Oxybenzone

Oxybenzone[1]
IUPAC name (2-Hydroxy-4-methoxyphenyl)- phenylmethanone
Other names Oxybenzone Benzophenone-3
Identifiers
CAS number	131-57-7 Y
PubChem	4632
ChemSpider	4471 Y
UNII	95OOS7VE0Y Y
DrugBank	DB01428
KEGG	D05309 Y
ChEBI	CHEBI:34283 N
ChEMBL	CHEMBL1625 Y
Jmol-3D images	Image 1
SMILES O=C(c1ccc(OC)cc1O)c2ccccc2
InChI InChI=1S/C14H12O3/c1-17-11-7-8-12(13(15)9-11)14(16)10-5-3-2-4-6-10/h2-9,15H,1H3 Y Key: DXGLGDHPHMLXJC-UHFFFAOYSA-N Y InChI=1/C14H12O3/c1-17-11-7-8-12(13(15)9-11)14(16)10-5-3-2-4-6-10/h2-9,15H,1H3 Key: DXGLGDHPHMLXJC-UHFFFAOYAX
Properties
Molecular formula	C14H12O3
Molar mass	228.24 g mol−1
Density	1.20 g cm−3 [2]
Melting point	62-65 °C, 335-338 K, 144-149 °F
Boiling point	224-227 °C, 497-500 K, 435-441 °F
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Oxybenzone (trade names Eusolex 4360, Escalol 567) is an organic compound used in sunscreens. It forms colorless crystals that are readily soluble in most organic solvents. A 2008 study by the US Centers for Disease Control and Prevention found the compound to be present in 96.8% of human urine samples analyzed as part of the National Health and Nutrition Examination Survey.^[3] The FDA and governing agencies in Canada and the EU have approved the use of oxybenzone as a safe and effective sunscreen ingredient. The safety of oxybenzone has also been reviewed and confirmed by the Cosmetic Ingredient Review expert panel.^[4]

It is used as an ingredient in sunscreen and other cosmetics because it absorbs UVB and short-wave UVA (ultraviolet) rays.^[5] Oxybenzone was one of the first compounds incorporated into sunscreen formulations to offer enhanced UVA protection because its absorption spectrum extends to less than 350 nm.^[6] Oxybenzone's ability to absorb UV rays is due to a variety of molecular interactions. In this compound, both of the phenyl rings can interact with the C=O group through inductive effects and mesomeric effects. The overlapping of the π bonds of both phenyl rings and that of the C=O creates a completely conjugated molecule as evidenced by the MO diagram. This causes the C=O group to lose part of its individual character as it integrates with the two phenyl rings. This stabilizes the system due to the transference of electron deficiency from the carbon of the carbonyl towards three of the carbons of the phenyl rings.^[7]

When examining the stability of the oxybenzone, which contributes to the absorption capabilities of the molecule, studies show that the molecule is basically locked into the conformation that places the OH group close to the C=O. Because the oxygen contains most of the electron density of the C=O bond, the electrons can interact with the hydrogen of the OH group. As a result, oxybenzone is more stable by 35.6 kJ/mol due to the presence of the intramolecular hydrogen bonding capabilities. The hydrogen bond can be classified as a "moderate" or "conventional-strong" bond, which has electrostatic character.^[8] It is this conformation that leads to oxybenzone's absorption capabilities. Research studies show that at room temperature, oxybenzone does not undergo benzophenone-like photoreduction and does not phosphoresce. 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.^[6]

Controversy

A study conducted on laboratory rats concluded that oxybenzone is "not toxic to rats when applied dermally at a dose of 100 mg/kg body wt. for 4 weeks."^[9]

Another study analyzed the topical application of oxybenzone on humans: "In this study, we sought to determine whether sufficient topically applied sunscreens penetrated into human viable epidermis to put the local keratinocyte cell populations at risk of toxicity. The penetration and retention of five commonly used sunscreen agents (avobenzone, octinoxate, octocrylene, oxybenzone and padimate O) in human skin was evaluated after application...It is concluded that the human viable epidermal levels of sunscreens are too low to cause any significant toxicity to the underlying human keratin."^[10]

In the EU products intended for skin protection with 0.5% or more oxybenzone must be labeled "contains oxybenzone".^[11][12] This organic compound has been shown to penetrate into the skin where it acts as a photosensitizer. This results in an increased production of free radicals under illumination,^[13] possibly making this substance a photocarcinogen.^{[citation needed]} This study concludes that "determining what, if any, type of damage is done by ROS generated by UV filters needs to be explored." This study is of oxybenzone and two other sunscreen active ingredients. Two years after the study this information is now reaching consumers,^[14] but it can still be found in many sunscreens. Oxybenzone is a derivative of benzophenone, which can attack DNA when illuminated. It generates strand breaks and various photoproducts.^[15] Already in 1993 the use of oxybenzone had been strongly criticized, based on its similarity to benzophenone.^[15]

The photomutagenic properties of these compounds might be a contributing factor to the increased melanoma incidence worldwide. Rising skin cancer rates might reflect a change in how doctors diagnose melanoma and the availability of skin cancer screenings along with improper sun safety measures. Other possibilities include consequent overexposure to sun without UVA protection, indoor tanning beds and lamps, and vitamin D deficiency from overuse of sunscreen.^[16] (see sunscreen controversy).

The source of these oxybenzone concerns is a Washington DC non-profit: Environmental Working Group (EWG). Chief Scientist, Dr. John Bailey with the Personal Care Products Council, a group representing the interests of the cosmetics industry, says the following about the EWG findings: "EWG’s report lacks scientific credibility", "EWG’s allegations are in direct conflict with the established scientific and FDA safety assessments of sunscreen products and their ingredients, including those from scientific and regulatory bodies in the European Union, Canada, and several other countries", "EWG invents its own sunscreen product rating system based on very questionable scientific methodology... proven to be inaccurate and unreliable by sunscreen experts around the world".^[17]

According to The Skin Cancer Foundation, "there has never been any evidence that oxybenzone, which has been available for 20 years, has any adverse health effect in humans. The ingredient is FDA-approved for human use based on exhaustive review. The Foundation’s volunteer Photobiology Committee reviewed the studies on oxybenzone and found no basis for concern." ^[18] Dr. Warwick Morison, MD, chairman of The Skin Cancer Foundation’s Photobiology Committee and Professor of Dermatology at Johns Hopkins University said, “The EWG has their own system for evaluating things which is nothing more than junk science.”^[18]

It has been seen that oxybenzone, along with other sunscreen ingredients such as ethylhexyl p-methoxycinnamate (EHMC) and octyl p-dimethylaminobenzoate (PABA), inhibited cell growth. It will also inhibit the cell cycle at the G1 phase. However, this effect has been observed with a dosage of 25-100 µg/mL and 24 hour exposure. In this study, sunscreen was applied to different cells for 24 hours with a 4-6 day recovery period. It was seen that cell death was seen in the cells C180-13S, MM96L, and HeLa. This particular study shows that cell death is observed in the presence of oxybenzone.^[19]

References

1. ^ *Merck Index, 11th Edition, 6907.
2. ^ Anonymous. Scifinder – Registry Detail 131-57-7. (accessed October 1, 2010).
3. ^ Antonia M. Calafat, Lee-Yang Wong, Xiaoyun Ye, John A. Reidy, and Larry L. Needham (2008). "Concentrations of the Sunscreen Agent, Benzophenone-3, in Residents of the United States: National Health and Nutrition Examination Survey 2003–2004" (in press). Environmental Health Perspectives 116 (7): 893–7. doi:10.1289/ehp.11269. PMC 2453157. PMID 18629311. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2453157. 
4. ^ Cosmetic Ingredient Review
5. ^ Skin cancer foundation: Understanding UVA and UVB
6. ^ ^{a b} Chrétien 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): 153–161. doi:10.1111/j.1751-1097.2009.00644.x. PMID 19930122. 
7. ^ Castro G.T.; Blanco S.E.; Giordano O.S. (2000). "UV Spectral Properties of Benzophenone. Influence of Solvent and Substituents". Molecules 5: 424. doi:10.3390/50300424. 
8. ^ Lago A.F.; Jimenez P.; Herrero R; Dávalos J.Z.; Abboud J.-L. M. (2009). "Thermochemistry and Gas-Phase Ion Energetics of 2-Hydroxy-4-methoxy-benzophenone (Oxybenzone)". J. Phys. Chem. A 112: 3201–3208. doi:10.1021/jp7111999. 
9. ^ Okereke, CS; Barat, SA; Abdel-Rahman, MS (October 1995). "Safety evaluation of benzophenone-3 after dermal administration in rats.". Toxicol Lett. Department of Pharmacology and Toxicology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103-2714, USA. http://www.ncbi.nlm.nih.gov/pubmed/7482593. Retrieved 16 May 2010. 
10. ^ Hayden, CG; Cross, SE; Anderson, C; Saunders, NA; Roberts, MS (20 May 2005). "Sunscreen penetration of human skin and related keratinocyte toxicity after topical application". Skin Pharmacol Physiol. Therapeutics Research Unit, University of Queensland, Southern Clinical School, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia. http://www.ncbi.nlm.nih.gov/pubmed/15908756. Retrieved 16 May 2010. 
11. ^ "Substance: Oxybenzone". European Commission. http://www.cosmeticsdatabase.com/product/200277/Avalon_Organics_Vitamin_C_Skin_Care%3A_Moisture_Plus_Lotion%2C_SPF_15/. 
12. ^ UV Absorber Portfolio Performance Data and Regulatory Status, cosmetics.basf.de
13. ^ Hanson Kerry M.; Gratton Enrico; Bardeen Christopher J. (2006). "Sunscreen enhancement of UV-induced reactive oxygen species in the skin". Free Radical Biology and Medicine 41 (8): 1205–1212. doi:10.1016/j.freeradbiomed.2006.06.011. PMID 17015167. 
14. ^ Simon Pitman. "EWG campaign highlights study on sunscreen ingredient". cosmetics design-europe. http://www.cosmeticsdesign-europe.com/news/ng.asp?id=84232. 
15. ^ ^{a b} Knowland, John; McKenzie, Edward A.; McHugh, Peter J.; Cridland, Nigel A. (1993). "Sunlight-induced mutagenicity of a common sunscreen ingredient". FEBS Letters 324 (3): 309–313. doi:10.1016/0014-5793(93)80141-G. PMID 8405372. 
16. ^ American Academy of Dermatology: Melanoma Trends
17. ^ Personal Care Products Council, Statement by John Bailey, Chief Scientist, Personal Care Products Council, Response to the 2010 EWG Sunscreen Report
18. ^ ^{a b} The Skin Cancer Foundation dispels concerns about sunscreen
19. ^ Xu, Chunxia; Parsons, Peter (1999). "Cell Cycle Delay, Mitochondrial Stress and Uptake of Hydrophobic Cations Induced by Sunscreens in Cultured Human Cells". Photochemistry and Photobiology 69 (5): 611-616.