Arbutin

Arbutin: A Comprehensive Reference Article

1. Identity and Chemical Characterization

1.1 Nomenclature and Chemical Structure

β-Arbutin, also known by its International Nomenclature of Cosmetic Ingredients (INCI) name arbutin, is a glycosylated derivative of hydroquinone. Chemically known as 4-hydroxyphenyl-beta-glucopyranoside, its molecular formula is C₁₂H₁₆O₇, and its IUPAC name is (2R,3S,4S,5R,6S)-2-Hydroxymethyl-6-(4-hydroxyphenoxy)oxane-3,4,5-triol. It is a β-glucoside derived from hydroquinone (HQ; 1,4-dihydroxybenzene). The compound exists as two distinct stereoisomers: β-arbutin, which is the naturally occurring form found abundantly in plants, and α-arbutin, a synthetic or enzymatically produced analog. α-Arbutin is the epimer of β-arbutin, and the spatial orientation of their glycosidic bonds is opposite.

β-Arbutin is soluble in water, presenting typically as a white powder that remains stable under standard storage conditions. It exhibits stability in both ethanol and water and demonstrates resistance to light exposure. When dissolved in water, β-arbutin may undergo hydrolysis, converting to hydroquinone, which can subsequently oxidize to benzoquinone.

1.2 Natural Sources and Botanical Distribution

Arbutin (also called β-arbutin) is a natural product occurring in the leaves of a variety of different plants, the bearberries of the Ericaceae and Saxifragaceae families being prominent examples. The compound is naturally occurring and can be extracted from several plant species. Traditionally extracted from the bearberry plant (Arctostaphylos uva-ursi), it also occurs in high levels in plants in the families of Ericaceae and Saxifragaceae, including the pear (Pyrus spp.) and certain species of wheat. It is also found in very small quantities in Viburnum opulus, Bergenia crassifolia, and Schisandra chinensis.

The bearberry plant contains diverse phytochemicals, including ursolic acid, tannic acid, gallic acid, some essential oils and resin, hydroquinones (mainly arbutin, up to 17%), tannins (up to 15%), phenolic glycosides and flavonoids. Arbutin has been identified in over 50 plant families, especially in the plants of the Asteraceae, Ericaceae, Proteaceae, and Rosaceae families.

The European Pharmacopoeia specifies that bearberry leaf (Uvae ursi folium) must contain not less than 7% of anhydrous arbutin (C₁₂H₁₆O₇; molecular weight 272.3), calculated with reference to anhydrous drug and determined using an HPLC method. The primary chemical component of uva ursi is arbutin, comprising 5% to 16% of the plant, and the arbutin content varies seasonally.

1.3 Common Forms and Preparations

The sources of α-arbutin and β-arbutin are completely different. β-Arbutin can be prepared by plant extraction, plant cell culture, and artificial synthesis. Alpha-arbutin is generally prepared by different microbial enzymes. Synthetically, β-arbutin can also be prepared from the reaction of acetobromoglucose and hydroquinone in the presence of an alkali.

In commerce, arbutin is available in several forms: topical cosmetic preparations (creams, serums, and lotions), standardized oral herbal extracts (capsules, tablets), aqueous infusions (teas), tinctures, and as an isolated purified ingredient for compounding. The main application of β-arbutin is in the cosmetic industry, where it is incorporated into various skin care products, including creams, serums, and lotions, aimed at lightening skin tone and correcting hyperpigmentation. The bearberry is a source of herbal material — bearberry leaf (Uvae ursi folium) — which is highly valued and sought by the pharmaceutical and cosmetic industries.

2. Traditional and Historical Use

2.1 Native American and Indigenous Traditions

Uva ursi has been used extensively in native cultures since the Middle Ages and is listed in the pharmacopoeias of many Western societies for the treatment of urinary conditions, primarily symptoms of urinary tract infection. From 1820 to 1936, a fluid extract made from the leaves of the herb was listed as a urinary antiseptic in the US Pharmacopeia and US National Formulary.

Uva ursi is an herbal extract derived from the leaves of Arctostaphylos, a small evergreen shrub, which has been used in Native American traditional medicine for treatment of urinary tract symptoms and as a diuretic. The common name kinnikinnick is an Algonquin word meaning "smoking mixture." Native Americans and early pioneers smoked the dried uva-ursi leaves and bark alone or mixed with other herbs, tobacco, or dried dogwood bark in pipes. Bearberry fruits and leaves are used by members of the Blackfeet Nation as food.

2.2 European Herbal Medicine

For many years, leaves of this plant have been used in traditional medicine as a diuretic, antimicrobial, and anti-inflammatory agent for various diseases of the urogenital tract. For centuries, β-arbutin has been used in phytotherapy, or herbal medicine. Extracted from the leaves of bearberry plants, it is used as a mixture with other herbal drugs as a treatment for urinary tract infections.

Uva ursi has been used to treat dysuria, cystitis, urethritis, and kidney and bladder stones. It has also been recommended for inducing diuresis and to treat constipation. Preparations traditionally included cold water macerates and warm infusions of the dried leaf, with cold maceration historically preferred to limit tannin extraction while retaining arbutin content.

2.3 Traditional Chinese Medicine

Arbutin has been identified in traditional Chinese folk medicines as having, inter alia, anti-microbial, anti-oxidant, and anti-inflammatory properties that are useful in the treatment of different ailments including urinary diseases. Arbutin is recognized as a major ingredient of the Chinese medicinal herb cowberry leaf, where it was traditionally valued for its antioxidant and anti-inflammatory activities.

2.4 Development as a Cosmetic Ingredient

The Japanese cosmetics company Shiseido developed arbutin as a whitening agent in the 1990s. Today, it is used worldwide for the treatment of skin ailments by way of depigmenting, meaning that arbutin is a component of many products in the cosmetics and healthcare industries. Hundreds of publications have appeared describing the isolation, structure determination, toxicology, synthesis, and biological properties of arbutin, as well as the molecular mechanism of melanogenesis (tyrosinase inhibition).

3. Key Constituents and Mechanisms of Action

3.1 Arbutin as Part of the Bearberry Phytochemical Profile

Other hydroquinone derivatives in bearberry include methyl arbutin, galloyl derivatives of arbutin, free hydroquinone, and methylhydroquinone. Other components include polyphenols (tannins), phenolic acids (mainly gallic), piceoside, flavonoids, iridoid glucoside, triterpenes, enzymes (beta-glucosidase), allantoin, resin, volatile oil, and wax. These co-occurring compounds are considered to contribute synergistically to the plant's traditional antimicrobial and anti-inflammatory effects, although arbutin is identified as the principal active constituent.

3.2 Tyrosinase Inhibition and Antimelanogenic Mechanism

Melanin, the major pigment that gives color to skin, may be over-produced with sun exposure or in conditions such as melasma or hyperpigmentary diseases. Tyrosinase is a key enzyme that catalyzes melanin synthesis in melanocytes; therefore, inhibitors of the tyrosinase enzyme could be used for cosmetic skin whitening.

Arbutin is a naturally occurring glucopyranoside derivative of hydroquinone that causes decreased tyrosinase activity without affecting messenger RNA expression. Arbutin also inhibits melanosome maturation. Arbutin inhibits the catalytic activity of tyrosinase (TYR). It also scavenges reactive oxygen species (ROS) from various sources that can induce melanin synthesis, apoptosis, or tumorigenesis. Arbutin is a compound of hydroquinone and D-glucose, and it has been over 30 years since there have been serious studies on the skin lightening action of this substance.

The predominant conclusion from mechanistic studies is that direct inhibition of melanosomal tyrosinase activity by α-arbutin hampers the melanogenesis process, rather than suppressing tyrosinase gene expression or cell growth. A secondary proposed mechanism involves an antioxidant effect: α-arbutin upregulates the Nrf2 transcription factor, which consequently activates target genes involved in antioxidant defense. Thus, arbutin and α-arbutin may reduce ROS levels by directly scavenging free radicals or indirectly enhancing the antioxidant capacity of cells through the activation of the Nrf2-ARE pathway.

Notably, the two stereoisomers differ in potency. In the alpha form, the glucose molecule is attached in the axial position — a structural arrangement that confers greater molecular stability in aqueous formulations and, in published comparative assessments, greater potency of tyrosinase inhibition relative to the beta form, where the glucose is attached in the equatorial position.

3.3 Pharmacokinetics: Oral Administration and Conversion to Hydroquinone

After oral administration, β-arbutin is absorbed in the small intestine and hydrolyzed in the liver by β-glucosidases to hydroquinone, which is subsequently conjugated with glucuronic acid or sulfuric acid. In these forms it is excreted by the kidney. In the case of a lower urinary tract infection, the conjugates are hydrolyzed in the urinary bladder, and the formed hydroquinone shows antibacterial effects.

In 16 healthy volunteers given arbutin either as tea made from uva ursi leaves or as an extract prepared as tablets, hydroquinone glucuronide and sulfate were rapidly detected in urine, with lesser amounts of free hydroquinone in all subjects regardless of the ingested form of uva ursi. This pharmacokinetic profile is central to understanding both the therapeutic rationale and the safety considerations for oral arbutin use.

A therapeutic recommended human daily dose of bearberry leaf extract (420 mg hydroquinone derivatives calculated as anhydrous arbutin) liberates free hydroquinone in urine at a maximum exposure level of 11 µg/kg body weight per day. By means of an experimental no-observed-effect-level value, a permitted daily exposure dose below which there is a negligible risk to human health was estimated for free HQ at 100 µg/kg body weight per day. Dietary sources of arbutin/HQ that are regularly consumed long term by humans generate comparable free HQ exposure levels.

3.4 Antimicrobial Mechanism

The glycoside arbutin is the main active constituent in uva ursi and comprises up to 10% of the plant by weight. Hydroquinone derived from arbutin and methylarbutin is a powerful anti-bacterial agent and is thought to be responsible for uva ursi's ability to treat urinary tract infections. It is believed to be most effective as a urinary tract antiseptic agent if the urine is alkaline. In vitro studies have demonstrated antibacterial activity against a variety of organisms including Escherichia coli, the most prevalent urinary pathogen. The antimicrobial action has been attributed to the hydroquinone derivatives, especially arbutin.

3.5 Anti-Inflammatory Mechanisms

Assessment of molecular docking revealed a strong binding interaction of arbutin against 5-LOX, IL-17, TNF-alpha, interleukin-6, cyclooxygenase-2, nuclear factor-κB, IL-4, and iNOS. As a result, arbutin has been shown to significantly reduce experimentally induced arthritis by modulation of anti-inflammatory cytokines including IL-10 and IL-4, and the pro-inflammatory cytokine panel such as NF-κB, TNF-alpha, IL-1β, IL-6, PGE-2, 5-LOX, and COX-2.

4. Scientific Evidence by Area of Use

4.1 Skin Depigmentation and Hyperpigmentation

Evidence summary: This is the best-studied area for arbutin. Evidence includes substantial in vitro and animal studies, a smaller but growing body of human clinical data, and official regulatory endorsement for topical use.

It has been over 30 years since there have been serious studies on the skin lightening action of arbutin. In the meantime, there have been debates and validation studies about the mechanism of action of this substance as well as its skin lightening efficacy and safety.

Sugimoto et al. (2004) studied the inhibitory effects of α-arbutin on melanin biosynthesis in cultured human melanoma cells and a three-dimensional human skin model. The authors reported a concentration-dependent inhibition of melanin synthesis by α-arbutin on human melanoma cells, HMV-II. The inhibitory effect on melanogenesis was achieved at noncytotoxic concentrations of α-arbutin. The authors concluded that direct inhibition of melanosomal tyrosinase activity hampered the melanogenesis process, rather than suppressing tyrosinase gene expression or cell growth.

Research found that arbutin both inhibits melanin production in B16 cells induced with α-MSH and decreases tyrosinase activity in a cell-free system. Furthermore, the hyperpigmentation effects of α-MSH were abrogated by the addition of arbutin to brownish guinea pig and human skin tissues. These results suggest that arbutin may be a useful agent for skin whitening.

In human clinical settings, all applications containing active ingredients showed significant skin lightening by the end of the fourth week compared to baseline; yet only arbutin was able to demonstrate significant diminution of pigmentation when compared to the inactive control. Arbutin has been found to be the most effective active ingredient in one comparative study, even more so than hydroquinone, despite being a naturally occurring derivative. Both arbutin and hydroquinone suppress melanogenesis in the late stage of differentiation when the process becomes active.

Arbutin is not toxic to melanocytes and is used in a variety of pigment-lightening preparations in Japan at concentrations of 3%. Higher concentrations are more efficacious than lower concentrations, but a paradoxic pigment darkening may occur.

The skin lightening efficacy of arbutin alone or in combination with other active ingredients has been clinically evaluated. Combined therapy with arbutin and laser could give enhanced depigmenting efficacy. Overall, while in vitro and animal evidence is robust, large-scale randomized controlled human trials remain limited. The evidence for topical use is considered sufficient by regulatory bodies (see Section 6), but the clinical dataset for oral arbutin as a skin lightening agent is very sparse.

4.2 Urinary Tract Infections and Urogenital Health

Evidence summary: Supported by pharmacological plausibility, in vitro data, traditional use recognition by EMA and German Commission E, and a small number of clinical studies. No large-scale, high-quality randomized controlled trials confirming efficacy have been published.

The European Medicines Agency (EMA) concluded that, based on its traditional use, the effectiveness of uva ursi extracts was plausible and that its use was safe. However, the EMA noted that clinical studies allowing final assessment of the potency and safety of β-arbutin were still lacking.

The leaf extract of Arctostaphylos uva-ursi (uva-ursi or bearberry) has been approved for use for urinary tract inflammation by the German Federal Institute for Drugs and Medical Devices and is available on prescription in Germany for this indication.

One study of 309 women found that those advised to use an over-the-counter preparation containing uva ursi experienced shorter illness duration compared to those who weren't given that advice. A smaller study of 57 women with recurrent UTIs found that a combination of uva ursi and dandelion root appeared to help prevent infections from coming back.

A larger German trial (called REGATTA) was designed to test whether uva ursi could reduce antibiotic use for uncomplicated UTIs, using a dose of 630 mg of arbutin daily for five to six days. This study aimed at investigating whether an initial treatment with uva ursi in women with UTI can reduce antibiotic use without significantly increasing the symptom burden or rate of complications. The trial was designed as a double-blind, randomized, and controlled comparative effectiveness trial.

While uva ursi has been used extensively in traditional medicine, there is no convincing medical evidence that it is effective in treating urinary tract infections or urinary symptoms. This assessment from the NIH LiverTox database reflects the current consensus that, despite biological plausibility and some preliminary positive data, the evidentiary base for clinical recommendation remains insufficient by modern standards.

4.3 Antioxidant and Anti-inflammatory Activity

Evidence summary: Preclinical (cell culture and animal model) evidence only. No human clinical trials on these endpoints have been published.

Arbutin, a naturally soluble glycosylated phenol, has demonstrated antioxidant, antimicrobial, antitumor, and anti-inflammatory properties. In a rat model, arbutin at oral doses of 25, 50, and 100 mg/kg was investigated in a CFA-induced arthritis model. Body weight changes, paw size, and joint diameter were recorded until the 28th day. Arbutin markedly decreased paw volume, PGE-2, anti-CCP, and 5-LOX levels, while maintaining metabolic and hematological balance and preventing weight loss.

Arbutin attenuated lipopolysaccharide-induced acute kidney injury in rats by inhibiting inflammation and apoptosis via the phosphoinositide 3-kinase/protein kinase B/Nrf2 pathway. Arbutin also decreased the levels of pro-inflammatory cytokines and enhanced myocardial antioxidant status, attenuating isoproterenol-induced cardiac hypertrophy in mice. These findings are, however, exclusively from animal models and cannot be directly extrapolated to human outcomes.

4.4 Hepatoprotective Effects

Evidence summary: Preclinical data only — rat models. No human data available.

Arbutin has shown protective effects against liver diseases in preclinical research. Administration of arbutin at doses of 25 and 50 mg/kg for two weeks markedly alleviated cyclophosphamide-induced hepatotoxicity in rats. In a separate study, rats were orally administered arbutin (50 mg/kg and 100 mg/kg) for 14 consecutive days against hepatotoxicity induced by a single dose of cisplatin (10 mg/kg) on day 15, and arbutin was found to act via Nrf2/HO-1 pathway upregulation. The findings demonstrate that arbutin is a potential protective adjuvant against cisplatin-induced hepatotoxicity via inhibition of hepatic oxidative stress, inflammation, and apoptosis. These findings require human validation.

4.5 Anticancer Potential

Evidence summary: In vitro and animal model data only. No human clinical trials. Evidence is preliminary and insufficient to support any therapeutic claim.

In addition to its skin whitening property, arbutin possesses other therapeutically relevant biological properties including antioxidant, antimicrobial, anti-inflammatory, and anticancer potential. A 2022 review for the first time provided a comprehensive overview of the distribution of arbutin in the plant kingdom and critically appraised its therapeutic potential as an anticancer agent. Published outputs suggest that arbutin has potential anticancer properties against bladder, bone, brain, breast, cervix, colon, liver, prostate, and skin cancers, and a low level of acute or chronic toxicity.

In hepatocellular carcinoma (HCC) cell research, arbutin effectively induced apoptosis in glioblastoma cells with an IC50 of 30 mM. Further experiments showed that arbutin at concentrations of 30 mM and 40 mM inhibited the proliferation and migration of Hep-3B and SNU-449 HCC cells. These are cell-culture concentrations far exceeding typical physiological exposures, and all evidence remains preclinical.

4.6 Neuroprotective Potential

Evidence summary: Preclinical data only. No human clinical trials. All evidence is from in vitro and animal model studies.

Ongoing research on arbutin has revealed its expanding applications in the treatment of various diseases, especially its promising role in neuroprotection. Arbutin has many pharmacological activities including anti-seizure, anti-hyperglycemic, anti-infective, hepatoprotective, anti-hyperlipidemic, and antiviral properties. Previous studies have reported that arbutin had neuroprotective potential in experimental models of various neurodegenerative diseases like Parkinson's disease, Alzheimer's disease, and epilepsy. These findings have not yet been replicated in human clinical trials.

4.7 Antidiabetic / Metabolic Effects

Evidence summary: Preclinical data only.

Arbutin modulates several pathways such as insulin-like growth factor-1 receptor (IGF-1R), 5′ adenosine monophosphate-activated protein kinase (AMPK), and major excitatory pathways and mechanisms including glucose-transporter-4 expression. These mechanistic findings come from preclinical models, and their clinical significance has not been established.

5. Body Systems and Health Areas of Association

• Integumentary (Skin) System: Inhibition of melanogenesis for treatment of hyperpigmentation, melasma, solar lentigo, and freckles; antioxidant protection of skin cells. This is the most clinically substantiated area of use.
• Urogenital System: Arbutin (hydroquinone β-D-glucoside) is a compound of plant origin possessing valuable therapeutic (urinary tract disinfection) and cosmetic (skin whitening) properties. Traditional and pharmacologically plausible use for urinary tract infections, cystitis, and urethritis, formally recognized by the EMA and German Commission E.
• Hepatic (Liver) System: Preclinical evidence for hepatoprotection via Nrf2/HO-1 pathways; no human data.
• Neurological System: Preclinical neuroprotective signals in Parkinson's, Alzheimer's, and epilepsy models; no human data.
• Musculoskeletal System: Anti-inflammatory activity in arthritis models; no human data.
• Metabolic System: Preclinical antidiabetic and anti-obesity signals; no human data.
• Oncological: Preliminary in vitro anticancer activity against multiple cancer cell lines; no human data and evidence is insufficient for any therapeutic assertion.

6. Dosage Forms and Reported Dosages

6.1 Topical (Cosmetic) Use

The European Commission's Scientific Committee on Consumer Safety (SCCS), in its 2023 opinion, confirmed that alpha-arbutin used in face creams up to a maximum concentration of 2% and in body lotions up to a concentration of 0.5% is safe, and that arbutin (β-arbutin) used in face creams up to a maximum concentration of 7% is safe. The SCCS also concluded that the aggregate exposure of alpha-arbutin with arbutin is considered safe for consumers. Arbutin is used in a variety of pigment-lightening preparations in Japan at concentrations of 3%.

6.2 Oral Use (Urinary Tract Applications)

Herbal preparations of Uvae ursi folium for medicinal use are currently quantified to 23.5% to 29.3% of HQ derivatives calculated as anhydrous arbutin. The recommended adult daily dose varies from 200 to 840 mg of HQ derivatives daily calculated as anhydrous arbutin. Commission E, WHO, and ESCOP monographs cite a daily dose ranging from 400 to 800 mg of arbutin per day, divided into 2, 3, or 4 doses, during a maximum period of treatment of 1 to 2 weeks respectively.

The EMA (2012) specifies 101 to 207 mg of anhydrous arbutin 4 times daily to support treatment of inflammatory disease of the urinary tract.

The German Commission E monograph suggests ½–¾ teaspoon (3 grams) of uva ursi steeped in about 5 ounces (150 ml) of boiling water and drunk as an infusion three to four times daily. For alcohol-based tinctures, 1 teaspoon (5 ml) three times per day can be used. Standardized extracts in capsules or tablets containing 20% arbutin, at 700–1,000 mg three times per day, can also be taken.

The EMA assessment report specifies for female adults and the elderly: 1.5–4 g of the comminuted herbal substance in 150 ml of boiling water as a herbal infusion or macerate, 2 to 4 times daily, corresponding to the maximum daily dose of 8 g.

Treatment duration is generally limited to a few weeks because of carcinogenic concerns with long-term hydroquinone use. Recommended dosages typically range from 400 to 800 milligrams of arbutin daily, and this should not exceed two weeks of use and five times a year due to potential toxicity concerns.

7. Safety Considerations and Drug Interactions

7.1 Hydroquinone as the Central Safety Concern

The leaves of bearberry contain arbutin, which metabolizes to form hydroquinone, a potential liver toxin. The safety profile of orally administered arbutin is therefore largely governed by the toxicology of the liberated hydroquinone metabolite. The effects of arbutins on the skin could be attributed to their gradual hydrolysis and release of hydroquinone.

Both HQ conjugates (hydroquinone glucuronide and sulfate) were found in high concentration in urine, and free HQ only in very small concentration or in traces. This pharmacokinetic detail is important: the bulk of systemically absorbed hydroquinone is detoxified by conjugation before urinary excretion, meaning that free hydroquinone exposure at recommended therapeutic doses is limited.

7.2 Duration Limits and Long-Term Risk

The German Institute of Food Research in Potsdam found that intestinal bacteria can transform arbutin into hydroquinone, which creates an environment favorable for intestinal cancer. This concern, based on hydroquinone's known genotoxic potential at high concentrations, is a primary reason why regulatory guidance restricts oral use to short courses.

Free hydroquinone had no activity promoting pancreatic, bladder, stomach, or liver carcinogenesis in the reviewed studies. In conclusion, under the recommended use conditions, Uvae ursi folium is a safe therapeutic option for treating lower urinary tract infections. However, this conclusion applies strictly to short-term, recommended-dose use.

7.3 Ocular Toxicity

A 57-year-old woman who ingested uva ursi tea preparations several times daily for 3 years developed "bull's eye" maculopathy typical of hydroxychloroquine macular injury, suggesting that hydroquinone from uva ursi, which inhibits tyrosine kinase and melanin synthesis, can cause macular injury as well. Uva ursi contains a chemical that can thin the retina in the eye. This could worsen the condition of people whose retinas are already too thin.

7.4 Gastrointestinal Effects

Ingestion of the dried leaves of uva ursi may cause a greenish-brown discoloration of the urine, which darkens upon exposure to air as a result of hydroquinone oxidation. Ingestion of uva ursi leaves may cause nausea and vomiting due to its high tannin content.

7.5 Contraindications

Uva ursi is contraindicated during pregnancy and lactation (WHO 2004). Large doses have been reported to stimulate uterine contractions, and the potential toxicity of hydroquinone makes it a poor choice for pregnant women. People with existing kidney disease should avoid uva ursi entirely, as the herb is specifically contraindicated when kidney function is already compromised. Use in children is not recommended.

7.6 Drug and Dietary Interactions

Urinary acidifying agents may diminish the therapeutic effect of uva ursi (WHO 2004). The antimicrobial activity of arbutin/hydroquinone can be blocked in acidic urine. Because uva ursi's antimicrobial activity can be blocked in acidic urine, ingestion of animal products or other foods known to acidify the urine should be decreased with its use. Administration of sodium or potassium bicarbonate may help to alkalinize the urine. Urinary pH should be greater than 7 for antimicrobial effectiveness. Vitamin C supplements and cranberry juice, which acidify urine, are thus counterproductive when arbutin is used for urinary tract purposes.

7.7 Topical Safety and EU Regulatory Restrictions

The SCCS stressed that the presence of hydroquinone should remain as low as possible in products containing alpha-arbutin or arbutin. Therefore, the use of alpha-arbutin is restricted to a maximum concentration of 2% in face creams and 0.5% in body lotions, while arbutin (β-arbutin) is restricted to a maximum concentration of 7% in face creams. The level of hydroquinone in cosmetic products containing alpha-arbutin or arbutin should not be higher than the unavoidable trace level.

The use of arbutin causes dermatitis rarely, and caution is recommended for the use of arbutin-containing products, especially from the viewpoint that hydroquinone may be generated during product use. Although arbutin is effective in reducing dark spots, its safety has been questioned by regulatory authorities due to its potential as an endocrine disruptor. These regulatory concerns have driven the establishment of concentration limits codified in EU Regulation 2024/996.

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