2,6-di-tert-butyl-4-methylphenol
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Butylated hydroxytoluene (BHT), also known as dibutylhydroxytoluene, is a lipophilic organic compound, chemically a derivative of phenol, that is useful for its
antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
properties. BHT 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 BHT 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 BHT was noncarcinogenic in an animal model, societal concerns over its broad use have been expressed. BHT has also been postulated as an antiviral drug, but as of December 2022 , use of BHT 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.


Natural occurrence

Phytoplankton Phytoplankton () are the autotrophic (self-feeding) components of the plankton community and a key part of ocean and freshwater ecosystems. The name comes from the Greek words (), meaning 'plant', and (), meaning 'wanderer' or 'drifter'. Ph ...
, including the green algae ''
Botryococcus braunii ''Botryococcus braunii'' is a green, pyramid-shaped planktonic microalga that is of potentially great importance in the field of biotechnology. Colonies held together by a lipid biofilm matrix can be found in temperate or tropical oligotrophic l ...
'', as well as three different
cyanobacteria Cyanobacteria (), also known as Cyanophyta, are a phylum of gram-negative bacteria that obtain energy via photosynthesis. The name ''cyanobacteria'' refers to their color (), which similarly forms the basis of cyanobacteria's common name, blu ...
(''
Cylindrospermopsis raciborskii ''Cylindrospermopsis raciborskii'' is a freshwater cyanobacterium. Introduction This bacterium is an aquatic photosynthetic bacteria belonging to the phylum Cyanobacteria. They are composed of chained filaments known as trichomes that can show ...
'', '' Microcystis aeruginosa'' and '' Oscillatoria'' sp.) are capable of producing BHT as a
natural product A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical syn ...
. The fruit lychee also produces BHT in its pericarp. Several fungi (for example '' Aspergillus conicus'') living in olives produce BHT.


Production


Biosynthesis


Industrial production

The chemical synthesis of BHT in industry has involved the reaction of ''p''-cresol (4-methylphenol) with isobutylene (2-methylpropene), catalyzed by
sulfuric acid Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid ( Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen and hydrogen, with the molecular formu ...
: Helmut Fiege, Heinz-Werner Voges, Toshikazu Hamamoto, Sumio Umemura, Tadao Iwata, Hisaya Miki, Yasuhiro Fujita, Hans-Josef Buysch, Dorothea Garbe, Wilfried Paulus "Phenol Derivatives" in ''Ullmann's Encyclopedia of Industrial Chemistry'', Wiley-VCH, Weinheim, 2002. Article Online Posting Date: June 15, 2000. :CH3(C6H4)OH + 2 CH2=C(CH3)2 → ((CH3)3C)2CH3C6H2OH Alternatively, BHT has been prepared from 2,6-di-''tert''-butylphenol by hydroxymethylation or aminomethylation followed by
hydrogenolysis Hydrogenolysis is a chemical reaction whereby a carbon–carbon or carbon–heteroatom single bond is cleaved or undergoes lysis (breakdown) by hydrogen.Ralph Connor, Homer Adkins. Hydrogenolysis Of Oxygenated Organic Compounds. J. Am. Chem. Soc. ...
.


Reactions

The species behaves as a synthetic
analog Analog or analogue may refer to: Computing and electronics * Analog signal, in which information is encoded in a continuous variable ** Analog device, an apparatus that operates on analog signals *** Analog electronics, circuits which use analo ...
of vitamin E, primarily acting as a terminating agent that suppresses autoxidation, a process whereby unsaturated (usually) organic compounds are attacked by atmospheric oxygen. BHT stops this autocatalytic reaction by converting peroxy radicals to hydroperoxides. It 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 BHT or related phenolic antioxidants. Each BHT consumes two peroxy radicals.


Applications

BHT 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

BHT is primarily used as an antioxidant food additive. In the United States, it is classified as generally recognized as safe (GRAS) based on a National Cancer Institute study from 1979 in rats and mice.Bioassay of Butylated Hydroxytoluene (BHT) for Possible Carcinogenicity
National Cancer Institute, CARCINOGENESIS Technical Report Series No. 150, 1979, 128 pp National Institutes of Health
It is approved for use in the U.S. by the Food and Drug Administration: For example, 21 CFR § 137.350(a)(4) allows BHT 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". It is permitted in the European Union under E321. BHT is used as a preservative ingredient in some foods. With this usage BHT 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 BHT from their products or have announced that they were going to phase it out.


Antioxidant

BHT is also used as an antioxidant in products such as
metalworking fluids Cutting fluid is a type of coolant and lubricant designed specifically for metalworking processes, such as machining and stamping. There are various kinds of cutting fluids, which include oils, oil-water emulsions, pastes, gels, aerosols (mists ...
, cosmetics,
pharmaceuticals A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and rel ...
, rubber, transformer oils, and embalming fluid. In the petroleum industry, where BHT is known as the
fuel additive Petrol additives increase petrol's octane rating or act as corrosion inhibitors or lubricants, thus allowing the use of higher compression ratios for greater efficiency and power. Types of additives include metal deactivators, corrosion inhib ...
AO-29, it is used in
hydraulic fluid A hydraulic fluid or hydraulic liquid is the medium by which power is transferred in hydraulic machinery. Common hydraulic fluids are based on mineral oil or water. Examples of equipment that might use hydraulic fluids are excavators and backhoe ...
s, turbine and gear oils, and
jet fuel Jet fuel or aviation turbine fuel (ATF, also abbreviated avtur) is a type of aviation fuel designed for use in aircraft powered by gas-turbine engines. It is colorless to straw-colored in appearance. The most commonly used fuels for commercial a ...
s.Michael Ash, Irene Ash, ''Handbook of Preservatives'', Synapse Information Resources, 2004. . BHT is also used to prevent peroxide formation in organic ethers and other solvents and laboratory chemicals. It is added to certain monomers as a polymerisation inhibitor to facilitate their safe storage. Some additive products contain BHT as their primary ingredient, while others contain the chemical merely as a component of their formulation, sometimes alongside
butylated hydroxyanisole Butylated hydroxyanisole (BHA) is a synthetic, waxy, solid petrochemical. Its antioxidant properties have caused it to be widely used as a preservative in food, food packaging, animal feed, cosmetics, pharmaceuticals, rubber, and petroleum produc ...
(BHA).


Health effects

Like many closely related
phenol antioxidant Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it requir ...
s, BHT has low acute toxicity (e.g., the
desmethyl In chemical nomenclature, nor- is a prefix to name a structural analog that can be derived from a parent compound by the removal of one carbon atom along with the accompanying hydrogen atoms. The nor-compound can be derived by removal of a , , or ...
analog of BHT,
2,6-di-tert-butylphenol 2,6-Di-''tert''-butylphenol is an organic compound with the structural formula 2,6-((CH3)3C)2C6H3OH. This colorless solid alkylated phenol and its derivatives are used industrially as UV stabilizers and antioxidants for hydrocarbon-based produc ...
, has an of >9 g/kg). The US Food and Drug Administration classifies BHT 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 BHT was noncarcinogenic in a mouse model. Nevertheless, the World Health Organization discussed a possible link between BHT 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 BHT in its "caution" column and recommends avoiding it. Based on various, disparate primary research reports, BHT 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 BHT 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 BHT 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 BHT 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 BHT. Hence, at present, the results do not present a scientific consensus in favour of the conclusion of the general antiviral potential of BHT 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 BHT products as an antiviral therapy or prophylactic.See for instance, this and the following two references:


References


External links


Why are BHA and BHT in foods? Are they safe?


{{Antioxidants Natural phenols Antioxidants Alkylphenols Fuel antioxidants Food antioxidants Tert-butyl compounds E-number additives