||The neutrality of this article is disputed. (May 2014)|
||This article needs more medical references for verification or relies too heavily on primary sources. (May 2014)|
- "Benzone" redirects here. It is not to be confused with benzene.
|Jmol-3D images||Image 1|
|Molar mass||228.24 g mol−1|
|Density||1.20 g cm−3|
|Melting point||62 to 65 °C (144 to 149 °F; 335 to 338 K)|
|Boiling point||224 to 227 °C (435 to 441 °F; 497 to 500 K)|
|Acidity (pKa)||7.6 (H2O)|
|Flash point||140.5 °C (284.9 °F; 413.6 K)|
|LD50||>12800 mg/kg (oral in rats)|
|Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)|
|(what is: / ?)|
Oxybenzone or benzophenone-3 (trade names Eusolex 4360, Escalol 567, KAHSCREEN BZ-3) is an organic compound used in sunscreens. The molecule was first synthesized in 1906, but the method for commercial production was not patented until 1975. It forms colorless crystals that are readily soluble in most organic solvents. Oxybenzone belongs to the class of aromatic ketones known as benzophenones. It provides broad-spectrum ultraviolet coverage, including 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. It is one of the most widely used organic UVA filters in sunscreens today. It is also found in nail polish, fragrances, hairspray, and cosmetics as a photostabilizer. Despite its photoprotective qualities, much controversy surrounds oxybenzone because of its possible hormonal and photoallergenic effects, leading many countries to regulate its use.
- 1 Structure and electronic structure
- 2 Production
- 3 Safety and controversy
- 4 Regulation
- 5 References
Structure and electronic structure
Being a conjugated molecule, oxybenzone absorbs at low energies. As in related compounds, the hydroxyl group is hydrogen bonded to the ketone. 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 only 24 ns. The short lifetime has been attributed to an extremely fast and reversible excited-state intramolecular hydrogen transfer between the oxygen of the C=O and the OH. This pathway provides an efficient energy-wasting pathway that is responsible for the absorption capabilities.
Although trace amounts occur naturally in some plants, oxybenzone is mainly a manufactured chemical. The US lists oxybenzone as a High Production Volume (HPV) chemical, meaning it was produced in or imported into the U.S. in >1 million pounds (>450,000 tonnes) in 1990 and/or 1994.
Methods of manufacturing
Oxybenzone is manufactured in several different countries including: Israel, The United Kingdom, France, Germany, Taiwan, Japan, and China.
One method of manufacturing oxybenzone is to condense benzoic acid with resorcinol monomethyl ether by heating the solution in the presence of ZnCl2 and polyphosphoric acid. Another method of production utilizes a Friedel-Crafts reaction of benzoyl chloride with 3-hydroxyanisole. The product of this reaction is subsequently recrystallized from a solution of water and methanol and then dried.
Oxybenzone is used in plastics as an ultraviolet light absorber and stabilizer. 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, in concentrations up to 1%, in nail polishes. Oxybenzone can also be used as a photostabilizer for synthetic resins.
Safety and controversy
There is much debate on whether oxybenzone poses a threat to the population as an endocrine disruptor. The safety of oxybenzone is difficult to assess, particularly in products such as sunscreen. Sunscreen is typically applied topically, but many studies that claim oxybenzone is hazardous were performed by injecting the compound directly into the test animal. Studies have shown that by topical application of sunscreen, oxybenzone is absorbed through the skin and excreted in urine. Up to 1–2% of the applied amount is estimated to be absorbed into the body. The method of administration discrepancy is the biggest issue when analyzing this data. A secondary debate arises because most of the studies done so far have tested zebrafish, rats, or pig skin rather than humans. This adds to the complication of extrapolating these studies to assess risks associated with human use.
The outstanding controversy over the potential adverse effects of oxybenzone on the human body is namely between the Environmental Working Group (EWG) and researchers who claim that that oxybenzone's impact is ultimately insignificant. According to EWG research, 84% of over 900 sunscreen products brands ineffectively protect against harmful rays or contain chemicals like oxybenzone. Sunscreen typically includes a combination of three to six active ingredients such as oxybenzone, avobenzone, octisalate, octocrylene, homosalate and octinoxate.
In vitro studies
Various studies have been done that show the estrogenic and anti-androgenic effects of oxybenzone. A study performed on a line of human breast cancer cells in 2003 validated these claims. This study showed that high concentrations of oxybenzone induced expression of the enzyme luciferase and it was not blocked by the estrogen antagonist. The data showed that there is anti-androgenic and estrogenic activity in vitro.
With exposure to sunlight, oxybenzone has been found to form free radicals through photogeneration, and therefore may be associated with cell damage. This only occurred when it was combined with other ingredients commonly found in sunscreen, like titanium oxide and octyl methoxycinnamate. On its own, oxybenzone was found to be a preferred UVA filter in 1996.
Three out of four studies since 2002 performed in vitro of rats found oxybenzone to have estrogenic potential, as it is a competitive binder of estrogen in the presence of estrogen receptors. These estrogenic effects are additive, meaning oxybenzone is more damaging when combined with other sunscreen ingredients such as benzophenone-1. However, all of these studies assert that the estrogenic potential is ultimately insignificant because in vivo, oxybenzone is broken down into metabolites that show little to no estrogenic activity.
In vivo studies
An in vivo study done in 2001 demonstrated that oxybenzone has estrogenic activity, meaning the molecule elicits an effect in a manner that mimics natural estrogen. It is difficult to take this result and assume that oxybenzone will produce the same effect in humans because the rats that were used in this particular study were administered an oral dosage of 1500 mg oxybenzone per kg body weight per day which is a phenomenally large dose. The dose used in the 2001 study is significantly larger than the recommended amount of topically applied commercial sunscreen which a study, done by Gonzalez and colleagues in 2002, approximated to be "40 g for an average body area of 2.0 m2." A 2006 study comparing the in vivo and in vitro effects of oxybenzone concluded that the estrogenic activity is abolished in vivo because of metabolism.
The most established risk associated with oxybenzone is its photoallergenic potential. Among common sunscreen chemicals, oxybenzone is most likely to be associated with allergic reactions triggered by sun exposure. In a study of 82 patients with photoallergic contact dermatitis, over one quarter showed photoallergic reactions to oxybenzone.
In a 2008 study of participants ages 6 and up, oxybenzone was detected in 96.8% of urine samples. 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. Oxybenzone is particularly penetrative because it is the least lipophilic of the three most common UV filters.
The studies that have been done in vitro and in vivo draw attention to the possible effects oxybenzone might have on reproductive hormones produced within the human body. To appraise the effects and risk of topically applied oxybenzone human clinical trials were performed. One such study was performed by several researchers in 2004. Their results showed no significant effect on hormone levels. Although the molecule was absorbed throughout the skin, it was not capable of disrupting the regulation of reproductive hormones in adults.
Most of these studies were only performed on adults. Young children not only have less developed systems of eliminating toxins, but they also have a larger surface area per body weight than adults. This suggests that children might intake larger amounts of compounds when applied topically. Sweden, for example, has advised that sunscreens containing oxybenzone may be unsuitable for children under two years of age. Children this young have not had a chance for the enzymes that degrade the molecule to fully develop and theoretically cannot eliminate the molecule as rapidly as adults putting them as a greater potential risk. For similar reasons, the Food and Drug Administration (FDA) and the International Dermal Institute both recommend to not apply sunscreen to infants because of high surface area to body weight ratios. A 2008 study also found a slightly positive correlation between women with high levels of oxybenzone in their system and high birth weight of their sons. There was no correlation with daughter birth weight.
When applied topically UV filters, such as oxybenzone, are absorbed through the skin, metabolized, and excreted primarily through the urine. 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). To form DHB the methoxy functional group undergoes o-dealkylation; to form THB the same ring is hydroxylated. Ring B in oxybenzone is hydroxylated to form DHMB.
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. The major metabolite detected was DHB and very small amounts of THB were found. By utilizing the Ames test in Salmonella typhimurium strains, DHB was determinted to be nonmutagenic.
Effects on coral
Revised as of 2007, the National Industrial Chemicals Notification and Assessment Scheme (NICNAS)) Cosmetic Guidelines allow oxybenzone for cosmetic use up to 10%.
The Scientific Committee on Consumer Products (SCCP) of the European Commission concluded in 2008 that it does not pose a significant risk to consumers, apart from contact allergenic potential. It is allowed in cosmetics up to 10%.
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 break it down. No regulations have come of this study yet.
Oxybenzone was approved for use in the US by the FDA in the early 1980s. Revised as of April 1, 2013, the FDA allows oxybenzone in cosmetic products up to 6%.
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