Oxybenzone

Oxybenzone or benzophenone-3 or BP-3 (trade names Milestab 9, Eusolex 4360, Escalol 567, KAHSCREEN BZ-3) is an organic compound belonging to the class of aromatic ketones known as benzophenones. It takes the form of pale-yellow crystals that are readily soluble in most organic solvents. It is widely used in sunscreen formulations, plastics, toys, furniture finishes, and other products to limit UV degradation.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In nature, it can be found in various flowering plants (angiosperms).<ref name=cdc>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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 (see section below).<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> As a result, sunscreens containing oxybenzone have been banned from sale in Hawaii,<ref name=":6" /> Palau,<ref>Template:Cite news</ref> and Thailand.<ref>Template:Cite news</ref>

Structure and electronic structure

Being a conjugated molecule, oxybenzone absorbs light at lower energies than many aromatic molecules.<ref name="Castro">Template:Cite journal</ref> As in related compounds, the hydroxyl group is hydrogen bonded to the ketone.<ref name="Lago">Template:Cite journal</ref> This interaction contributes to oxybenzone's light-absorption properties. At low temperatures, however, it is possible to observe both the phosphorescence 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.<ref name="Chrétien">Template:Cite journal</ref>

Production

Oxybenzone is produced by the Friedel-Crafts reaction of benzoyl chloride with 3-methoxyphenol.<ref name=toxnet>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Synthesis of oxybenzone by Friedel-Crafts reaction

Uses

Oxybenzone is used in plastics as an ultraviolet light absorber and stabilizer.<ref name="toxnet"/> It is used, along with other benzophenones, 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.<ref name="toxnet"/> Oxybenzone can also be used as a photostabilizer for synthetic resins.<ref name="toxnet"/> This substance can leach from food packaging, and is widely used as photo-initiators to activate a chemical that dries ink faster.<ref name="pmid20640959">Template:Cite journal</ref> 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.

Sunscreen

Oxybenzone provides a broad-spectrum ultraviolet coverage which includes UVB and short-wave UVA rays. As a photoprotective agent, it has an absorption profile spanning from 270 to 350 nm with absorption peaks at 288 and 350 nm.<ref name="Burnett, M. E 2011">Template:Cite journal</ref>

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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Some brands market their sunscreens as "oxybenzone free"<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> due to the generally negative perception of benzophenones by both the consuming public and scientific researchers.

Safety

In vivo studies

The incidence of oxybenzone causing skin eruptions is extremely uncommon,<ref name="Darvay 597–601">Template:Cite journal</ref> however, oxybenzone has been associated with rare allergic reactions triggered by sun exposure. In a study of 82 patients with photoallergic contact dermatitis, just over one quarter showed photoallergic reactions to oxybenzone.<ref>Template:Cite journal</ref> Evidence points to oxybenzone having contact allergen effects.<ref name="Burnett, M. E 2011" /><ref name="Darvay 597–601" /> Oxybenzone is allegedly the most common allergen found in sunscreens.<ref name=":2">Template:Cite book</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

In a 2008 study of participants ages 6 and up, oxybenzone was detected in 96.8% of urine samples.<ref>Template:Cite journal</ref> 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.<ref name= "Gonzalez">Template:Cite journal</ref> Because oxybenzone is the least lipophilic of the three most common UV filters, it is the least likely to end up trapped in the stratum corneum and the most likely to be absorbed and metabolized.<ref name= "Hanson">Template:Cite journal</ref>

When applied topically, UV filters, such as oxybenzone, are absorbed through the skin, metabolized, and excreted primarily through the urine.<ref name= "Chisvert">Template:Cite journal</ref> The method of biotransformation, 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).<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> To form DHB the methoxy functional group undergoes O-dealkylation; to form THB the same ring is hydroxylated.<ref name= "Chisvert"/> Ring B in oxybenzone is hydroxylated to form DHMB.<ref name= "Chisvert"/>

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.<ref name= "Sarveiya">Template:Cite journal</ref> The major metabolite detected was DHB and very small amounts of THB were found.<ref name= "Sarveiya"/> By utilizing the Ames test in Salmonella typhimurium strains, DHB was determined to be nonmutagenic.<ref>"Hazardous Substances Data Bank". 2,4-Dihydroxybenzophenone. National Library of Medicine (US), Division of Specialized Information Services. Retrieved 19 April 2014.</ref> In 2019, the U.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."<ref>Template:Cite journal</ref> Oxybenzone can also occur as a natural product.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Environmental effects

Studies have shown possible links between oxybenzone exposure and mortality in coral larvae, coral bleaching, and to genetic damage in marine invertebrates.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref name="Downs 132880">Template:Cite journal</ref> However, some of these studies have been criticised for not having control groups or representing real-world conditions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Nevertheless, these have led to the ban of oxybenzone-containing sunscreen in many areas<ref>Template:Cite journal</ref> such as Palau,<ref>Template:Cite news</ref> Hawaii,<ref name=":6" /> nature reserves in Mexico, Bonaire, the Marshall Islands, the United States Virgin Islands, Thailand's marine natural parks,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> the Northern Mariana Islands,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and Aruba.<ref name=":7" />

Health and environmental regulation

Aruba

Aruba banned the use of oxybenzone in sunscreens due to environmental concerns in 2019.<ref name=":7">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Australia

As of 2023, the maximum concentration of oxybenzone in a sunscreen cannot exceed 10% according to the TGA (Therapeutic Goods Administration).<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Bonaire

As of 2019 Bonaire banned oxybenzone due to coral toxicity concerns, with regards to coral larvae<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Canada

Revised as of 2012, Health Canada allows oxybenzone for cosmetic use up to 6%.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

European Union

The European Food Safety Authority categorises all the benzophenones, such as oxybenzone, as persistent, bio-accumulative, toxic, and a possible human carcinogen and endocrine disruptor.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The Scientific Committee on Consumer Products (SCCP) of the European Commission concluded that it poses a significant risk to consumers as a contact allergenic potential.<ref name=Aguirre>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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%.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Japan

Revised as of 2001, the Ministry of Health, Labour, and Welfare notification allows oxybenzone for cosmetic use up to 5%.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Mexico

Nature Reserves across Mexico have banned the usage of sunscreens containing Oxybenzone<ref>Template:Cite journal</ref>

Palau

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.<ref>Template:Cite news</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Sweden

The Swedish 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.<ref name="toxnet"/>

Thailand

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.<ref>Template:Cite news</ref>

United States

In 2021 the U.S. FDA changed their classification of oxybenzone and no longer regard it as GRASE (Generally Recognised As Safe and Effective)<ref name=":4">Template:Cite journal</ref> due to the lack of safety data to support the classification.

The Hawaii State Legislature has legislated oxybenzone as illegal for use in sunscreens 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.<ref name=":6">Template:Cite news</ref><ref>Template:Cite journal</ref>

Key West has also banned the sale of sunscreens that contain the ingredients oxybenzone (and octinoxate). The ban was to be effective as of January 1, 2021.<ref>Template:Cite news</ref> However, this legislation was superseded by the Florida State Legislature by Senate Bill 172,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.