Butylated hydroxytoluene or BHT or Hydroxy toluene butylate or Toluene hydroxylated butylate or 2,6-di-tert-butyl-p-cresol, is an organic chemical compound, lipophilic phenol, obtained synthetically by the reaction of 4-methylphenol with isobutylene and catalysed by sulphuric acid.

The synthesis process takes place in different steps:

• Preparation. The raw materials are p-cresol (a phenol) and isobutene (a hydrocarbon).
• Alkylation. p-cresol is reacted with isobutene in the presence of a catalyst, such as sulphuric acid, at a controlled temperature and pressure. This process is known as alkylation and attaches the tert-butyl groups to the p-cresol molecule.
• Separation. The reaction mixture is then separated to isolate the 2,6-di-tert-butyl-p-cresol by various methods, including distillation, in which the mixture is heated and the components that vaporise at different temperatures are separated.
• Purification.  The separated product is purified to remove any unreacted materials and by-products by processes such as washing, filtration and drying.
• Quality control. The final product is tested to ensure that it meets the necessary quality standards.

It appears as a white, stable but photosensitive powder. Flammable. Incompatible with oxidising agents, acid chlorides, bases, brass, acid anhydrides, copper, copper alloys, steel.

What it is used for and where

Food

A synthetic antioxidant generally considered safe in food. It has the ability to control free radicals by eliminating peroxyl radicals and to control free radical generation by inhibiting or retarding oxidation (1). The FDA-authorised maximum use dose is 0.02% in meat and meat products from the meat processing industry.

Ingredient included in the list of European food additives as E321, antioxidant.

Cosmetics

BHT is a restricted ingredient as   a Relevant Item in the Annexes of the European Cosmetics Regulation 1223/2009. Ingredient at risk: 2,6-Di-Tert-Butyl-4-Methylphenol

It is included in formulations of shower gels, shampoos, lipsticks as an antioxidant to improve the stability of fat-soluble cosmetics and prevent their deterioration. 

Antioxidant agent. Ingredient that counteracts oxidative stress and prevents cell damage. Free radicals, pathological inflammatory processes, reactive nitrogen species and reactive oxygen species are responsible for the ageing process and many diseases caused by oxidation.

Fragrance. It plays a decisive and important role in the formulation of cosmetic products as it provides the possibility of enhancing, masking or adding fragrance to the final product, increasing its marketability. It is able to create a perceptible pleasant odour, masking a bad smell. The consumer always expects to find a pleasant or distinctive scent in a cosmetic product. 

Other uses

Also used in petroleum products, rubber, plastic foam as an antioxidant stabiliser, polyester resin, ABS resin, polyethylene, polystyrene, cellulose, transformer oil, white and clear latex.

In natural rubber processing it acts as an antioxidant and stabiliser 

Safety

BHT is a skin and eye irritant but no conclusions can be drawn on the additive's potential for skin sensitisation. It is considered safe by EFSA in animal feed (2) but this study recommends monitoring and limiting its use (3) and suggests that BHT consumption should not exceed 0.5 mg/kg body weight (4).

For more information:

BHT studies

Typical commercial product characteristicsBHT Butylated Hydroxy Toluene

Appearance	White powder
Boiling Point	265ºC
Melting Point	69-71ºC
Flash Point	127ºC
Density	1.048
PSA	20.23000
Vapor Pressure	0.0±0.6 mmHg at 25°C
Vapor density	7.6
LogP	5.32
Refraction Index	1.499
Sulphate SO4	≤ 0.002 w/%
Arsenic	≤ 1 mg/kg
Cauterized residue	≤ 0.004 w/%
Free phenol (p-cresol)	≤ 0.01 w/%
Water	≤0.1%
Safety

• Molecular Formula   C₁₅H₂₄O
• Linear Formula [(CH₃)₃C]₂C₆H₂(CH₃)OH
• Molecular Weight 220.356 g/mol
• Exact Mass    220.182709
• UNII: 1P9D0Z171K
• CAS: 128-37-0  
• DSSTox Substance ID  
• IUPAC  2,6-ditert-butyl-4-methylphenol
• InChl=  1S/C15H24O/c1-10-8-11(14(2,3)4)13(16)12(9-10)15(5,6)7/h8-9,16H,1-7H3
• InChl Key      NLZUEZXRPGMBCV-UHFFFAOYSA-N
• SMILES  CC1=CC(=C(C(=C1)C(C)(C)C)O)C(C)(C)C
• EC Number: 204-881-4  
• FEMA Number: 2184
• PubChem Substance ID 329749182
• MDL number MFCD00011644
• Beilstein Registry Number 1911640

Synonyms

• 2,6-Di-tert-butyl-4-methylphenol
• Butylated hydroxytoluene
• Butylhydroxytoluene
• 2,6-Di-tert-butyl-p-cresol
• 2,6-Di-t-butyl-4-methylphenol
• Ionol
• Parabar 441
• Paranox 441
• 2,6-Di-tert-butyl-4-cresol
• DBPC
• Dibunol
• Stavox
• Phenol, 2,6-bis(1,1-dimethylethyl)-4-methyl-
• BHT
• Ionol CP
• Antrancine 8
• Butylated hydroxytoluol
• Vulkanox KB
• Impruvol
• Topanol
• Dalpac
• 2,6-ditert-butyl-4-methylphenol
• Di-tert-butyl-p-cresol
• Dibutylated hydroxytoluene
• Deenax
• Ionole
• Vianol
• Antioxidant KB
• 3,5-Di-tert-butyl-4-hydroxytoluene
• 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

References______________________________________________________________________

(1) Zahid MA, Eom JU, Parvin R, Seo JK, Yang HS. Changes in Quality Traits and Oxidation Stability of Syzygium aromaticum Extract-Added Cooked Ground Beef during Frozen Storage. Antioxidants (Basel). 2022 Mar 11;11(3):534. doi: 10.3390/antiox11030534.

(2) EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), Bampidis V, Azimonti G, Bastos ML, Christensen H, Dusemund B, Fašmon Durjava M, Kouba M, López-Alonso M, López Puente S, Marcon F, Mayo B, Pechová A, Petkova M, Ramos F, Sanz Y, Villa RE, Woutersen R, Finizio A, Teodorovic I, Aquilina G, Bories G, Gropp J, Nebbia C, Innocenti M. Safety and efficacy of a feed additive consisting of butylated hydroxytoluene (BHT) for all animal species (Katyon Technologies Limited). EFSA J. 2022 May 10;20(5):e07287. doi: 10.2903/j.efsa.2022.7287. 

(3) Abou-Hadeed AH, Mohamed AT, Hegab DY, Ghoneim MH. Ethoxyquin and Butylated Hydroxy Toluene Distrub the Hematological Parameters and Induce Structural and Functional Alterations in Liver of Rats. Arch Razi Inst. 2021 Dec 30;76(6):1765-1776. doi: 10.22092/ari.2021.356439.1844. 

(4) Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev. 2010 Jul;4(8):118-26. doi: 10.4103/0973-7847.70902.

Compendium of the most significant studies with reference to properties, intake, effects.

Panico A, Serio F, Bagordo F, Grassi T, Idolo A, DE Giorgi M, Guido M, Congedo M, DE Donno A. Skin safety and health prevention: an overview of chemicals in cosmetic products. J Prev Med Hyg. 2019 Mar 29;60(1):E50-E57. doi: 10.15167/2421-4248/jpmh2019.60.1.1080.

Abstract. Introduction: Cosmetic products contain a wide range of chemicals to which we are exposed every day. The aim of the study was to determine the presence of potential dangerous substances which can cause adverse health effects by examining product labels.....Conclusions: The use of many of these substances is allowed within certain limits, due to their toxicity at higher concentrations. Other important aspects should be considered as, for instance, the possibility of long-term effects. On the other hand, other substances may induce several acute adverse side-effects, i.e. contact dermatitis and allergic reactions. For these reasons, an enhancement of the criteria used for cosmetics formulation is required since many chemicals used singularly or combined are potentially unsafe.

Cai P, Fang SQ, Yang HL, Yang XL, Liu QH, Kong LY, Wang XB. Donepezil-butylated hydroxytoluene (BHT) hybrids as Anti-Alzheimer's disease agents with cholinergic, antioxidant, and neuroprotective properties. Eur J Med Chem. 2018 Sep 5;157:161-176. doi: 10.1016/j.ejmech.2018.08.005.

Abstract. The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A novel family of donepezil-butylated hydroxytoluene (BHT) hybrids were designed, synthesized and evaluated as multifunctional ligands against AD. ...Copyright © 2018 Elsevier Masson SAS. 

Yehye WA, Rahman NA, Ariffin A, Abd Hamid SB, Alhadi AA, Kadir FA, Yaeghoobi M. Understanding the chemistry behind the antioxidant activities of butylated hydroxytoluene (BHT): a review. Eur J Med Chem. 2015 Aug 28;101:295-312. doi: 10.1016/j.ejmech.2015.06.026. 

Abstract. ...Our strategy involved investigation on understanding the chemistry behind the antioxidant activities of BHT, whether through hydrogen or electron transfer mechanism to enable promising anti-oxidant candidates to be synthesized. Copyright © 2015 Elsevier Masson SAS. 

Castro LDS, Bracht L, Comar JF, Peralta RM, Bracht A. A reappraisal of the proposed metabolic and antioxidant actions of butylated hydroxytoluene (BHT) in the liver. J Biochem Mol Toxicol. 2017 Aug;31(8). doi: 10.1002/jbt.21924.

Abstract. Butylated hydroxytoluene (BHT) was investigated for its metabolic actions in the perfused rat liver. Contrary to what is expected from an uncoupler, BHT up to 500 μM did not stimulate oxygen uptake nor did it inhibit gluconeogenesis from lactate. Transformation of fructose into glucose was also not affected by BHT; only lactate production was slightly increased at the concentration of 100 μM. ....© 2017 Wiley Periodicals, Inc.

Baishya SK , Biswas RK , Govindasamy K , Deka BC , Sinha S , Singh M . Pre-freezing Treatment with Butylated Hydroxytoluene and Cholesterol-loaded Methyl-β-cyclodextrin Improves Quality of Cryopreserved Boar Semen. Cryo Letters. 2018 Sep/Oct;39(5):336-344. 

Abstract. Background: Pre-freezing treatment of boar sperm with additives improves the quality of post-thaw sperms....Conclusion: Treatment of boar spermatozoa with BHT and CLC improved post-thaw sperm quality.

Martins V, Teodoro WR, Velosa APP, Andrade P, Farhat C, Fabro AT, Capelozzi VL. Butylated hydroxytoluene induces type-V collagen and overexpression of remodeling genes/proteins in experimental lung fibrosis. Histol Histopathol. 2018 Oct;33(10):1111-1123. doi: 10.14670/HH-18-010.

.Abstract. Anomalous histoarchitecture with increased levels of type-V collagen (Col V) in lungs of human idiopathic pulmonary fibrosis (IPF) and bleomycin (BLM) airway-centered interstitial fibrosis suggest that this collagen can be a possible trigger involved in the pathogenesis of these diseases. Butylated hydroxytoluene (BHT) injury model revealed a distal involvement of lung parenchyma with significant endothelial injury and fibrotic response, contrasting with the BLM airway-centered insult. We undertook this study to analyze whether BHT alters distal airway/alveolar epithelial cells (AECs) and extracellular matrix (ECM) signaling involved in the initiation and progression of pulmonary fibrosis in a different pathway concerning overexpression of Col V. Female mice C57BL/6 (n=6) were instilled intraperitoneally with 400 mg/kg of BHT dissolved in 1 mL of corn oil and euthanized at day 14 or 21 after BHT administration. Morphometry, immunohistochemistry and transmission electron microscopy were performed to characterize microscopic and submicroscopic changes of AECs and endothelial cells through transforming growth factor beta (TGF-β) basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) expression. Immunofluorescence and immunogold electron microscopy were performed to characterize Col V. Quantitative polymerase chain reaction (qPCR) was used to confirm differential levels of RNA messenger. BHT lungs showed marked fibrotic areas and hyperplastic AECs. The alveolar damage caused destruction of elastic fibers and a critical increase of Col V in ECM of distal lung parenchyma. Fibrogenesis-promoting markers TGF-β, bFGF and VEGF were also overexpressed in situ, coinciding with up-regulation in remodeling enzymes, growth factors, cytokines, transduction and transcription genes. BHT alters distal lung parenchyma signaling involved in pulmonary fibrosis highlighted similarities to human IPF in a pathway involving Col V arising as a promissory model to identify effective therapeutic targets.

García Ibarra V, Sendón R, García-Fonte XX, Paseiro Losada P, Rodríguez Bernaldo de Quirós A. Migration studies of butylated hydroxytoluene, tributyl acetylcitrate and dibutyl phthalate into food simulants. J Sci Food Agric. 2019 Mar 15;99(4):1586-1595. doi: 10.1002/jsfa.9337.

Abstract. ... ..The present study investigated the process of migration of two common plasticizers [tributyl acetylcitrate (ATBC) and dibutyl phthalate (DBP)] and one antioxidant [butylated hydroxytoluene (BHT)] from a common plastic material used in food packaging (low density polyethylene) into 50% ethanol (v/v), 95% ethanol (v/v) and isooctane. A mathematical model based on Fick's second law was used to determine the partition and diffusion coefficients. In addition, the effect of temperature on the diffusion was studied by applying the Arrhenius equation....© 2018 Society of Chemical Industry.

Pop A, Drugan T, Gutleb AC, Lupu D, Cherfan J, Loghin F, Kiss B. Estrogenic and anti-estrogenic activity of butylparaben, butylated hydroxyanisole, butylated hydroxytoluene and propyl gallate and their binary mixtures on two estrogen responsive cell lines (T47D-Kbluc, MCF-7). J Appl Toxicol. 2018 Jul;38(7):944-957. doi: 10.1002/jat.3601. 

Abstract. The estrogenic and anti-estrogenic effects of butylparaben (BuPB), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and propyl gallate (PG) were evaluated for individual compounds as well as for binary mixtures, using an estrogen-dependent reporter gene assay in T47D-Kbluc breast cancer cells and an estrogen-dependent proliferation assay in MCF-7 breast cancer cells....Copyright © 2018 John Wiley & Sons, Ltd.

Yu LL, Yu HH, Liang XF, Li N, Wang X, Li FH, Wu XF, Zheng YH, Xue M, Liang XF. Dietary butylated hydroxytoluene improves lipid metabolism, antioxidant and anti-apoptotic response of largemouth bass (Micropterus salmoides). Fish Shellfish Immunol. 2018 Jan;72:220-229. doi: 10.1016/j.fsi.2017.10.054.

Abstract. A 10-week growth trail was conducted to investigate the efficacy and tolerance of dietary butylated hydroxytoluene (BHT) by evaluating inflammation, apoptosis and hepatic disease related to oxidative stress in largemouth bass (Micropterus salmoides).....Copyright © 2017 Elsevier Ltd.

Tao J, Zhu Q, Qin F, Wang M, Chen J, Zheng ZP. Preparation of steppogenin and ascorbic acid, vitamin E, butylated hydroxytoluene oil-in-water microemulsions: Characterization, stability, and antibrowning effects for fresh apple juice. Food Chem. 2017 Jun 1;224:11-18. doi: 10.1016/j.foodchem.2016.12.045.

Abstract. Oil-in-water microemulsions (O/W MEs) allow the preparation of insoluble compounds into liquid. In this study, we prepared O/W MEs to improve the solubility and stability of steppogenin (S) in aqueous liquid, and studied their ability to inhibit fresh apple juice browning. ...Copyright © 2016 Elsevier Ltd.