Editor’s note: This two-part article is controversial. In part I, it reviews a number of concerns about the safety of traditional sunscreens. In part II, scheduled for February, the authors propose new approaches to move past these issues. Whether or not you feel these concerns are valid, this article is presented in the spirit of advancing cosmetic science to provoke thought, and in no way suggests consumers should stop using sun protection. We invite you to engage in this discussion by emailing [email protected] or commenting on our Cosmetics & Toiletries LinkedIn page.
Modern sun care should go beyond sunglasses and high-SPF lotions. Consumers, marketers and the scientific community seek means to protect against not only all spectra of radiation, but other harmful agents including peroxides, nitrogen and sulfur oxides, free radicals and other solar-activated molecules including ozone, either present in the atmosphere or generated in the body.
Reactive oxygenated and nitrogenated species are represented by superoxide anion radical, hydroxyl, alkoxyl and lipid peroxyl radicals, nitric oxide and peroxynitrite.1 The formation of such agents in the body can occur via a combination of sun, moisture, UV absorbers and photo-unstable ingredients inadvertently formulated or generated in situ in skin care products. Their contact with human skin can set in motion a cascade of inflammatory responses.
Zinc oxide nanoparticles, for example, have been found to induce oxidative and nitrosative stress in human monocytes, leading to increased inflammatory response via activation of redox sensitive NF-κB and MAPK signaling pathways.2 Titanium dioxide nanoparticles have been shown, in a cell bioassay test, to dose-dependently increase DNA damage, lipid peroxidation and protein carbonylation, and significantly decrease the activities of superoxide dismutase, catalase, total glutathione levels and total antioxidant capacity—all of which indicates oxidative stress.3 The wide application of zinc oxide and titanium dioxide nanoparticles in, for example, cosmetics, paints, biosensors, drug delivery, food packaging and as anti-cancer agents, also increases the risk of human exposure to such materials.
An understanding also has grown for how UV-induced changes in the skin culminate in UV-induced immunosuppression and are implicated in the cascade of events related to non-melanoma skin cancer. But this holds promise for the development of more effective protection strategies.4
There is also the misguided belief that “the higher the SPF, the better a sunscreen.” Indeed, an SPF 15 product absorbs about 94% of UVB rays; SPF 30 absorbs nearly 97%; and SPF 45, about 98%—but these numbers represent UV absorption, not transmission. So a higher SPF may not in fact be better. Put another way, for an SPF of 15, 6% of UV is still transmitted to the skin. With an SPF of 30, only 3% can reach the skin. So based on these calculations, an SPF 15 allows twice as much UV to reach the skin as the SPF 30. But again, this UV is absorbed by the UV filter, and since SPF 30 filter(s) absorb twice as much as the SPF 15, depending on the filter(s), this puts the higher SPF formula at a greater risk for secondary reactions.
Of course, higher SPFs can be obtained using various combinations of filters and vehicles. There also is no evidence that higher concentrations of UV filters have anything to do with skin penetration; although sunscreen over-use or misuse, such as failure to re-apply, can lead to an increased risk of skin cancer.5 In fact, one study gave inconclusive results for skin protection while sunbathing with and without sunscreen due to a variance in application.6
Taken together, more effective and safer sunscreen actives are warranted. While some exist, their availability has been limited in certain countries due to regulatory restrictions; i.e., where SPF products are regulated as drugs. This makes finding alternatives a high priority.7
So the question now becomes: If certain and/or higher levels of UV filters are used, and they can produce unwanted agents from secondary reactions, how does the UV protection they provide compare with the undesired entities they might produce? This article considers the mechanisms of sunscreens and identifies several next-generation technologies that hold potential for developing safer and more effective sun protection formulas.
Why Use Sunscreens?
First, it is important to consider why sunscreens are necessary. Sunscreens as well as clothing, sunglasses and other physical approaches can protect the skin against the detrimental effects of photo-exposure. UV can penetrate the skin (see Figure 1), where it mainly produces reactive oxygen species (ROS). This leads to DNA, cell and tissue damage.8 It alters immune function,9 causes skin pigmentation via tyrosinase activation, and is responsible for visual photoaging.10
UV-induced skin damage can further trigger a cascade of DNA damage response signaling pathways, including cell cycle arrest, DNA repair and apoptosis (cell death).11 UV also induces genotoxic stress12 and UVA in particular is implicated in the etiology of photo-dermatoses and photo-contact allergy.13 Exposure to UV affects regulatory and dendritic cells as well, causing chemokines and cytokines to be released from the skin.14
As a consequence, to provide minimally adequate protection, sunscreens need, among many other elements, an efficient combination of UVA and UVB filters. Not surprising, one study15 of the effects of different solar spectra on the development of free radicals suggests current solar protection schemes should be entirely reconsidered—i.e., that a comprehensive protection scheme must shield against not only UVA and UVB, but also visible and near infrared energy. Existing examples of infrared-protective active agents include mitochondrially-targeted antioxidants.16 In the end, it’s all about effective and safe sun protection.17
Protective Strategies
Two main approaches are taken to formulate UV protection: physical (also inorganic or mineral) and chemical (also organic or synthetic). As is well-known, physical or mineral sunscreens, such as zinc oxide or titanium dioxide, physically prevent solar radiation from penetrating the stratum corneum. Previously, these were believed to act by reflecting UV rays similarly to white paint reflecting light but recent work has shown they also work partially by absorbing UV.18
It is interesting that the mechanism of UV-blocking function of inorganic oxides is not clear. While for TiO2, for example, some believe it provides UV protection by reflecting and/or scattering most of the UV rays through its high refractive index. Others believe it absorbs UV radiation due to its semi-conductive properties. A band theory also has been proposed; i.e., if the energy per photon is smaller than the band gap, the light cannot excite electrons from the valence to conduction band. So, the photon will pass through the material without being absorbed. If the energy is larger than the band gap, the light will excite electrons and be (partially) absorbed.19
Organic or chemical sunscreens, such as avobenzone or oxybenzone, absorb UV radiation through their conjugated chemical bonds, which causes them to reach an excited state. These excited state molecules then return to their normal state by transforming the absorbed energy into visible light, heat or phosphorescence. However, such transformations can initiate secondary reactions in skin. As stated, exposure to UV radiation triggers a cascade of chemical reactions, and molecular products (photolesions) from such reactions have been isolated that are potentially unsafe for the cellular system. The early steps of UV absorption by DNA and generation of excited electronic states, leading to photolesions, have been studied.20
Relative to the dissipation of excited-state energy in organic sunscreens, the triplet-triplet UV absorption, phosphorescence and phosphorescence-excitation spectra of benzophenone, methyl anthranilate, ethylhexyl triazone, methylphenyl cinnamate, 2-ethylhexyl salicylate and homomenthyl salicylate have been studied.21 The results could pave the way for the development of more effective sunscreens with reduced phototoxicity.
Another consideration is the body’s own natural sunscreens, eumelanin and pheomelanin, which provide protection by absorbing solar radiation and dissipating it as heat—without detriment to their polymeric structure.22
Upon Application and Exposure
What happens to sunscreen after it is applied to skin? First, consider consumers prefer formulas that rapidly absorb without an oily feel or white appearance. For these effects, chemical (organic) sunscreens generally work best. However, in one study, oxybenzone was shown to rapidly photo-oxidize, yielding oxybenzone semiquinone, which reacted with thiol (-SH) groups on several antioxidant enzymes such as thioredoxin reductase and glutathione peroxidase. So while oxybenzone is an excellent broad spectrum UVA filter, its skin absorption23 and rapid oxidation, followed by the inactivation of the described antioxidant systems, suggests it could be harmful to the epidermis.
In relation, a study using an animal model found the protective capability of organic sunscreens may decrease upon UV exposure, and the sunscreens could behave as photo-oxidants. Furthermore, they can form degradation products under UVR that either inhibit enzymes or generate reactive species in the skin.24 Additionally, oxybenzone has been found to react rapidly with chlorine, such as that found in swimming pools. The stable transformation product 2,4,6-trichloro-3-methoxyphenol was identified, as were high amounts of chloroform, trichloroacetic acid, dichloroacetic acid and chloral hydrate; and significantly elevated genotoxicity has been observed from chlorinated oxybenzone byproducts.25
An understanding has grown for how UV-induced changes in skin culminate in immunosuppression. This holds promise for more effective protection strategies.
TiO2 composites also are sometimes used as UV filters in sunscreen products in combination with the organic sunscreens butyl methoxydibenzoyl methane (avobenzone) and octyl methoxycinnamate (OMC). Most formulators know to avoid this combination since TiO2 nanocomposites (NCs) promote the photolysis of OMC.
The photo-oxidation of other organic sunscreens and their relevance to human safety have also been reported.26 For example, the high-resolution spectroscopy of cinnamate-based UV filters has shown the excited state dynamics of a delicate balance between favorable and adverse, skin-damaging effects. Contrary to common belief, the excitation to the “bright” ππ* state does not directly lead to repopulation of the electronic ground state. Instead, internal conversion to another electronically excited state, identified as the “dark” nπ* state, is a major decay pathway that impedes fast energy dissipation, resulting in photo-oxidation and the formation of ROS in the skin.27
The human epidermis defends against reactive oxygen species (ROS) generated by UV or x-ray exposure, as well as heat and radiation energy sources. In particular, the roles of thioredoxin (T) and thioredoxin reductase (TR) in the skin are well-recognized. Thioredoxin has been shown to protect against both UVB-induced skin injury and damage by peroxides.28 Thioredoxin reductase brings oxidized thioredoxin to its reduced state by nicotinamide adenine dinucleotide phosphate (NADPH).
Reduced thioredoxin then serves as an electron donor for thioredoxin peroxidase (TPx), which subsequently reduces H2O2 to H2O. This is crucial since UVB generates H2O2 in the epidermis in a dose-dependent manner.28 Furthermore, this TR/T/TPx system in epidermal cells controls cofactor (6R)-L-erythro 5,6,7,8 tetrahydrobiopterin (6BH(4)) homeostasis.
In the case of oxybenzone, however, UVB photo-oxidation may deactivate thioredoxin reductase in darker-skinned individuals by Michael addition of oxybenzone semiquinone to the thiolate active site of this enzyme. This is illustrative of how photo-oxidized oxybenzone can cause melanocyte cytotoxicity in darker-skinned individuals—potentially posing a greater risk than bypassing this sunscreen type altogether.29
Potential Side Effects
The potential for side effects from chemical UV filters in cosmetics has been studied, taking three key observations into consideration: 1) the use of sunscreens containing chemical UV filters is increasing worldwide, 2) sunscreens should protect against malignant melanoma but its incidence is rising, and 3) several UV filters are suspected of endocrine disruption.30, 31
Regarding point 2, in a case-control study from southern Sweden, the association between sunscreen use and malignant melanoma was evaluated. Sunscreen users reported greater sun exposure than non-users. In individuals who used sunscreens, however, their risk of malignant melanoma did not decrease. Instead, a significantly elevated ratio for developing malignant melanoma after regular sunscreen use was found32—although a recent study provides contradictory results.33 In another study, no significant protection against skin cancer by sunscreen use was reported.34 These inconclusive reports suggest the need for more studies in this area, and the use of sunscreens as the sole means of protection against solar-initiated skin cancer warrants caution.
For point 3, the endocrine-disrupting property of several sunscreen actives has received much attention in recent years. In relation, it seems pertinent to evaluate whether exposure to UV filters contributes to possible adverse effects on the developing organs of fetuses and children.35 Benzophenone derivatives have been detected in more than 95% of randomly collected human urine samples from adults and premature infants, and these derivatives may have estrogenic potential.36
Increasing consumer awareness of this concern, albeit contradictory in some aspects, requires the further risk assessment of sunscreens.37 Benzophenone derivatives are UV-absorbing chemicals used widely in pharmaceutical, cosmetic and industrial applications. Studies of their potential endocrine-disrupting properties have focused mostly on their interaction with human estrogen receptor alpha (hERalpha). In one test, for example, endocrine receptors of human and fish origin were used to assess the potential effects of benzophenone derivatives. Overall, the observed anti-androgenic potencies of these derivatives support further investigation of their role as endocrine disrupters in humans and wildlife.38
In another recent study, the UV filters 3-benzylidene camphor and benzylidene camphor sulfonic acid were found to competitively inhibit progesterone-induced Ca2+ signals. However, in vivo studies are needed to investigate whether the UV filter affects human fertility;39 as mentioned, benzophenone has been detected in randomly collected human urine samples and it could have estrogenic potential.36 Indeed, the potential exposure hazards of several sunscreen agents on human health are an active area of research.40
In yet another study, zinc oxide (ZnO), which is known to deliver broad UV protection, was assessed in both its micronized and nano-sized form for potential toxicity. Depending on the formula composition, topically applied ZnO did not appear to penetrate the viable epidermis.41 However, the reaction of water with ZnO on the skin surface was found to increase zinc ion levels in the stratum corneum, viable epidermis and subsequently, in systemic circulation and urine.42
A recent hazard analysis of zinc oxide and titanium dioxide nanoparticles showed both materials could cause DNA damage,43 and exposure to titanium dioxide nanoparticles resulted in microglia activation, reactive oxygen species production and the activation of signaling pathways involved in inflammation and cell death, both in vitro and in vivo.44 And contrary to the findings stated above, another study suggested some penetration of coated and uncoated nano-sized ZnO (ZnO-NP) into the viable stratum granulosum epidermis.45 Thus, the safety of ZnO and TiO2 nanoparticles in sunscreens has been reviewed, albeit with contradictory conclusions.46
In a related study of radiolabeled zinc oxide, levels of Zn68 in blood and urine from human panelists using a nano sunscreen appeared to be higher than subjects using a bulk sunscreen. It was not known whether Zn68 absorbed as ZnO particles, soluble Zn or both.47 A rat model study revealed similar results for both nano- and larger size ZnO sunscreens.47 However, comparative data is lacking. As such, an international collaboration is needed to understand the potential for dermal absorption of not only micronized and nanoparticles but also their detection under normal conditions of sunscreen use.48
The use of sunscreens can have indirect implications as well, primarily by giving consumers a false sense of security so they remain for too long in the sun without proper protection. In fact, sunscreen users reported significantly more sunburns and were even more likely to use indoor tanning devices than non-sunscreen users.49
Environmental Presence
Recent evidence also suggests both organic and inorganic UV filters used widely in sunscreens and other personal care products may also impact ecosystems. Sunscreen compounds are released into the coastal aquatic environment in significant amounts from beach-goers, and the effects of these potential pollutants on microbiota are not well-known.
Phytoplankton, for example, is a key component of the microbiota, and any change in its natural population can affect the structure of aquatic biota. In one experiment50 performed outdoors with natural UV light and without it, four species of mixed microalgae were exposed to three commercial sunscreens with variable titanium dioxide concentrations. The toxicity mediated by hydrogen peroxide production associated with the concentration of TiO2 NPs was examined; the organic compounds in the sunscreens also were taken into account. The results indicated the sensitivity of microalgae to sunscreens and TiO2 nanoparticles could produce a change in the dynamics of phytoplankton populations and provoke undesirable ecological effects.50
In another study, the toxicities of five types of TiO2 nanoparticles with different particle sizes (10-50 nm) and crystal phases were investigated using Escherichia coli as the test organism. The effect of water chemistry on the nanotoxicity also was examined. Transmission electron microscopy showed the concentration build-up of the anatase TiO2, especially of smaller particle sizes on the cell surfaces, leading to membrane damage and internalization.51
Photo-oxidized oxybenzone can cause melanocyte cytotoxicity in darker-skinned individuals—potentially posing a greater risk than bypassing this sunscreen type altogether.
In yet another study, eight different nano-sized TiO2 suspensions of five different concentrations were tested in conjunction with changes in water quality parameters (pH, temperature and ionic strength), light sources and light intensities, to mimic different environmental conditions. The results indicated nano-TiO2 particles, both in the absence and presence of a light source, i.e., photoactived, induced lipid peroxidation and disrupted cellular respiration.52
Besides TiO2, the widespread use of benzophenone-3 (BP-3) in sunscreens and other consumer products has resulted in its release into the water environment, hence its potential impact on aquatic ecosystems has become a concern. BP-3 transforms into three major metabolites in vivo: benzophenone-1 (BP-1), benzophenone-8 (BP-8) and 2, 3, 4-trihydroxybenzophenone (THB). BP-1 has a longer biological half-life than its parent compound and exhibits greater estrogenic potency in vitro. BP-3 has been detected in water, soil, sediments, sludge and biota. The maximum detected level in ambient fresh water and sea water is 125 ng/L and 577.5 ng/L, respectively; and in wastewater influent, 10,400 ng/L.
Other sunscreens routinely detected in the environment include butyl methoxy dibenzoylmethane, ethylhexyl dimethyl p-aminobenzoate and 4-methylbenzylidene camphor. Considering the limited ecotoxicological information currently available, further studies on environmental monitoring in aquatic ecosystems are warranted.53
In relation, there is a pressing need to standardize methods that represent realistic environmental conditions to evaluate the ecotoxicity of sunscreens in aquatic media. Interestingly, it was found that the organic matter present in aquatic systems interfered in the toxicological estimation of titanium dioxide in a river ecosystem.54
Lab-scale water-sediment test systems have shown55 sorption to be the primary mechanism for removing UV filters from the sunscreen formula water phase. Furthermore, biotransformation is the predominant factor for the degradation of these compounds in water-sediment systems. Additionally, the UV filters tested were found to be slightly resistant to the microbes in these sediment systems, with DT50 and DT90 values. Here, the disappearance time (DT) describes the time in which the initial total mass of the UV filters in the whole system is reduced by 50% and 90%, which ranged between 18 and 31 days, and 68 and 101 days, respectively.55
Sunscreens collect in swimming pool water as well, which becomes a sink full of chlorinated and UV-degradation byproducts. In fact, concentrations in the μg/L range have been found for benzophenone and crylene derivatives in swimming pools.56
Recent studies have evaluated the bioaccumulation and biomagnification of organic sunscreen compounds in both fresh and salt water, and terrestrial food chains including: animal species, e.g., macroinvertebrates, fish and birds; habitats such as lakes, rivers and the sea; and benzophenone and camphor UV filters. Biomagnification in predator-prey pairs, for example bird-fish and fish-invertebrates, was observed. Ecotoxicological data and preliminary environmental assessment of the risk of UV filters also have been discussed.57 Lipophilic sunscreens were prevalent with concentrations of up to 7,112 ng/g homosalate in mussels and 3,100 ng/g homosalate in fish. High concentrations have also been reported for 4-ethylbenzilidenecamphor, up to 1800 ng/g, and octocrylene at 2,400 ng/g;57 although it should be noted that the source of these chemicals, i.e. from sunscreens, and/or the effects of their presence was not established.
In another study, the occurrence and distribution of eight UV filters including benzophenone, benzophenone-3, ethylhexyl methoxy cinnamate, 4-methylbenzylidene camphor, 2-ethylhexyl 4-dimethylaminobenzoate, 2-ethylhexyl salicylate, isoamyl benzoate and benzyl cinnamate in eleven sites among three rivers, five sewage treatment plants, and four wastewater treatment plants located in different parts of Korea was investigated.58 The biological treatment processes favored the removal of UV filters. However, complete removal was not achieved before discharge into the rivers58 and a risk analysis indicated that benzophenone-3 and ethylhexyl methoxy cinnamate discharged from treatment plants may pose high risk to fish in the local environment.59
Lab-scale water sediment test systems have shown sorption to be the primary mechanism for removing sunscreen filters from the sunscreen formula water phase.
Additional Concerns
Circling back to the initial concern: the safety of sunscreens. As noted, some evidence suggests organic sunscreens and inorganic nanoparticulate sunscreens can penetrate the skin. Thus, the assessment of their potential to cause skin sensitization and damage are of high importance both from product safety and regulatory viewpoints.60
While sunscreens have been used for decades with no serious safety issues, recent work has brought consumer concerns to light that merit further research. For example, relative to the prevention of basal cell carcinoma and melanoma, a significant benefit from regular sunscreen use has not yet been demonstrated. Sunscreens also do not prevent actinic keratoses, squamous cell carcinomas, or skin aging.5 And a number of organic UV filters, e.g., PABA derivatives, cinnamates, benzophenones and octocrylene, have been reported to cause photo-allergy.13
Furthermore, as described, the endocrine-disrupting activity of small-sized organic and nano-sized inorganic UV filters has been reported.61 Also, sunscreens impair vitamin D synthesis—the deficiency of which has become a public health concern.62
Of course, contrary opinions exist.63 For instance, a number of patients who reported photo-contact allergy to octocrylene may have previously used other topical products containing the non-steroidal anti-inflammatory drug ketoprofen. But contact allergy from octocrylene-based sunscreens in the absence of ketoprofen also occurs, mostly in children.64
Another issue is with benzophenone (BP), which as noted can be released in the environment from sunscreens and is a suspected indirect endocrine disrupter. While BP itself has not shown estrogenic activity, two estrogenic photoproducts were detected after irradiating an aqueous solution of BP with UV or sunlight: 3-hydroxy BP (BP-3OH) and 4-hydroxyBP (BP-4OH). The formation of H2O2 also was found with increasing levels of UV, and the addition of H2O2 to the BP solution increased BP-3OH and BP-4OH production under UV irradiation.
These results suggest the involvement of photochemically generated H2O2 and hydroxyl radical in BP hydroxylation. Notably, BP-4OH is more potent than BP-3OH for promoting estrogen receptor-mediated transcription and uterotrophic activity. Therefore, it can be concluded that BP can be converted into ring-hydroxylated derivatives that have estrogenic activity after exposure to UV.65 Considering all the concerns described, it is worth exploring how to take sunscreens in a new direction. Recent research has focused on nature’s approaches to protecting living organisms; this will be the focus of part II in this series, to appear in the February Cosmetics & Toiletries.
Engage in this discussion by e-mailing the editor, [email protected], or posting on our LinkedIn page.
References
- Pisoschi et al, The role of antioxidants in the chemistry of oxidative stress: A review, Eur J Med Chem 97 55-74 (Jun 5, 2015) doi: 10.1016/j.ejmech.2015.04.040
- Senepati et al, ZnO nanoparticles induced inflammatory response and genotoxicity in human blood cells: A mechanistic approach, Food Chem Toxicol 85 61-70 (Nov 2015) doi: 10.1016/j.fct.2015.06.018
- Dubey et al, Oxidative stress and nano-toxicity induced by TiO2 and ZnO on WAG cell line, PLoS One 10(5) e0127493 (May 26, 2015) doi: 10.1371/journal.pone.0127493
- Prasad et al, Crosstalk among UV-induced inflammatory mediators, DNA damage and epigenetic regulators facilitates suppression of the immune system, Photochem Photobiol (Dec 9, 2016) doi: 10.1111/php.12687; Pillai et al, Ultraviolet radiation and skin aging: Roles of reactive oxygen species, inflammation and protease activation, and strategies for prevention of inflammation-induced matrix degradation—A review, Int J Cosmet Sci 27(1) 17-34 (Feb 2005) doi: 10.1111/j.1467-2494.2004.00241.x; ncbi.nlm.nih.gov/pubmed/1849217; Dacup et al, Impact of the circadian clock on UV-induced DNA damage response and photocarcinogenesis, Photochem Photobiol (Nov 12, 2016) doi: 10.1111/php.12662
- Autier, Sunscreen abuse for intentional sun exposure, Br J Dermatol 161 suppl 3 40-5 (Nov 2009) doi: 10.1111/j.1365-2133.2009.09448.x; Chesnut et al, Is there truly no benefit with sunscreen use and basal cell carcinoma? A critical review of the literature and the application of new sunscreen labeling rules to real-world sunscreen practices, J Skin Cancer 480985(2012) doi: 10.1155/2012/480985
- Thieden et al, Sunscreen use related to UV exposure, age, sex and occupation based on personal dosimeter readings and sun-exposure behavior diaries, Arch Dermatol 141(8) 967-73 (Aug 2005); ncbi.nlm.nih.gov/pubmed/16103325
- Cefali et al, Plant-based active photoprotectants for sunscreens, Int J Cosmet Sci 38(4) 346-53 (Aug 2016) doi: 10.1111/ics.12316; ncbi.nlm.nih.gov/pubmed/26919163
- Zeng et al, Analysis of lncRNAs expression in UVB-induced stress responses of melanocytes, J Dermatol Sci 81(1):53-60 (Jan 2016) doi: 10.1016/j.jdermsci.2015.10.019; Ghanizadeh et al, UV-B exposure reduces locomotor performance by impairing muscle function but not mitochondrial ATP production, J Exp Biol 219 (Pt 1) 96-102 (Jan 2016) doi: 10.1242/jeb.131615; Patwardhan et al, Ultraviolet-B protective effect of flavonoids from Eugenia caryophylata on human dermal fibroblast cells, Pharmacogn Mag 11suppl 3 S397-406 (Oct 2015) doi: 10.4103/0973-1296.168979
- Katiyar, Dietary proanthocyanidins inhibit UV radiation-induced skin tumor development through functional activation of the immune system, Mol Nutr Food Res (Mar 15, 2016) doi: 10.1002/mnfr.201501026; Damiani et al., Understanding the connection between platelet-activating factor, a UV-induced lipid mediator of inflammation, immune suppression and skin cancer, Prog Lipid Res 63 14-27 (Apr 9, 2016); doi: 10.1016/j.plipres.2016.03.004; Kripke et al, Modulation of immune function by UV radiation, J Invest Dermatol 85(1 suppl) 62s-66s (Jul 1985)
- Gu et al, Additive effect of heat on the UVB-induced tyrosinase activation and melanogenesis via ERK/p38/MITF pathway in human epidermal melanocytes, Arch Dermatol Res 306(6) 583-90 (Aug 2014) doi: 10.1007/s00403-014-1461-y; Yanase et al, Possible involvement of ERK 1/2 in UVA-induced melanogenesis in cultured normal human epidermal melanocytes, Pigment Cell Res 14(2) 103-9 (Apr 2001); Tagashira et al, UVB stimulates the expression of endothelin B receptor in human melanocytes via a sequential activation of the p38/MSK1/CREB/MITF pathway, which can be interrupted by a French maritime pine bark extract through a direct inactivation of MSK1, PLoS One 10(6) e0128678 (Jun 1, 2015) doi: 10.1371/journal.pone.0128678; Mizutani et al, A single UVB exposure increases the expression of functional KIT in human melanocytes by up-regulating MITF expression through the phosphorylation of p38/CREB, Arch Dermatol Res 302(4) 283-94 (May 2010) doi: 10.1007/s00403-009-1007-x; Kim et al, UV decreases the synthesis of free fatty acids and triglycerides in the epidermis of human skin in vivo, contributing to development of skin photoaging, J Dermatol Sci 57(1) 19-26 (Jan 2010) doi: 10.1016/j.jdermsci.2009.10.008
- Sample et al, Autophagy in UV damage response, Photochem Photobiol (Dec 9, 2016) doi: 10.1111/php.12691; ncbi.nlm.nih.gov/pubmed/27935061
- Lindsey-Boltz, Bringing it all together: Coupling excision repair to the DNA damage checkpoint, Photochem Photobiol (Nov 14, 2016) doi: 10.1111/php.12667; ncbi.nlm.nih.gov/pubmed/27861980
- Zimmer et al, Unique co-existence of cold and solar urticaria and its efficient treatment, Br J Dermatol (Dec 18, 2015) doi: 10.1111/bjd.14354; Chong et al, Solar urticaria in Singapore: An uncommon photodermatosis seen in a tertiary dermatology center over a 10-year period, Photodermatol Photoimmunol Photomed 20(2) 101-4 (Apr 2004); de Groot et al, Contact and photocontact allergy to octocrylene: A review, Contact Dermatitis 70(4) 193-204 (Apr 2014) doi: 10.1111/cod.12205; Hanson et al, Sensitivity to multiple benzophenone sunscreen agents, Dermatitis 26(4) 192-4 (Jul/Aug 2015) doi: 10.1097/DER.0000000000000131
- Kim et al, UV-induced inhibition of adipokine production in subcutaneous fat aggravates dermal matrix degradation in human skin, Sci Rep 6 25616 (May 10, 2016) doi: 10.1038/srep25616; Fourtanier et al, Sunscreens containing the broad-spectrum UVA absorber Mexoryl SX prevent the cutaneous detrimental effects of UV exposure: A review of clinical study results, Photodermatol Photoimmunol Photomed 24(4) 164-74 (Aug 2008) doi: 10.1111/j.1600-0781.2008.00365.x; Lucas et al, Ultraviolet radiation, vitamin D and multiple sclerosis, Neurodegener Dis Manag 5(5) 413-24 (Oct 2015) doi: 10.2217/nmt.15.33
- Lohan et al, Free radicals induced by sunlight in different spectral regions—In vivo vs. ex vivo study, Exp Dermatol (Feb 22, 2016) doi: 10.1111/exd.12987; Darvin et al, Radical production by infrared A irradiation in human tissue, Skin Pharmacol Physiol 23(1) 40-6 (2010) doi: 10.1159/000257262; Zastrow et al, Light—Instead of UV protection: New requirements for skin cancer prevention, Anticancer Res 36(3) 1389-93 (Mar 2016)
- Schroeder et al, What is needed for a sunscreen to provide complete protection, Skin Therapy Lett 15(4) 4-5 (Apr 2010)
- Rai et al, Update on photoprotection, Indian J Dermatol 57(5) 335-42 (Sep 2012) doi: 10.4103/0019-5154.100472; Moyal, The development of efficient sunscreens, Indian J Dermatol Venereol Leprol 78 suppl 1 S31-4 (Jun 2012) doi: 10.4103/0378-6323.97353
- Cole et al, Metal oxide sunscreens protect skin by absorption, not by reflection or scattering, Photodermatol Photoimmunol Photomed 32(1) 5-10 (Jan 2016) doi: 10.1111/phpp.12214
- Yang et al, Studying the mechanisms of titanium dioxide as ultraviolet-blocking additive for films and fabrics by an improved scheme, J Applied Polymer Sci 92 3201–3210 (2004); http://physics.stackexchange.com/questions/105262/why-is-titanium-dioxide-transparent-for-visible-light-but-not-for-uv
- Schreier et al, Early events of DNA photodamage, Annu Rev Phys Chem 66 497-519 (Apr 2015) doi: 10.1146/annurev-physchem-040214-121821; ncbi.nlm.nih.gov/pubmed/25664840
- Marchetti et al, Theoretical insights into the photo-protective mechanisms of natural biological sunscreens: Building blocks of eumelanin and pheomelanin, Phys Chem 18(5) 3644-58 (Jan 27, 2016) doi: 10.1039/c5cp06767g; Kumasaka et al, Photoexcited states of UV absorbers, benzophenone derivatives, Photochem Photobiol 90(4) 727-33 (Jul/Aug 2014) doi: 10.1111/php.12257; Sugiyama et al, Optical and electron paramagnetic resonance studies of the excited triplet states of UV-B absorbers: 2-Ethylhexyl salicylate and homomenthyl salicylate, Photochem Photobiol Sci 14(9) 1651-9 (Sep 26, 2015) doi: 10.1039/c5pp00138b; Tsuchiya et al, Photoexcited triplet states of UV-B absorbers: Ethylhexyl triazone and diethylhexylbutamido triazone, Photochem Photobiol Sci 14(4) 807-14 (Apr 2015) doi: 10.1039/c4pp00373j; Kikuchi et al, Excited states of menthyl anthranilate: A UV-A absorber, Photochem Photobiol Sci 12(2) 246-53 (Feb 2013) doi: 10.1039/c2pp25190f
- Krol et al, Photoprotective actions of natural and synthetic melanins, Chem Res Toxicol 11(12) 1434-40 (Dec 1998); ncbi.nlm.nih.gov/pubmed/9860484; D'Mello et al, Signaling pathways in melanogenesis, Int J Mol Sci 17(7) (Jul 15, 2016) pii: E1144 doi: 10.3390/ijms17071144; ncbi.nlm.nih.gov/pubmed/27428965; Vij et al, Bioinspired functionalized melanin nanovariants with a range of properties provide effective color-matched photoprotection in skin, Biomacromolecules 17(9) 2912-9 (Sep 12, 2016) doi: 10.1021/acs.biomac.6b00740; ncbi.nlm.nih.gov/pubmed/27477067
- Roussel et al, Measurement, analysis and prediction of topical UV filter bioavailability, Int J Pharm 478(2) 804-10 (Jan 30, 2015) doi: 10.1016/j.ijpharm.2014.12.026; ncbi.nlm.nih.gov/pubmed/25526673; Chatelain et al, Skin penetration and sun protection factor of five UV filters: Effect of the vehicle, Skin Pharmacol Appl Skin Physiol 6(1) 28-35 (Jan/Feb 2003); ncbi.nlm.nih.gov/pubmed/12566826
- Vilela 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 80(2) 387-92 (Feb 2012) doi: 10.1016/j.ejpb.2011.10.005; ncbi.nlm.nih.gov/pubmed/22036989
- Zhang et al, Chlorination of oxybenzone: Kinetics, transformation, disinfection byproducts formation and genotoxicity changes, Chemosphere 154 521-7 (Jul 2016) doi: 10.1016/j.chemosphere.2016.03.116; ncbi.nlm.nih.gov/pubmed/27085067
- Schallreuter et al, Oxybenzone oxidation following solar irradiation of skin: Photoprotection versus antioxidant inactivation, J Invest Dermatol 106(3) 583-6 (Mar 1996); ncbi.nlm.nih.gov/pubmed/8648199; J Moore et al, Direct evidence for oxidation of oxybenzone in the human epidermis, J Invest Dermatol 108 (1997) 666; Hojerova' et al, Photoprotective efficacy and photostability of fifteen sunscreen products having the same label SPF subjected to natural sunlight, Int J Pharm 408(1-2) 27-38 (Apr 15, 2011) doi: 10.1016/j.ijpharm.2011.01.040; Nash et al, Relevance of UV filter/sunscreen product photostability to human safety, Photodermatol Photoimmunol Photomed 30(2-3) 88-95 (Apr-Jun 2014) doi: 10.1111/phpp.12113; Kim et al, Photolysis of the organic UV filter avobenzone combined with octyl methoxycinnamate by nano-TiO2 composites, J Photochem Photobiol B 149 196-203 (Aug 2015) doi: 10.1016/j.jphotobiol.2015.05.011; Masnec et al, New option in photoprotection, Coll Antropol 34 suppl 2 257-62 (Apr 2010)
- Trossini et al,Theoretical study of tautomers and photoisomers of avobenzone by DFT methods, J Mol Model 21(12) 319 (Dec 2015) doi: 10.1007/s00894-015-2863-2; Tan et al, Excited-state dynamics of isolated and microsolvated cinnamate-based UV-B sunscreens, J Phys Chem Lett 5(14) 2464-8 (Jul 17, 2014) doi: 10.1021/jz501140b
- Schallreuter et al, Thioredoxin reductase—Its role in epidermal redox status, J Photochem Photobiol B 64(2-3) 179-84 (Nov 15, 2001); ncbi.nlm.nih.gov/pubmed/11744405; Schllreuter et al, Quinones are reduced by 6-tetrahydrobiopterin in human keratinocytes, melanocytes and melanoma cells, Free Radic Biol Med 44(4) 538-46(Feb 15, 2008); ncbi.nlm.nih.gov/pubmed/17997383
- Sundaram et al, The effect of UV radiation and sun blockers on free radical defense in human and guinea pig epidermis, Arch Dermatol Res 282(8) 526-31(1990)
- Krause et al, Sunscreens: Are they beneficial for health? An overview of endocrine disrupting properties of UV-filters, Int J Androl 35(3) 424-36 (Jun 2012) doi: 10.1111/j.1365-2605.2012.01280.x; ncbi.nlm.nih.gov/pubmed/22612478
- Bens, Sunscreens, Adv Exp Med Biol 810 429-63 (2014); ncbi.nlm.nih.gov/pubmed/25207381; Loden et al, Sunscreen use: Controversies, challenges and regulatory aspects, Br J Dermatol 165(2) 255-62 (Aug 2011) doi: 10.1111/j.1365-2133.2011.10298.x; ncbi.nlm.nih.gov/pubmed/21410663
- Westerdahlet al, Sunscreen use and malignant melanoma, Int J Cancer 87(1) 145-50 (Jul 1, 2000); ncbi.nlm.nih.gov/pubmed/10861466
- Ghiasvand et al, Sunscreen use and subsequent melanoma risk: A population-based cohort study, J Clin Oncol (Sep 12, 2016) pii: JCO675934; ncbi.nlm.nih.gov/pubmed/27621396
- Sanchez et al, Sun protection for preventing basal cell and squamous cell skin cancers, Cochrane Database Syst Rev 7 CD011161 (Jul 25, 2016) doi: 10.1002/14651858.CD011161.pub2; ncbi.nlm.nih.gov/pubmed/27455163
- Ibid Ref 30, Krause; Zhao et al, Regulation of microRNAs and the correlations of microRNAs and their targeted genes by zinc oxide nanoparticles in ovarian granulosa cells, PLoS One 11(5) e0155865 (May 19, 2016) doi: 10.1371/journal.pone.0155865; ncbi.nlm.nih.gov/pubmed/27196542
- Nakamura et al, Effects of maternal and lactational exposure to 2-hydroxy-4-methoxybenzone on development and reproductive organs in male and female rat offspring, Birth Defects Res B Dev Reprod Toxicol 104(1) 35-51 (Feb 2015) doi: 10.1002/bdrb.21137; ncbi.nlm.nih.gov/pubmed/25707689
- Kermanizadeh et al, An in vitro assessment of panel of engineered nanomaterials using a human renal cell line: Cytotoxicity, pro-inflammatory response, oxidative stress and genotoxicity, BMC Nephrol 14 96 (Apr 25, 2013) doi: 10.1186/1471-2369-14-96; ncbi.nlm.nih.gov/pubmed/23617532; Farcal et al, Comprehensive in vitro toxicity testing of a panel of representative oxide nanomaterials: First steps toward an intelligent testing strategy, PLoS One 10(5) e0127174 (May 21, 2015) doi: 10.1371/journal.pone.0127174; ncbi.nlm.nih.gov/pubmed/25996496
- Molina-Molina et al, Profiling of benzophenone derivatives using fish and human estrogen receptor-specific in vitro bioassay, Toxicol Appl Pharmacol 232(3) 384-95 (Nov 1, 2008) doi: 10.1016/j.taap.2008.07.017; ncbi.nlm.nih.gov/pubmed/18706922; Kunz et al, Multiple hormonal activities of UV filters and comparison of in vivo and in vitro estrogenic activity of ethyl-4-aminobenzoate in fish, Aquat Toxicol 79(4) 305-24 (Oct 12, 2006); ncbi.nlm.nih.gov/pubmed/16911836
- Rehfeld et al, Chemical UV filters mimic the effect of progesterone on Ca2+ signaling in human sperm cells, Endocrinology 157(11) 4297-4308 (Nov 2016); ncbi.nlm.nih.gov/pubmed/27583790
- Liu et al, Ozonation of the UV filter benzophenone-4 in aquatic environments: Intermediates and pathways, Chemosphere 149 76-83 (Apr 2016) doi: 10.1016/j.chemosphere.2016.01.097; ncbi.nlm.nih.gov/pubmed/26855209; Calafat et al, Concentrations of the sunscreen agent benzophenone-3 in residents of the United States: National health and nutrition examination survey 2003-2004, Env Health Perspect 116 893–897 (2008); Coronado et al, Estrogenic activity and reproductive effects of the UV-filter oxybenzone (2-hydroxy-4-methoxyphenyl-methanone) in fish, Aquat Toxicol 90 182–187 (2008); Hayden et al, Sunscreen penetration of human skin and related keratinocyte toxicity after topical application, Skin Pharmacol Physiol 18 170–174 (2005); Janjua 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 123 57–61 (2004); Janjua et al, Sunscreens in human plasma and urine after repeated whole-body topical application, J Eur Acad Dermatol Venereol 22 456–461 (2008); Kim et al,Effect of 2, 2ʹ,4, 4ʹ-tetrahydroxybenzophenone (BP2) on steroidogenesis in testicular Leydig cells, Toxicology 288 18–26 (2011); Kunisue et al, Urinary concentrations of benzophenone-type UV filters in U.S. women and their association with endometriosis, Environ Sci Technol 46 4624–4632 (2012); Nakagawa et al, 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 139 115–128 (2002); Nashev et al, The UV-filter benzophenone-1 inhibits 17B-hydroxysteroid dehydrogenase type 3: Virtual screening as a strategy to identify potential endocrine disrupting chemicals, Biochem Pharmacol 79 1189–1199 (2010); Suzuki et al, Estrogenic and antiandrogenic activities of 17 benzophenone derivatives used as UV stabilizers and sunscreens, Toxicol Appl Pharmacol 203 9–17 (2005); Song et al, Biological effect of food additive titanium dioxide nanoparticles on intestine: An in vitro study, J Appl Toxicol 35(10) 1169-78 (oct 2015) doi: 10.1002/jat.3171; ncbi.nlm.nih.gov/pubmed/26106068
- Leite-Silva et al, Human skin penetration and local effects of topical nano zinc oxide after occlusion and barrier impairment, Eur J Pharm Biopharm 104 140-7 (Jul 2016) doi: 10.1016/j.ejpb.2016.04.022; ncbi.nlm.nih.gov/pubmed/27131753; Leite-Silva et al, The effect of formulation on the penetration of coated and uncoated zinc oxide nanoparticles into the viable epidermis of human skin in vivo, Eur J Pharm Biopharm 84(2) 297-308 (Jun 2013) doi: 10.1016/j.ejpb.2013.01.020; ncbi.nlm.nih.gov/pubmed/23454052
- Holmes et al, Relative penetration of zinc oxide and zinc ions into human skin after application of different zinc oxide formulations, ACS Nano (Jan 21, 2016); ncbi.nlm.nih.gov/pubmed/26741484
- Yamani et al, In vitro genotoxicity testing of four reference metal nanomaterials, titanium dioxide, zinc oxide, cerium oxide and silver: Toward reliable hazard assessment, Mutagenesis (Nov 12, 2016) pii: gew060; ncbi.nlm.nih.gov/pubmed/27838631; Ursini et al, Evaluation of cytotoxic, genotoxic and inflammatory response in human alveolar and bronchial epithelial cells exposed to titanium dioxide nanoparticles, J Appl Toxicol 34(11) 1209-19 (Nov 2014) doi: 10.1002/jat.3038; ncbi.nlm.nih.gov/pubmed/25224607
- Czaika et al, Toxicity of titanium dioxide nanoparticles in central nervous system, Toxicol In Vitro 29(5) 1042-52 (Aug 2015) doi: 10.1016/j.tiv.2015.04.004; ncbi.nlm.nih.gov/pubmed/25900359; Rollerova et al, Titanium dioxide nanoparticles: Some aspects of toxicity/focus on the development, Endocr Regul 49(2) 97-112 (Apr 2015); ncbi.nlm.nih.gov/pubmed/25960011
- Leite-Silva et al, The effect of formulation on the penetration of coated and uncoated zinc oxide nanoparticles into the viable epidermis of human skin in vivo, Eur J Pharm Biopharm 84(2) 297-308 (Jun 2013) doi: 10.1016/j.ejpb.2013.01.020; ncbi.nlm.nih.gov/pubmed/23454052
- Nohynek et al, Nano-sized cosmetic formulations or solid nanoparticles in sunscreens: A risk to human health? Arch Toxicol 86(7) 1063-75 (Jul 2012) doi: 10.1007/s00204-012-0831-5; Choi et al, Skin corrosion and irritation test of sunscreen nanoparticles using reconstructed 3D human skin model, Environ Health Toxicol 29 e2014004 (Jul 21, 2014) doi: 10.5620/eht.2014.29.e2014004; Kubac et al, Characteristics of titanium dioxide microdispersions with different photo-activity suitable for sunscreen formulations, Int J Pharm 481(1-2) 91-6 (Mar 15, 2015) doi: 10.1016/j.ijpharm.2015.02.004
- Gulson et al, Small amounts of zinc from zinc oxide particles in sunscreens applied outdoors are absorbed through human skin, Toxicol Sci 118(1) 140-9 (Nov 2010) doi: 10.1093/toxsci/kfq243; ncbi.nlm.nih.gov/pubmed/20705894; Osmond-McLeod et al, Dermal absorption and short-term biological impact in hairless mice from sunscreens containing zinc oxide nano- or larger particles, Nanotoxicology 8 suppl 1 72-84 (Aug 2014) doi: 10.3109/17435390.2013.855832; ncbi.nlm.nih.gov/pubmed/24266363
- Gulson et al, A review of critical factors for assessing the dermal absorption of metal oxide nanoparticles from sunscreens applied to humans, and a research strategy to address current deficiencies, Arch Toxicol 89(11) 1909-30 (Nov 2015) doi: 10.1007/s00204-015-1564-z; ncbi.nlm.nih.gov/pubmed/26140917
- Ghiasvand et al, Sunscreen use and subsequent melanoma risk: A population-based cohort study, J Clin Oncol (Sep 12, 2016) pii: JCO675934; ncbi.nlm.nih.gov/pubmed/27621396
- Sendra et al, Effects of TiO2 nanoparticles and sunscreens on coastal marine microalgae: Ultraviolet radiation is key variable for toxicity assessment, Environ Int 98 62-68 (Jan 2017) doi: 10.1016/j.envint.2016.09.024; ncbi.nlm.nih.gov/pubmed/27712934; Tovar-Sanchez et al, Sunscreen products as emerging pollutants to coastal waters, PLoS One 8(6) e65451 (Jun 5, 2013) doi: 10.1371/journal.pone.0065451; ncbi.nlm.nih.gov/pubmed/23755233
- Lin et al, Toxicity of TiO2 nanoparticles to Escherichia coli: Effects of particle size, crystal phase and water chemistry, PLoS One 9(10) e110247 (Oct 13, 2014) doi: 10.1371/journal.pone.0110247; ncbi.nlm.nih.gov/pubmed/25310452
- Erdem et al, The short-term toxic effects of TiO2 nanoparticles toward bacteria through viability, cellular respiration, and lipid peroxidation, Environ Sci Pollut Res Int 22(22) 17917-24 (Nov 2015) doi: 10.1007/s11356-015-5018-1; ncbi.nlm.nih.gov/pubmed/26165996
- Kim et al, Occurrences, toxicities and ecological risks of benzophenone-3, a common component of organic sunscreen products: A mini-review, Environ Int 70 143-57 (Sep 2014) doi: 10.1016/j.envint.2014.05.015; ncbi.nlm.nih.gov/pubmed/24934855
- Cerillo et al, Toward the standardization of nanoecotoxicity testing: Natural organic matter 'camouflages' the adverse effects of TiO2 and CeO2 nanoparticles on green microalgae, Sci Total Environ 543(Pt A) 95-104 (Feb 1, 2016) doi: 10.1016/j.scitotenv.2015.10.137 (Nov 12, 2015); ncbi.nlm.nih.gov/pubmed/26580731
- Li et al, Sorption and degradation of selected organic UV filters (BM-DBM, 4-MBC, and OD-PABA) in laboratory water-sediment systems, Environ Sci Pollut Res Int (Feb 5, 2016); ncbi.nlm.nih.gov/pubmed/26846244
- Ramos et al, Advances in analytical methods and occurrence of organic UV-filters in the environment—A review, Sci Total Environ 526 278-311 (Sep 1, 2015) doi: 10.1016/j.scitotenv.2015.04.055
- Gago-Ferreo et al, An overview of UV-absorbing compounds (organic UV filters) in aquatic biota, Anal Bioanal Chem 404(9) 2597-610 (Nov 2012) doi: 10.1007/s00216-012-6067-7
- Ekpeghere et al, Distribution and seasonal occurrence of UV filters in rivers and wastewater treatment plants in Korea, Sci Total Environ, 542(Pt A) 121-8 (Jan 15, 2016) doi: 10.1016/j.scitotenv.2015.10.033
- Tsui et al, Seasonal occurrence, removal efficiencies and preliminary risk assessment of multiple classes of organic UV filters in wastewater treatment plants, Water Res 53 58-67 (Apr 15, 2014) doi: 10.1016/j.watres.2014.01.014
- Stiefel at al, Photoprotection in changing times—UV filter efficacy and safety, sensitization processes and regulatory aspect, Int J Cosmet Sci 37(1) 2-30 (Feb 2015) doi: 10.1111/ics.12165
- Bens, Sunscreens, Adv Exp Med Biol 810 429-63 (2014)
- Holick, Sunlight, ultraviolet radiation, vitamin D and skin cancer: How much sunlight do we need? Adv Exp Med Biol 810 1-16 (2014); ncbi.nlm.nih.gov/pubmed/25207357; Kannan et al, Photoprotection and vitamin D: A review, Photodermatol Photoimmunol Photomed 30(2-3) 137-45 (Apr-Jun 2014) doi: 10.1111/phpp.12096; ncbi.nlm.nih.gov/pubmed/24313629
- van der Pols et al, Prolonged prevention of squamous cell carcinoma of the skin by regular sunscreen use, Cancer Epidemiol Biomarkers Prev. 2006 Dec;15(12):2546-8; Green edt al., Reduced melanoma after regular sunscreen use: randomized trial follow-up, J Clin Oncol. 2011 Jan 20;29(3):257-63.
- de Groot et al, Contact and photocontact allergy to octocrylene: A review, Contact Dermatitis 70(4) 193-204 (Apr 21014) doi: 10.1111/cod.12205; Avenel-Audran et al, Octocrylene, an emerging photoallergen, Arch Dermatol 146(7) 753-7 (Jul 2010) doi: 10.1001/archdermatol.2010.132
- Hayashi et al, Formation of estrogenic products from benzophenone upon exposure to sunlight, Toxicol Lett 167 1 (2006)