Benzoyl peroxide

Benzoyl peroxide is a chemical compound (specifically, an organic peroxide) with structural formula (C
6H
5−C(=O)O−)
2, often abbreviated as (BzO)2. In terms of its structure, the molecule can be described as two benzoyl (C
6H
5−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, which is principally used as in the production of polymers.[2]

Benzoyl peroxide
Skeletal formula (top) Ball-and-stick model (bottom)
Clinical data
Trade namesBenzac, Clearasil, PanOxyl, others
Other namesbenzoperoxide, dibenzoyl peroxide (DBPO)
AHFS/Drugs.comProfessional Drug Facts
MedlinePlusa601026
License data
ATC code
Legal status
Legal status
  • US: OTC / Rx-only
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
E numberE928 (glazing agents, ...)
CompTox Dashboard (EPA)
ECHA InfoCard100.002.116
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)
Data page
Benzoyl peroxide (data page)

As a bleach, it has been used as a medication and a water disinfectant.[3][4] In specialized contexts, the name may be abbreviated as BPO.

As a medication, benzoyl peroxide is mostly used to treat acne, either alone or in combination with other treatments.[5] Some versions are sold mixed with antibiotics such as clindamycin.[6][7] It is on the WHO List of Essential Medicines,[8] and, in the US, it is available as an over-the-counter and generic medication.[9][6] It is also used in dentistry for teeth whitening.

Benzoyl peroxide is also used for bleaching flour, hair, and textiles[10][4] It is also used in the plastics industry.[3]

History

Benzoyl peroxide was first prepared and described by Liebig in 1858.[11] It was the first organic peroxide prepared intentionally.

In 1901, J. H. Kastle and his graduate student A. S. Loevenhart observed that the compound made the tincture of guaiacum tincture turn blue, a sign of oxygen being released.[12] Around 1905, Loevenhart reported on the successful 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.[13][10][14]

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.[14] However, preparations were often of questionable quality.[10] It was officially approved for the treatment of acne in the US in 1960.[10]

Medical uses

Acne treatment
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.[15][16] 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, an unusual formulation considering most retinoids are deactivated by peroxides. 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.[16]

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%.[15] No strong evidence supports the idea that higher concentrations of benzoyl peroxide are more effective than lower concentrations.[15]

Mechanism of action

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.[15][17] 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,[10] and it was thought to decrease sebum production, but disagreement exists within the literature on this.[17][18]

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.[18]

Side effects
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.[5][9]

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.[18][19] Irritation can also be reduced by avoiding harsh facial cleansers and wearing sunscreen prior to sun exposure.[19]

One in 500 people experience hypersensitivity to BPO and are liable to suffer burning, itching, crusting, and possibly swelling.[20][21] About one-third of people experience phototoxicity under exposure to ultraviolet (UVB) light.[22]

Dosage

In the U.S., 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.

Other medical uses

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

Non-medical uses

Benzoyl peroxide is one of the most important organic peroxides in terms of applications and the scale of its production. It is often used as a convenient oxidant in organic chemistry.

Bleaching

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.[23]

Polymerization

Benzoyl peroxide is also used as a radical initiator to induce chain-growth polymerization reactions,[2] such as for polyester and poly(methyl methacrylate) (PMMA) resins and dental cements and restoratives.[24] 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.[25][26] It is also used in rubber curing and as a finishing agent for some acetate yarns.[24]

Safety

Explosion hazard

Concentrated benzoyl peroxide is potentially explosive[27] 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.

Toxicity

Benzoyl peroxide breaks down in contact with skin, producing benzoic acid and oxygen, neither of which is very toxic.[28]

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".[29]

A 1999 IARC review of carcinogenicity studies found no convincing evidence linking BPO acne medication to skin cancers in humans. However, some animal studied found that the compound could act as a carcinogen and enhance the effect of known carcinogens.[24]

Skin irritation

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.[30]

The U.S. National Institute for Occupational Safety and Health has developed criteria for a recommended standard for occupational exposure to benzoyl peroxide.[31]

Cloth staining
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.[32]

Reactivity

The original 1858 synthesis by Liebig reacted benzoyl chloride with barium peroxide,[11] 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 C
6H
5CO•
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.[33]

References
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