyl-4-Cresol, also known as dibutylhydroxytoluene, is a lipophilic organic compound, chemically a derivative of phenol, that is useful for its antioxidant properties.
2,6-Di-Tert-Butyl-4-Cresol 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 2,6-Di-Tert-Butyl-4-Cresol 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 2,6-Di-Tert-Butyl-4-Cresol was noncarcinogenic in an animal model, societal concerns over its broad use have been expressed.
2,6-Di-Tert-Butyl-4-Cresol has also been postulated as an antiviral drug, but as of December 2022, use of 2,6-Di-Tert-Butyl-4-Cresol 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.
Since 2,6-Di-Tert-Butyl-4-Cresol is used in many near consumer products population wide exposure is expected.
The antioxidant 2,6-Di-Tert-Butyl-4-Cresol is contained in food, adhesive glues, industrial oils and greases, including cutting fluids.
Sensitization seems very rare.
2,6-Di-Tert-Butyl-4-Cresol is a synthetic antioxidant.
2,6-Di-Tert-Butyl-4-Cresol 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 in vitro when used at a concentration of 45 μg/ml.
2,6-Di-Tert-Butyl-4-Cresol reduces freeze-thaw-induced malondialdehyde (MDA) production and increases sperm viability in boar spermatozoa preparations.
Formulations containing 2,6-Di-Tert-Butyl-4-Cresol 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.
2,6-Di-Tert-Butyl-4-Cresol is phenolic and undergoes reactions characteristic of phenols.
2,6-Di-Tert-Butyl-4-Cresol is incompatible with strong oxidizing agents such as peroxides and permanganates.
Contact with oxidizing agents may cause spontaneous combustion.
Iron salts cause discoloration with loss of activity.
Heating with catalytic amounts of acids causes rapid decomposition with the release of the flammable gas isobutene.
2,6-Di-Tert-Butyl-4-Cresol is a phenolic antioxidant.
2,6-Di-Tert-Butyl-4-Cresol can inhibit lipid peroxidation and cause lung injury in mice and promote tumor growth, which may be due to the metabolites of 2,6-Di-Tert-Butyl-4-Cresol, 6-tert-butyl-2-[2′-(2′-hydroxymethyl)-propyl]-4-Methylphenol.
2,6-Di-Tert-Butyl-4-Cresol 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 2,6-Di-Tert-Butyl-4-Cresol (60mg/kg body weight) into rats caused a significant increase in nuclear DNA methyltransferase activity in the liver, kidney, heart, spleen, brain, and lung.
2,6-Di-Tert-Butyl-4-Cresol Chemical Properties
Melting point: 69-73 °C(lit.)
Boiling point: 265 °C(lit.)
Vapor density: 7.6 (vs air)
Capor 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
pka: pKa 14(H2O t = 25 c = 0.002 to 0.01) (Uncertain)
Odor: faint characteristic odor
Water Solubility: insoluble
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.
CAS DataBase Reference: 128-37-0(CAS DataBase Reference)
NIST Chemistry Reference: 2,6-Di-Tert-Butyl-4-Cresol (128-37-0)
IARC: 3 (Vol. 40, Sup 7) 1987
EPA Substance Registry System: 2,6-Di-Tert-Butyl-4-Cresol (128-37-0)
2,6-Di-Tert-Butyl-4-Cresol is white or light yellow crystal.
2,6-Di-Tert-Butyl-4-Cresol 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 2,6-Di-Tert-Butyl-4-Cresol 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.
2,6-Di-Tert-Butyl-4-Cresol is insoluble in water, 10NaOH solution, glycerol, and propylene glycol.
2,6-Di-Tert-Butyl-4-Cresol is odorless, odorless with good thermal stability.
2,6-Di-Tert-Butyl-4-Cresol is monohydric phenolic antioxidants that, prior to their introduction and acceptance in the food industry, were used to protect petroleum against oxidative degumming.
2,6-Di-Tert-Butyl-4-Cresol has a very faint, musty, occasional cresylictype odor.
2,6-Di-Tert-Butyl-4-Cresol is 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 2,6-Di-Tert-Butyl-4-Cresol act as “chain breaks” in the autooxidation processes under the usual conditions of processing, storage and use of fat-containing foods.
2,6-Di-Tert-Butyl-4-Cresol is a white to pale yellow crystalline solid or powder.
2,6-Di-Tert-Butyl-4-Cresol occurs as a white or pale yellow crystalline solid or powder with a faint characteristic phenolic odor.
2,6-Di-Tert-Butyl-4-Cresol species behaves as a synthetic analog of vitamin E, primarily acting as a terminating agent that suppresses autoxidation, a process whereby unsaturated (usually) organic compounds are attacked by atmospheric oxygen.
2,6-Di-Tert-Butyl-4-Cresol stops this autocatalytic reaction by converting peroxy radicals to hydroperoxides.
2,6-Di-Tert-Butyl-4-Cresol effects this function by donating a hydrogen atom:
RO2• + ArOH → ROOH + ArO•
RO2• + ArO• → nonradical products
where R is alkyl or aryl, and where ArOH is 2,6-Di-Tert-Butyl-4-Cresol or related phenolic antioxidants.
Each 2,6-Di-Tert-Butyl-4-Cresol consumes two peroxy radicals.
The applications of 2,6-Di-Tert-Butyl-4-Cresol have been reported as following:
• 2,6-Di-Tert-Butyl-4-Cresol 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-Cresol with fluorine (II) - benzophenone dianion complex.
• Food additive 2,6-Di-Tert-Butyl-4-Cresol can promote acute lung toxicity and tumor growth in mice.
• 2,6-Di-Tert-Butyl-4-Cresol can be used to prepare organoaluminum compound methylaluminum bis (2, 6-di-tert-butyl-4-alkylphenol oxide).
2,6-Di-Tert-Butyl-4-Cresol 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, 2,6-Di-Tert-Butyl-4-Cresol can inhibit lipid peroxidation and exhibit electrophilic quinone methyl ether toxicity mediated by oxidative metabolism.
The 2,6-Di-Tert-Butyl-4-Cresol metabolites, 6-tert-butyl-2- [2 ′-(2′-hydroxymethyl) -propyl] -4-methylphenol, may cause lung damage in mice and promote tumor growth.
Because they prevent rancidity, antioxidants are of great interest to the food industry.
For example, 2,6-Di-Tert-Butyl-4-Cresol, butylated hydroxyanisole (BHA), and EDTA are frequently used to preserve various foods, such as cheese or fried products.
2,6-Di-Tert-Butyl-4-Cresol is a powerful inhibitor of lipid peroxidation, yet large doses of it can induce oxidative DNA damage and cancer development in the rat forestomach.
2,6-Di-Tert-Butyl-4-Cresol is also known as butylated hydroxy toluene.
2,6-Di-Tert-Butyl-4-Cresol is an anti-oxidant that also has preservative and masking capabilities.
2,6-Di-Tert-Butyl-4-Cresol is an antioxidant that functions similarly to butylated hydroxyanisole (BHA) but is less stable at high temperatures.
2,6-Di-Tert-Butyl-4-Cresol is also termed 2,6-di-tert-butyl-para-cresol. See Butylated Hydroxyanisole.
2,6-Di-Tert-Butyl-4-Cresol as general antioxidants is used widely in polymer materials, petroleum products and food processing industries.
2,6-Di-Tert-Butyl-4-Cresol is commonly used rubber antioxidant, heat, oxygen aging have some protective effect, but also can inhibit copper harm.
2,6-Di-Tert-Butyl-4-Cresol does not change color, not pollution.
2,6-Di-Tert-Butyl-4-Cresol high solubility in oil, no precipitation, less volatile, non-toxic and non-corrosive.
Antioxidant for food, animal feed, petroleum products, synthetic rubbers, plastics, animal and vegetable oils, soaps.
Antiskinning agent in paints and inks.
2,6-Di-Tert-Butyl-4-Cresol 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.
2,6-Di-Tert-Butyl-4-Cresol is primarily used as an antioxidant food additive.
In the United States, 2,6-Di-Tert-Butyl-4-Cresol is classified as generally recognized as safe (GRAS) based on a National Cancer Institute study from 1979 in rats and mice.
2,6-Di-Tert-Butyl-4-Cresol is permitted in the European Union under E321.
2,6-Di-Tert-Butyl-4-Cresol is used as a preservative ingredient in some foods.
With this usage 2,6-Di-Tert-Butyl-4-Cresol maintains freshness or prevents spoilage; it may be used to decrease the rate at which the texture, color, or flavor of food changes.
Some food companies have voluntarily eliminated 2,6-Di-Tert-Butyl-4-Cresol from their products or have announced that they were going to phase it out.
2,6-Di-Tert-Butyl-4-Cresol 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 2,6-Di-Tert-Butyl-4-Cresol is known as the fuel additive AO-29, it is used in hydraulic fluids, turbine and gear oils, and jet fuels.
2,6-Di-Tert-Butyl-4-Cresol is also used to prevent peroxide formation in organic ethers and other solvents and laboratory chemicals.
2,6-Di-Tert-Butyl-4-Cresol is added to certain monomers as a polymerisation inhibitor to facilitate their safe storage.
Some additive products contain 2,6-Di-Tert-Butyl-4-Cresol as their primary ingredient, while others contain the chemical merely as a component of their formulation, sometimes alongside butylated hydroxyanisole (BHA).
2,6-Di-Tert-Butyl-4-Cresol is used as an antioxidant in cosmetics, foods, and pharmaceuticals.
2,6-Di-Tert-Butyl-4-Cresol is mainly used to delay or prevent the oxidative rancidity of fats and oils and to prevent loss of activity of oil-soluble vitamins.
2,6-Di-Tert-Butyl-4-Cresol is also used at 0.5–1.0% w/w concentration in natural or synthetic rubber to provide enhanced color stability.
2,6-Di-Tert-Butyl-4-Cresol has some antiviral activity and has been used therapeutically to treat herpes simplex labialis.
2,6-Di-Tert-Butyl-4-Cresol is produced commercially by the alkylation of para-cresol with isobutylene.
2,6-Di-Tert-Butyl-4-Cresol is also produced by several western European manufacturers, production/processing plants in Germany, France, the Netherlands, United Kingdom and Spain.
Phenols, such as 2,6-Di-Tert-Butyl-4-Cresol, 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^[-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.
2,6-Di-Tert-Butyl-4-Cresol or Butylated Hydroxytoluene is of relatively low acute toxicity in animals, and there is no evidence of either acute or chronic effects among exposed workers.
2,6-Di-Tert-Butyl-4-Cresol is a phenolic antioxidant.
2,6-Di-Tert-Butyl-4-Cresol has been shown to inhibit lipid peroxidation.
2,6-Di-Tert-Butyl-4-Cresol 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 2,6-Di-Tert-Butyl-4-Cresol 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 2,6-Di-Tert-Butyl-4-Cresol (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 2,6-Di-Tert-Butyl-4-Cresol significantly reduced the level of TNF-α which may explain the mechanism by which this antioxidant reduces inflammation.
Preincubation of aspirin-treated platelets with 2,6-Di-Tert-Butyl-4-Cresol inhibits the secretion, aggregation, and protein phosphorylation induced by protein kinase C activators.
2,6-Di-Tert-Butyl-4-Cresol was also found to inhibit the initiation of hepatocarcinogenesis by aflatoxin B1.
2,6-Di-Tert-Butyl-4-Cresol is contained in food, adhesive glues, industrial oils, and greases, including cutting fluids.
Sensitization seems very rare.
The IARC has determined that there is limited evidence for the carcinogenicity of 2,6-Di-Tert-Butyl-4-Cresol in experimental animals.
2,6-Di-Tert-Butyl-4-Cresol has given primarily negative results in a large number of in vivo and in vitro genotoxic assays.
No significant reproductive effects were observed in three-generation toxicity studies in mice administered up to 0.4% in the diet.
The 2003 ACGIH threshold limit valuetime- weighted average (TLV-TWA) for 2,6-Di-Tert-Butyl-4-Cresol is 2mg/m3.
2,6-Di-Tert-Butyl-4-Cresol is a white crystalline solid.
2,6-Di-Tert-Butyl-4-Cresol is insoluble in water and alkalies; but soluble in most common organic solvents such as alcohol and ether.
2,6-Di-Tert-Butyl-4-Cresol's melting point is 70°C, boiling point is 265°C, flash point is 127°C, and specific gravity is 1.048 at 20°C.
Catalin antioxydant 1
FEMA No. 2184
Butyl hydroxy toluene
Bht (food grade)
Antioxidant T 501
Caswell No. 291A
Dbpc (technical grade)
EPA Pesticide Chemical Code 022105
4-Methyl-2,6-di-terc. butylfenol [Czech]
BHT, food grade
2, food grade
Hydagen DEO (Salt/Mix)
2,6-di-t-butyl 4-methyl phenol
2.6-di- t-butyl- 4-methylphenol
2,6-di-tert. butyl-4-methyl phenol
BUTYLHYDROXYTOLUENE [EP MONOGRAPH]
BUTYLHYDROXYTOLUENUM [WHO-IP LATIN]
2,6-Di-tert-butyl-4-methylphenol, puriss., 99%
2,6-Di-tert-butyl-4-methylphenol, purum, >=99.0% (GC)
WLN: 1X1 & 1 & R BQ E1 CX1 & 1 & 1
2,6-Di-tert-butyl-4-methylphenol, >=99.0% (GC), powder
2,6-Di-tert-butyl-4-methylphenol, SAJ first grade, >=99.0%
2,6-Di-tert-butyl-4-methylphenol, tested according to Ph.Eur.
3,5-Di-tert-4-butylhydroxytoluene (BHT), analytical standard
2,6-Di-tert-butyl-4-methylphenol 1000 microg/mL in Acetonitrile
Butylhydroxytoluene, European Pharmacopoeia (EP) Reference Standard
2,6-Di-tert-butyl-4-methylphenol, certified reference material, TraceCERT(R)