Octyl methoxycinnamate: Difference between revisions

{{Short description|UV-B protectant used in sunscreens}}

{{Use dmy dates|date=August 2020}}

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 402511567

| Reference=<ref>''[[Merck Index]]'', 11th Edition, '''6687'''.</ref>

| ImageFile=Octyl_methoxycinnamate.svg

| IUPACName= (''RS'')-2-Ethylhexyl (2''E'')-3-(4-methoxyphenyl)prop-2-enoate

| OtherNames=Ethylhexyl methoxycinnamate<br>Octinoxate<br>Uvinul MC80<br>(''E'')-3-(4-methoxyphenyl) prop-2-enoic acid 2-ethylhexyl ester

|Section1={{Chembox Identifiers

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 4511170

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 1200608

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| PubChem=5355130

| SMILES = O=C(OCC(CC)CCCC)\C=C\c1ccc(OC)cc1

|Section2={{Chembox Properties

| C=18 | H=26 | O=3

| Appearance=

| Density=1.01 g/cm³

| MeltingPtC = -25

| BoilingPtC=198 to 200

| Solubility=

|Section6={{Chembox Pharmacology

| ATCCode_prefix = D02

| ATCCode_suffix = BA02

| Legal_status = Banned in Thailand, Palau and Hawaii

}}

|Section7={{Chembox Hazards

| MainHazards=

| FlashPt=

| AutoignitionPt =

| NFPA-H= 1

| NFPA-F= 1

| NFPA-R= 0

'''Octyl methoxycinnamate''' or '''ethylhexyl methoxycinnamate''' ([[INCI]]) or '''octinoxate''' ([[United States Adopted Name|USAN]]), trade names '''Eusolex 2292''' and '''Uvinul MC80''', is an [[organic compound]] that is an ingredient in some [[sunscreen]]s and [[lip balm]]s. It is an [[ester]] formed from [[methoxycinnamic acid]] and [[2-Ethylhexanol|2-ethylhexanol]]. It is a liquid that is insoluble in water.

It is primarily used in sunscreens and other cosmetics to absorb [[UV-B]] rays from the [[sun]], protecting the skin from damage. It is also used to reduce the appearance of scars.

==Uses==

Octyl methoxycinnamate is the most common [[active ingredient]] in sunscreens for protection against [[Ultraviolet#Subtypes|UV-B rays]].<ref name=":0" /><ref>{{Cite web|last=Ngan|first=Vanessa|date=2012|title=Allergy to cinnamate|url=https://dermnetnz.org/topics/allergy-to-cinnamate|access-date=2021-10-18|website=DermNet NZ}}</ref> It may be combined with [[oxybenzone]] and [[titanium oxide]].<ref name=":0">{{cite journal |doi=10.1039/B206338G |pmid=12661594 |title=An in vitro systematic spectroscopic examination of the photostabilities of a random set of commercial sunscreen lotions and their chemical UVB/UVA active agents |journal=Photochemical & Photobiological Sciences |volume=1 |issue=12 |pages=970–81 |year=2002 |last1=Serpone |first1=Nick |last2=Salinaro |first2=Angela |last3=Emeline |first3=Alexei V. |last4=Horikoshi |first4=Satoshi |last5=Hidaka |first5=Hisao |last6=Zhao |first6=Jincai |s2cid=27248506 }}</ref>

Studies have evaluated the efficacy of octyl methoxycinnamate in preventing postoperative peritoneal adhesions and determined that octyl methoxycinnamate covering peritoneal surfaces decreases adhesion formation. This effect is more notable when octyl methoxycinnamate is applied before the induction of trauma.<ref>{{Cite journal|last1=Aysan|first1=Erhan|last2=Bektas|first2=Hasan|last3=Kaygusuz|first3=Arslan|date=December 2009|title=Efficacy of octyl methoxycinnamate in preventing postoperative peritoneal adhesions: An experimental model|url=https://onlinelibrary.wiley.com/doi/10.1111/j.1447-0756.2009.01077.x|journal=Journal of Obstetrics and Gynaecology Research|language=en|volume=35|issue=6|pages=1102–1108|doi=10.1111/j.1447-0756.2009.01077.x|pmid=20025636|s2cid=24582333}}</ref>

Chromophore groups, such as C=C, C=O, and O-N=O, have loosely held electrons that are excited by radiation. Hence, octyl methoxycinnamate is able to absorb radiation when the electron energy level is increased to an excited state.<ref>{{Cite web|last=PubChem|title=Octinoxate|url=https://pubchem.ncbi.nlm.nih.gov/compound/21630|access-date=2021-11-13|website=pubchem.ncbi.nlm.nih.gov|language=en}}</ref>

== Properties ==

The UV spectra of octyl methoxycinnamate contains a maximum at 310 nm.<ref>{{Cite web|last=PubChem|title=Octinoxate|url=https://pubchem.ncbi.nlm.nih.gov/compound/21630|access-date=2021-11-13|website=pubchem.ncbi.nlm.nih.gov|language=en}}</ref>

== Synthesis ==

Olefin metathesis has been widely studied. One of the synthesis pathways for octyl methoxycinnamate includes cross metathesis. The high efficiency of the nitro-Grela catalyst has been used in the cross metathesis of ''trans''-anethole with 2-ethylhexyl acrylate to produce octyl methoxycinnamate (86% yield).<ref>{{Cite journal|last1=Kaczanowska|first1=Katarzyna|last2=Trzaskowski|first2=Bartosz|last3=Peszczyńska|first3=Aleksandra|last4=Tracz|first4=Andrzej|last5=Gawin|first5=Rafał|last6=Olszewski|first6=Tomasz K.|last7=Skowerski|first7=Krzysztof|date=2020|title=Cross metathesis with acrylates: N-heterocyclic carbene (NHC)- versus cyclic alkyl amino carbene (CAAC)-based ruthenium catalysts, an unanticipated influence of the carbene type on efficiency and selectivity of the reaction|journal=ChemCatChem|language=en|volume=12|issue=24|pages=6366–6374|doi=10.1002/cctc.202001268|s2cid=225155345|issn=1867-3899|doi-access=free}}</ref>

{{more medical citations needed|section|date=April 2013}}

One study performed in 2000 raised safety concerns about octyl methoxycinnamate by demonstrating toxicity to mouse cells at concentrations lower than typical levels in sunscreens.<ref>[https://www.newscientist.com/article/mg16822591.900-sinister-side-of-sunscreens.html Sinister side of sunscreens], Rob Edwards, ''New Scientist'', 7 October 2000</ref><ref>{{cite journal |doi=10.1093/oxfordjournals.rpd.a033219 |id={{INIST|1532995}} |title=Toxicity and Phototoxicity of Chemical Sun Filters |journal=Radiation Protection Dosimetry |volume=91 |pages=283–6 |year=2000 |last1=Butt |first1=S.T. |last2=Christensen |first2=T. }}</ref>{{Medcn|date=April 2013}} However, another study concluded that octyl methoxycinnamate and other sun screening agents do not penetrate the outer skin in sufficient concentration to cause any significant toxicity to the underlying human [[keratinocyte]]s.<ref>{{cite journal |doi=10.1159/000085861 |pmid=15908756 |title=Sunscreen Penetration of Human Skin and Related Keratinocyte Toxicity after Topical Application |journal=Skin Pharmacology and Physiology |volume=18 |issue=4 |pages=170–4 |year=2005 |last1=Hayden |first1=C.G.J. |last2=Cross |first2=S.E. |last3=Anderson |first3=C. |last4=Saunders |first4=N.A. |last5=Roberts |first5=M.S. |s2cid=7914504 }}</ref>

Estrogenic and neurological effects were noted in laboratory animals at concentrations close to those experienced by sunscreen users<ref>{{cite book |first=Marta Axelstad |last=Petersen |type=PhD Thesis |year=2011 |title=Thyroid hormone disrupting chemicals and their influence on the developing rat brain |publisher=DTU Food, National Food Institute |isbn=978-87-92158-94-9 |oclc=826386040 |url=http://orbit.dtu.dk/en/publications/thyroid-hormone-disrupting-chemicals-and-their-influence-on-the-developing-rat-brain(de54df85-73cf-4570-a8a4-1a6a0fb28ffb).html }}{{page needed|date=June 2017}}</ref><ref>{{cite journal |doi=10.1016/j.taap.2010.10.031 |pmid=21059369 |title=Effects of pre- and postnatal exposure to the UV-filter Octyl Methoxycinnamate (OMC) on the reproductive, auditory and neurological development of rat offspring |journal=Toxicology and Applied Pharmacology |volume=250 |issue=3 |pages=278–90 |year=2011 |last1=Axelstad |first1=Marta |last2=Boberg |first2=Julie |last3=Hougaard |first3=Karin Sørig |last4=Christiansen |first4=Sofie |last5=Jacobsen |first5=Pernille Rosenskjold |last6=Mandrup |first6=Karen Riiber |last7=Nellemann |first7=Christine |last8=Lund |first8=Søren Peter |last9=Hass |first9=Ulla }}</ref> and were also shown [[in vitro]].{{citation needed|date=June 2017}} Octyl methoxycinnamate has been shown to be light sensitive with a decrease in UV absorption efficiency upon light exposure.<ref>{{Cite journal |last1=Pattanaargson |first1=Supason |last2=Munhapol |first2=Thitinun |last3=Hirunsupachot |first3=Piyawan |last4=Luangthongaram |first4=Pamornwan |date=2004-01-30 |title=Photoisomerization of octyl methoxycinnamate |url=https://www.sciencedirect.com/science/article/pii/S101060300300282X |journal=Journal of Photochemistry and Photobiology A: Chemistry |language=en |volume=161 |issue=2 |pages=269–274 |doi=10.1016/S1010-6030(03)00282-X |issn=1010-6030|url-access=subscription }}</ref> This degradation causes formation of the Z-octyl-p-methoxycinnamate from the E-octyl-p-methoxycinnamate. In contrast, the OMC does not show degradation when kept in darkness for extended periods of time.{{citation needed|date=June 2017}}

A study carried out in 2017 by the Research Centre for Toxic Compounds in the Environment at Masaryk University, Czech Republic, indicates that octyl methoxycinnamate (EHMC) may damage human cell DNA. When exposed to sun rays, the spatial arrangement of its molecules changes and isomerisation takes place. While until now only unchanged EHMC has been researched, Massaryk University researchers focused on its isomers and found out that it has a significant genotoxic effect under lab conditions. It means that it may potentially damage human DNA and cause genome mutations which may lead to serious health risks.<ref>{{cite journal |doi=10.1016/j.scitotenv.2017.03.043 |pmid=28340478 |title=Different DNA damage response of cis and trans isomers of commonly used UV filter after the exposure on adult human liver stem cells and human lymphoblastoid cells |journal=Science of the Total Environment |volume=593-594 |pages=18–26 |year=2017 |last1=Sharma |first1=Anežka |last2=Bányiová |first2=Katarína |last3=Babica |first3=Pavel |last4=El Yamani |first4=Naouale |last5=Collins |first5=Andrew Richard |last6=Čupr |first6=Pavel |bibcode=2017ScTEn.593...18S }}</ref>

In swimming pools with hypochlorite in aqueous solution, octyl methoxycinnamate has been shown to produce chlorine-substituted intermediates. The chlorination intermediates of octyl methoxycinnamate demonstrated weak mutagenic effects on the Salmonella typhimurium TA 100 strain. The reactions depended on the pH, compound structures, and chlorine dose.<ref>{{Cite journal|last1=Nakajima|first1=Mariko|last2=Kawakami|first2=Tsuyoshi|last3=Niino|first3=Tatsuhiro|last4=Takahashi|first4=Yasuo|last5=Onodera|first5=Sukeo|date=2009|title=Aquatic Fate of Sunscreen Agents Octyl-4-methoxycinnamate and Octyl-4-dimethylaminobenzoate in Model Swimming Pools and the Mutagenic Assays of Their Chlorination Byproducts|url=http://www.jstage.jst.go.jp/article/jhs/55/3/55_3_363/_article|journal=Journal of Health Science|language=en|volume=55|issue=3|pages=363–372|doi=10.1248/jhs.55.363|issn=1344-9702|doi-access=free}}</ref>

==Ecological damage==

Concern about effects on [[coral reef]]s resulted in a bill in the [[Hawaii State Legislature|state legislature of Hawaii]] to limit use of sunscreens containing octyl methoxycinnamate and [[oxybenzone]].<ref name="Bever_2018-05-03">{{Citation |last=Bever |first=Lindsey |date=2018-05-03 |title=Hawaii might be about to ban your favorite sunscreen to protect its coral reefs |newspaper=[[The Washington Post]] |url=https://www.washingtonpost.com/news/energy-environment/wp/2018/05/02/hawaii-might-be-about-to-ban-your-favorite-sunscreen-to-protect-its-coral-reefs/ |access-date=2018-05-03 |postscript=.}}</ref><ref>{{Cite journal|last1=Galamgam|first1=Jayden|last2=Linou|first2=Natalia|last3=Linos|first3=Eleni|date=1 November 2018|title=Sunscreens, cancer, and protecting our planet|journal=The Lancet Planetary Health|volume=2|issue=11|pages=e465–e466|doi=10.1016/S2542-5196(18)30224-9|pmid=30396433|doi-access=free}}</ref>

For the same reasons, the government of [[Palau]] signed a law in 2018 (becoming effective in 2020) that restricted the sale and use of sunscreen and skincare products that contain a list of ten different chemicals, including the UV filters octyl methoxycinnamate, oxybenzone and octocrylene, with fines of {{US$|1,000}} for retailers who violate the law and the power to confiscate such products from non-commercial users.<ref name="bbc_palau_sunscreen_ban">{{cite news |last=McGrath |first=Matt |date=2018-11-01 |title=Coral: Palau to ban sunscreen products to protect reefs |url=https://www.bbc.co.uk/news/science-environment-46046064 |work=BBC |access-date=2018-11-02 }}</ref>

== Stereochemistry ==

Octinoxate contains a stereocenter and a double bond. It has the following stereoisomers<ref name="Photoisomerization">S. Pattanaargson, T. Munhapol, P. Hirunsupachot, P. Luangthongaram (ed.): '' Photoisomerization of octyl methoxycinnamate. '' In: '' Journal of Photochemistry and Photobiology A: Chemistry '', Elsevier Verlag, vol. 161, no. 2-3, 30 January 2004, pp. 269-274.</ref><ref name = "Patent">Process for producing 2-ethylhexanol: [https://www.google.com/patents/EP0216151B1? CL = DE 3530839A1], 29 August 1985; [https://www.google.com/patents/DE3530839A1?cl=en EP 0216151 B1], 20 August 1986.</ref> Therefore, octinoxate could consist of the following four stereoisomers:

{| class="wikitable" style="text-align:center"

|- class="hintergrundfarbe6"

! colspan="3"| Enantiomers of Octinoxate

|-

|

| (''R'')-shape

| (''S'')-shape

|-

| (''E'')-shape

| [[File:(E,R)-Octinoxat Structural Formula V2.svg|290 px]]

| [[File:(E,S)-Octinoxat Structural Formula V2.svg|290 px]]

|-

| (''Z'')-shape

| [[File:(Z,R)-Octinoxat Structural Formula V2.svg|200 px]]

| [[File:(Z,S)-Octinoxat Structural Formula V2.svg|200 px]]

|}

*[[Amiloxate]], a chemically related sunscreening agent

*{{annotated link|Avobenzone}}

[[Category:Cinnamate esters]]

[[Category:Sunscreening agents]]

[[Category:2-Ethylhexyl esters]]