Benzoyl peroxide

Benzoyl peroxide is a chemical compound (specifically, an organic peroxide) with structural formula (C6H5−C(=O)O−)2, often abbreviated as (BzO)2. In terms of its structure, the molecule can be described as two benzoyl (C6H5−C(=O)−, Bz) groups connected by a peroxide (−O−O−). It is a white granular solid with a faint odour of benzaldehyde, poorly soluble in water but soluble in acetone, ethanol, and many other organic solvents. Benzoyl peroxide is an oxidizer, but it is principally used as in the production of polymers.[4]

Benzoyl peroxide
Benzoyl-peroxide.svg
Clinical data
Trade namesBenzac, Panoxyl, others
Other namesbenzoperoxide, dibenzoyl peroxide (DBPO)
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MedlinePlusa601026
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administration
Topical
ATC code
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Legal status
Identifiers
  • benzoic peroxyanhydride[3]
CAS Number
PubChem CID
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ECHA InfoCard100.002.116 Edit this at Wikidata
Chemical and physical data
FormulaC14H10O4
Molar mass242.230 g·mol−1
3D model (JSmol)
Density1.334 g/cm3
Melting point103 to 105 °C (217 to 221 °F) decomposes
Solubility in waterpoor mg/mL (20 °C)
  • c1ccc(cc1)C(=O)OOC(=O)c2ccccc2
  • InChI=1S/C14H10O4/c15-13(11-7-3-1-4-8-11)17-18-14(16)12-9-5-2-6-10-12/h1-10H checkY
  • Key:OMPJBNCRMGITSC-UHFFFAOYSA-N
Data page
Benzoyl peroxide (data page)

Benzoyl peroxide is mainly used in production of plastics[4] and for bleaching flour, hair, plastics and textiles.[5][6]

Synthesis, structure, and chemical reactivityEdit

 
Structure of dibenzoyl peroxide from X-ray crystallography. The O=C-O-O dihedral angle is 90″. The O-O distance is 1.434 Å.[7]

The original 1858 synthesis by Liebig reacted benzoyl chloride with barium peroxide,[8] a reaction described by the following idealized equation:

2 C6H5C(O)Cl + BaO2 → (C6H5CO)2O2 + BaCl2

Benzoyl peroxide is usually prepared by treating hydrogen peroxide with benzoyl chloride under alkaline conditions.

2 C6H5C(O)Cl + H2O2 → (C6H5CO)2O2 + 2 HCl

As in many other peroxides, the C-O-O-C linkage has a dihedral angle near 90°.[9]

The oxygen–oxygen bond in peroxides is weak, although this weakness is not indicated by the O-O bond distance. Thus, benzoyl peroxide undergoes homolysis (symmetrical fission), forming free radicals:

(C6H5CO)2O2 ⇌ 2 C6H5CO2

The symbol indicates that the products are radicals; i.e., they contain at least one unpaired electron. Such species are highly reactive. The homolysis is usually induced by heating. The half-life of benzoyl peroxide is one hour at 92 °C. At 131 °C, the half-life is one minute.[10]

It has long been known that the compound has oxidizing properties.[11] This property led to the use of BPO to treat various skin conditions, including burns, chronic varicose leg tumors, and tinea sycosis. He also reported animal experiments that showed the relatively low toxicity of the compound.[12][5][13]

Treatment with benzoyl peroxide was proposed for wounds by Lyon and Reynolds in 1929, and for sycosis vulgaris and acne varioliformis by Peck and Chagrin in 1934.[13] However, preparations were often of questionable quality.[5] It was officially approved for the treatment of acne in the US in 1960.[5]

UsesEdit

PolymerizationEdit

Benzoyl peroxide is mainly used as a radical initiator to induce chain-growth polymerization reactions,[4] such as for polyester and poly(methyl methacrylate) (PMMA) resins and dental cements and restoratives.[14] It is the most important among the various organic peroxides used for this purpose, a relatively safe alternative to the much more hazardous methyl ethyl ketone peroxide.[15][16] It is also used in rubber curing and as a finishing agent for some acetate yarns.[14]

Other usesEdit

 
Tube of a water-based 5% benzoyl peroxide preparation for the treatment of acne

Benzoyl peroxide is effective for treating acne lesions. It does not induce antibiotic resistance.[17][18] It may be combined with salicylic acid, sulfur, erythromycin, or clindamycin (antibiotics), or adapalene (a synthetic retinoid). Two common combination drugs include benzoyl peroxide/clindamycin and adapalene/benzoyl peroxide, adapalene being a chemically stable retinoid that can be combined with benzoyl peroxide[19] unlike Tazarotene and tretinoin. Combination products such as benzoyl peroxide/clindamycin and benzoyl peroxide/salicylic acid appear to be slightly more effective than benzoyl peroxide alone for the treatment of acne lesions.[18] The combination tretinoin/benzoyl peroxide was approved for medical use in the United States in 2021.

Benzoyl peroxide for acne treatment is typically applied to the affected areas in gel, cream, or liquid, in concentrations of 2.5% increasing through 5.0%, and up to 10%.[17] No strong evidence supports the idea that higher concentrations of benzoyl peroxide are more effective than lower concentrations.[17]

Like most peroxides, it is a powerful bleaching agent. It has been used for the bleaching of flour, fats, oils, waxes, and cheeses, as well as a stain remover for ink stains on dolls.[20][21]

Mechanism of actionEdit

Classically, benzoyl peroxide is thought to have a three-fold activity in treating acne. It is sebostatic, comedolytic, and inhibits growth of Cutibacterium acnes, the main bacterium associated with acne.[17][22] In general, acne vulgaris is a hormone-mediated inflammation of sebaceous glands and hair follicles. Hormone changes cause an increase in keratin and sebum production, leading to blocked drainage. C. acnes has many lytic enzymes that break down the proteins and lipids in the sebum, leading to an inflammatory response. The free-radical reaction of benzoyl peroxide can break down the keratin, therefore unblocking the drainage of sebum (comedolytic). It can cause nonspecific peroxidation of C. acnes, making it bactericidal,[5] and it was thought to decrease sebum production, but disagreement exists within the literature on this.[22][23]

Some evidence suggests that benzoyl peroxide has an anti-inflammatory effect as well. In micromolar concentrations it prevents neutrophils from releasing reactive oxygen species, part of the inflammatory response in acne.[23]

As a medication, benzoyl peroxide is mostly used to treat acne, either alone or in combination with other treatments.[24] Some versions are sold mixed with antibiotics such as clindamycin.[25][26] It is on the WHO List of Essential Medicines,[27] and, in the US, it is available as an over-the-counter and generic medication.[28][25] It is also used in dentistry for teeth whitening.

Side effectsEdit

 
Skin irritation due to benzoyl peroxide

Application of benzoyl peroxide to the skin may result in redness, burning, and irritation. This side effect is dose-dependent.[24][28]

Because of these possible side effects, it is recommended to start with a low concentration and build up as appropriate, as the skin gradually develops tolerance to the medication. Skin sensitivity typically resolves after a few weeks of continuous use.[23][29] Irritation can also be reduced by avoiding harsh facial cleansers and wearing sunscreen prior to sun exposure.[29]

One in 500 people experience hypersensitivity to BPO and are liable to experience burning, itching, crusting, and possibly swelling.[30][31] About one-third of people experience phototoxicity under exposure to ultraviolet (UVB) light.[32]

Other usesEdit

As a bleach, it has been used as a medication and a water disinfectant.[33][6] In specialized contexts, the name may be abbreviated as BPO.

Benzoyl peroxide is used in dentistry as a tooth whitening product.

SafetyEdit

Explosion hazardEdit

Benzoyl peroxide is potentially explosive[34] like other organic peroxides, and can cause fires without external ignition. The hazard is acute for the pure material, so the compound is generally used as a solution or a paste. For example, cosmetics contain only a small percentage of benzoyl peroxide and pose no explosion risk.

ToxicityEdit

Benzoyl peroxide breaks down in contact with skin, producing benzoic acid and oxygen, neither of which is very toxic.[35]

With regards to BPO's carcinogenic potential, one study concluded, "caution should be recommended in the use of this and other free radical-generating compounds".[36] A 1999 IARC review of carcinogenicity studies found no evidence linking BPO acne medication to skin cancers in humans. However, some animal studies found that the compound could act as a carcinogen and enhance the effect of known carcinogens.[14]

Skin irritationEdit

In a 1977 study using a human maximization test, 76% of subjects acquired a contact sensitization to benzoyl peroxide. Formulations of 5% and 10% were used.[37]

The U.S. National Institute for Occupational Safety and Health has developed criteria for a recommended standard for occupational exposure to benzoyl peroxide.[38]

Cloth stainingEdit

 
A bleached fabric stain caused by contact with benzoyl peroxide

Contact with fabrics or hair, such as from still-moist acne medication, can cause permanent color dampening almost immediately. Even secondary contact can cause bleaching, for example, contact with a towel that has been used to wash off benzoyl peroxide-containing hygiene products.[39]

Use During PregnancyEdit

The use of topical benzoyl peroxide has not been studied during breastfeeding. Because only about 5% is absorbed following topical application, it is considered a low risk to the nursing infant. However, it is important to ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated. Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking.[40]

ReferencesEdit

  1. ^ "Epsolay- benzoyl peroxide cream". DailyMed. 25 April 2022. Archived from the original on 16 May 2022. Retrieved 15 May 2022.
  2. ^ "Epsolay- benzoyl peroxide cream". DailyMed. 5 May 2022. Archived from the original on 20 June 2022. Retrieved 19 June 2022.
  3. ^ IUPAC Chemical Nomenclature and Structure Representation Division (2013). "P-65.7.5". In Favre HA, Powell WH (eds.). Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013. IUPACRSC. ISBN 978-0-85404-182-4.
  4. ^ a b c Herbert K, Götz PH, Siegmeier R, Mayr W. "Peroxy Compounds, Organic". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a19_199.
  5. ^ a b c d e Plewig G, Kligman AM (2012). ACNE and ROSACEA (3 ed.). Springer Science & Business Media. p. 613. ISBN 9783642597152. Archived from the original on 18 September 2017.
  6. ^ a b Pommerville JC (2012). Alcamo's Fundamentals of Microbiology: Body Systems. Jones & Bartlett Publishers. p. 214. ISBN 9781449605957. Archived from the original on 18 September 2017.
  7. ^ McBride JM, Vary MW (1982). "Radical pair in crystalline dibenzoyl peroxide evidence for triplet ground states". Tetrahedron. 38 (6): 765–775. doi:10.1016/0040-4020(82)80157-9.
  8. ^ Brodie BC (1858). "Ueber die Bildung der Hyperoxyde organischer Säureradicale" [On the Formation of the Peroxides of Organic Acid Radicals]. Justus Liebigs Ann. Chem. 108: 79–83. doi:10.1002/jlac.18581080117. Archived from the original on 29 November 2020. Retrieved 2 July 2019.
  9. ^ Gougoutas JZ, Clardy JC (1970). "The crystal and molecular structures of (A) 2,2'-diiodo- (B) 2,2'-dibromo- (C) 2,2'-dichloro- (D) 2-iodo-2'-bromo- and (E) 2-iodo-2'-chlorodibenzoyl peroxides". Acta Crystallographica Section B Structural Crystallography and Crystal Chemistry. 26 (12): 1999–2008. doi:10.1107/S0567740870005307.
  10. ^ Li III H (1998). "Chapter 2" (PDF). Synthesis, Characterization and Properties of Vinyl Ester Matrix Resins (Ph.D.). University of Vermont. hdl:10919/30521. Archived from the original on 20 September 2006. Retrieved 17 February 2007.
  11. ^ Kastle JH, Loevenhart AS (1901). "On the Nature of Certain Oxidizing Ferments". American Chemical Journal. 2: 539–566.
  12. ^ Loevenhart AS (1905). "Benzoylsuperoxyds, ein neues therapeutisches Agens". Therap Monatscheftel (in German). 12: 426–428.
  13. ^ a b Merker PC (March 2002). "Benzoyl peroxide: a history of early research and researchers". International Journal of Dermatology. 41 (3): 185–8. doi:10.1046/j.1365-4362.2002.01371.x. PMID 12010349. S2CID 24091844.
  14. ^ a b c International Agency for Research on Cancer (1999): "Benzoyl peroxide". in Re-evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide Archived 15 July 2020 at the Wayback Machine. Monographs on the Evaluation of Carcinogenic Risks to Humans, number 71, pages 345–358. ISBN 92-832-1271-1
  15. ^ "Initiation By Diacyl Peroxides". Polymer Properties Database. Archived from the original on 19 October 2018. Retrieved 19 October 2018.
  16. ^ "Error - Evonik Industries AG" (PDF). Archived from the original on 29 August 2021. Retrieved 12 April 2011.
  17. ^ a b c d Simonart T (December 2012). "Newer approaches to the treatment of acne vulgaris". American Journal of Clinical Dermatology. 13 (6): 357–64. doi:10.2165/11632500-000000000-00000. PMID 22920095. S2CID 12200694.
  18. ^ a b Seidler EM, Kimball AB (July 2010). "Meta-analysis comparing efficacy of benzoyl peroxide, clindamycin, benzoyl peroxide with salicylic acid, and combination benzoyl peroxide/clindamycin in acne". Journal of the American Academy of Dermatology. 63 (1): 52–62. doi:10.1016/j.jaad.2009.07.052. PMID 20488582.
  19. ^ Tolaymat L, Dearborn H, Zito PM (2022). "Adapalene". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 29494115. Retrieved 24 July 2022.
  20. ^ Wallace, Dawn. "ACNE GEL FOR GREEN EAR SYNDROME? A STUDY ON COPPER CORROSION STAIN REMOVAL FROM POLY (VINYL CHLORIDE)" (PDF). SUNY– Buffalo State, Art Conservation Department.
  21. ^ "Future Engineers :: Name that Molecule Challenge :: Gallery :: Benzoyl peroxide". Future Engineers. Retrieved 5 January 2023.
  22. ^ a b Cotterill JA (1 January 1980). "Benzoyl peroxide". Acta Dermato-Venereologica. Supplementum. 89: 57–63. doi:10.2340/00015555895763. PMID 6162349.
  23. ^ a b c Worret WI, Fluhr JW (April 2006). "[Acne therapy with topical benzoyl peroxide, antibiotics and azelaic acid]" [Acne therapy with topical benzoyl peroxide, antibiotics and azelaic acid]. Journal der Deutschen Dermatologischen Gesellschaft (in German). 4 (4): 293–300. doi:10.1111/j.1610-0387.2006.05931.x. PMID 16638058. S2CID 6924764.
  24. ^ a b World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. pp. 307–308. hdl:10665/44053. ISBN 9789241547659.
  25. ^ a b British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 820. ISBN 9780857111562.
  26. ^ Braun-Falco O, Plewig G, Wolff HH, Burgdorf W (2012). Dermatology (2 ed.). Springer Science & Business Media. p. 1039. ISBN 9783642979316. Archived from the original on 18 September 2017.
  27. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  28. ^ a b Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 173. ISBN 9781284057560.
  29. ^ a b Alldredge BK, Koda-Kimble MA, Young LY, eds. (2013). Applied Therapeutics: The Clinical Use of Drugs (10th ed.). Baltimore: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 949. ISBN 978-1609137137.
  30. ^ Cunliffe WJ, Burke B (1 January 1982). "Benzoyl peroxide: lack of sensitization". Acta Dermato-Venereologica. 62 (5): 458–9. doi:10.2340/00015555462458459 (inactive 31 December 2022). PMID 6183909. Archived from the original on 27 February 2021. Retrieved 17 July 2020.{{cite journal}}: CS1 maint: DOI inactive as of December 2022 (link)
  31. ^ "Benzoyl peroxide". Mayo Clinic. 1 January 2016. Archived from the original on 18 July 2016.
  32. ^ Jeanmougin M, Pedreiro J, Bouchet J, Civatte J (1 January 1983). "[Phototoxic activity of 5% benzoyl peroxide in man. Use of a new methodology]". Dermatologica. 167 (1): 19–23. doi:10.1159/000249739. PMID 6628794.
  33. ^ Stellman JM (1998). Encyclopaedia of Occupational Health and Safety: Guides, indexes, directory. International Labour Organization. p. 104. ISBN 9789221098171. Archived from the original on 18 September 2017.
  34. ^ Cartwright H (17 March 2005). "Chemical Safety Data: Benzoyl peroxide". Oxford University. Archived from the original on 12 October 2010. Retrieved 13 August 2011.
  35. ^ Benzoyl peroxide (PDF), SIDS Initial Assessment Report, Geneva: United Nations Environment Programme, April 2004
  36. ^ Slaga TJ, Klein-Szanto AJ, Triplett LL, Yotti LP, Trosko KE (August 1981). "Skin tumor-promoting activity of benzoyl peroxide, a widely used free radical-generating compound". Science. 213 (4511): 1023–5. Bibcode:1981Sci...213.1023S. doi:10.1126/science.6791284. PMID 6791284.
  37. ^ Leyden JJ, Kligman AM (October 1977). "Contact sensitization to benzoyl peroxide". Contact Dermatitis. 3 (5): 273–5. doi:10.1111/j.1600-0536.1977.tb03674.x. PMID 145346. S2CID 33553359.
  38. ^ "Criteria for a Recommended Standard: Occupational Exposure to Benzoyl Peroxide (77-166)". CDC - NIOSH Publications and Products. 6 June 2014. doi:10.26616/NIOSHPUB76128. Archived from the original on 9 August 2016. Retrieved 15 July 2016.
  39. ^ Bojar RA, Cunliffe WJ, Holland KT (February 1995). "The short-term treatment of acne vulgaris with benzoyl peroxide: effects on the surface and follicular cutaneous microflora". The British Journal of Dermatology. 132 (2): 204–8. doi:10.1111/j.1365-2133.1995.tb05014.x. PMID 7888356. S2CID 22468429.
  40. ^ "Benzoyl Peroxide", Drugs and Lactation Database (LactMed®), Bethesda (MD): National Institute of Child Health and Human Development, 2006, PMID 30000481, retrieved 17 January 2023

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