BHA (butylated hydroxyanisole)

Other Names

(1,1-Dimethylethyl)-4-methoxyphenol2(3)-t-Butyl-4-hydroxyanisole2(3)-t-Butylhydroquinone monomethyl ether2(3)-tert-Butyl-4-hydroxyanisole2-terc.Butyl-4-methoxyfenol2-tert-Butyl-4-hydroxyanisole2-tert-Butyl-4-methoxyphenol3-tert-Butyl-4-hydroxyanisole3-tert-Butyl-4-methoxyphenol3-tertiary-butyl-4-hydroxyanisole4-Hydroxy-3-tert-butylanisole4-Methoxy-2-(1,1-dimethylethyl)phenol4-Methoxy-2-tert-butylphenolAnisole, butylated hydroxy-Antioxyne BBHABOAButyl hydroxyanisoleButylated hydroxyanisoleButylhydroxyanisolButylhydroxyanisoleButylohydroksyanizolE320EEC No. E320INS 320Mixture of 3- and 2-tertiary-butyl-4-hydroxyanisolePhenol, (1,1-dimethylethyl)-4-methoxy-Phenol, 2-(1,1-dimethylethyl)-4-methoxy-Phenol, tert-butyl-4-methoxy-t-Butyl hydroxyanisoletert-Butyl hydroxyanisoletert-Butyl-4-hydroxyanisoletert-Butyl-4-methoxyphenoltert-Butyl-p-Hydroxyanisoltert-Butyl-p-hydroxyanisoletert-Butyl-p-methoxyphenoltert-ButylhydroxyanisoleTertiary butyl hydroxyanisole

Synopsis

Butylated Hydroxyanisole (BHA)

1. Identity: Chemical Names, Structure, and Physical Properties

Butylated hydroxyanisole (abbreviated BHA) is a synthetic, fat-soluble, phenolic antioxidant compound. It is a synthetic, waxy, solid petrochemical with broad applications across the food, cosmetic, pharmaceutical, and industrial sectors. Its antioxidant properties have caused it to be widely used as a preservative in food, food packaging, animal feed, cosmetics, pharmaceuticals, rubber, and petroleum products.

BHA consists of a mixture of two isomeric organic compounds, 2-tert-butyl-4-hydroxyanisole and 3-tert-butyl-4-hydroxyanisole. BHA is an aromatic organic compound with the chemical names of 2- and 3-tert-butyl-4-methoxyphenol. The compound bears the CAS registry number 25013-16-5. BHA used in food is a mixture of predominantly 3-tert-butyl-4-hydroxyanisole (3-BHA, CAS No. 121-00-6), with varying amounts of 2-tert-butyl-4-hydroxyanisole (2-BHA, CAS No. 88-32-4). Food-grade BHA contains over 85% 3-BHA and less than 15% 2-BHA, while cosmetic-grade BHA contains 90% 3-BHA and 8% 2-BHA. The purity of BHA is specified to be not less than 85% 3-BHA isomer in the mixture according to EU legislation and JECFA.

In its pure form, BHA is a waxy white or pale yellow solid with a melting point of 118.4–131°F (48–55°C) and a boiling point of 507.2–518°F (264–270°C). BHA is insoluble in water, but is soluble in fats, oils, propylene glycol, petroleum ether, chloroform, and 50% alcohol.

BHA is assigned the European food additive code E number E320. It is prepared from 4-methoxyphenol and isobutylene, and the conjugated aromatic ring of BHA is able to stabilize free radicals.

Relationship to Chemically Similar Compounds

BHA is chemically related to butylated hydroxytoluene (BHT) and tert-butylhydroquinone (TBHQ), a metabolic product of BHA, both of which are sometimes used in conjunction with BHA in food formulations. BHA is frequently used in combination with other antioxidants, particularly butylated hydroxytoluene and alkyl gallates, and with sequestrants or synergists such as citric acid.

Note on naming ambiguity: BHA the preservative (butylated hydroxyanisole) is completely different from BHA the exfoliant (beta hydroxy acid / salicylic acid). They share an abbreviation but are unrelated chemicals.

2. Historical and Traditional Use

BHA is entirely synthetic and has no botanical origin or traditional herbal use. Its history is therefore industrial rather than ethnobotanical.

BHA was first synthesized in the late 1940s as an effective antioxidant in various foods, cosmetics, packaging and other products. Since 1947, BHA has been added to edible fats and fat-containing foods for its antioxidant properties as it prevents rancidification of food, which creates objectionable odors. It is also used in foods cooked or fried in animal oils, because of its high thermal stability and its ability to remain active in baked and fried foods.

The FDA listed BHA as Generally Recognized as Safe (GRAS) in 1958 and approved it as a food additive in 1961. In 1984, the International Life Sciences Institute indicated that approximately 50 countries allowed the use of BHA as a food additive.

First used as an antioxidant in 1947, BHA is now added to a wide variety of foods, including beverages, ice cream, candy, baked goods, instant mashed potatoes, edible fats and oils, breakfast cereals, dry yeast, and sausages. BHA is added to butter, lard, meats, cereals, baked goods, sweets, beer, vegetable oils, potato chips, snack foods, nuts and nut products, dehydrated potatoes, and flavoring agents. It is used in sausage, poultry and meat products, dry mixes for beverages and desserts, glazed fruits, chewing gum, active dry yeast, defoaming agents for beet sugar and yeast, and emulsion stabilizers for shortening.

BHA has also been used extensively in cosmetics, especially lipsticks and eye shadow. There is widespread human exposure to this compound by ingestion and skin application.

3. Key Constituents and Active Compounds

Because BHA is itself a single (though commercially mixed) synthetic chemical rather than a plant extract, the relevant chemistry concerns its two principal isomers and their metabolites.

3-tert-Butyl-4-hydroxyanisole (3-BHA): The 3-isomer is considered to be a better antioxidant and represents 90% of the commercial BHA.
2-tert-Butyl-4-hydroxyanisole (2-BHA): The minor isomer, comprising up to 15% in food-grade material.
tert-Butylhydroquinone (TBHQ): Under different conditions, BHA can produce different metabolites, with tert-butyl hydroquinone (TBHQ) being one of the major products. BHA is biotransformed to tert-butylhydroquinone (TBHQ), which readily auto-oxidizes to the electrophilic metabolite tert-butylbenzoquinone (TBQ).

4. Mechanisms of Action

4.1 Free Radical Scavenging

The conjugated aromatic ring of BHA is able to stabilize free radicals, sequestering them. By acting as free radical scavengers, further free radical reactions are prevented. When used in foods, it is used to delay or prevent oxidative rancidity of fats and oils and to prevent loss of activity of oil-soluble vitamins.

4.2 Nrf2 Pathway Activation

BHA's chemopreventive properties are attributed to its ability to activate the transcription factor NF-E2 p45-related factor 2 (Nrf2), which directs central genetic programs of detoxification and protection against oxidative stress. BHA and TBHQ activate Nrf2, a transcription factor that is negatively regulated by Keap1 and plays a role in the initial response to chemicals causing oxidative or electrophilic stress, although the exact mechanism of Nrf2 activation remains unclear.

The antioxidant responsive element (ARE), located on many phase II/antioxidant genes, binds with the transcription factor Nrf2 and is required for the activation of these phase II/antioxidant gene expressions induced by many natural and synthetic cancer chemopreventive compounds. In one cell study, ARE transcriptional activity and HO-1 protein expression were increased dose-dependently after treatment with BHA in HepG2 cells.

4.3 Induction of Phase II Detoxifying Enzymes

BHA is a commonly used food preservative with broad biological activities, including protection against acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, and induction of phase II detoxifying enzymes. Studies in mice demonstrate that BHA elicited differential expression patterns of phase II-detoxifying enzymes in the liver and small intestine, demonstrating a cell-type-specific response to BHA in vivo.

4.4 Antimutagenic Activity

When tested in combination with other chemicals (usually known mutagens or carcinogens), BHA often modified their DNA-damaging, mutagenic, and clastogenic activities. In most studies, BHA reduced the activity of indirectly-acting mutagens/carcinogens. The protective effect of BHA on mutagen-induced mutagenicity is best explained by the antioxidative activity of BHA, which may scavenge free radicals that participate in mutagen-induced mutagenicity.

5. Scientific Evidence by Area of Use

5.1 Food Preservation and Antioxidant Efficacy

BHA's primary and best-established use is as a food antioxidant preservative. Since 1947, BHA has been added to edible fats and fat-containing foods as an antioxidant. It serves an important role in preserving food by preventing oxidative rancidity of fats and oils as well as preventing the loss of activity of oil-soluble vitamins. BHA is extensively used in bulk oils and oil-in-water emulsions. It proved to be a very effective protector in animal fats, but relatively ineffective in vegetable oils. BHA can be added to packaging materials in order to provide protection to foods inside the package through the volatilization of the antioxidant.

Evidence strength: Robust; decades of applied industrial food science confirm efficacy in preventing rancidity, and this function is undisputed across regulatory authorities worldwide.

5.2 Cancer Biology: Anticarcinogenic Versus Pro-Carcinogenic Effects

The scientific picture of BHA and cancer is notably complex and dual-faceted. Animal and in vitro studies show both pro-carcinogenic effects (at high doses in rodent species with a forestomach) and anticarcinogenic effects (inhibition of carcinogenesis by other agents).

Pro-carcinogenic findings (animal data): BHA is classified as reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals. Dietary exposure to BHA caused benign and malignant tumors of the forestomach (papilloma and squamous-cell carcinoma) in rats of both sexes and in male mice and hamsters. Dietary administration of BHA to fish (hermaphroditic Rivulus marmoratus) as larvae also caused liver cancer (hepatocellular carcinoma) in the adult fish.

Key species-relevance caveat: IARC classified BHA as Group 2B ("possibly carcinogenic to humans") on the basis of forestomach tumors in rodents following chronic dietary exposure to high levels. IARC later determined that the mechanism by which BHA induces forestomach tumors is not relevant to humans; however, the classification has not been revoked. Reports of carcinogenicity from BHA free-radical metabolites are limited to rodent squamous cells of the forestomach, an organ that does not have a human counterpart.

BHA is not DNA-reactive, and the epigenetic mechanism of tumor formation involves cytotoxicity and enhanced cell proliferation, which are mostly reversible. Humans lack a forestomach and, therefore, are predicted to be much less sensitive than rodents to the effects of BHA.

Anti-carcinogenic and antimutagenic findings (primarily animal/in vitro): BHA given orally or parenterally to mice and rats was shown to inhibit the carcinogenic effects of a broad range of chemical carcinogens. BHA has been shown to inhibit mutagenesis and was not a mutagenic agent in standard in vitro tests. One review of experimental studies of genotoxicity and carcinogenicity concluded that BHA and BHT pose no cancer hazard and, to the contrary, may be anticarcinogenic at current levels of food additive use.

The fact that phenolic antioxidants such as BHA are capable of inhibiting the initiation of chemical carcinogenesis was one of the discoveries that helped establish the cancer chemoprevention field.

Human epidemiological data: The data available from epidemiological studies are inadequate to evaluate the relationship between human cancer and exposure specifically to BHA. Since BHA was listed in the Sixth Annual Report on Carcinogens, one epidemiological study of BHA has been identified. When examining human population statistics, the usual low intake levels of BHA show no significant association with an increased risk of cancer.

Evidence strength: Carcinogenicity in rodent forestomach is well established but of uncertain human relevance (rodent-specific organ). Human epidemiological evidence is insufficient to draw conclusions. The anticarcinogenic effects against other carcinogens are supported by animal and in vitro studies but lack human clinical evidence.

5.3 Endocrine-Disrupting Properties

BHA is extensively used as an antioxidant in foods, food packaging, cosmetics and pharmaceuticals. In recent years, it has raised concerns regarding its possible endocrine disrupting effect. The existing in vitro studies indicate that BHA presents a weak estrogenic effect and also anti-androgenic properties, while one in vivo study found it to have antiestrogenic properties. There is no sufficient data available at the moment to draw a conclusion regarding the safety of BHA when referring to its endocrine disrupting effect.

BHA was found to have effects on estrogenic and androgenic hormones, although the evidence was not considered strong enough to clearly indicate that BHA disrupted the endocrine system. Endocrine disruption, if any, is only likely to be present at levels vastly exceeding the intake as a food.

Several studies have shown that BHA could cause thyroid system damage, metabolic and growth disorders, neurotoxicity, and carcinogenesis. Mechanisms such as endocrine disruption, genotoxicity, disturbances of energy metabolism, reactive oxygen species (ROS) production, signaling pathways, and imbalances in calcium homeostasis appear to be associated with the toxic effects of BHA.

Evidence strength: Endocrine disruption signals come primarily from in vitro and some in vivo animal studies. Human clinical evidence is absent. The effect appears weak and conflicting across study designs.

5.4 Nrf2 Activation and Chemoprevention (Preclinical)

In a preclinical mouse study examining Nrf2 signaling, investigators examined histological changes of Nrf2 and its regulated phase II enzymes in wild-type and Nrf2-knockout mice. The mice were given a 200 mg/kg oral dose of BHA daily for three days. Immunohistochemistry revealed that, in the liver from wild-type mice, BHA increased Nqo1 staining in hepatocytes, predominately in the pericentral region.

In a rodent study of estrogen-induced breast carcinogenesis, female ACI rats were treated with estradiol (E2) alone or in combination with vitamin C or BHA for up to 240 days; mRNA and protein levels of a DNA repair enzyme (OGG1) and NRF2 were quantified in mammary and tumor tissues. The investigators concluded that BHA provides protection against oxidative DNA damage and E2-induced mammary carcinogenesis, at least in part, through NRF2-mediated induction of OGG1.

Evidence strength: These are animal and in vitro findings. No human clinical trials have investigated BHA as a chemopreventive agent.

5.5 Genotoxicity (Standard Assays)

Butylated hydroxyanisole was not mutagenic to Salmonella typhimurium, Drosophila melanogaster or to Chinese hamster cells in vitro. It did not cause chromosomal effects in D. melanogaster or in cultured Chinese hamster cells. BHA was found not to induce chromosomal aberrations when tested in cultured Chinese hamster cells. No effect on the occurrence of chromosomal aberrations or sister chromatid exchanges was found in a Chinese hamster cell line exposed to BHA. IARC acknowledged that BHA is not genotoxic in bacterial and mammalian assays and further acknowledged that when tested in combination with other chemicals, BHA reduced the activity of other mutagens/carcinogens.

Evidence strength: Standard genotoxicity assays are consistently negative for BHA. The compound is not considered a direct genotoxin/DNA-reactive agent.

6. Body Systems and Health Areas Associated with BHA

Gastrointestinal system: High-dose rodent exposures cause forestomach hyperplasia, ulceration, and tumors, an effect specific to species with a forestomach (rodents, hamsters). In rats, feeding BHA in the diet caused superficial necrosis, ulceration and hyperplasia of the squamous epithelium of the forestomach. Induction of forestomach hyperplasia also occurs in hamsters. Administration of BHA by gavage to monkeys was associated with an elevated mitotic index in the squamous epithelium of the distal oesophagus.
Liver: BHA activates Nrf2-regulated detoxifying enzymes differentially in hepatocytes. In 1978, the FDA's own Select Committee on GRAS Substances found that additional studies were needed because of uncertainty that BHA could impact liver function.
Endocrine system: In vitro evidence suggests weak estrogenic and anti-androgenic activity; some animal studies raise thyroid concerns at higher doses.
Reproductive system: BHA administered to rats at maternally toxic and occasionally lethal doses during or before and after gestation induced developmental effects.
Immune system: BHA is considered to be an anticarcinogenic substance in experimental animals and has been shown to have immunosuppressive activity in vitro.
Oxidative stress / cellular defense: BHA is a potent activator of the Nrf2/ARE axis, upregulating phase II enzymes including NQO1, HO-1, glutathione S-transferases, and related proteins involved in electrophilic and oxidative stress defense.

7. Absorption, Distribution, Metabolism, and Excretion

BHA is rapidly absorbed from the gastrointestinal tract; it is metabolised rapidly and excreted as such and as metabolites in the urine and faeces. The proportions of the different metabolites vary depending on species and dose. No accumulation of BHA or metabolites was observed in tissues.

Overall, oral absorption of BHA is at least 86% in rats, 44% in dogs, and 32–100% in humans. The majority of the dose is excreted in the urine of both humans and rats during the first two days after oral administration (rat: approximately 49%, human: approximately 39%), primarily in conjugated form.

In a human pharmacokinetic study, high-resolution capillary gas chromatography–mass spectrometry was used to measure BHA in the plasma and urine of human volunteers after oral administration of 30 or 5 mg of the compound in olive oil. Pharmacokinetic studies showed similar plasma-concentration profiles in subjects treated with either level of BHA. About 20% of the administered dose was excreted as BHA glucuronide in the urine within the first 24 hours.

Following oral administration, BHA is absorbed and rapidly excreted by the rat, rabbit and man, with little evidence of long-term tissue storage. The major metabolic pathways for BHA are conjugation (phase 2) reactions, oxidative metabolism (O-demethylation) being relatively unimportant. In the rabbit, BHA was conjugated mainly with glucuronic acid or sulfuric acid; a small amount of unchanged BHA was excreted in the urine. In rats, the 2-tert-butyl isomer was chiefly excreted as glucuronide, while the 3-tert-butyl isomer was excreted mainly as ethereal sulfate.

Both animal and human studies have shown that BHA is absorbed from the gastrointestinal tract and metabolized. Tissue storage may occur with BHA because of its lipid solubility. However, the amount stored is limited by rapid metabolism and excretion.

8. Dosage Forms, Regulatory Limits, and Reported Study Dosages

8.1 Food Additive Regulatory Limits

FDA regulations direct that the total content of antioxidant in vegetable oils and direct food additives shall not exceed 0.02% w/w (200 ppm) of fat or oil content or essential (volatile) oil content of food.
USDA regulations require that the total content of antioxidant shall not exceed 0.01% w/w (100 ppm) of any one antioxidant or 0.02% w/w combined total of any antioxidant combination in animal fats.
An Acceptable Daily Intake (ADI) of 0–0.5 mg/kg body weight has been allocated to BHA by JECFA (the Joint FAO/WHO Expert Committee on Food Additives).
The EFSA FEEDAP Panel retains an acceptable daily intake (ADI) of 1 mg/kg body weight as proposed by the EFSA Scientific Panel on Additives and Nutrient Sources added to Food (ANS).

8.2 Animal Feed

The EFSA FEEDAP Panel concluded that no concern for consumer safety would arise from the use of BHA as a feed additive at the maximum concentration of 150 mg/kg feed. A highly conservative estimate of consumer exposure resulting from consumption of food from animals fed BHA at the highest feed concentration of 150 mg BHA/kg resulted in 5 mg BHA per person per day, corresponding to about 8% of the ADI.

8.3 Cosmetics

Based on the risk assessment, the SCCS considers the use of BHA in leave-on and rinse-off cosmetic products up to a concentration of 0.07% as safe. On April 16, 2026, the Scientific Committee on Consumer Safety (SCCS) of the European Union issued its final opinion (SCCS/1682/25) on Butylated Hydroxyanisole. This SCCS Scientific Advice considered only dermal use and hence is applicable for dermally applied products, and not for oral care products or cosmetic products that may lead to exposure of the end-user's lungs by inhalation.

8.4 Dosages Reported in Preclinical Studies

In a mouse Nrf2 induction study, mice were given a 200 mg/kg oral dose of BHA daily for three days.
In a human pharmacokinetic study, volunteers received oral administration of 30 mg or 5 mg of BHA in olive oil.
In an immunological mouse study, male Swiss-Webster mice were fed semisynthetic diets containing 0.02% or 0.2% BHA.

8.5 Forms and Formulations

BHA is not produced or sold as a standalone dietary supplement for human consumption. Its antioxidant properties have caused it to be widely used as a preservative in food, food packaging, animal feed, cosmetics, pharmaceuticals, rubber, and petroleum products. In cosmetics, it is commonly found in lipsticks, foundations, creams, and sunscreens, where it also serves as a masking agent to neutralize odors. BHA is synthetically produced through the butylation of hydroxyanisole with isobutylene or tert-butyl chloride in the presence of a catalyst like sulfuric acid. The reaction yields a mixture of 2- and 3-tert-butyl isomers, purified to meet cosmetic standards. Derived from petrochemical sources, it is manufactured industrially for consistent purity and efficacy.

9. Safety Considerations and Regulatory Status

9.1 Carcinogenicity Classifications

Based on the results of chronic rodent studies, BHA has been classified as a carcinogen by several regulatory/advisory bodies including IARC, the State of California, and the NTP's Report on Carcinogens. IARC reviewed BHA in October 1985 and classified it in Group 2B (Possible Human Carcinogen) based on "sufficient evidence of carcinogenicity in experimental animals" and "no data were available on the carcinogenicity" in human beings.

The National Toxicology Program (NTP) determined that BHA is "reasonably anticipated to be a human carcinogen" based on sufficient evidence of carcinogenicity from studies in experimental animals.

The European Commission conducted an evaluation of the literature. They noted the lack of potential for the compound to induce carcinogenic effects in humans; studies showing carcinogenic effects in hamsters are not relevant to humans, which lack a forestomach.

9.2 Endocrine Disruption Classification

BHA is listed as a category 1 endocrine disrupting chemical on the European Union list of potential endocrine disruptors. Since a fraction of the population might be exposed to doses superior to the ADI, it is important to gather more in vitro and in vivo data concerning the potential effects that BHA might have alone, but also in mixtures with natural hormones or other endocrine disrupting compounds.

9.3 Ongoing FDA Review

The U.S. Food and Drug Administration launched a comprehensive re-assessment of BHA in 2026. The review will consider whether BHA is safe under its current conditions of use in food and as a food contact substance, based on the latest scientific information. As part of this re-assessment, the agency issued a Request for Information on the use and safety of BHA. The FDA identified BHA as a top priority for review. In February 2026, BHA was added to the FDA's List of Select Chemicals in the Food Supply Under FDA Review.

9.4 Acute Toxicity

Reported acute oral LD50 values for BHA in rats varied from 2.0 to greater than 5.0 g/kg. Formulations containing BHA elicited, at most, minimal or moderate skin and eye irritation in rabbits.

9.5 Worker/Handler Safety

The additive should be considered a skin and eye irritant and a potential skin sensitiser. Exposure of the user via inhalation is considered unlikely; therefore, a risk is not expected.

9.6 Interaction with Co-Administered Antioxidants

In rats, the simultaneous administration of BHT and BHA significantly decreased the absorption of BHT from the gastrointestinal tract in the first few hours after treatment; the plasma kinetics of BHA were not influenced by the simultaneous administration of BHT. In human female volunteers, no alterations in plasma BHT or BHA profiles were seen after the simultaneous ingestion of BHT (0.25 mg/kg body weight) and BHA (0.25 mg/kg body weight).

9.7 Historical Regulatory Uncertainties

In 1978, the FDA's own Select Committee on GRAS Substances (SCOGS) found that additional studies were needed because of uncertainty that BHA could impact liver function. It is unclear whether FDA has resolved those uncertainties with new studies. Despite this long history of safety concerns, BHA continues to be approved for use in the US food supply and the food industry still designates it as GRAS.

9.8 Summary of the Carcinogenicity Debate

BHA was classified as Group 2B by IARC ("possibly carcinogenic to humans") on the basis of forestomach tumors in rodents following chronic dietary exposure to high levels. IARC later determined that the mechanism by which BHA induces forestomach tumors is not relevant to humans; however, the classification has not been revoked. One peer-reviewed review concluded that BHA poses no cancer hazard and, to the contrary, may be anticarcinogenic at current levels of food additive use. This remains an area of unresolved scientific and regulatory debate.

References

Health Conditions

Health conditions that BHA (butylated hydroxyanisole) may help support.

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Body Systems

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