Butylated hydroxytoluene

Template:Chembox image cellTemplate:Chembox image cellTemplate:Chembox AllOtherNamesTemplate:Chembox headerbarTemplate:Chembox IndexlistTemplate:Chembox JmolTemplate:Chembox ChEMBLTemplate:Chembox ECHATemplate:Chembox E numberTemplate:Chembox IUPHAR ligandTemplate:Chembox UNIITemplate:Chembox CompToxTemplate:Chembox headerbarTemplate:Chembox SolubilityInWaterTemplate:Chembox headerbarTemplate:Chembox OHS (set)Template:Chembox GHS (set)Template:Chembox Lethal amounts (set)Template:Chembox setHeaderTemplate:Chembox setDatarowTemplate:Chembox setDatarowTemplate:Chembox setDatarowTemplate:Chembox SDSTemplate:Chembox headerbarTemplate:Chembox Datapage checkTemplate:Chembox Footer

Butylated hydroxytoluene

Template:Longitem	Template:Unbulleted list
ChEBI	Template:Unbulleted list
ChemSpider	Template:Unbulleted list
DrugBank	Template:Unbulleted list
EC Number	Template:Unbulleted list
KEGG	Template:Unbulleted list
Template:Longitem	Template:Unbulleted list
RTECS number	Template:Unbulleted list
Template:Longitem	Template:Chembox Elements/molecular formula
Molar mass	Template:Chem molar mass
Appearance	White to yellow powder
Odor	Slight, phenolic
Density	1.048 g/cm3
Melting point	Template:Chembox CalcTemperatures
Boiling point	Template:Chembox CalcTemperatures
log P	5.32
Vapor pressure	0.01mmHg (20°C)
NFPA 704 (fire diamond)	Template:NFPA 704 diamond
Flash point	Template:Chembox CalcTemperatures
Template:Longitem	Butylated hydroxyanisole

Butylated hydroxytoluene (BHT), also known as dibutylhydroxytoluene, is a lipophilic organic compound, chemically a derivative of phenol, that is useful for its antioxidant properties and is widely used as a food preservative in different parts of the world. 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 US FDA—which considers BHT to be "generally recognized as safe"—allow small amounts to be added to foods.

Yet, according to the Environmental Working Group that does independent analyses and compiles peer-reviewed research, BHT is shown in multiple studies to cause damage to cells through production of metabolites and oxidative stress (Xu et al., 2021). These are mechanisms associated with a number of diseases including cancer. BHT is not a listed carcinogen, but some data have shown that it does cause cancer in animals. In high dose studies in animals it has been linked to hepatic toxicity, and the promotion of tumors in the liver, bladder, and lungs (Liu & Mabury, 2020; Xu et al., 2021). BHT has been shown to cause developmental effects and thyroid changes in animals, suggesting that it may be able to disrupt endocrine signaling (European Food Safety Authority,2012).

In certain high exposure scenarios, EFSA noted that children's dietary intake of BHT could exceed its acceptable daily intake, or ADI.

Natural occurrence

Phytoplankton, including the green algae Botryococcus braunii, as well as three different cyanobacteria (Cylindrospermopsis raciborskii, 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. Volatile organic compounds such as BHT and cresol are produced by resident fungi when olives are being stored awaiting pressing.

It has been detected in higher plants and herbivorous insects, but it is not clear whether the BHT is produced by the plant, the insect, or some other organism living in association.

Production

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:

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, 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. The electron-donating alkyl groups on the ortho and para positions of BHT increase the electron density of the phenolic hydroxyl moiety through the inductive effect and the hyperconjugation effect, reduce the bond dissociation energy of the phenolic hydroxyl group, and enhance its reactivity to lipid free radicals. Meanwhile, the phenoxy radical generated by BHT is stabilized due to the delocalization of unpaired electrons around the aromatic ring and the steric hindrance effect of ortho tert-butyl groups. Isobutene is one of the possible degradation products formed by BHT oxidation with computational studies suggesting that there are two possible mechanism that can lead to isobutene formation with the OH addition pathways at the C2 site of BHT more likely to result in isobutene formation than pathways of H abstracts from the t-butyl group.

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 and cosmetic ingredient, pesticide ingredient, plastic and rubber ingredient and medical and 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.

Recent research, however indicates reasons for health concerns (see Health effects section below for more details). Recently, as EWG states: "BHT was shown in multiple studies to cause damage to cells through production of metabolites and oxidative stress (Xu et al., 2021). These are mechanisms associated with a number of diseases including cancer. BHT is not a listed carcinogen, but some data have shown that it does cause cancer in animals. In high dose studies in animals it has been linked to hepatic toxicity, and the promotion of tumors in the liver, bladder, and lungs (Liu & Mabury, 2020; Xu et al., 2021). BHT has been shown to cause developmental effects and thyroid changes in animals, suggesting that it may be able to disrupt endocrine signaling (European Food Safety Authority,2012).

In certain high exposure scenarios, EFSA noted that children's dietary intake of BHT could exceed its acceptable daily intake, or ADI. Also, BHT is commonly consumed with other compounds in ultra-processed food (UPF), raising children's food additive levels. There are data gaps for multiple routes of BHT exposure and how well it is absorbed, as well as health effects of co-exposure with other synthetic phenolic antioxidants (Liu & Mabury, 2020)."

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.

A reassessment of BHT safety was planned by the FDA for February, 2026. (EWG).

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, pharmaceuticals, rubber, transformer oils, and embalming fluid. In the petroleum industry, where BHT is known as the fuel additive AO-29 (Innospec), it is used in hydraulic fluids, turbine and gear oils, and jet fuels. 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 (BHA).

BHT is also added as an antioxidant in consumer products such as polyurethane, which is used in mattresses, plastics, carpets and printing inks. From these products, it can migrate into the air and settle in house dust.

Although food is the most significant source of BHT exposure, dust has been reported to be an important source indoors (Liu & Mabury 2020), especially in children, who ingest more dust, on average (Wang et al 2015).

Cosmetics

The European Union restricts the use of BHT in mouthwash to 0.001% concentration, in toothpaste to 0.01% concentration, and to 0.8% in other cosmetics.

File:No BHT in food packaging.png

Food packaging label "no BHT in food packaging"

Health effects

Like many closely related phenolic antioxidants, BHT 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 BHT as generally recognized as safe (GRAS) food preservative when used in an approved manner. In 1979, the National Cancer Institute determined that BHT was noncarcinogenic in a mouse model. Yet recent research suggests reason for concern (see below).

The World Health Organization discussed a possible link between BHT and cancer risk in a 1986 report concluding there is limited evidence for carcinogenicity from animal studies. Primary research studies in the 1970s–1990s reported both potential for increased risk and potential for decreased risk in the area of oncology. Even at that time, increased cancer risk was therefore acknowledged. A review report published in 2002 noted that BHT has shown anticarcinogenic effects, no effect, or tumor promoting effects depending on animal species and target organ considered. Because of this uncertainty, the Center for Science in the Public Interest puts BHT in its "caution" column and recommends avoiding it.

from EWG: "The breakdown of BHT in the body into metabolites produces reactive intermediates that may pose risks to human health. While the cytotoxicity of BHT has long been recognized, recent studies published after its major regulatory evaluations have further clarified the precise mechanisms behind this cellular damage.

The tumor-promoting effects of BHT are mainly influenced by production of quinone methylation metabolites such as BHT-QM (Xu et al., 2021). Its metabolites are electrophilic, which means they bind well to cellular proteins and DNA (Lanigan and Yamarik, 2002).

Like BHA, its metabolite production causes oxidative stress, DNA damage and cell death (Castro et al., 2017). While BHT is not considered a carcinogen by IARC, its mechanisms are related to carcinogenesis.

High-dose animal studies have linked BHT exposure to hepatic toxicity, endocrine disruption and the promotion of tumors in the liver, bladder, and lungs (Liu & Mabury 2020; Xu et al., 2021). Oral studies in rats showed renal and hepatic damage at acute doses of 0.5 to 1.0 g/kg (Lanigan and Yamarik 2002). Subacute exposure at lower doses was linked to liver toxicity in rats (Moon et al., 1987).

BHT has been found in human cord blood (Du et al., 2019), breast milk (Zhang et al., 2020), serum (Liu & Mabury 2018), urine (Liu & Mabury 2018) and adipose tissue (Collings & Sharratt, 1970).

An exposure study conducted in 2019 found that U.S. residents had some of the highest levels of BHT, compared to other countries, with the highest exposures exceeding the ADI (Wang & Kannan, 2019)."

External links

• Chemistry of BHA and BHT Food Preservatives
• CDC – NIOSH Pocket Guide to Chemical Hazards