Octinoxate

Octinoxate is commonly used as a UVB filter in cosmetic and skin care products. Because it breaks down when exposed to light, octinoxate needs to be formulated with other UV absorbers or photostabilizers.

Effects


Grade Level of Evidence
A Multiple double-blind, controlled clinical trials.
B 1 double-blind, controlled clinical trial.
C At least 1 controlled or comparative clinical trial.
D Uncontrolled, observational, animal or in-vitro studies only.
Grade Effect Size of Effect Comments

D

Photoprotection

Moderate

Absorbs UVB radiation. Though relatively weak, it can be quite effective at a concentration of 10%, the highest authorized in the EU.

Looking to buy skin care products containing Octinoxate?

Buy from Amazon.com.

Scientific Research


Caution: Please read wisderm.com's medical disclaimer.

Table of contents:

1. Sources

1.1 In personal care products

Octinoxate is an organic compound that can be enzymatically synthesized from p-methoxycinnamic acid and 2-ethyl hexanol.[1] Despite being a relatively weak UVB absorber,[2] it is nevertheless a very popular sunscreen active. It was found in 96 out of 101 (95%) commercial suncare products from South Korea[3] and in 59 out of 116 (51%) personal care products from Switzerland.[4] In a larger study of 4,447 cosmetic products, it was detected in 38.5% of the products, a proportion that was lower than only titanium dioxide (40.1%) and avobenzone (48.7%).[5]

1.2 In the environment

UV filters occur in the aquatic environment through 2 principal sources: direct inputs from recreational activities in the water and indirect wastewater- and river-borne inputs.[6] Octinoxate has been detected in seawater samples from Italy,[7] environmental water samples from Slovenia,[8] Japanese and Swiss rivers and lakes,[9][10][11] as well as in Mediterranean rivers.[6] It appears to accumulate in marine life, having been detected in marine mussels from French coastal regions[12] and in macroinverterbrates and fish from Switzerland.[13] It has even been found in tap water samples from Spain.[14]

In addition, one study found that octinoxate was ubiquitous in samples of indoor dust from private flats, public buildings and vehicle cabins, where it was measured at a maximum concentration of 15 µg/g.[15]

2. Skin penetration

An ideal sunscreen agent should remain localized close to the skin surface without penetrating into the deeper layers of the skin to be safe and effective.[16]

Experiments on animal skin have shown that octinoxate can penetrate through baby mouse skin[17] and dermatomed micro-Yucatan pig skin,[18] but not the skin of the hairless rat.[19]

In vitro experiments using real or reconstituted human skin suggest that octinoxate can penetrate significantly into the skin[18][20] and reach the viable epidermis,[21] but that it does not penetrate across the skin.[19][20] 2 in vivo studies involving daily repeated whole-body topical applications of creams containing 10% octinoxate, 10% oxybenzone and 10% enzacamene have however clearly shown systemic absorption, as evidenced by the detection of octinoxate in the plasma after just the first application.[22][23] Moreover, for the male subjects in both studies the 96-hour median plasma concentrations of octinoxate were higher than the 24-hour concentrations, suggesting that accumulation occurred during the treatment period.[22][23]

The penetration and retention of octinoxate in the skin is formulation-dependent. For instance, the in vitro skin release and permeation of octinoxate from cosmetic emulsions varies with different types of emulsions,[24] different emulsifiers[16][25] and different oil phases.[26][27] Applying octinoxate solubilized in an emulsion gel to the skin also led to higher concentrations of it in the stratum corneum compared to octinoxate solubilized in petrolatum.[28]

Encapsulating octinoxate in liposomes,[29][30][31] lipid microspheres[32] or microparticles,[33] nanoparticles,[34][35][36][37][38] nanocapsules[39][40][41] or nanostructured lipid carriers[42] can diminish its systemic absorption by limiting its release and/or increasing its retention in the outermost skin layers.

On the other hand, nanoemulsions seem to increase the extent of octinoxate penetration and skin deposition compared to nanocapsules or conventional oil-in-water emulsions,[40][43] especially when formulated with sucrose laureate.[44]

Application temperature does not appear to influence the stratum corneum adsorption of octinoxate.[28]

3. Effects on the skin

3.1 Photoprotection

Octinoxate absorbs radiation in the 290-320 nm region of the UV spectrum,[36] with a maximum absorbance at 311 nm.[45] Its sun protection factor (SPF) corresponds to its concentration in the formulation.[46] In vitro and in vivo testing found that a lotion containing 2% octinoxate had an SPF of ~5, which increased to 10 at a concentration of 4.5%, and 15/16 at a concentration of 7.5%.[47] Though considered a weak UVB absorber (an order of magnitude less potent than Padimate O)[2] that must be combined with other UV filters in order to achieve an adequate SPF,[45] when compared to 17 other sun filters at their highest concentrations authorized in the European Union, octinoxate was actually among the most efficacious.[48]

Because octinoxate absorbs UVB radiation, it can prevent UVB-induced damage such as the formation of sunburn cells and pyridimine dimers,[49][50][51] thought it does not seem to protect against oxidative DNA lesions.[52]

In mouse models, it was also able to provide partial protection against UV-induced immunosuppression,[53][54] apparently by inhibiting the depletion of Langerhans cells[55] and by directly inactivating epidermal cis-urocanic acid,[56] a known mediator of photoimmunosuppression.[57][58]

Further, octinoxate appears to inhibit UV-induced tumour promotion. When applied before UV irradiation to mice, it afforded effective protection from the overt expression of tumours such as squamous cell carcinomas.[59][60][61] However, it failed to reduce the UV-induced increase in melanoma incidence in mice in another study.[62]

The photoprotective efficacy of octinoxate can be enhanced in several ways. Some plant extracts can intensify the SPF values of octinoxate formulations,[63] and the bioconvertible antioxidants tocopheryl acetate and sodium ascorbyl phosphate can improve photoprotection by converting to vitamin E and vitamin C, which then deactivate reactive oxygen species generated by UV photons.[64] Incorporating octinoxate within certain vehicles can also increase the photoprotection it provides. Liposomes containing octinoxate, for instance, may interact with the cells of the stratum corneum, promoting the retention of octinoxate in this layer and increasing the SPF.[30] Likewise, polymethylmethacrylate (PMMA) microspheres of octinoxate had nearly 4 times the SPF of a similar formulation containing free octinoxate,[65] and octinoxate nanocapsules provided better protection against UV-induced erythema than a conventional gel or emulsion.[66][41] The encapsulation of octinoxate within nanoparticles has also been demonstrated to improve its photoprotection, as evidenced by increased absorbance[67] and higher SPF values.[68][38]

Octinoxate should be combined with a UVA filter like avobenzone or zinc oxide to enable broad-spectrum protection.[69][70] In one study, a SPF 15 sunscreen containing octinoxate and avobenzone was found to reduce UV-induced free radical damage to the skin by 21%.[71]

4. Stability

Octinoxate degrades rapidly upon exposure to light through photoisomerization and photodimerization.[72] When mouse skins were applied with a typical skin coverage of octinoxate in one study, UVB exposure induced approximately 50% photoisomerization, resulting in a 25% loss of octinoxate's UV filtering efficiency.[73]

A recent survey of >300 sunscreen products in the US revealed that 19% contained octinoxate and avobenzone,[74] a combination that is known to lead to the photolysis of both sunscreen agents upon irradiation, with a consequent loss of UV protection.[75][76][77]

Fortunately, other UV absorbers such as octocrylene and Tinosorb S can help stabilize both octinoxate and avobenzone, as can the photostabilizer SolaStay S1.[78][79][80] It is also possible to improve the photostability of octinoxate through nanoencapsulation. Poly(D,L-lactide) nanocapsules and chitosan nanoparticles have been shown to minimize the photoisomerization of octinoxate,[81][34] and poly-epsilon-caprolactone nanocapsules, poly-D,L-lactide-co-glycolide (PLGA) nanocapsules and viscosized nanostructured lipid carriers were also efficient at reducing the extent of light-induced octinoxate degradation.[82][83][37] Still, not all nanodelivery systems are able to influence the photostability of octinoxate.[42][83]

Other ways in which octinoxate can be photostabilized include complexation with β-cyclodextrin,[84] incorporation within solid lipid microspheres[32] and entrapment within the pores of the mesoporous silicate MCM-41 as a particulate carrier.[85] In addition, quercetin has also been proven to photostabilize the combination of octinoxate and avobenzone more effectively and at a lower concentration than octocrylene and other antioxidants (vitamin E, butylated hydroxyanisole) through comparative photodegradation studies.[86]

5. Safety

Octinoxate is approved by the US FDA as a sunscreen active ingredient in cosmetic products up to a concentration of 7.5%.[87] It is also an approved UV filter under the EU Cosmetics Directive, which stipulates a maximum concentration of 10%.[88]

5.1 Effects on skin cells

Octinoxate can delay the cell cycle, cause mitochondrial stress and induce the uptake of hydrophobic cations in cultured human cells.[89] However, the amount of octinoxate that reaches the viable epidermis after topical application is probably too low to cause toxicity to human keratinocytes.[21]

5.2 Production of reactive oxygen species

A 4-hour illumination of a solution containing octinoxate with simulated sunlight was found to generate carbon-centered free radicals in one study.[90] Another study showed that if octinoxate penetrates into the nucleated layers of the skin, it can increase the levels of reactive oxygen species in the skin over that naturally produced by epidermal chromophores under UV illumination.[91] Further, a cream gel formulation containing octinoxate, oxybenzone and octisalate significantly decreased the activity of superoxide dismutase, an important antioxidant defense in the skin, in irradiated mice, indicating that they may have formed degradation producted under UV radiation that either inhibited the enzyme or generated reactive species in the skin.[92]

Complexation of octinoxate with β-cyclodextrin appears to markedly inhibit the formation of free radicals it generates under UV exposure however, minimizing its photosensitizing potential.[90]

5.3 Possible genotoxicity

Octinoxate appeared to be mutagenic in a Salmonella/microsome assay, and seemingly increased the frequency of sex-linked recessive lethal alleles in the fruit fly Drosophila melanogaster. However, it is possible that these findings may be invalid, as many samples were obtained from several sources and the results were batch-related, implicating the presence of a trace contaminant.[93]

A more recent study confirmed that octinoxate is not photogenotoxic, finding no increase in DNA damage in mouse lymphoma cells following irradiation.[94]

5.4 Reproductive toxicity

In a reproductive toxicity study on rats, octinoxate was continuously administered in the diet through 2 successive generations at doses up to 100 mg/kg body weight/day. This had no adverse effects on estrous cycles, mating behavior, conception, parturition, lactation and weaning, sperm and follicle parameters or the macropathology and histopathology of the sexual organs. The highest dose did however reduce parental food consumption and body weight, increase liver weights, produce hepatic cytoplasmic eosinophilia and erosion/ulceration of glandular stomach mucosa, and lead to a slightly decreased implantation rate in dams from both generations. In addition, pups from both generations had reduced lactation weight gain, reduced organ weights and delayed sexual maturation landmarks.[95]

5.5 Enhanced herbicide absorption

Octinoxate at approved concentrations in sunscreens can enhance the dermal penetration of the herbicide 2,4-dichlorophenoxyacetic acid,[96] which is exacerbated with the consumption of alcohol.[97] This suggests that it may pose a risk to agricultural workers; however, limiting excessive alcohol consumption is more important than limiting the use of sunscreens for individuals with potential herbicide exposure, since the consequences of UV-induced skin cancer are far more serious than the risks associated with increased exposure to herbicides.[97]

5.6 Photoallergic contact dermatitis

Although the incidence of allergic contact dermatitis to sunscreens in considered low, there are several reports in the medical literature of reactions towards octinoxate.[98][99][100][101][102] In 2014, a study published in the British Journal of Dermatology identified octinoxate as one of 2 most common UV filters responsible for positive photopatch reactions in an analysis of 157 children.[103] This may be due to the carbonyl groups of octinoxate reacting with peptides or free amino acids of the human skin.[104]

5.7 Developmental effects

Significantly, perinatal exposure to octinoxate led to effects on the reproductive, auditory and neurological development of rat offspring. Female offspring had decreased motor activity levels, while male offspring had reduced prostate and testis weights, lower sperm counts and testosterone levels, but improved spatial learning abilities.[105]

5.8 Potential endocrine disruptor

Octinoxate can increase the uterine weights of rats when administered by the oral route, but only at high doses. One study found no detectable effect at doses up to 333 mg/kg/day,[106] while another showed that the median effective dose was 934 mg/kg/day.[107] A third study on rodents indicated that octinoxate has very mild estrogenic effects in the uterus and vagina, but not in the bone.[108]

Additional evidence that octinoxate is a endocrine active chemical comes from studies investigating the effects of octinoxate on the hypothalamic-pituitary thyroid axis, which demonstrate that it changes the serum levels of several hormones, alters the expression of some hormone receptors, and affects the release of neurotransmitters from the hypothalamus.[109][110][111][112]

Octinoxate has also shown that it can affect the expression of endocrine-related genes in the insect Chironomum riparius, and in various species of fish.[113][114][115][116] Moreover, it acted as a partial agonist in a human breast cancer cell line, stimulating the cells' proliferation though not to the maximal level observed with estradiol.[107]

When a cream formulation containing 10% octinoxate + 10% oxybenzone + 10% enzacamene was topically applied to 32 human volunteers for 1 week, the sunscreens did not appear to have any influence on the levels of endogenous reproductive hormones in either the men or the women enrolled in the study, despite being systematically absorbed.[22] A similar study observed statistically significant differences in the levels of some thyroid hormones, but these were too minor to be biologically significant.[117]

Scientific References


  1. Lee GS, Widjaja A, Ju YH. Enzymatic synthesis of cinnamic acid derivatives. Biotechnol Lett. (2006)
  2. Wolverton SE. Sunscreens. Comprehensive Dermatologic Drug Therapy. (2012)
  3. Kim K, et. al. Simultaneous determination of nine UV filters and four preservatives in suncare products by high-performance liquid chromatography. J Chromatogr Sci. (2011)
  4. Manová E, et. al. Organic UV filters in personal care products in Switzerland: a survey of occurrence and concentrations. Int J Hyg Environ Health. (2013)
  5. Uter W, et. al. Coupled exposure to ingredients of cosmetic products: III. Ultraviolet filters. Contact Dermatitis. (2014)
  6. Amine H, et. al. UV filters, ethylhexyl methoxycinnamate, octocrylene and ethylhexyl dimethyl PABA from untreated wastewater in sediment from eastern Mediterranean river transition and coastal zones. Mar Pollut Bull. (2012)
  7. Nguyen KT, et. al. Rapid and selective determination of UV filters in seawater by liquid chromatography-tandem mass spectrometry combined with stir bar sorptive extraction. Talanta. (2011)
  8. Cuderman P, Heath E. Determination of UV filters and antimicrobial agents in environmental water samples. Anal Bioanal Chem. (2007)
  9. Kameda Y, Kimura K, Miyazaki M. Occurrence and profiles of organic sun-blocking agents in surface waters and sediments in Japanese rivers and lakes. Environ Pollut. (2011)
  10. Balmer ME, et. al. Occurrence of some organic UV filters in wastewater, in surface waters, and in fish from Swiss Lakes. Environ Sci Technol. (2005)
  11. Poiger T, et. al. Occurrence of UV filter compounds from sunscreens in surface waters: regional mass balance in two Swiss lakes. Chemosphere. (2004)
  12. Bachelot M, et. al. Organic UV filter concentrations in marine mussels from French coastal regions. Sci Total Environ. (2012)
  13. Fent K, Zenker A, Rapp M. Widespread occurrence of estrogenic UV-filters in aquatic ecosystems in Switzerland. Environ Pollut. (2010)
  14. Díaz-Cruz MS, et. al. Analysis of UV filters in tap water and other clean waters in Spain. Anal Bioanal Chem. (2012)
  15. Negreira N, et. al. Determination of selected UV filters in indoor dust by matrix solid-phase dispersion and gas chromatography-tandem mass spectrometry. J Chromatogr A. (2009)
  16. Montenegro L, Paolino D, Puglisi G. Effects of silicone emulsifiers on in vitro skin permeation of sunscreens from cosmetic emulsions. J Cosmet Sci. (2004)
  17. Gupta VK, Zatz JL, Rerek M. Percutaneous absorption of sunscreens through micro-yucatan pig skin in vitro. Pharm Res. (1999)
  18. Klinubol P, et. al. Transdermal penetration of UV filters. Skin Pharmacol Physiol. (2008)
  19. Monti D, et. al. Skin permeation and distribution of two sunscreens: a comparison between reconstituted human skin and hairless rat skin. Skin Pharmacol Physiol. (2008)
  20. Sarveiya V, Risk S, Benson HA. Liquid chromatographic assay for common sunscreen agents: application to in vivo assessment of skin penetration and systemic absorption in human volunteers. J Chromatogr B Analyt Technol Biomed Life Sci. (2004)
  21. Hayden CG, et. al. Sunscreen penetration of human skin and related keratinocyte toxicity after topical application. Skin Pharmacol Physiol. (2005)
  22. Janjua NR, et. al. 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. J Invest Dermatol. (2004)
  23. Janjua NR, et. al. Sunscreens in human plasma and urine after repeated whole-body topical application. J Eur Acad Dermatol Venereol. (2008)
  24. Durand L, et. al. In vitro evaluation of the cutaneous penetration of sprayable sunscreen emulsions with high concentrations of UV filters. Int J Cosmet Sci. (2009)
  25. Montenegro L, et. al. In vitro skin permeation of sunscreen agents from O/W emulsions. Int J Cosmet Sci. (2008)
  26. Montenegro L, Carbone C, Puglisi G. Vehicle effects on in vitro release and skin permeation of octylmethoxycinnamate from microemulsions. Int J Pharm. (2011)
  27. Montenegro L, Puglisi G. Evaluation of sunscreen safety by in vitro skin permeation studies: effects of vehicle composition. Pharmazie. (2013)
  28. Clarys P, et. al. There is no influence of a temperature rise on in vivo adsorption of UV filters into the stratum corneum. J Dermatol Sci. (2001)
  29. Golmohammadzadeh S, Jaafarixx MR, Khalili N. Evaluation of liposomal and conventional formulations of octyl methoxycinnamate on human percutaneous absorption using the stripping method. J Cosmet Sci. (2008)
  30. Monteiro MS, et. al. Evaluation of octyl p-methoxycinnamate included in liposomes and cyclodextrins in anti-solar preparations: preparations, characterizations and in vitro penetration studies. Int J Nanomedicine. (2012)
  31. Mota Ade C, et. al. In vivo and in vitro evaluation of octyl methoxycinnamate liposomes. Int J Nanomedicine. (2013)
  32. Yener G, Incegül T, Yener N. Importance of using solid lipid microspheres as carriers for UV filters on the example octyl methoxy cinnamate. Int J Pharm. (2003)
  33. Scalia S, Mezzena M, Ramaccini D. Encapsulation of the UV filters ethylhexyl methoxycinnamate and butyl methoxydibenzoylmethane in lipid microparticles: effect on in vivo human skin permeation. Skin Pharmacol Physiol. (2011)
  34. Anumansirikul N, et. al. UV-screening chitosan nanocontainers: increasing the photostability of encapsulated materials and controlled release. Nanotechnology. (2008)
  35. Puglia C, et. al. Evaluation of percutaneous absorption of the repellent diethyltoluamide and the sunscreen ethylhexyl p-methoxycinnamate-loaded solid lipid nanoparticles: an in-vitro study. J Pharm Pharmacol. (2009)
  36. Vettor M, et. al. Skin absorption studies of octyl-methoxycinnamate loaded poly(D,L-lactide) nanoparticles: estimation of the UV filter distribution and release behaviour in skin layers. J Microencapsul. (2010)
  37. Puglia C, et. al. Lipid nanoparticles as carrier for octyl-methoxycinnamate: in vitro percutaneous absorption and photostability studies. J Pharm Sci. (2012)
  38. do Nascimento DF, et. al. Characterization and evaluation of poly(epsilon-caprolactone) nanoparticles containing 2-ethylhexyl-p-methoxycinnamate, octocrylene, and benzophenone-3 in anti-solar preparations. J Nanosci Nanotechnol. (2012)
  39. Weiss-Angeli V, et. al. Development of an original method to study drug release from polymeric nanocapsules in the skin. J Pharm Pharmacol. (2010)
  40. Hanno I, Anselmi C, Bouchemal K. Polyamide nanocapsules and nano-emulsions containing Parsol® MCX and Parsol® 1789: in vitro release, ex vivo skin penetration and photo-stability studies. Pharm Res. (2012)
  41. Jiménez MM, et. al. Influence of encapsulation on the in vitro percutaneous absorption of octyl methoxycinnamate. Int J Pharm. (2004)
  42. Puglia C, et. al. Evaluation of nanostructured lipid carriers (NLC) and nanoemulsions as carriers for UV-filters: characterization, in vitro penetration and photostability studies. Eur J Pharm Sci. (2014)
  43. Olvera-Martínez BI, et. al. Preparation of polymeric nanocapsules containing octyl methoxycinnamate by the emulsification-diffusion technique: penetration across the stratum corneum. J Pharm Sci. (2005)
  44. Calderilla-Fajardo SB, et. al. Influence of sucrose esters on the in vivo percutaneous penetration of octyl methoxycinnamate formulated in nanocapsules, nanoemulsion, and emulsion. Drug Dev Ind Pharm. (2006)
  45. Kullavanijaya P, Lim HW. Photoprotection. J Am Acad Dermatol. (2005)
  46. Würbach G, Kewitsch H. Experiences with cinnamic acid esters as sunscreening agents. Dermatol Monatsschr. (1989)
  47. Santos EP, et. al. In vitro and in vivo determinations of sun protection factors of sunscreen lotions with octylmethoxycinnamate. Int J Cosmet Sci. (1999)
  48. Couteau C, et. al. Study of the efficacy of 18 sun filters authorized in European Union tested in vitro. Pharmazie. (2007)
  49. Ley RD, Fourtanier A. Sunscreen protection against ultraviolet radiation-induced pyrimidine dimers in mouse epidermal DNA. Photochem Photobiol. (1997)
  50. McVean M, Liebler DC. Prevention of DNA photodamage by vitamin E compounds and sunscreens: roles of ultraviolet absorbance and cellular uptake. Mol Carcinog. (1999)
  51. Bernerd F, Vioux C, Asselineau D. Evaluation of the protective effect of sunscreens on in vitro reconstructed human skin exposed to UVB or UVA irradiation. Photochem Photobiol. (2000)
  52. Duale N, et. al. Octyl methoxycinnamate modulates gene expression and prevents cyclobutane pyrimidine dimer formation but not oxidative DNA damage in UV-exposed human cell lines. Toxicol Sci. (2010)
  53. Reeve VE, et. al. Differential protection by two sunscreens from UV radiation-induced immunosuppression. J Invest Dermatol. (1991)
  54. Bestak R, et. al. Sunscreen protection of contact hypersensitivity responses from chronic solar-simulated ultraviolet irradiation correlates with the absorption spectrum of the sunscreen. J Invest Dermatol. (1995)
  55. Walker SL, et. al. Relationship between the ability of sunscreens containing 2-ethylhexyl-4'-methoxycinnamate to protect against UVR-induced inflammation, depletion of epidermal Langerhans (Ia+) cells and suppression of alloactivating capacity of murine skin in vivo. J Photochem Photobiol B. (1994)
  56. Reeve VE, Bosnic M, Domanski D. Interaction of UVB-absorbing sunscreen ingredients with cutaneous molecules may alter photoimmune protection. Photochem Photobiol. (2001)
  57. De Fabo EC, Noonan FP. Mechanism of immune suppression by ultraviolet irradiation in vivo. I. Evidence for the existence of a unique photoreceptor in skin and its role in photoimmunology. J Exp Med. (1983)
  58. Gibbs NK, Norval M. Urocanic acid in the skin: a mixed blessing? J Invest Dermatol. (2011)
  59. Gallagher CH, et. al. Ultraviolet carcinogenesis in the hairless mouse skin. Influence of the sunscreen 2-ethylhexyl-p-methoxycinnamate. Aust J Exp Biol Med Sci. (1984)
  60. Reeve VE, et. al. Effect of immunosuppressive agents and sunscreens on UV carcinogenesis in the hairless mouse. Aust J Exp Biol Med Sci. (1985)
  61. Bestak R, Halliday GM. Sunscreens protect from UV-promoted squamous cell carcinoma in mice chronically irradiated with doses of UV radiation insufficient to cause edema. Photochem Photobiol. (1996)
  62. Wolf P, Donawho CK, Kripke ML. Effect of sunscreens on UV radiation-induced enhancement of melanoma growth in mice. J Natl Cancer Inst. (1994)
  63. Ramos MF, et. al. Preliminary studies towards utilization of various plant extracts as antisolar agents. Int J Cosmet Sci. (1996)
  64. Hanson KM, Clegg RM. Bioconvertible vitamin antioxidants improve sunscreen photoprotection against UV-induced reactive oxygen species. J Cosmet Sci. (2003)
  65. Gogna D, et. al. Microsphere based improved sunscreen formulation of ethylhexyl methoxycinnamate. Curr Drug Deliv. (2007)
  66. Alvarez-Román R, et. al. Biodegradable polymer nanocapsules containing a sunscreen agent: preparation and photoprotection. Eur J Pharm Biopharm. (2001)
  67. Durand L, et. al. Encapsulation of ethylhexyl methoxycinnamate, a light-sensitive UV filter, in lipid nanoparticles. J Microencapsul. (2010)
  68. Nikolić S, et. al. Skin photoprotection improvement: synergistic interaction between lipid nanoparticles and organic UV filters. Int J Pharm. (2011)
  69. Velasco MV, et. al. Broad spectrum bioactive sunscreens. Int J Pharm. (2008)
  70. Stanfield JW, Feldman SR, Levitt J. Sun protection strength of a hydroquinone 4%/retinol 0.3% preparation containing sunscreens. J Drugs Dermatol. (2006)
  71. Haywood R, et. al. Measuring sunscreen protection against solar-simulated radiation-induced structural radical damage to skin using ESR/spin trapping: development of an ex vivo test method. Free Radic Res. (2012)
  72. MacManus-Spencer LA, et. al. Aqueous photolysis of the organic ultraviolet filter chemical octyl methoxycinnamate. Environ Sci Technol. (2011)
  73. Pangnakorn P, et. al. Monitoring 2-ethylhexyl-4-methoxycinnamate photoisomerization on skin using attenuated total reflection fourier transform infrared spectroscopy. Appl Spectrosc. (2007)
  74. Wang SQ, et. al. The evolution of sunscreen products in the United States--a 12-year cross sectional study. Photochem Photobiol Sci. (2013)
  75. Sayre RM, et. al. Unexpected photolysis of the sunscreen octinoxate in the presence of the sunscreen avobenzone. Photochem Photobiol. (2005)
  76. Dondi D, Albini A, Serpone N. Interactions between different solar UVB/UVA filters contained in commercial suncreams and consequent loss of UV protection. Photochem Photobiol Sci. (2006)
  77. Hojerová J, Medovcíková A, Mikula M. Photoprotective efficacy and photostability of fifteen sunscreen products having the same label SPF subjected to natural sunlight. Int J Pharm. (2011)
  78. Gaspar LR, Maia Campos PM. Evaluation of the photostability of different UV filter combinations in a sunscreen. Int J Pharm. (2006)
  79. Chatelain E, Gabard B. Photostabilization of butyl methoxydibenzoylmethane (Avobenzone) and ethylhexyl methoxycinnamate by bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S), a new UV broadband filter. Photochem Photobiol. (2001)
  80. Kikuchi A, et. al. Photoexcited singlet and triplet states of a UV absorber ethylhexyl methoxycrylene. Photochem Photobiol. (2013)
  81. Vettor M, et. al. Poly(D,L-lactide) nanoencapsulation to reduce photoinactivation of a sunscreen agent. Int J Cosmet Sci. (2008)
  82. Jiménez MM, et. al. Poly-epsilon-caprolactone nanocapsules containing octyl methoxycinnamate: preparation and characterization. Pharm Dev Technol. (2004)
  83. Perugini P, et. al. Effect of nanoparticle encapsulation on the photostability of the sunscreen agent, 2-ethylhexyl-p-methoxycinnamate. Int J Pharm. (2002)
  84. Scalia S, et. al. Comparative studies of the influence of cyclodextrins on the stability of the sunscreen agent, 2-ethylhexyl-p-methoxycinnamate. J Pharm Biomed Anal. (2002)
  85. Ambrogi V, et. al. Mesoporous silicate MCM-41 as a particulate carrier for octyl methoxycinnamate: Sunscreen release and photostability. J Pharm Sci. (2013)
  86. Scalia S, Mezzena M. Photostabilization effect of quercetin on the UV filter combination, butyl methoxydibenzoylmethane-octyl methoxycinnamate. Photochem Photobiol. (2010)
  87. US Food and Drug Administration. CFR - Code of Federal Regulations Title 21, Part 352, Subpart B, Section 352.10. Code of Federal Regulations. (2013)
  88. European Commission. List of UV filters allowed in cosmetic products. Cosmetics Directive. (2011)
  89. Xu C, Parsons PG. Cell cycle delay, mitochondrial stress and uptake of hydrophobic cations induced by sunscreens in cultured human cells. Photochem Photobiol. (1999)
  90. Molinari A, et. al. Influence of complexation with cyclodextrins on photo-induced free radical production by the common sunscreen agents octyl-dimethylaminobenzoate and octyl-methoxycinnamate. Pharmazie. (2006)
  91. Hanson KM, Gratton E, Bardeen CJ. Sunscreen enhancement of UV-induced reactive oxygen species in the skin. Free Radic Biol Med. (2006)
  92. Vilela FM, et. al. Effect of ultraviolet filters on skin superoxide dismutase activity in hairless mice after a single dose of ultraviolet radiation. Eur J Pharm Biopharm. (2012)
  93. Bonin AM, et. al. UV-absorbing and other sun-protecting substances: genotoxicity of 2-ethylhexyl P-methoxycinnamate. Mutat Res. (1982)
  94. Struwe M, et. al. The photo comet assay--a fast screening assay for the determination of photogenotoxicity in vitro. Mutat Res. (2007)
  95. Schneider S, et. al. Octyl methoxycinnamate: two generation reproduction toxicity in Wistar rats by dietary administration. Food Chem Toxicol. (2005)
  96. Pont AR, Charron AR, Brand RM. Active ingredients in sunscreens act as topical penetration enhancers for the herbicide 2,4-dichlorophenoxyacetic acid. Toxicol Appl Pharmacol. (2004)
  97. Brand RM, et. al. Transdermal absorption of the herbicide 2,4-dichlorophenoxyacetic acid is enhanced by both ethanol consumption and sunscreen application. Food Chem Toxicol. (2007)
  98. Kimura K, Katoh T. Photoallergic contact dermatitis from the sunscreen ethylhexyl-p-methoxycinnamate (Parsol MCX). Contact Dermatitis. (1995)
  99. Ricci C, et. al. Contact sensitization to sunscreens. Am J Contact Dermat. (1997)
  100. Ferriols AP, Boniche AA. Photoallergic eczema caused by sunscreens in a 12-year-old girl. Contact Dermatitis. (2000)
  101. Collaris EJ, Frank J. Photoallergic contact dermatitis caused by ultraviolet filters in different sunscreens. Int J Dermatol. (2008)
  102. Beach RA, Pratt MD. Chronic actinic dermatitis: clinical cases, diagnostic workup, and therapeutic management. J Cutan Med Surg. (2009)
  103. Haylett AK, et. al. Sunscreen photopatch testing: a series of 157 children. Br J Dermatol. (2014)
  104. Stiefel C, Schwack W. Rapid screening method to study the reactivity of UV filter substances towards skin proteins by high-performance thin-layer chromatography. Int J Cosmet Sci. (2013)
  105. Axelstad M, et. al. Effects of pre- and postnatal exposure to the UV-filter octyl methoxycinnamate (OMC) on the reproductive, auditory and neurological development of rat offspring. Toxicol Appl Pharmacol. (2011)
  106. Jarry H, et. al. Effects of the putative xenoestrogens Benzophenone-2 (BP2) and Octyl-methoxycinnamate (OMC) on gene expression in the rat pituitary. Exp Clin Endocrinol Diabetes. (2005)
  107. Schlumpf M, et. al. In vitro and in vivo estrogenicity of UV screens. Environ Health Perspect. (2001)
  108. Seidlová-Wuttke D, et. al. Comparison of effects of estradiol (E2) with those of octylmethoxycinnamate (OMC) and 4-methylbenzylidene camphor (4MBC)--2 filters of UV light - on several uterine, vaginal and bone parameters. Toxicol Appl Pharmacol. (2006)
  109. Klammer H, et. al. Multi-organic risk assessment of estrogenic properties of octyl-methoxycinnamate in vivo A 5-day sub-acute pharmacodynamic study with ovariectomized rats. Toxicology. (2005)
  110. Seidlová-Wuttke D, et. al. Comparison of effects of estradiol with those of octylmethoxycinnamate and 4-methylbenzylidene camphor on fat tissue, lipids and pituitary hormones. Toxicol Appl Pharmacol. (2006)
  111. Klammer H, et. al. Effects of a 5-day treatment with the UV-filter octyl-methoxycinnamate (OMC) on the function of the hypothalamo-pituitary-thyroid function in rats. Toxicology. (2007)
  112. Szwarcfarb B, et. al. Octyl-methoxycinnamate (OMC), an ultraviolet (UV) filter, alters LHRH and amino acid neurotransmitters release from hypothalamus of immature rats. Exp Clin Endocrinol Diabetes. (2008)
  113. Ozáez I, Martínez-Guitarte JL, Morcillo G. Effects of in vivo exposure to UV filters (4-MBC, OMC, BP-3, 4-HB, OC, OD-PABA) on endocrine signaling genes in the insect Chironomus riparius. Sci Total Environ. (2013)
  114. Christen V, Zucchi S, Fent K. Effects of the UV-filter 2-ethyl-hexyl-4-trimethoxycinnamate (EHMC) on expression of genes involved in hormonal pathways in fathead minnows (Pimephales promelas) and link to vitellogenin induction and histology. Aquat Toxicol. (2011)
  115. Zucchi S, Oggier DM, Fent K. Global gene expression profile induced by the UV-filter 2-ethyl-hexyl-4-trimethoxycinnamate (EHMC) in zebrafish (Danio rerio). Environ Pollut. (2011)
  116. Inui M, et. al. Effect of UV screens and preservatives on vitellogenin and choriogenin production in male medaka (Oryzias latipes). Toxicology. (2003)
  117. Janjua NR, et. al. Sunscreens and thyroid function in humans after short-term whole-body topical application: a single-blinded study. Br J Dermatol. (2007)