Oxybenzone orbenzophenone-3 orBP-3 (trade namesMilestab 9,Eusolex 4360,Escalol 567,KAHSCREEN BZ-3) is anorganic compound belonging to the class of aromaticketones known asbenzophenones. It takes the form of pale-yellow crystals that are readily soluble in most organic solvents. It is widely used insunscreen formulations, plastics, toys, furniture finishes, and other products to limit UV degradation.[4] In nature, it can be found in various flowering plants (angiosperms).[5] The compound was first synthesised in Germany by chemists König and Kostanecki in 1906.
The use of oxybenzone as sunscreen ingredient is currently under scrutiny by the scientific community due to controversies about the molecule's environmental impact and safety profile (seesection below).[6] As a result, sunscreens containing oxybenzone have been banned from sale inHawaii,[7]Palau,[8] and Thailand.[9]
Being aconjugated molecule, oxybenzone absorbs light at lower energies than many aromatic molecules.[10] As in related compounds, thehydroxyl group is hydrogen bonded to the ketone.[11] This interaction contributes to oxybenzone's light-absorption properties. At low temperatures, however, it is possible to observe both thephosphorescence and the triplet-triplet absorption spectrum. At 175 K the triplet lifetime is 24 ns. The short lifetime has been attributed to a fast intramolecular hydrogen transfer between the oxygen of the C=O and the OH.[12]
Oxybenzone is used in plastics as an ultraviolet light absorber and stabilizer.[13] It is used, along with otherbenzophenones, in sunscreens, hair sprays, and cosmetics because they help prevent potential damage from sunlight exposure. It is also found, as a stabilizer in concentrations up to 1%, in nail polishes.[13] Oxybenzone can also be used as a photostabilizer forsynthetic resins.[13] This substance can leach from food packaging, and is widely used as photo-initiators to activate a chemical that dries ink faster.[14] Despite its photoprotective qualities, much controversy surrounds oxybenzone because of possible negative hormonal and photoallergenic effects, leading many countries to regulate use in sunscreen products.
Oxybenzone provides a broad-spectrum ultraviolet coverage which includesUVB and short-waveUVA rays. As aphotoprotective agent, it has anabsorption profile spanning from 270 to 350 nm with absorption peaks at 288 and 350 nm.[15]
Due to toxicity and environmental concerns, the percentage of sunscreen products on the market containing oxybenzone in the USA dropped to 13% in 2023 from 60% in 2019.[16] Some brands market their sunscreens as "oxybenzone free"[17] due to the generally negative perception of benzophenones by both the consuming public and scientific researchers.
The incidence of oxybenzone causing skin eruptions is extremely uncommon,[18] however, oxybenzone has been associated with rare allergic reactions triggered by sun exposure. In a study of 82 patients with photoallergic contactdermatitis, just over one quarter showed photoallergic reactions to oxybenzone.[19] Evidence points to oxybenzone havingcontact allergen effects.[15][18] Oxybenzone is allegedly the most common allergen found in sunscreens.[20][21][22][23]
In a 2008 study of participants ages 6 and up, oxybenzone was detected in 96.8% of urine samples.[24] Humans can absorb anywhere from 0.4% to 8.7% of oxybenzone after one topical application of sunscreen, as measured in urine excretions. This number can increase after multiple applications over the same period of time.[25] Because oxybenzone is the leastlipophilic of the three most common UV filters, it is the least likely to end up trapped in thestratum corneum and the most likely to be absorbed andmetabolized.[26]
When applied topically, UV filters, such as oxybenzone, are absorbed through the skin, metabolized, and excreted primarily through the urine.[27] The method ofbiotransformation, the process by which a foreign compound is chemically transformed to form a metabolite, was determined by Okereke and colleagues through oral and dermal administration of oxybenzone to rats. The scientists analyzed blood, urine, feces, and tissue samples and found three metabolites: 2,4-dihydroxybenzophenone (DHB), 2,2-dihydroxy-4-methoxybenzophenone (DHMB) and 2,3,4-trihydroxybenzophenone (THB).[28][29] To form DHB the methoxy functional group undergoes O-dealkylation; to form THB the same ring is hydroxylated.[27] Ring B in oxybenzone is hydroxylated to form DHMB.[27]
A study done in 2004 measured the levels of oxybenzone and its metabolites in urine. After topical application to human volunteers, results revealed that up to 1% of the applied dose was found in the urine.[30] The major metabolite detected was DHB and very small amounts of THB were found.[30] By utilizing theAmes test inSalmonella typhimurium strains, DHB was determined to be nonmutagenic.[31] In 2019, theU.S. Food and Drug Administration (FDA) noted in their recommendations for future study that, "While research indicates that some topical drugs can be absorbed into the body through the skin, this does not mean these drugs are unsafe."[32] Oxybenzone can also occur as anatural product.[33][34]
TheEuropean Food Safety Authority categorises All the benzophenones, such as oxybenzone, as persistent, bio-accumulative, toxic, and a possible human carcinogen and endocrine disruptor.[53] TheScientific Committee on Consumer Products (SCCP) of theEuropean Commission concluded that it poses a significant risk to consumers as a contact allergenic potential.[54] It is allowed in face, hand, and lip products up to 6%, in body products up to 2.2%, and in other formulations up to 0.5%.[55]
The Palau government has signed a law that restricts the sale and use of sunscreen and skincare products that contain oxybenzone, and nine other chemicals. The ban came into force in 2020.[58][59]
TheSwedish Research Council has determined that sunscreens with oxybenzone are unsuitable for use in young children, because children under the age of two years have not fully developed the enzymes that are believed to break it down. No regulations have come of this study yet.[13]
Thailand has prohibited sunscreens containing chemicals harmful to corals, including oxybenzone, in all its marine national parks. This decision was driven by evidence highlighting the detrimental effects of certain sunscreen ingredients on coral larvae, reproduction, and inducing reef bleaching. Violators face fines up to 100,000 baht (£2,100), although enforcement methods remain unspecified.[60]
In 2021 the U.S. FDA changed their classification of oxybenzone and no longer regard it asGRASE (Generally Recognised As Safe and Effective)[61] due to the lack of safety data to support the classification.
TheHawaii State Legislature has legislated oxybenzone as illegal for use insunscreens and personal care products since 2021 due to its environmental effects, such as mortality in developing coral, coral bleaching, genetic damage to coral, and other marine organisms.[7][62]
Key West has also banned the sale of sunscreens that contain the ingredients oxybenzone (andoctinoxate). The ban was to be effective as of January 1, 2021.[63] However, this legislation was superseded by theFlorida State Legislature by Senate Bill 172,[64] which prohibits local governments from regulating over-the-counter proprietary drugs and cosmetics (such as sunscreen containing oxybenzone and octinoxate). The statute became effective July 1, 2020.
^Fontanals N, Cormack PA, Sherrington DC, Marcé RM, Borrull F (April 2010). "Weak anion-exchange hypercrosslinked sorbent in on-line solid-phase extraction-liquid chromatography coupling to achieve automated determination with an effective clean-up".Journal of Chromatography A.1217 (17):2855–61.doi:10.1016/j.chroma.2010.02.064.PMID20303088.
^Lago AF, Jimenez P, Herrero R, Dávalos JZ, Abboud JL (April 2008). "Thermochemistry and gas-phase ion energetics of 2-hydroxy-4-methoxy-benzophenone (oxybenzone)".The Journal of Physical Chemistry A.112 (14):3201–8.Bibcode:2008JPCA..112.3201L.doi:10.1021/jp7111999.PMID18341312.
^Chrétien MN, Heafey E, Scaiano JC (2010). "Reducing adverse effects from UV sunscreens by zeolite encapsulation: comparison of oxybenzone in solution and in zeolites".Photochemistry and Photobiology.86 (1):153–61.doi:10.1111/j.1751-1097.2009.00644.x.PMID19930122.S2CID43408456.
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^Rodríguez E, Valbuena MC, Rey M, Porras de Quintana L (August 2006). "Causal agents of photoallergic contact dermatitis diagnosed in the national institute of dermatology of Colombia".Photodermatology, Photoimmunology & Photomedicine.22 (4):189–92.doi:10.1111/j.1600-0781.2006.00212.x.PMID16869867.S2CID36123270.
^DeLeo VA, Suarez SM, Maso MJ (November 1992). "Photoallergic contact dermatitis. Results of photopatch testing in New York, 1985 to 1990".Archives of Dermatology.128 (11):1513–8.doi:10.1001/archderm.1992.01680210091015.PMID1444508.
^Scheuer E, Warshaw E (March 2006). "Sunscreen allergy: A review of epidemiology, clinical characteristics, and responsible allergens".Dermatitis.17 (1):3–11.doi:10.2310/6620.2006.05017.PMID16800271.S2CID42168353.
^Gonzalez H, Farbrot A, Larkö O, Wennberg AM (February 2006). "Percutaneous absorption of the sunscreen benzophenone-3 after repeated whole-body applications, with and without ultraviolet irradiation".The British Journal of Dermatology.154 (2):337–40.doi:10.1111/j.1365-2133.2005.07007.x.PMID16433806.S2CID1001823.
^abcChisvert A, León-González Z, Tarazona I, Salvador A, Giokas D (November 2012). "An overview of the analytical methods for the determination of organic ultraviolet filters in biological fluids and tissues".Analytica Chimica Acta.752:11–29.Bibcode:2012AcAC..752...11C.doi:10.1016/j.aca.2012.08.051.PMID23101648.
^Okereke CS, Kadry AM, Abdel-Rahman MS, Davis RA, Friedman MA (1993). "Metabolism of benzophenone-3 in rats".Drug Metabolism and Disposition.21 (5):788–91.PMID7902237.
^Okereke CS, Abdel-Rhaman MS, Friedman MA (August 1994). "Disposition of benzophenone-3 after dermal administration in male rats".Toxicology Letters.73 (2):113–22.doi:10.1016/0378-4274(94)90101-5.PMID8048080.
^abSarveiya V, Risk S, Benson HA (April 2004). "Liquid chromatographic assay for common sunscreen agents: application to in vivo assessment of skin penetration and systemic absorption in human volunteers".Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences.803 (2):225–31.doi:10.1016/j.jchromb.2003.12.022.PMID15063329.
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