Benzoyl peroxide

Benzoyl peroxide was first prepared and described by Justus von Liebig in 1858.

Donald Holroyde Hey FRS{{Cite journal | vauthors = Cadogan JI, Davies DI | author-link1 = John Cadogan | doi = 10.1098/rsbm.1988.0011 | title = Donald Holroyde Hey. 12 September 1904-21 January 1987 | journal = Biographical Memoirs of Fellows of the Royal Society | volume = 34 | pages = 294–320 | year = 1988 | jstor = 770054| doi-access = free }} (12 September 1904 – 21 January 1987) was a Welsh organic chemist who inferred that the decomposition of benzoyl peroxide generated free phenyl radicals.{{Cite journal | vauthors = Hey DH | author-link = Donald Holroyde Hey| title = 432. Amphoteric aromatic substitution. Part II. Reactions of benzoyl peroxide and phenylazotriphenylmethane | doi = 10.1039/JR9340001966 | journal = Journal of the Chemical Society (Resumed) | page = 1966| year = 1934 }}{{cite book | veditors = Davies J, Jenkins N, Menna B, Lynch PI | editor1-link=John Davies (historian) |title=The Welsh Academy Encyclopaedia of Wales |year=2008 |publisher=University of Wales Press |location=Cardiff |pages=367–368 |isbn=978-0-7083-1953-6}}

File:Dibenzoyl peroxide (CSD code =DBEZPO01).png. The O=C-O-O dihedral angle is 90°. The O-O distance is 1.434 Å.{{cite journal |doi=10.1016/0040-4020(82)80157-9|title=Radical pair in crystalline dibenzoyl peroxide evidence for triplet ground states |year=1982 | vauthors = McBride JM, Vary MW |journal=Tetrahedron |volume=38 |issue=6 |pages=765–775 }}]]

The original 1858 synthesis by Liebig reacted benzoyl chloride with barium peroxide,{{cite journal | vauthors = Brodie BC | title = Ueber die Bildung der Hyperoxyde organischer Säureradicale | trans-title = On the Formation of the Peroxides of Organic Acid Radicals | journal = Justus Liebigs Ann. Chem. | year = 1858 | volume = 108 | pages = 79–83 | doi = 10.1002/jlac.18581080117 | url = https://zenodo.org/record/1427113 | access-date = 2 July 2019 | archive-date = 29 November 2020 | archive-url = https://web.archive.org/web/20201129112907/https://zenodo.org/record/1427113 | url-status = live }} a reaction that probably follows this 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 C₆H₅COCl + H₂O₂ + 2 NaOH → (C₆H₅CO)₂O₂ + 2 NaCl + 2 H₂O

The oxygen–oxygen bond in peroxides is weak. Thus, benzoyl peroxide readily undergoes homolysis (symmetrical fission), forming free radicals:

:(C₆H₅CO)₂O₂ → 2 {{chem|C|6|H|5|CO|2|•}}

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.{{cite thesis | vauthors = Li III H | title = Synthesis, Characterization and Properties of Vinyl Ester Matrix Resins | chapter-url = http://hdl.handle.net/10919/30521 | type = Ph.D. | publisher = University of Vermont | chapter = Chapter 2 | year = 1998 | hdl = 10919/30521 | url-status = dead | archive-url = https://web.archive.org/web/20060920122734/http://scholar.lib.vt.edu/theses/available/etd-42198-113329/unrestricted/ch2.pdf | archive-date = 20 September 2006 | access-date = 17 February 2007 }}

In 1901, it was observed that the compound made the tincture of guaiacum tincture turn blue, a sign of oxygen being released.{{cite journal | vauthors = Kastle JH, Loevenhart AS | date = 1901 | title = On the Nature of Certain Oxidizing Ferments | journal = American Chemical Journal | volume = 2 | pages = 539–566 }} Around 1905, Loevenhart reported on the successful use of benzoyl peroxide 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.{{cite journal | vauthors = Loevenhart AS | date = 1905 | title = Benzoylsuperoxyds, ein neues therapeutisches Agens | language = German | journal = Therap Monatscheftel | volume = 12 | pages = 426–428 }}{{cite journal | vauthors = Merker PC | title = Benzoyl peroxide: a history of early research and researchers | journal = International Journal of Dermatology | volume = 41 | issue = 3 | pages = 185–8 | date = March 2002 | pmid = 12010349 | doi = 10.1046/j.1365-4362.2002.01371.x | s2cid = 24091844 }}

Treatment with benzoyl peroxide was proposed for wounds in 1929, and for sycosis vulgaris and acne varioliformis in 1934. However, preparations were often of questionable quality.{{cite book| vauthors = Plewig G, Kligman AM |title=ACNE and ROSACEA|date=2012|publisher=Springer Science & Business Media |isbn=978-3-642-59715-2 |page=613 |edition=3 |url=https://books.google.com/books?id=0cD-CAAAQBAJ&pg=PA613|language=en|url-status=live|archive-url=https://web.archive.org/web/20170918185335/https://books.google.com/books?id=0cD-CAAAQBAJ&pg=PA613|archive-date=18 September 2017}} It was officially approved for the treatment of acne in the US in 1960.

Benzoyl peroxide is mainly used as a radical initiator to induce chain-growth polymerization reactions,{{Ullmann | vauthors = Herbert K, Götz PH, Siegmeier R, Mayr W | title = Peroxy Compounds, Organic | doi = 10.1002/14356007.a19_199}} such as for polyester and poly(methyl methacrylate) (PMMA) resins and dental cements and restoratives. 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.{{cite web |url= https://polymerdatabase.com/polymer%20chemistry/Diaroyl%20Peroxides.html |website= Polymer Properties Database |title= Initiation By Diacyl Peroxides |access-date= 19 October 2018 |archive-date= 19 October 2018 |archive-url= https://web.archive.org/web/20181019121759/https://polymerdatabase.com/polymer%20chemistry/Diaroyl%20Peroxides.html |url-status= live }}{{cite web|url=http://www.degaroute.com/sites/dc/Downloadcenter/Evonik/Product/DEGAROUTE/en/Degaroute%20Brosch%C3%BCre.pdf|title=Error - Evonik Industries AG|access-date=12 April 2011|archive-date=29 August 2021|archive-url=https://web.archive.org/web/20210829105907/https://www.degaroute.com/en/degaroute-road-markings|url-status=live}} It is also used in rubber curing and as a finishing agent for some acetate yarns.

Image:Benzoyl peroxide gel.jpg]]

Benzoyl peroxide is effective for treating acne lesions. It does not induce antibiotic resistance.{{cite journal | vauthors = Simonart T | s2cid = 12200694 | title = Newer approaches to the treatment of acne vulgaris | journal = American Journal of Clinical Dermatology | volume = 13 | issue = 6 | pages = 357–64 | date = December 2012 | pmid = 22920095 | doi = 10.2165/11632500-000000000-00000 }} 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{{cite book | vauthors = Tolaymat L, Dearborn H, Zito PM | chapter = Adapalene |date=2022 | chapter-url=http://www.ncbi.nlm.nih.gov/books/NBK482509/ | title = StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=29494115 |access-date=24 July 2022 }} unlike tezarotene 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.{{cite journal | vauthors = Seidler EM, Kimball AB | title = Meta-analysis comparing efficacy of benzoyl peroxide, clindamycin, benzoyl peroxide with salicylic acid, and combination benzoyl peroxide/clindamycin in acne | journal = Journal of the American Academy of Dermatology | volume = 63 | issue = 1 | pages = 52–62 | date = July 2010 | pmid = 20488582 | doi = 10.1016/j.jaad.2009.07.052 }} 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%. No strong evidence supports the idea that higher concentrations of benzoyl peroxide are more effective than lower concentrations.

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.{{cite journal | vauthors = Cotterill JA | title = Benzoyl peroxide | journal = Acta Dermato-Venereologica. Supplementum | volume = 89 | pages = 57–63 | date = 1 January 1980 | doi = 10.2340/00015555895763 | pmid = 6162349 | doi-access = free }} 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, and it was thought to decrease sebum production, but disagreement exists within the literature on this.{{cite journal | vauthors = Worret WI, Fluhr JW | title = [Acne therapy with topical benzoyl peroxide, antibiotics and azelaic acid] | language = German | journal = Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology | volume = 4 | issue = 4 | pages = 293–300 | date = April 2006 | pmid = 16638058 | doi = 10.1111/j.1610-0387.2006.05931.x | trans-title = Acne therapy with topical benzoyl peroxide, antibiotics and azelaic acid | s2cid = 6924764 }}

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.

File:BenzoperoxideRx.JPG

Application of benzoyl peroxide to the skin may result in redness, burning, and irritation. This side effect is dose-dependent.{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 978-92-4-154765-9 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | pages = 307–308 }}{{cite book| vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=978-1-284-05756-0|page=173}}

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.{{cite book| veditors = Alldredge BK, Koda-Kimble MA, Young LY |title=Applied Therapeutics: The Clinical Use of Drugs|date=2013|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins|location=Baltimore|isbn=978-1-60913-713-7|page=949|edition=10th}} Irritation can also be reduced by avoiding harsh facial cleansers and wearing sunscreen prior to sun exposure.

One in 500 people experience hypersensitivity to benzoyl peroxide and are liable to experience burning, itching, crusting, and possibly swelling.{{cite journal | vauthors = Cunliffe WJ, Burke B | title = Benzoyl peroxide: lack of sensitization | journal = Acta Dermato-Venereologica | volume = 62 | issue = 5 | pages = 458–9 | date = 1982 | pmid = 6183909 | doi = 10.2340/0001555562458459 |doi-access=free }}{{cite web|url=http://www.mayoclinic.org/drugs-supplements/benzoyl-peroxide-topical-route/side-effects/drg-20062425|title=Benzoyl peroxide|publisher=Mayo Clinic|date=1 January 2016|url-status=live|archive-url=https://web.archive.org/web/20160718155333/http://www.mayoclinic.org/drugs-supplements/benzoyl-peroxide-topical-route/side-effects/drg-20062425|archive-date=18 July 2016}} About one-third of people experience phototoxicity under exposure to ultraviolet (UVB) light.{{cite journal | vauthors = Jeanmougin M, Pedreiro J, Bouchet J, Civatte J | title = [Phototoxic activity of 5% benzoyl peroxide in man. Use of a new methodology] | journal = Dermatologica | volume = 167 | issue = 1 | pages = 19–23 | date = 1 January 1983 | doi = 10.1159/000249739 | pmid = 6628794 }}

In the US, the typical concentration for benzoyl peroxide is 2.5% to 10% for both prescription and over-the-counter drug preparations that are used in treatment for acne.{{Cite web |title=Benzoyl Peroxide: Side Effects, Uses, Dosage, Interactions, Warnings |url=https://www.rxlist.com/benzoyl_peroxide/generic-drug.htm |access-date=2024-08-11 |website=RxList |language=en}}

Benzoyl peroxide is used in dentistry as a tooth whitening product.{{Cite web |title=Some Facts On Teeth Whitening |url=https://worldofdentistry.co.in/some-facts-on-teeth-whitening.php |access-date=2024-11-06 |website=worldofdentistry.co.in}}

Benzoyl peroxide is potentially explosive{{cite web| vauthors = Cartwright H |title=Chemical Safety Data: Benzoyl peroxide|url=http://cartwright.chem.ox.ac.uk/hsci/chemicals/benzoyl_peroxide.html|publisher=Oxford University|access-date=13 August 2011|date=17 March 2005|url-status=live|archive-url=https://web.archive.org/web/20101012224750/http://cartwright.chem.ox.ac.uk/hsci/chemicals/benzoyl_peroxide.html|archive-date=12 October 2010}} 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.

Benzoyl peroxide breaks down in contact with skin, producing benzoic acid and oxygen, neither of which is very toxic.{{SIDS-ref | title = Benzoyl peroxide | id = BENZOYLPER | date = April 2004}}

The carcinogenic potential of benzoyl peroxide has been investigated. A 1981 study published in the journal Science found that although benzoyl peroxide is not a carcinogen, it does promote cell growth when applied to an initiated tumor. The study concluded, "caution should be recommended in the use of this and other free radical-generating compounds".{{cite journal | vauthors = Slaga TJ, Klein-Szanto AJ, Triplett LL, Yotti LP, Trosko KE | title = Skin tumor-promoting activity of benzoyl peroxide, a widely used free radical-generating compound | journal = Science | volume = 213 | issue = 4511 | pages = 1023–5 | date = August 1981 | pmid = 6791284 | doi = 10.1126/science.6791284 | bibcode = 1981Sci...213.1023S }}

A 1999 IARC review of carcinogenicity studies found no convincing evidence linking benzoyl peroxide 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.International Agency for Research on Cancer (1999): "Benzoyl peroxide". in [https://publications.iarc.fr/89 Re-evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide] {{Webarchive|url=https://web.archive.org/web/20200715120252/https://publications.iarc.fr/89 |date=15 July 2020 }}. Monographs on the Evaluation of Carcinogenic Risks to Humans, number 71, pages 345–358. {{isbn|92-832-1271-1}}

Benzoyl peroxide can break down into carcinogen benzene at temperatures above 50 °C.{{cite journal | vauthors = Kucera K, Zenzola N, Hudspeth A, Dubnicka M, Hinz W, Bunick CG, Dabestani A, Light DY | title = Benzoyl Peroxide Drug Products Form Benzene | journal = Environmental Health Perspectives | volume = 132 | issue = 3 | pages = 37702 | date = March 2024 | pmid = 38483533 | doi = 10.1289/EHP13984 | pmc = 10939128 | bibcode = 2024EnvHP.132c7702K }}{{Cite web |title=USP Statement on Third Party Laboratory Benzene Findings {{!}} USP |url=https://www.usp.org/news/statement-on-third-party-laboratory-benzene-findings |access-date=2024-03-16 |website=www.usp.org |language=en}}

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.{{cite journal | vauthors = Leyden JJ, Kligman AM | title = Contact sensitization to benzoyl peroxide | journal = Contact Dermatitis | volume = 3 | issue = 5 | pages = 273–5 | date = October 1977 | pmid = 145346 | doi = 10.1111/j.1600-0536.1977.tb03674.x | s2cid = 33553359 }}

The US National Institute for Occupational Safety and Health has developed criteria for a recommended standard for occupational exposure to benzoyl peroxide.{{Cite journal |date=6 June 2014 |title=Criteria for a Recommended Standard: Occupational Exposure to Benzoyl Peroxide (77-166) |url=https://www.cdc.gov/niosh/docs/77-166/default.html |url-status=live |doi=10.26616/NIOSHPUB76128 |archive-url=https://web.archive.org/web/20160809050327/http://www.cdc.gov/niosh/docs/1970/77-166.html |archive-date=9 August 2016 |access-date=15 July 2016 |doi-access=free |website=CDC - NIOSH Publications and Products|url-access=subscription }}

File:Benzoyl peroxide stain.jpg

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.{{cite journal | vauthors = Bojar RA, Cunliffe WJ, Holland KT | title = The short-term treatment of acne vulgaris with benzoyl peroxide: effects on the surface and follicular cutaneous microflora | journal = The British Journal of Dermatology | volume = 132 | issue = 2 | pages = 204–8 | date = February 1995 | pmid = 7888356 | doi = 10.1111/j.1365-2133.1995.tb05014.x | s2cid = 22468429 }}

{{clear}}

• Clearasil

{{Reflist}}

• {{ICSC|0225|02}}
• {{PGCH|0052}}
• {{SIDS | title = Benzoyl peroxide | id = BENZOYLPER}}
• [https://www.americanchemistry.com/industry-groups/organic-peroxide-producers-safety-division-oppsd Organic Peroxide Producers Safety Division (OPPSD)]

{{E number infobox 920-929}}

{{Acne Agents}}

{{Portal bar | Medicine}}

{{Authority control}}

{{DEFAULTSORT:Benzoyl Peroxide}}

Category:Acne treatments

Category:Anti-acne preparations

Category:Benzene derivatives

Category:IARC Group 3 carcinogens

Category:Organic peroxides

Category:Radical initiators

Category:Wikipedia medicine articles ready to translate

Category:World Health Organization essential medicines