Oxybenzone

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"Benzone" redirects here. It is not to be confused with benzene.
Oxybenzone[1]
Oxybenzone
Identifiers
CAS number 131-57-7 YesY
PubChem 4632
ChemSpider 4471 YesY
UNII 95OOS7VE0Y YesY
DrugBank DB01428
KEGG D05309 YesY
ChEBI CHEBI:34283 N
ChEMBL CHEMBL1625 YesY
Jmol-3D images Image 1
Properties
Molecular formula C14H12O3
Molar mass 228.24 g mol−1
Density 1.20 g cm−3[2]
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)[3]
Hazards[2]
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)
 N (verify) (what is: YesY/N?)
Infobox references

Oxybenzone or benzophenone-3 (trade names Eusolex 4360, Escalol 567, KAHSCREEN BZ-3) is an organic compound used in sunscreens. 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 UV coverage, including UVB and short-wave UVA (ultraviolet) rays. As a photoprotective agent, it has an absorption profile spanning from 270 to 350 nm with absorption peaks at 288 and 350 nm.[4] The molecule was first synthesized in 1906, but the method for commercial production was not patented until 1975.[5] It is one of the most widely used organic UVA filters in sunscreens today.[4] It is also found in nail polish, fragrances, hairspray, and cosmetics as a photostabilizer. Despite the photoprotection, much controversy surrounds oxybenzone, leading many countries to regulate its use.

Structure and electronic structure[edit]

Being a conjugated molecule, oxybenzone absorbs at low energies.[6] As in related compounds, the hydroxyl group is hydrogen bonded to the ketone.[7] This interaction contributes to oxybenzone's light-absorption properties. At low temperatures, however, it is possible to observe both the phosphoresce and the triplet-triplet absorption spectrum. At 175K 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.[8]

Production[edit]

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 in 1990 and/or 1994.[5]

Safety and controversy[edit]

There is much debate on whether oxybenzone poses a threat to the population as an endocrine disruptor.[4] The safety of oxybenzone is difficult to assess, particularly in products such as sunscreen.[4] 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 proven that by topical application of sunscreen, oxybenzone is absorbed through the skin and excreted in urine.[9] Up to 1-2% of the applied amount is estimated to be absorbed into the body.[10] The method of administration discrepancy is the biggest issue when analyzing this data. A secondary debate arises because most of the studies done 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 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.[11]

In Vitro studies[edit]

Various studies have been done that clearly 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.[12]

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.[13] On its own, oxybenzone was found to be a preferred UVA filter in 1996.[14]

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.[15][16][17][18] These estrogenic effects are additive, meaning oxybenzone is more damaging when combined with other sunscreen ingredients.[19] 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[edit]

A 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.[16] 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.[20]

Human studies[edit]

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.[21]

In a 2008 study of participants ages 6 and up, oxybenzone was detected in 96.8% of urine samples.[22] 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.[9] Oxybenzone is particularly penetrative because it is the least lipophilic of the three most common UV filters.[10]

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. However, the most effective means of appraising the effects and risk of topically applied oxybenzone are from human clinical trials. 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.[23]

All 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.[23] Sweden, for example, has taken precautions against this and has deemed the use of oxybenzone unsuitable for children under two years of age.[24] 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.[24] For similar reasons, the FDA and the International Dermal Institute both recommend to not apply sunscreen to infants because of high surface area to body weight ratios.[25][26] 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.[27]

Regulation[edit]

Country Oxybenzone Permitted
Australia 10%
Canada 6%
European Union 10%
Japan 5%
Sweden unregulated
United States 6%

Australia[edit]

Revised as of 2007, the NICNAS Cosmetic Guidelines allow Oxybenzone for cosmetic use up to 10%.[28]

Canada[edit]

Revised as of 2012, Health Canada allows Oxybenzone for cosmetic use up to 6%.[29]

European Union[edit]

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.[26] It is allowed in cosmetics up to 10%.

Japan[edit]

Revised as of 2001, the Ministry of Health and Welfare Notification allows Oxybenzone for cosmetic use up to 5%.[30]

Sweden[edit]

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.[5]

United States[edit]

Oxybenzone was approved for use in the US by the Food and Drug Administration (FDA) in the early 1980s. Revised as of April 1, 2013, the FDA allows oxybenzone in cosmetic products up to 6%.[31]

References[edit]

  1. ^ Merck Index, 11th Edition, 6907
  2. ^ a b 131-57-7 Methanone
  3. ^ Fontanals, Núria; Cormack, Peter A.G.; Sherrington, David C.; Marcé, Rosa M.; Borrull, Francesc (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. PMID 20303088. 
  4. ^ a b c d Burnett, M. E. and Wang, S. Q. (2011), Current sunscreen controversies: a critical review. Photodermatology, Photoimmunology & Photomedicine, 27: 58–67
  5. ^ a b c "Hazardous Substances Data Bank". 2-HYDROXY-4-METHOXYBENZOPHENONE. National Library of Medicine (US), Division of Specialized Information Services. Retrieved 9 March 2014. 
  6. ^ Castro, G. T.; Blanco, S. E.; Giordano, O. S. (2000). "UV Spectral Properties of Benzophenone. Influence of Solvents and Substituents". Molecules 5 (3): 424. doi:10.3390/50300424. 
  7. ^ Lago, A. F.; Jimenez, P.; Herrero, R.; Dávalos, J. Z.; Abboud, J.-L. M. (2008). "Thermochemistry and Gas-Phase Ion Energetics of 2-Hydroxy-4-methoxy-benzophenone (Oxybenzone)". The Journal of Physical Chemistry A 112 (14): 3201–8. doi:10.1021/jp7111999. PMID 18341312. 
  8. ^ Chrã©Tien, Michelle N.; Heafey, Eve; Scaiano, Juan C. (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. PMID 19930122. 
  9. ^ a b H. Gonzalez, H., Farbrot, A., Larko. O., and Wennberg, A. M. (2006), Percutaneous absorption of the sunscreen benzophenone-3 after repeated whole-body applications, with and without ultraviolet irradiation. British Journal of Dermatology , 154:337-340.
  10. ^ a b Hanson KM, Gratton E, Bardeen CJ. 2006. Sunscreen enhancement of UV-induced reactive oxygen species in the skin. Free radical biology & medicine 41(8): 1205-1212
  11. ^ Centers for Disease Control. CDC: Americans Carry Body Burden of Toxic Sunscreen Chemical. Environmental Working Group. EWG, 25 Mar. 2008. Web. 14 Mar. 2014. <http://www.ewg.org/news/testimony-official-correspondence/cdc-americans-carry-body-burden-toxic-sunscreen-chemical>
  12. ^ Ma R, et al. UV filters with antagonistic action at androgen receptors in the MDA-kb2 cell transcriptional-activation assay. Toxicol Sci 2003; 74: 43–50.
  13. ^ Serpone N, Salinaro A, Emeline AV, Horikoshi S, Hidaka H, Zhao JC. 2002. An in vitro systematic spectroscopic examination of the photostabilities of a random set of commercial sunscreen lotions and their chemical UVB/UVA active agents. Photochemical & Photobiological Sciences 1(12): 970-981.
  14. ^ Allen JM, Gossett CJ, Allen SK. 1996. Photochemical formation of singlet molecular oxygen in illuminated aqueous solutions of several commercially available sunscreen active ingredients. Chemical research in toxicology 9(3): 605-609.
  15. ^ Nakagawa Y, Suzuki T. 2002. Metabolism of 2-hydroxy-4-methoxybenzophenone in isolated rat hepatocytes and xenoestrogenic effects of its metabolites on MCF-7 human breast cancer cells. Chem Biol Interact 139(2): 115-128.
  16. ^ a b Schlumpf M, Cotton B, Conscience M, Haller V, Steinmann B, Lichtensteiger W. 2001. In vitro and in vivo estrogenicity of UV screens. Environmental health perspectives 109(3): 239-244.
  17. ^ Kunz PY, Galicia HF, Fent K. Comparison of in vitro and in vivo estrogenic activity of UV filters in fish. Toxicol Sci 90(2): 349-361.
  18. ^ Van Liempd SM, Kool J, Meerman JH, Irth H, Vermeulen NP. 2007. Metabolic profiling of endocrine-disrupting compounds by on-line cytochrome p450 bioreaction coupled to on-line receptor affinity screening. Chemical research in toxicology 20(12): 1825-1832.
  19. ^ Heneweer M, Muusse M, van den Berg M, Sanderson JT. 2005. Additive estrogenic effects of mixtures of frequently used UV filters on pS2-gene transcription in MCF-7 cells. Toxicology and Applied Pharmacology 208(2): 170-177.
  20. ^ Kunz PY, Galicia HF, Fent K. Comparison of in vitro and in vivo estrogenic activity of UV filters in fish. Toxicol. Sci. 2006;90:349-361.
  21. ^ Rodriguez E, Valbuena MC, Rey M, Porras de Quintana L. 2006. Causal agents of photoallergic contact dermatitis diagnosed in the national institute of dermatology of Colombia. Photodermatol Photoimmunol Photomed 22(4): 189-192.
  22. ^ Calafat AM, Wong L-Y, Ye X, Reidy JA, Needham LL. 2008. Concentration of the sunscreen agent, benzophenone-3, in residents of the United States: National Health and Nutrition Examination Survey 2003-2004. Environmental health perspectives 116: Available online March 21, 2008.
  23. ^ a b Janjua, N. R., et. al. (2004), Systemic Absorption of the Sunscreens Benzophenone-3, Octyl-Methoxycinnamate, and 3-(4-Methyl-Benzylidene) Camphor After Whole-Body Topical Application and Reproductive Hormone Levels in Humans, 123:56:61.
  24. ^ a b "Sunscreens with benzophenone-3 unsuitable for children." Swedish Research Council. N.p., 6 Nov. 2006. Web. 14 Mar. 2014. <http://www.eurekalert.org/pub_releases/2006-11/src-swb110606.php>.
  25. ^ "Should You Put Sunscreen on Infants? Not Usually." U.S. Food and Drug Administration. U.S. Food and Drug Administration, 10 Feb. 2014. Web. 14 Mar. 201 <http://www.fda.gov/forconsumers/consumerupdates/ucm309136.htm>
  26. ^ a b Aguirre, Claudia, Dr. "Shedding Light on Sun Safety - Part Two." International Dermal Institute. International Dermal Institute, n.d. Web. 14 Mar. 2014 <http://dermalinstitute.com/us/library/66_article_Shedding_Light_on_Sun_Safety_Part_Two.html>
  27. ^ Wolff MS, Engel SM, Berkowitz GS, Ye X, Silva MJ, Zhu C, et al. 2008. Prenatal phenol and phthalate exposures and birth outcomes. Environmental health perspectives 116: Available online March 20, 2008.
  28. ^ "NICNAS COSMETICS GUIDELINES". Australian Government Department of Health. Retrieved 9 March 2014. 
  29. ^ "Guidance Document Sunscreen Monograph". Health Canada. Retrieved 9 March 2014. 
  30. ^ "Standards for Cosmetics". Ministry of Health and Welfare Notification No.331 of 2000. Japanese Government. Retrieved 9 March 2014. 
  31. ^ "SUNSCREEN DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE". Code of Federal Regulations Title 21. FDA. Retrieved 9 March 2014.