Butylated hydroxytoluene (BHT), also known as dibutylhydroxytoluene, is a lipophilic

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...

, chemically a derivative of

phenol 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 r ...

, that is useful for its antioxidant properties. BHT is widely used to prevent free radical-mediated

oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or ...

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 The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. T ...

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 Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do n ...

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 The regulation of therapeutic goods, defined as drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the national level by a single agency. In other jurisdictions they are reg ...

for use as an antiviral.

Natural occurrence

Phytoplankton, including the green algae '' Botryococcus braunii'', as well as three different cyanobacteria (''

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. 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 As a topic of chemistry, chemical synthesis (or combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In mod ...

of BHT in industry has involved the reaction of ''p''-cresol (4-methylphenol) with

isobutylene Isobutylene (or 2-methylpropene) is a hydrocarbon with the chemical formula . It is a four-carbon branched alkene (olefin), one of the four isomers of butylene. It is a colorless flammable gas, and is of considerable industrial value. Producti ...

(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 fo ...

: 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.

Reactions

The species behaves as a synthetic analog of vitamin E, primarily acting as a terminating agent that suppresses

autoxidation Autoxidation (sometimes auto-oxidation) refers to oxidations brought about by reactions with oxygen at normal temperatures, without the intervention of flame or electric spark. The term is usually used to describe the gradual degradation of organic ...

, 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 In organic chemistry, an alkyl group is an alkane missing one hydrogen. The term ''alkyl'' is intentionally unspecific to include many possible substitutions. An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloa ...

aryl In organic chemistry, an aryl is any functional group or substituent derived from an aromatic ring, usually an aromatic hydrocarbon, such as phenyl and naphthyl. "Aryl" is used for the sake of abbreviation or generalization, and "Ar" is used ...

, 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

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 The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the lat ...

It is approved for use in the U.S. by the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

: 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 Poultry () are domesticated birds kept by humans for their eggs, their meat or their feathers. These birds are most typically members of the superorder Galloanserae (fowl), especially the order Galliformes (which includes chickens, qu ...

"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,

cosmetics Cosmetics are constituted mixtures of chemical compounds derived from either natural sources, or synthetically created ones. Cosmetics have various purposes. Those designed for personal care and skin care can be used to cleanse or protec ...

, pharmaceuticals, rubber,

transformer oil Transformer oil or insulating oil is an oil that is stable at high temperatures and has excellent electrical insulating properties. It is used in oil-filled transformers (wet transformers), some types of high-voltage capacitors, fluorescent lamp b ...

s, and embalming fluid. In the

petroleum industry The petroleum industry, also known as the oil industry or the oil patch, includes the global processes of exploration, extraction, refining, transportation (often by oil tankers and pipelines), and marketing of petroleum products. The larg ...

, where BHT is known as the fuel additive AO-29, it is used in hydraulic fluids, turbine and

gear A gear is a rotating circular machine part having cut teeth or, in the case of a cogwheel or gearwheel, inserted teeth (called ''cogs''), which mesh with another (compatible) toothed part to transmit (convert) torque and speed. The basic ...

oils, and jet fuels.Michael Ash, Irene Ash, ''Handbook of Preservatives'', Synapse Information Resources, 2004. . BHT is also used to prevent

peroxide In chemistry, peroxides are a group of compounds with the structure , where R = any element. The group in a peroxide is called the peroxide group or peroxo group. The nomenclature is somewhat variable. The most common peroxide is hydrogen p ...

formation in organic

ether In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again ...

s 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 (BHA).

Health effects

Like many closely related phenol antioxidants, BHT has low acute toxicity (e.g., the desmethyl 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 pro ...

, 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

determined that BHT was noncarcinogenic in a mouse model. Nevertheless, the

World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...

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