Avobenzone

Avobenzone was patented in 1973 and was approved in the EU in 1978. It was approved by the FDA in 1988. As of 2021, the FDA announced that they do not support avobenzone as being generally recognized as safe and effective (GRASE) citing the need for additional safety data. Avobenzone was banned in 2020 by the Palau government citing reef-toxicity concerns.{{Cite web |date=2020 |title=REGULATIONS PROHIBITING REEF-TOXIC SUNSCREENS |url=https://www.palaugov.pw/wp-content/uploads/2020/03/Sunscreen-Regulations-2020.pdf |publisher=The Palau Government}}

Pure avobenzone is a whitish to yellowish crystalline powder with a weak odor,{{cite web|title=Making Cosmetics®, Avobenzone|website=Makingcosmetics.com|url=http://www.makingcosmetics.com/Avobenzone_p_258.html|access-date=2015-07-29|archive-date=2015-08-01|archive-url=https://web.archive.org/web/20150801210149/http://www.makingcosmetics.com/Avobenzone_p_258.html|url-status=dead}} dissolving in isopropanol, dimethyl sulfoxide, decyl oleate, capric acid/caprylic, triglycerides and other oils. It is not soluble in water.

Avobenzone is a dibenzoylmethane derivative. Avobenzone exists in the ground state as a mixture of the enol and keto forms, favoring the chelated enol.{{cite journal

| title = A Blocked Diketo Form of Avobenzone: Photostability, Photosensitizing Properties and Triplet Quenching by a Triazine-derived UVB-filter

| date = January–February 2009

| vauthors = Paris C, Lhiaubet-Vallet V, Jimenez O, Trullas C, Miranda M

| journal = Photochemistry and Photobiology| volume=85 | pages=178–184

| pmid = 18673327

| issue = 1

| doi = 10.1111/j.1751-1097.2008.00414.x| doi-access = free

}} This enol form is stabilized by intramolecular hydrogen-bonding within the β-diketone.{{cite journal

| title = Influence Of Substituent On UV Absorption And Keto–Enol Tautomerism Equilibrium Of Dibenzoylmethane Derivatives

| date = October 2012 | pmid=22925908

| vauthors = Zawadiak J, Mrzyczek M

| journal = Spectrochimica Acta Part A: Molecular Spectroscopy| volume=96 | pages=815–819

| doi=10.1016/j.saa.2012.07.109

| bibcode=2012AcSpA..96..815Z}} Its ability to absorb ultraviolet light over a wider range of wavelengths than many other sunscreen agents has led to its use in many commercial preparations marketed as "broad spectrum" sunscreens. Avobenzone has an absorption maximum of 357 nm.{{cite journal

| title = Sunscreens with an absorption maximum of > or =360 nm provide optimal protection against UVA1-induced expression of matrix metalloproteinase-1, interleukin-1, and interleukin-6 in human dermal fibroblasts

| date = March 2006| pmid=16520862

| vauthors = Vielhaber G, Grether-Beck S, Koch O, Johncock W, Krutmann J

| journal = Photochem Photobiol Sci| volume=5 | pages=275–282

| doi = 10.1039/b516702g

| issue = 3

| s2cid = 37910033}}

Avobenzone, a petroleum-based sunscreen active ingredient,{{Cite web |title=Why Evaluate the Sunscreen Active Oxybenzone (Benzophenone-3) for Carcinogenicity and Reproductive Toxicology or Consider it Unsafe for Human Use? |url=https://www.scivisionpub.com/pdfs/why-evaluate-the-sunscreen-active-oxybenzone-benzophenone3-for-carcinogenicity-and-reproductive-toxicology-or-consider-it-unsafe-f-932.pdf}} is not generally recognised as safe and effective (GRASE) by the FDA for lack of sufficient data to support this claim.{{Cite journal |last=Research |first=Center for Drug Evaluation and |date=2021-11-16 |title=Questions and Answers: FDA posts deemed final order and proposed order for over-the-counter sunscreen |url=https://www.fda.gov/drugs/understanding-over-counter-medicines/questions-and-answers-fda-posts-deemed-final-order-and-proposed-order-over-counter-sunscreen |journal=FDA |language=en}} However, it is still the only FDA approved UVA filter (up to 3% concentration).{{Cite web |title=After More Than A Decade, FDA Still Won't Allow New Sunscreens|url=https://cen.acs.org/articles/93/i20/Decade-FDA-Still-Wont-Allow.html}} Avobenzone is also approved in all other jurisdictions, such as EU (up to 5%), Australia, and Japan.

A 2017 study at Lomonosov Moscow State University found that chlorinated water and ultraviolet light can cause avobenzone to disintegrate into various other organic compounds, including; phenolic acids, aldehydes, phenols, and acetophenones which can cause adverse health effects.{{Cite web |title=Sunscreen creams break down into dangerous chemical compounds under the sunlight |url=https://www.eurekalert.org/pub_releases/2017-06/lmsu-scb062717.php |access-date=2017-06-30 |website=EurekAlert! |language=en}}{{Cite journal |last1=Wang |first1=Cheng |last2=Bavcon Kralj |first2=Mojca |last3=Košmrlj |first3=Berta |last4=Yao |first4=Jun |last5=Košenina |first5=Suzana |last6=Polyakova |first6=Olga V. |last7=Artaev |first7=Viatcheslav B. |last8=Lebedev |first8=Albert T. |last9=Trebše |first9=Polonca |date=September 2017 |title=Stability and removal of selected avobenzone's chlorination products |journal=Chemosphere |volume=182 |pages=238–244 |bibcode=2017Chmsp.182..238W |doi=10.1016/j.chemosphere.2017.04.125 |pmid=28500968}}{{Cite journal |last1=Trebše |first1=Polonca |last2=Polyakova |first2=Olga V. |last3=Baranova |first3=Maria |last4=Kralj |first4=Mojca Bavcon |last5=Dolenc |first5=Darko |last6=Sarakha |first6=Mohamed |last7=Kutin |first7=Alexander |last8=Lebedev |first8=Albert T. |date=2016-09-15 |title=Transformation of avobenzone in conditions of aquatic chlorination and UV-irradiation |journal=Water Research |volume=101 |pages=95–102 |doi=10.1016/j.watres.2016.05.067 |pmid=27258620|bibcode=2016WatRe.101...95T }}

Avobenzone is sensitive to the properties of the solvent, being relatively stable in polar protic solvents and unstable in nonpolar environments. Also, when it is irradiated with UVA light, it generates a triplet excited state in the keto form which can either cause the avobenzone to degrade or it can transfer energy to biological targets and cause deleterious effects.

Avobenzone has been shown to degrade significantly in light, resulting in less protection over time.{{cite journal| title = Photostabilization of Butyl methoxydibenzoylmethane (Avobenzone) and Ethylhexyl methoxycinnamate by Bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S), a new UV broadband filter| date = September 2001| pmid=11594052| vauthors = Chatelain E, Gabard B| journal = Photochemistry and Photobiology| volume=74 | pages=401–406| doi = 10.1562/0031-8655(2001)0740401POBMAA2.0.CO2| issue = 3 | s2cid = 29879472| issn = 0031-8655}}Image:Free text.png {{cite journal| title = Changes in ultraviolet absorption of sunscreens after ultraviolet irradiation| date = October 1999| pmid=10504439| vauthors = Tarras-Wahlberg N, Stenhagen G, Larko O, Rosen A, Wennberg AM, Wennerstrom O

| journal = Journal of Investigative Dermatology| volume=113 | pages=547–553| doi = 10.1046/j.1523-1747.1999.00721.x| issue = 4| doi-access = free}}{{cite journal

| title = A new long-chain UV absorber derived from 4-tert-butyl-4'-methoxydibenzoylmethane: absorbance stability under solar irradiation| date = Mar–Apr 2005| pmid=15870853 |url=https://library.scconline.org/v056n02/55 | vauthors = Wetz F, Routaboul C, Denis A, Rico-Lattes I| journal = Journal of Cosmetic Science| volume=56 | pages=135–148| issue = 2| doi=10.1562/2004-03-09-ra-106 | doi-broken-date = 10 December 2024}} The UV-A light in a day of sunlight in a temperate climate is sufficient to break down most of the compound. Data presented to the Food and Drug Administration by the Cosmetic, Toiletry and Fragrance Association indicates a −36% change in avobenzone's UV absorbance following one hour of exposure to sunlight.{{cite web|url=https://www.fda.gov/ohrms/dockets/dailys/00/Sep00/090600/c000573_10_Attachment_F.pdf|title=CTFA letter re: Tentative Final Monograph for OTC Sunscreen|publisher=Food and Drug Administration}} For this reason, in sunscreen products, avobenzone is always formulated together with a photostabilizer, such as octocrylene. Other photostabilizers include:

• 4-Methylbenzylidene camphor (USAN Enzacamene)
• Tinosorb S (USAN Bemotrizinol, INCI Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine)
• Tinosorb M (USAN Bisoctrizole, INCI Methylene Bis-Benzotriazolyl Tetramethylbutylphenol)
• Butyloctyl Salicylate (Tradename HallBrite BHB - [https://web.archive.org/web/20111002150609/http://www.hallstar.com/pis.php?product=12231])
• Hexadecyl Benzoate
• Butyloctyl Benzoate
• HallBrite PSF (INCI Undecylcrylene DimethiconeE){{Cite web |url=http://www.hallstar.com/pis.php?product=1A054 |title=Hallbrite® PSF |access-date=2011-05-25 |archive-url=https://web.archive.org/web/20111002150713/http://www.hallstar.com/pis.php?product=1A054 |archive-date=2011-10-02 |url-status=dead }}
• Mexoryl SX (USAN Ecamsule, INCI Terephthalylidene Dicamphor Sulfonic Acid)
• Synoxyl HSS (INCI Trimethoxybenzylidene Pentanedione)RK Chaudhuri, MA Ollengo, P Singh and BS Martincigh, 3-(3,4,5-Trimethoxybenzylidene)-2,4-pentanedione: Design of a Novel Photostabilizer with In-vivo SPF Boosting Properties and Its Use in Developing Broad-spectrum Sunscreen Formulations, International Journal of Cosmetic Science, 39(1):25-35, 2017; First published 29 June 2016 | doi: 10.1111/ics.12344

• Corapan TQ (INCI Diethylhexyl 2,6-Naphthalate){{cite journal| title=A new photostabilizer for full spectrum sunscreens| year=2000| author=Bonda C.| author2=Steinberg D. C.| journal= Cosmetics & Toiletries | volume=115 | issue = 6 | pages=37–45}}
• Parsol SLX (INCI Polysilicone-15){{Cite web |url=http://www.dsm.com/en_US/downloads/dnp/Parsol_SLX_Skin.pdf |title=Archived copy |access-date=2007-12-03 |archive-date=2008-02-24 |archive-url=https://web.archive.org/web/20080224034351/http://www.dsm.com/en_US/downloads/dnp/Parsol_SLX_Skin.pdf |url-status=dead }}
• Oxynex ST (INCI Diethylhexyl Syringylidene Malonate{{cite journal

| title = Design of a photostabilizer having built-in antioxidant functionality and its utility in obtaining broad-spectrum sunscreen formulations

| date = May–Jun 2006| pmid=16492073

| vauthors = Chaudhuri RK, Lascu Z, Puccetti G, Deshpande AA, Paknikar SK

| journal = Photochemistry and Photobiology| volume=82 | pages=823–828

| doi = 10.1562/2005-07-15-RA-612

| issue = 3

| s2cid = 23707972}}

• Polycrylene (INCI Polyester-8)http://www.hallstar.com/techdocs/Polycrylene&CorapanTQAvobenzoneStabilization.pdf {{dead link|date=March 2024}}
• SolaStay S1 (INCI Ethylhexyl Methoxycrylene){{cite web|url=http://www.hallstar.com/pis.php?product=1H044|title=Product Information Sheet: SolaStay S1|publisher=The HallStar Company|access-date=16 February 2010|archive-url=https://web.archive.org/web/20111002150645/http://www.hallstar.com/pis.php?product=1H044|archive-date=2 October 2011|url-status=dead}}
• Octyl Salicylate (INCI Ethylhexyl Salicylate){{Cite journal|title=Synthesis of phenylalanine and leucine dipeptide functionalized silica-based nanoporous material as a safe UV filter for sunscreen|url=https://link.springer.com/article/10.1007/s10971-020-05417-6|journal=Journal of Sol-Gel Science and Technology|year=2021|doi=10.1007/s10971-020-05417-6|last1=Ma|first1=Haohua|last2=Wang|first2=Jianqiang|last3=Zhang|first3=Wenpei|last4=Guo|first4=Cheng|volume=97|issue=2|pages=466–478|s2cid=221937086}}

Complexing avobenzone with cyclodextrins may also increase its photostability.{{cite journal

| title = Influence of hydroxypropyl-beta-cyclodextrin on photo-induced free radical production by the sunscreen agent, butyl-methoxydibenzoylmethane

| date = November 2002| pmid=12495559

| vauthors = Scalia S, Simeoni S, Barbieri A, Sostero S

| journal = Journal of Pharmacy and Pharmacology| volume=54 | pages=1553–1558

| doi = 10.1211/002235702207

| issue = 11

| s2cid = 40228301| doi-access = free

}} Formulations of avobenzone with hydroxypropyl-beta-cyclodextrin have shown significant reduction in photo-induced degradation, as well as decreased transdermal penetration of the UV absorber when used in high concentrations.{{cite journal

| title = Influence of hydroxypropyl-β-cyclodextrin on transdermal penetration and photostability of avobenzone

| date = June 2008| pmid=18226883

| vauthors = Yang J, Wiley C, Godwin D, Felton L

| journal = European Journal of Pharmaceutics and Biopharmaceutics | volume=69 | pages=605–612

| doi = 10.1016/j.ejpb.2007.12.015

| issue = 2

}}

The photostability of avobenzone is further increased when sunscreens are formulated with antioxidant compounds. Mangiferin, glutathione, ubiquinone, vitamin C, vitamin E, beta-carotene and trans-resveratrol have all demonstrated some ability to protect avobenzone from photodegradation.{{Cite journal|last1=Kawakami|first1=Camila Martins|last2=Gaspar|first2=Lorena Rigo|date=October 2015|title=Mangiferin and naringenin affect the photostability and phototoxicity of sunscreens containing avobenzone|url=https://pubmed.ncbi.nlm.nih.gov/26318281/|journal=Journal of Photochemistry and Photobiology B: Biology|volume=151|pages=239–247|doi=10.1016/j.jphotobiol.2015.08.014|issn=1873-2682|pmid=26318281|bibcode=2015JPPB..151..239K }}{{Cite journal|last1=Govindu|first1=Panchada Ch V.|last2=Hosamani|first2=Basavaprabhu|last3=Moi|first3=Smriti|last4=Venkatachalam|first4=Dhananjeyan|last5=Asha|first5=Sabreddy|last6=John|first6=Varun N.|last7=Sandeep|first7=V.|last8=Gowd|first8=Konkallu Hanumae|date=2019-01-01|title=Glutathione as a photo-stabilizer of avobenzone: an evaluation under glass-filtered sunlight using UV-spectroscopy|journal=Photochemical & Photobiological Sciences|volume=18|issue=1|pages=198–207|doi=10.1039/c8pp00343b|issn=1474-9092|pmid=30421772|s2cid=53291937 |doi-access=|bibcode=2019PhPhS..18..198G }}{{Cite journal|last1=Afonso|first1=S.|last2=Horita|first2=K.|last3=Sousa e Silva|first3=J. P.|last4=Almeida|first4=I. F.|last5=Amaral|first5=M. H.|last6=Lobão|first6=P. A.|last7=Costa|first7=P. C.|last8=Miranda|first8=Margarida S.|last9=Esteves da Silva|first9=Joaquim C. G.|last10=Sousa Lobo|first10=J. M.|date=November 2014|title=Photodegradation of avobenzone: stabilization effect of antioxidants|url=https://pubmed.ncbi.nlm.nih.gov/25086322/|journal=Journal of Photochemistry and Photobiology B: Biology|volume=140|pages=36–40|doi=10.1016/j.jphotobiol.2014.07.004|issn=1873-2682|pmid=25086322|bibcode=2014JPPB..140...36A }}{{Cite journal|last1=Freitas|first1=Juliana Vescovi|last2=Lopes|first2=Norberto Peporine|last3=Gaspar|first3=Lorena Rigo|date=2015-10-12|title=Photostability evaluation of five UV-filters, trans-resveratrol and beta-carotene in sunscreens|url=https://pubmed.ncbi.nlm.nih.gov/26159738/|journal=European Journal of Pharmaceutical Sciences|volume=78|pages=79–89|doi=10.1016/j.ejps.2015.07.004|issn=1879-0720|pmid=26159738}} The stability and efficacy of avobenzone seems to continue to increase as a greater amount of antioxidants are added to the sunscreen.

According to some studies, "the most effective sunscreens contain avobenzone and titanium dioxide."{{cite journal

| author = Warwick L. Morison, M.D.

| title = Photosensitivity

| journal = The New England Journal of Medicine

| date = March 11, 2004

| volume = 350

| pages = 1111–1117

| doi = 10.1056/NEJMcp022558

| pmid = 15014184

| issue = 11

}}{{cite web

|title=Sunscreen Drug Products for Over-the-Counter use; Marketing Status of Products Containing Avobenzone; Enforcement Policy

|publisher=US Food and Drug Administration

|date=1997-04-30

|url=https://www.fda.gov/cder/otcmonographs/Sunscreen/sunscreen_avobenzone_enforc_policy_19970420.pdf

|page=23354

|access-date=2007-06-03

|archive-url=https://web.archive.org/web/20070226040442/https://www.fda.gov/cder/otcmonographs/Sunscreen/sunscreen_avobenzone_enforc_policy_19970420.pdf

|archive-date=2007-02-26

|url-status=live

}} Avobenzone can degrade faster in light in combination with mineral UV absorbers like zinc oxide and titanium dioxide, though with the right coating of the mineral particles this reaction can be reduced.Stability Study of Avobenzone with Inorganic Sunscreens, Kobo Products Poster, 2001, [http://www.koboproductsinc.com/Downloads/NYSCC-Avobenzone.pdf Online version] {{webarchive |url=https://web.archive.org/web/20070507210110/http://www.koboproductsinc.com/Downloads/NYSCC-Avobenzone.pdf |date=May 7, 2007 }} A manganese doped titanium dioxide may be better than undoped titanium dioxide to improve avobenzone's stability.{{cite journal| title=The effects of manganese doping on UVA absorption and free radical generation of micronised titanium dioxide and its consequences for the photostability of UVA absorbing organic sunscreen components|date=July 2004| pmid=15238999| vauthors=Wakefield G, Lipscomb S, Holland E, Knowland J| journal=Photochem Photobiol Sci| volume=3 | pages=648–652| doi=10.1039/b403697b| issue=7| doi-access=free|bibcode=2004PhPhS...3..648W }}

As an enolate, avobenzone forms with heavy metal ions (such as Fe³⁺) colored complexes, and chelating agents can be added to suppress them. Stearates, aluminum, magnesium and zinc salts can lead to poorly soluble precipitates. Manufacturers also recommend to avoid the inclusion of iron and ferric salts, heavy metals, formaldehyde donors and PABA and PABA esters.{{Citation needed|date=March 2020}}

Avobenzone in sunscreen may stain clothes yellow-orange and make them sticky if washed in iron-rich water, as it reacts with iron to produce rust. The damage can be undone with a rust remover or stain remover.{{cite web |title=How to Remove Summer Stains From Your Clothes |url=https://www.consumerreports.org/appliances/laundry/how-to-remove-summer-stains-from-your-clothes-a3477204035/ |publisher=Consumer Reports |date=17 August 2022}}{{cite web |title=The secret to removing sunscreen stains is this unexpected cleaning product |url=https://edition.cnn.com/cnn-underscored/home/how-to-remove-sunscreen-stains |publisher=CNN |date=18 July 2022}} The staining properties of sunblock made with avobenzone are particularly noticeable on fiberglass boats with white gelcoat.{{Citation needed|date=March 2020}}

Avobenzone also reacts with boron trifluoride to form a stable crystalline complex that is highly fluorescent under UV irradiation. The emission color of the crystals depends on the molecular packing of the boron avobenzone complex. The photoluminescence may also be altered by mechanical force in the solid state, resulting in a phenomenon called "mechanochromic luminescence". The altered emission color recovers itself slowly at room temperature or more swiftly at higher temperatures.{{cite journal|title=Polymorphism and Reversible Mechanochromic Luminescence for Solid-State Difluoroboron Avobenzone|date=February 2010| author = Zhang G|author2 = Lu J|author3 = Sabat M|author4 = Fraser, CL|s2cid=30823815|journal= Journal of the American Chemical Society| volume=132 | pages=2160–2162|doi=10.1021/ja9097719|pmid=20108897|issue=7|bibcode=2010JAChS.132.2160Z }}

Avobenzone has a peak absorbance around 360 nm when dissolved. The peak may shift slightly depending on the solvent.

File:Absorbance of 0.01 g-L avobenzone in DMSO.pdf

The compound is prepared by reacting 4-tert-butylbenzoic methyl ester (from 4-tert-butylbenzoic acid by esterification with methanol) with 4-methoxyacetophenone in toluene in the presence of sodium amide via Claisen condensation.{{Patent|Land = US|V-Nr =4387089 |Code= |Titel= 4-(1,1-Dimethylethyl)-4′-methoxydibenzoylmethane |V-Datum =1983-6-7 |A-Datum =1981-5-18 |Erfinder=K.-F. De Polo |Anmelder=Givaudan Corp.}}

File:Avobenzone Synthesis V1.png

According to a recent patent application,{{Patent|Land = WO|V-Nr =2012084770 |Code=A1 |Titel=Process for the manufacture of dibenzoylmethane derivatives |V-Datum =2012-6-28 |A-Datum =2011-12-19 |Erfinder=C. Wehrli |Anmelder=DSM IP Assets B.V.}} yields of up to 95% are obtained with the same starting materials in toluene in the presence of potassium methoxide.

It is subject to keto-enol tautomerism and exists predominantly enol when dissolved. Upon UV radiation, it may convert to keto form, while converting back to enol form after placing in dark.{{citation |title=Photostability of the sunscreening agent 4-tert-butyl-4-methoxydibenzoylmethane (avobenzone) in solvents of different polarity and proticity |date=2008 |periodical=J. Photochem. Photobiol.: Chemistry |volume=200 |issue=2–3 |pages=410–420 |doi=10.1016/j.jphotochem.2008.09.007 |surname1=G. J. Mturi, B. S. Martincigh|bibcode=2008JPPA..200..410M }}

File:Avobenzone Tautomeric Forms V1.svg

See also

• Sun protection factor

{{reflist}}

{{Sunscreening agents}}

Category:Aromatic ketones

Category:Piceol ethers

Category:Sunscreening agents

Category:Tert-butyl compounds

Category:4-Methoxyphenyl compounds