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Monobenzone
Monobenzone
Monobenzone
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Monobenzone
Clinical data
Other namesHydroquinone benzyl ether, Hydroquinone monobenzyl ether, Benzyl p-hydroxyphenyl ether, Benzyl hydroquinone, Benzoquin, 4-(phenylmethoxy)phenol
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Topical
ATC code
Legal status
Legal status
  • CA: Unscheduled
  • US: ℞-only Unscheduled
Identifiers
  • 4-(benzyloxy)phenol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.002.804 Edit this at Wikidata
Chemical and physical data
FormulaC13H12O2
Molar mass200.237 g·mol−1
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Monobenzone, also called 4-(Benzyloxy)phenol and monobenzyl ether of hydroquinone (MBEH) is an organic chemical in the phenol family with chemical formula C6H5CH2OC6H4OH.[1][2] It is used as a topical drug for medical depigmentation.[3] It is a colourless solid that is classified as the monobenzyl ether of hydroquinone. Monobenzone is soluble in alcohol, benzene, and diethyl ether, and practically insoluble in water.

Pharmacology

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The topical application of monobenzone in animals increases the excretion of melanin from melanocytes. The same action is thought to be responsible for the depigmenting effect of the drug in humans. Monobenzone may cause destruction of melanocytes and permanent depigmentation. [citation needed]

The histology of the skin after depigmentation with topical monobenzone is the same as that seen in vitiligo; the epidermis is normal except for the absence of identifiable melanocytes. Therefore, monobenzone is used as a topical medicine to permanently depigment normal skin surrounding vitiliginous lesions only in patients with disseminated (greater than 50 percent of body surface area) idiopathic vitiligo. Monobenzone is also being considered for the treatment of melanoma.[4]

References

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Further reading

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Monobenzone

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from Grokipedia
Monobenzone, chemically known as monobenzyl ether of (MBEH), is a potent topical depigmenting agent with the molecular formula C₁₃H₁₂O₂, primarily used to induce permanent lightening in patients with extensive affecting more than 50% of the . By acting as a inhibitor and inducing an that destroys melanocytes, it causes irreversible loss of these pigment-producing cells, allowing the depigmented areas of to blend evenly with surrounding through uniform lightening of unaffected regions. Approved by the U.S. (FDA) for medical , monobenzone is available as a 20% topical cream formulation, which may be compounded since the brand Benoquin is discontinued, and is prescribed exclusively for severe, widespread cases where repigmentation therapies have failed or are unsuitable. Application involves twice-daily topical use on pigmented skin, typically requiring 1–4 months for initial effects and up to a year for full , after which maintenance applications may be needed to prevent uneven recoloring. As a , monobenzone acts as a selective that triggers immune-mediated loss, distinguishing it from milder bleaching agents like , which are unsuitable for due to their reversible effects. However, its use demands caution, as it can cause severe irritation, allergic reactions, or unintended if applied beyond -affected areas, and it is contraindicated in patients with or incomplete involvement. Emerging research also explores its potential beyond , including anti-melanoma properties through inhibition of demethylase , though these applications remain investigational.

Chemical Properties

Structure and Formula

Monobenzone has the molecular formula C13H12O2C_{13}H_{12}O_2. Its IUPAC name is 4-(benzyloxy)phenol. Common alternative names include monobenzyl ether of (MBEH) and 4-benzyloxyphenol. These designations reflect its classification as an in the phenol family. Structurally, monobenzone is a phenol derivative derived from , where one of the two hydroxyl groups on the 1,4-dihydroxybenzene backbone is etherified with a (−CH2C6H5-CH_2C_6H_5). This results in a monosubstituted form, featuring a phenolic ring with a free hydroxyl group para to an oxygen connected via a to an unsubstituted phenyl ring. The key linkage (−O−CH2−-O-CH_2-) between the two aromatic systems imparts distinct chemical properties compared to di-substituted ethers.

Physical and Chemical Characteristics

Monobenzone is a , almost tasteless crystalline powder at . This compound exhibits good solubility in alcohol but is practically insoluble in , which influences its handling and formulation in non-aqueous media. The of monobenzone ranges from 119 to 120 °C, indicating its thermal stability up to moderate temperatures before transitioning to a state. Under standard ambient conditions, monobenzone remains chemically stable, with no significant observed during typical storage. However, it demonstrates reactivity with oxidizing agents, potentially leading to oxidative degradation if exposed to such substances. As a phenolic , its linkage contributes to overall chemical inertness in neutral environments, though it may undergo cleavage in the presence of harsh conditions.

Medical Uses

Depigmentation Therapy for Vitiligo

Monobenzone is indicated for the permanent of normally pigmented in patients with extensive affecting more than 50% of the (BSA), where the goal is to achieve a uniform tone by lightening the remaining pigmented areas to match the depigmented patches. This therapy is particularly suitable for cases of universalis or widespread stable disease that has not responded to repigmentation treatments, such as topical corticosteroids or phototherapy. Patient selection emphasizes individuals with treatment-resistant and requires assessment of psychological readiness, including screening for realistic expectations and ability to cope with the permanent alteration in color and potential social implications. The standard application involves a at a 20% concentration, such as Benoquin, applied twice daily to the hyperpigmented skin surrounding vitiliginous areas and any desired treatment zones. Patients are instructed to rub the cream gently into the skin until absorbed, avoiding sun exposure on treated areas and using broad-spectrum to prevent uneven results, with treatment progressing gradually to cover all targeted regions. Higher concentrations, such as 40%, have been evaluated in clinical trials but are not standard due to increased irritation risk. Initial typically becomes noticeable after 1–4 months of consistent use, with full effects requiring 6–12 months or longer, up to 1–3 years in some cases, after which the process is irreversible due to permanent destruction of melanocytes. Once initiated, discontinuation does not reverse the changes, necessitating lifelong sun protection to maintain uniformity. Clinical outcomes demonstrate high , with studies reporting successful in 80–90% of appropriately selected patients, achieving uniform skin tone when adherence is maintained; for instance, one analysis found 84% of severe cases showed , with 44% reaching complete uniformity. Recent research confirms with 60-90% reduction in patches after 3 months but notes increased and potential systemic effects. Success depends on the extent of initial involvement and patient compliance, with monitoring via and BSA assessments recommended every 1–2 months to guide progression.

Off-Label and Other Uses

Monobenzone has been misused cosmetically for general skin lightening and bleaching, particularly in attempts to treat conditions like , despite lacking regulatory approval for such purposes and carrying significant risks of permanent and chemical . This illicit application often occurs through unregulated topical formulations, leading to uneven tone and long-term complications that outweigh any temporary aesthetic benefits. In limited clinical contexts, monobenzone has been explored off-label for treating post-inflammatory , especially in cases unresponsive to milder agents like . Case reports and early evaluations indicate potential efficacy in reducing stubborn pigmented lesions, but its use is constrained by the drug's irreversible effects and the scarcity of controlled studies supporting broader application. Experimentally, monobenzone serves as a tool in dermatological research for inducing ablation and studying , particularly in models of and . Its ability to haptenate and trigger T-cell responses against pigmented cells has been investigated for potential therapeutic modulation of melanocyte destruction, though clinical translation remains investigational. Preliminary research as of 2025 has investigated monobenzone for treatment, showing potential therapeutic effects in early studies. Historically, monobenzone exposure in the rubber industry caused accidental among workers, resulting in occupational vitiligo-like conditions from contact with cured rubber products containing as an . This led to widespread cases of contact leukoderma in the mid-20th century, prompting its removal from many industrial formulations and highlighting the compound's potent depigmenting hazards beyond medical use. Due to the discontinuation of some commercial formulations like Benoquin in certain markets, monobenzone is often prepared as compounded creams in specialized pharmacies to meet custom patient needs, such as varying concentrations for targeted depigmentation. This approach allows for tailored application but requires oversight to ensure safety and efficacy in off-label scenarios.

Pharmacology

Mechanism of Action

Monobenzone primarily acts as a cytotoxic agent toward melanocytes, the pigment-producing cells in the skin, resulting in their destruction and a permanent loss of production. This occurs through selective targeting of melanocytes in normally pigmented areas, where the compound interacts with active synthesis pathways, leading to that typically develops over 1 to 4 months of topical application. Several proposed biochemical pathways contribute to this effect. Monobenzone increases the excretion of from melanocytes, reducing accumulation in the skin. It also generates (ROS) within melanocytes, inducing and cellular damage that promotes cell death. Additionally, monobenzone inhibits , the rate-limiting enzyme in biosynthesis, by forming reactive intermediates that haptenate melanosomal proteins, further disrupting production. The formation of these quinone-haptens, particularly with , increases the of melanocytes, triggering a T-cell-mediated autoimmune response that contributes to the selective destruction of cells and ensures the permanence of . The irreversibility of monobenzone's stems from the complete ablation of melanocytes, as histological examinations post-treatment reveal an absence of identifiable melanocytes in the , in contrast to reversible agents like that merely suppress synthesis temporarily without cell destruction. In vitro studies support these mechanisms, demonstrating that exposure of cultured human melanocytes to monobenzone triggers oxidative damage, ROS production, and subsequent necrotic or apoptotic , often marked by activation and .

Pharmacokinetics

Monobenzone, applied topically as a 20% , demonstrates poor systemic absorption through intact , resulting in minimal uptake and primarily local effects at the site of application. This limited absorption profile contributes to its targeted depigmenting action without widespread systemic exposure under normal use conditions. Distribution of monobenzone is largely confined to the treated area and adjacent dermal layers, where it interacts with melanocytes to induce . No significant plasma concentrations are typically observed, reflecting its localized and low beyond the application site. However, application to extensive surfaces or regions prone to higher absorption, such as inflamed or compromised barriers, may increase the risk of systemic uptake. In the skin, monobenzone undergoes metabolism primarily through enzymatic oxidation by tyrosinase within melanocytes, generating reactive ortho-quinone species that form haptens and contribute to melanocyte cytotoxicity. This local biotransformation supports the drug's depigmenting mechanism without evidence of extensive hepatic involvement. Detailed pathways beyond tyrosinase-mediated oxidation remain underexplored. Elimination details for monobenzone are not well-characterized due to its topical administration and negligible systemic levels; any absorbed fraction is presumed to be metabolized locally and excreted as unidentified metabolites, though specific data are lacking. The plasma has not been established, consistent with the drug's minimal circulation.

Adverse Effects

Common Side Effects

The most frequently reported adverse reactions to monobenzone are mild, localized skin responses at the application site, including characterized by redness (), itching (pruritus), and dryness (xerosis). These effects arise due to the topical nature of the depigmenting agent and are generally transient, though they can cause discomfort during early treatment phases. In randomized clinical trials evaluating monobenzone creams at concentrations of 20% and 40% for , irritation occurred in approximately 57% of patients treated with the 20% (36.8% mild and 20.1% moderate to severe) and up to 85% with the 40% (25% mild and 60% moderate to severe). Cracking, scaling, or peeling of the treated may accompany these symptoms, often linked to the drug's cytotoxic impact on melanocytes and surrounding tissue. Mild burning or stinging sensations are also prevalent, particularly in the first few weeks of application, affecting a notable proportion of users but typically diminishing as tolerance develops. Allergic contact dermatitis represents a less common but notable sensitization reaction, potentially resulting in an eczematous rash or heightened inflammatory response upon repeated exposure. Case reports document instances of contact hypersensitivity, underscoring the need for patch testing in susceptible individuals, though overall incidence remains low in clinical settings. Management of these common side effects focuses on supportive measures to enhance tolerability without interrupting therapy. Strategies include reducing application frequency (e.g., from twice daily to once nightly or alternate days), incorporating emollients or moisturizers to combat dryness, and applying low-potency topical corticosteroids for . Cold compresses can alleviate acute burning or . In most cases, these reactions subside with continued use, and discontinuation due to side effects is infrequent, occurring in fewer than 10% of trial participants. Patients should monitor for persistence or worsening and consult a dermatologist promptly.

Serious Risks and Contraindications

Monobenzone induces permanent by destroying melanocytes in treated areas, rendering the skin color loss irreversible and often requiring months to fully manifest. This effect can unpredictably spread to untreated distant sites, such as the face, genitals, or other body regions, leading to irregular and excessive that may be cosmetically distressing and permanent. Application near the eyes poses significant risks, including unintended permanent of periorbital and distant sites, as well as reported ocular effects such as corneal pigment deposition and conjunctival . To mitigate this, monobenzone should never be applied to eyelids or periocular regions. Contraindications include known to hydroquinone derivatives like , as well as active inflammatory conditions or infections, which may exacerbate local reactions or interfere with safe application. It is also contraindicated in children under 12 years due to unestablished and , and during (FDA Category C), where it should only be used if benefits clearly outweigh potential fetal risks, as no adequate reproduction studies exist. Long-term use heightens UV sensitivity in depigmented skin, necessitating lifelong strict sun protection measures like broad-spectrum SPF 30+ and protective clothing to prevent sunburn, premature aging, or . The profound alteration in appearance from widespread can have notable psychological impacts, including social discomfort or adjustment challenges, though some patients report improved post-therapy. Regular dermatological monitoring is essential throughout treatment and maintenance to detect over-depigmentation early, adjust application frequency, and ensure patient adherence to protective protocols. A 2024 study found that monobenzone treatment significantly increased markers (total and ) and proinflammatory cytokines (IL-1β and IL-18), suggesting potential contributions to and long-term health issues such as organ failures, although no changes in organ function were observed in the study cohort and further research is required.

History

Discovery and Development

The depigmenting effects of monobenzone, chemically known as monobenzyl ether of , were first identified accidentally in 1939 through occupational exposure among workers in a rubber processing facility. Dermatologists E. A. , L. Schwartz, and L. H. Warren observed patchy on the hands of approximately 50% of affected employees who handled rubber containing monobenzone as an , with patch testing confirming the compound's role in inducing leukoderma. This incident highlighted monobenzone's potent skin-lightening properties, initially viewed as an industrial rather than a potential therapeutic tool. In the , early laboratory research began to explore monobenzone's depigmenting potential, building on the occupational observations. Researchers C. R. Denton, A. B. Lerner, and T. B. Fitzpatrick conducted pivotal studies demonstrating that monobenzone, alongside , inhibited formation by blocking activity in animal models such as guinea pigs and cats, establishing its selective action on melanocytes. These findings positioned monobenzone as a candidate for treating hyperpigmentary conditions, though concerns over its irreversible effects prompted cautious evaluation. Fitzpatrick, a leading dermatologist, played a key role in advancing phenolic depigmenting agents like monobenzone through these investigations, which laid the groundwork for clinical translation.48268-5/pdf) By the 1950s, clinical trials marked a significant development milestone, confirming monobenzone's efficacy for intentional in patients with extensive . Trials demonstrated that topical application achieved uniform skin lightening by progressively destroying melanocytes in remaining pigmented areas, offering a viable option for those with over 50% body involvement where repigmentation was impractical. This era saw monobenzone transition from an industrial chemical implicated in accidental to a targeted medical agent, selected over other compounds for its reliability in achieving complete , albeit with acknowledgment of its permanent nature.

Regulatory History

Monobenzone, marketed as Benoquin Cream 20%, received approval from the Food and Drug Administration (FDA) in 1952 for the permanent depigmentation of extensive in patients with greater than 50% involvement, establishing it as a prescription-only medication restricted to final-stage treatment under dermatological supervision. The formulation was specifically indicated for topical application to depigment remaining normally pigmented skin areas, aiming to achieve a uniform skin tone, and was never approved for cosmetic skin lightening or over-the-counter use. In 2003, the FDA revised the labeling for Benoquin to strengthen warnings regarding its irreversible effects, including a prominent stating that the drug is destructive to and may cause permanent , with potential risks such as exogenous and heightened sensitivity to in treated areas. These updates emphasized the need for patient counseling on the therapy's permanence, prohibiting its use on sun-exposed areas without protection, and contraindicating it for individuals under 12 years or those with to derivatives. Internationally, monobenzone holds varying regulatory statuses, with approval in for depigmentation therapy in under similar prescription-only restrictions as the FDA, though it is prohibited in products due to safety concerns. In the , it has been banned for use in cosmetics since 2001 owing to risks of irreversible and potential carcinogenicity, limiting its availability to medical prescriptions in select member states for management. In contrast, countries like have banned monobenzone-containing products for cosmetic skin lightening since the late 1990s, following reports of misuse leading to chemical and other adverse effects, with enforcement focusing on unregulated imports and sales. Post-marketing in the highlighted instances of misuse for unauthorized bleaching, prompting regulatory agencies, including the FDA, to issue warnings against over-the-counter availability and emphasize its niche role in to prevent off-label abuse and associated complications like uneven pigmentation and increased risk. These efforts underscored the drug's limited therapeutic window, with data reinforcing restrictions to supervised medical use only. Currently, Benoquin is no longer commercially marketed , leading to its preparation through pharmacies to meet patient-specific needs, such as custom concentrations up to 40% in creams or ointments for depigmentation. This shift has resulted in no generic competition, as the drug's specialized, low-volume application discourages large-scale manufacturing, ensuring availability remains tied to prescription under regulatory oversight.

References

  1. https://pubchem.ncbi.nlm.nih.gov/compound/Monobenzone
  2. https://www.drugs.com/mtm/monobenzone-topical.html
  3. https://pmc.ncbi.nlm.nih.gov/articles/PMC6850206/
  4. https://pmc.ncbi.nlm.nih.gov/articles/PMC3533321/
  5. https://pmc.ncbi.nlm.nih.gov/articles/PMC9564123/
  6. https://www.drugs.com/pro/benoquin.html
  7. https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08173slr015_benoquin_lbl.pdf
  8. https://pmc.ncbi.nlm.nih.gov/articles/PMC3662797/
  9. https://www.drugs.com/sfx/monobenzone-topical-side-effects.html
  10. https://pmc.ncbi.nlm.nih.gov/articles/PMC8084583/
  11. https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2156828.htm
  12. https://go.drugbank.com/drugs/DB00600
  13. https://www.mobelbiochem.com/Content/upload/pdf/202339219/Monobenzone-Powder-SDS.pdf
  14. https://dermnetnz.org/topics/depigmentation-therapy-for-vitiligo
  15. https://www.sciencedirect.com/topics/medicine-and-dentistry/monobenzone
  16. https://cdn.mdedge.com/files/s3fs-public/Document/September-2017/CT091050248.pdf
  17. https://www.researchgate.net/publication/346408457_Monobenzyl_ether_of_hydroquinone_20_and_40_cream_in_depigmentation_of_patients_with_vitiligo_a_randomized_controlled_trial
  18. https://ijdvl.com/depigmentation-therapies-in-vitiligo/
  19. https://www.intechopen.com/chapters/69638
  20. https://globalvitiligofoundation.org/depigmentation/
  21. https://pmc.ncbi.nlm.nih.gov/articles/PMC11626302/
  22. https://jpad.com.pk/index.php/jpad/article/view/2102
  23. https://www.jpad.com.pk/index.php/jpad/article/download/2102/1923
  24. https://jamanetwork.com/journals/jama/fullarticle/1177933
  25. https://www.semanticscholar.org/paper/Evaluation-of-monobenzone.-Becker-Spencer/813e8ae07347d75b3889d23723db38d01eb89562
  26. https://www.sciencedirect.com/science/article/pii/S0022202X15352866
  27. https://www.jwatch.org/jd201108050000004/2011/08/05/monobenzone-immunotherapy-melanoma
  28. https://pmc.ncbi.nlm.nih.gov/articles/PMC11837647/
  29. https://pmc.ncbi.nlm.nih.gov/articles/PMC5362111/
  30. https://dermnetnz.org/topics/contact-leukoderma
  31. https://www.cfspharmacy.pharmacy/blog/post/compounded-monobenzone-for-vitiligo-depigmentation
  32. https://pubmed.ncbi.nlm.nih.gov/21326294/
  33. https://www.globalrx.com/articles?article=monobenzone-usp-clinical-profile&product_id=92420
  34. https://onlinelibrary.wiley.com/doi/10.1111/jdv.19450
  35. https://www.mdpi.com/1422-0067/24/8/6990
  36. https://pubmed.ncbi.nlm.nih.gov/19610592/
  37. https://www.medicinenet.com/monobenzone-topical/article.htm
  38. https://www.drugs.com/sfx/benoquin-side-effects.html
  39. https://journals.lww.com/jewds/fulltext/2020/17030/monobenzyl_ether_of_hydroquinone_20_and_40__cream.2.aspx
  40. https://pubmed.ncbi.nlm.nih.gov/9771988/
  41. https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0536.1998.tb05863.x
  42. https://medtigo.com/drug/monobenzone/
  43. https://pubmed.ncbi.nlm.nih.gov/6849655/
  44. https://pmc.ncbi.nlm.nih.gov/articles/PMC10039329/
  45. https://doi.org/10.1111/jocd.16544
  46. https://jamanetwork.com/journals/jama/fullarticle/292501
  47. https://www.sciencedirect.com/science/article/pii/S0022202X15482685
  48. https://ijdvl.com/history-of-hydroquinone/
  49. https://www.sciencedirect.com/science/article/pii/S2667031323000337
  50. https://pmc.ncbi.nlm.nih.gov/articles/PMC12092322/
  51. https://www.canada.ca/en/health-canada/services/consumer-product-safety/cosmetics/cosmetic-ingredient-hotlist-prohibited-restricted-ingredients/hotlist.html
  52. https://www.fda.gov/media/146674/download
  53. https://umc.edu/news/News_Articles/2016/January/Vitiligo-treatments-help-patients-get-through-rough-patch.html
  54. https://www.cfspharmacy.pharmacy/monobenzone-compounded
  55. https://www.hillscompounding.com/
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