User login
Skin cancer is the most common form of cancer in the United States and continues to rise in incidence and mortality each year.1 It is common knowledge that UV light plays a major role in the development of skin cancer.2,3 Studies have long demonstrated that using sunscreen on a daily basis can help prevent the development of skin cancer, premature aging, and exacerbation of photodermatoses.4-7 Although there are several photoprotective measures available, sunscreen remains the most popular and widely used among patients.8 Sunscreens that are on the market today contain either organic or inorganic UV filters or a combination of both based on their chemical composition and photoprotection mechanisms.9 Concerns about these ingredients causing cancer have created confusion among consumers. I will attempt to clarify these concerns by critically analyzing available evidence-based data on sunscreen use so that as dermatology residents we will be more knowledgeable about sunscreen safety topics and will be able to provide accurate and up-to-date information to our patients.
Organic UV Filters
Organic UV filters are classified as aromatic compounds that provide photoprotection by absorbing UV light.10 Aside from the photoallergic potential of organic UV filters, controversy has arisen in response to studies reporting their possible hormone disruptive effects.11-18 Although there are several US Food and Drug Administration (FDA)–approved organic UV filters in use today, one of the most commonly manufactured and controversial agents is oxybenzone.10 Claims regarding the estrogenic and antiandrogenic effects of oxybenzone have been investigated with results refuting the claims or concluding that more sensitive studies are needed to determine if these organic ingredients pose such risks.10,19,20 One study demonstrated that nearly 300 years of daily sunscreen application would be needed to reach similar exposure levels of oxybenzone used and described in prior animal studies.21 Additionally, most of the studied adverse effects of UV filters have been evaluated based on oral exposure rather than actual dermal application.11 Although these compounds are absorbed systemically, studies have reported that the amounts are insignificant and noncumulative in the body.10,22-24 Furthermore, the binding affinity of oxybenzone for estrogen receptors has been shown to be much weaker and near insignificant compared to estrogen and estradiol.24,25 Although numerous important studies examining systemic absorption have not shown a clinically significant disruption of hormonal homeostasis or acute toxicity in humans by organic UV filters, further studies are needed.
Inorganic UV Filters
Used as the main active ingredients in sunscreen for decades, titanium dioxide (TiO2) and zinc oxide (ZnO) compounds generally are more photostable and less photoallergic than their organic counterparts.10 In recent years, the safety of these long-used photoprotectors has been questioned because of the development of nanoparticle (<100 nm) formulas that are less opaque on application. Although this formula provides a thin, transparent, and cosmetically appealing medium, there is concern that the metal oxides penetrate the skin and cause local and systemic toxicities.26-28 Several recent scientific studies have shown no percutaneous permeation of these particles in normal adult human skin and reported no causal damage to mammalian cells.10,29-31 Although skin penetration of TiO2 and ZnO has been described as insignificant, focus has shifted to health risks associated with inhaling TiO2 through the use of spray or powder products following statements made by the International Agency for Research on Cancer in 2006.32 Several studies investigating increased health risks, specifically lung cancer, in factory workers who were subjected to TiO2 and ZnO inhalation concluded that exposure was unlikely to pose substantial health risks or subchronic toxicity.33,34 Despite a relatively strong safety profile, a major concern of using these metal oxides as UV filters has been potential free radical formation.35-39 For this reason, the Scientific Committee on Emerging and Newly Identified Health Risks extensively researched and delivered opinions on the use of TiO2 and ZnO in cosmetics, concluding that topical application of either compound does not result in toxicity or other adverse effects.30,40-42 Additionally, an effort has been made by manufacturers to encapsulate nanoparticles with magnesium and other materials to quench the reactive oxygen species along with the human body’s own antioxidant defense system.10 In summary, it appears that the current weight of scientific evidence suggests that percutaneous absorption and toxicity by UV filters in humans may be overestimated and that the use of nanoparticles in sunscreens poses no or negligible potential risks to human health.43,44
Concerns Beyond Organic and Inorganic UV Filters
Beyond these concerns with organic and inorganic UV filters, there are several other claims regarding sunscreen safety that have stirred up controversy, including the side-effect profile of retinyl palmitate, vitamin D deficiency, phototoxicity, environmental effects, futility of sun protection factor levels greater than 50, and increased health risks in children. Although some studies report mixed results, the majority of scientific investigations have addressed and refuted several of these claims, again confirming the relative safety of sunscreen use. It is beyond the scope of this article to further discuss these topics specifically. However, it is worth mentioning that consumer studies report that the actual use of sunscreens is 0.5 mg/cm2 or less compared to the ideal application of 2 mg/cm2, thereby confounding many of the claims made about sunscreen use, such as vitamin D deficiency.45 Sunscreens often contain a combination of several UV filters. To date, only a few existing studies have shown that mixtures of the photoprotective agents discussed might interact and exhibit toxic activity when combined, even when there is no observed adverse toxic effect when used individually in products.46-48
The current FDA ruling on sunscreen labeling does not require manufacturers to state if inorganic UV filters have been formulated into nanoparticles; however, manufacturers are now required to include a statement on all sunscreen labels warning consumers to avoid using sunscreen on damaged or broken skin49 in an effort to prevent the active ingredients from getting under the skin, potentially causing inflammation and/or health risks, because available data do not provide conclusive evidence on increased penetration of open skin.50 Additional information regarding the 2011 FDA sunscreen ruling can be found in a prior Cutis Resident Corner column.51
Final Thoughts
As health care providers, we should take advantage of opportunities to educate our patients about other sun safety practices, such as avoiding excessive sun exposure during peak hours (10 am to 2 pm), seeking shade, and wearing photoprotective clothing (eg, wide-brimmed hats, sunglasses).
The research is quite clear: Using broadband sunscreens that absorb and/or block UV radiation results in reduced damage to the skin’s DNA, a fact that should be considered when taking into account the risks and benefits of sunscreen use.2,3 Although sunscreen use is highly recommended in addition to the other sun protection methods, it is ultimately the patient’s choice. If a patient is still concerned about the active ingredients of UV filters, even given the high probability of safety, there are products available on the market that do not include organic filters or nanoparticles. Given the established benefits of UV protection, the use of sunscreens remain one of the most important photoprotective methods, and with increased usage by the public, continuous monitoring of the overall safety and benefit profile of future products is prudent.
1. Skin cancer statistics. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/cancer/skin/statistics/index.htm. Updated September 2, 2014. Accessed December 30, 2014.
2. World Health Organization, International Agency for Research on Cancer. Solar and ultraviolet radiation. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 55. Lyon, France: International Agency for Research on Cancer; 1992.
3. Green AC, Williams GM, Logan V, et al. Reduced melanoma after regular sunscreen use: randomized trial follow-up. J Clin Oncol. 2011;29:257-263.
4. Darlington S, Williams G, Neale R, et al. A randomized controlled trial to assess sunscreen application and beta carotene supplementation in the prevention of solar keratoses. Arch Dermatol. 2003;139:451-455.
5. Van der Pols JC, Williams GM, Pandeya N, et al. Prolonged prevention of squamous cell carcinoma of the skin by regular sunscreen use. Cancer Epidemiol Biomarkers Prev. 2006;15:2546-2548.
6. Hughes MC, Williams GM, Baker P, et al. Sunscreen and prevention of skin aging: a randomized trial. Ann Intern Med. 2013;158:781-790.
7. Bissonnette R, Nigen S, Bolduc C. Influence of the quantity of sunscreen applied on the ability to protect against ultraviolet-induced polymorphous light eruption. Photodermatol Photoimmunol Photomed. 2012;28:240-243.
8. Cancer trends progress report 2011/2012 update: sun protection. National Cancer Institute Web site. http://progressreport.cancer.gov/doc_detail.asp?pid¡1&did¡2009&chid¡91&coid¡911. Accessed December 30, 2014.
9. Sunscreen Drug Products for Over-the-counter Human Use, 21 CFR §352.10. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=352.10. Updated September 1, 2014. Accessed December 30, 2014.
10. Burnett ME, Wang SQ. Current sunscreen controversies: a critical review. Photodermatol Photoimmunol Photomed. 2011;27:58-67.
11. Krause M, Klit A, Blomberg Jensen M, et al. Sunscreens: are they beneficial for health? an overview of endocrine disrupting properties of UV-filters. Int J Androl. 2012;35:424-436.
12. Schlumpf M, Cotton B, Conscience M, et al. In vitro and in vivo estrogenicity of UV screens. Environ Health Perspect. 2001;109:239-244.
13. Schlumpf M, Schmid P, Durrer S, et al. Endocrine activity and developmental toxicity of cosmetic UV filters–an update. Toxicol. 2004;205:113-122.
14. Schlumpf M, Kypke K, Vökt C, et al. Endocrine active UV filters: developmental toxicity and exposure through breast milk. Chimia. 2008;62:345-351.
15. Nakagawa Y, Suzuki T. 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. 2002;139:115-128.
16. Ma R, Cotton B, Lichtensteiger W, et al. UV filters with antagonistic action at androgen receptors in the MDA-kb2 cell transcriptional-activation assay. Toxicol Sci. 2003;74:43-50.
17. Heneweer M, Muusse M, van den Berg M, et al. Additive estrogenic effects of mixtures of frequently used UV filters on pS2-gene transcription in MCF-7 cells. Toxicol Appl Pharmacol. 2005;208:170-177.
18. Knobler E, Almeida L, Ruzkowski AM, et al. Photoallergy to benzophenone. Arch Dermatol. 1989;125:801-804.
19. Draelos ZD. Are sunscreens safe? J Cosmet Dermatol. 2010;9:1-2.
20. Gilbert E, Pirot F, Bertholle V. Commonly used UV filter toxicity on biological functions: review of last decade studies. Int J of Cosmet Sci. 2013;35:208-219.
21. Wang SQ, Burnett ME, Lim HW. Safety of oxybenzone: putting numbers into perspective. Arch Dermatol. 2011;147:865-866.
22. Mancebo SE, Hu JY, Wang SQ. Sunscreens: a review of health benefits, regulations, and controversies. Dermatol Clin. 2014;32:427-438.
23. Jansen R, Osterwalder U, Wang SQ, et al. Photoprotection: part II. sunscreen: development, efficacy, and controversies. J Am Acad Dermatol. 2013;69:867.e1-867.e14.
24. Janjua NR, Mogensen B, Andersson AM, et al. Systemic absorption of the sunscreens benzo- phenone-3, octyl-methoxycinnamate, and 3-(4-methyl-benzy-lidene) camphor after whole-body topical application and reproductive hormone levels in humans. J Invest Dermatol. 2004;123:57-61.
25. Kadry AM, Chukwuemeka SO, Mohamed S, et al. Pharmacokinetics of benzophenone-3 after oral exposure in male rats. J Appl Toxicol. 1995;15:97-102.
26. Gulson B, McCall M, Korsch M, et al. Small amounts of zinc from zinc oxide particles in sunscreens applied outdoors are absorbed through human skin. Toxicol Sci. 2010;118:140-149.
27. Gulson B, Wong H, Korsch M, et al. Comparison of dermal absorption of zinc from different sunscreen formulations and differing UV exposure based on stable isotope tracing. Sci Total Environ. 2012:420:313-318.
28. Benech-Kieffer F, Meuling WJ, Leclerc C, et al. Percutaneous absorption of Mexoryl SX in human volunteers: comparison with in vitro data. Skin Pharmacol Appl Skin Physiol. 2003;16:343-355.
29. Nash JF. Human safety and efficacy of ultraviolet filters and sunscreen products. Dermatol Clin. 2006;24:35-51.
30. Nohynek GJ, Lademann J, Ribaud C, et al. Grey goo on the skin? nanotechnology, cosmetic and sunscreen safety. Crit Rev Toxicol. 2007;37:251-277.
31. Sadrieh N, Wokovich AM, Gopee NV, et al. Lack of significant dermal penetration of titanium dioxide from sunscreen formulations containing nano- and submicron-size TiO2 particles. Toxicol Sci. 2010;115:156-166.
32. International Agency for Research on Cancer. Carbon black, titanium dioxide, and talc. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 93. Lyon, France: International Agency for Research on Cancer; 2006.
33. Liao CM, Chiang YH, Chio CP. Model-based assessment for human inhalation exposure risk to airborne nano/fine titanium dioxide particles. Sci Total Environ. 2008:15;407:165-177.
34. Adamcakova-Dodd A, Stebounova LV, Kim JS, et al. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models. Part Fibre Toxicol. 2014;11:15.
35. Wamer WG, Yin JJ, Wei RR. Oxidative damage to nucleic acids photosensitized by titanium dioxide. Free Radic Biol Med. 1997;23:851-858.
36. Nakagawa Y, Wakuri S, Sakamoto K, et al. The photogenotoxicity of titanium dioxide particles. Mutat Res. 1997;394:125-132.
37. Dunford R, Salinaro A, Cai L, et al. Chemical oxidation and DNA damage catalysed by inorganic sunscreen ingredients. FEBS Lett. 1997;418:87-90, 99.
38. Hidaka H, Kobayashi H, Koike T, et al. DNA damage photoinduced by cosmetic pigments and sunscreen agents under solar exposure and artificial UV illumination. J Oleo Sci. 2006;55:249-261.
39. Dufour EK, Kumaravel T, Nohynek GJ, et al. Clastogenicity, photo-clastogenicity or pseudo-photo-clastogenicity: genotoxic effects of zinc oxide in the dark, in pre-irradiated or simultaneously irradiated Chinese hamster ovary cells [published online ahead of print June 21, 2006]. Mutat Res. 2006;607:215-224.
40. Opinion of the Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers concerning titanium dioxide. http://ec.europa.eu/health/archive/ph_risk/committees/sccp/documents/out135_en.pdf. Published October 24, 2000. Accessed December 30, 2014.
41. The Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers opinion concerning zinc oxide. http://ec.europa.eu/health/archive/ph_risk/committees/sccp/documents/out222_en.pdf. Published June 24-25, 2003. Accessed December 30, 2014.
42. Hackenberg S, Friehs G, Kessler M, et al. Nanosized titanium dioxide particles do not induce DNA damage in human peripheral blood lymphocytes. Environ Mol Mutagen. 2010;52:264-268.
43. Bach-Thomsen M, Wulf HC. Sunbather’s application of sunscreen is probably inadequate to obtain the sun protection factor assigned to the preparation. Photodermatol Photoimmunol Photomed. 1993:9;242-244.
44. Nohynek GJ, Antignac E, Re T, et al. Safety assessment of personal care products/cosmetics and their ingredients. Toxicol Appl Pharmacol. 2010:1;243:239-259.
45. Diffey BL. Sunscreens: use and misuse. In: Giacomoni PU, ed. Sun Protection in Man. Vol 3. Amsterdam, the Netherlands: Elsevier Science BV; 2001:521-534.
46. Heneweer M, Muusse M, Van den BM, et al. Additive estrogenic effects of mixtures of frequently used UV-filters on pS2-gene transcription in MCF-7 cells. Toxicol Appl Pharmacol. 2005;208:170-177.
47. Kunz PY, Galicia HF, Fent K. Comparison of in vitro and in vivo estrogenic activity of UV-filters in fish. Toxicol Sci. 2006;90:349-361.
48. Kortenkamp A, Faust M, Scholze M, et al. Low-level exposure to multiple chemicals: reason for human health concerns? Environ Health Perspect. 2007;115(suppl 1):106-114.
49. Labeling and effectiveness testing: sunscreen drug products for over-the-counter human use—small entity compliance guide. US Food and Drug Administration Web site. http://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/guidances/ucm330694.htm. Published December 2012. Updated May 13, 2014. Accessed December 30, 2014.
50. Schafer-Korting M, Korting HC, Ponce-Poschl E. Liposomal tretinoin for uncomplicated acne vulgaris. Clin Investig. 1994;72:1086-1091.
51. Bronfenbrener R. Simplifying sun safety: a guide to the new FDA sunscreen monograph. Cutis. 2014;93:e17-e19.
Skin cancer is the most common form of cancer in the United States and continues to rise in incidence and mortality each year.1 It is common knowledge that UV light plays a major role in the development of skin cancer.2,3 Studies have long demonstrated that using sunscreen on a daily basis can help prevent the development of skin cancer, premature aging, and exacerbation of photodermatoses.4-7 Although there are several photoprotective measures available, sunscreen remains the most popular and widely used among patients.8 Sunscreens that are on the market today contain either organic or inorganic UV filters or a combination of both based on their chemical composition and photoprotection mechanisms.9 Concerns about these ingredients causing cancer have created confusion among consumers. I will attempt to clarify these concerns by critically analyzing available evidence-based data on sunscreen use so that as dermatology residents we will be more knowledgeable about sunscreen safety topics and will be able to provide accurate and up-to-date information to our patients.
Organic UV Filters
Organic UV filters are classified as aromatic compounds that provide photoprotection by absorbing UV light.10 Aside from the photoallergic potential of organic UV filters, controversy has arisen in response to studies reporting their possible hormone disruptive effects.11-18 Although there are several US Food and Drug Administration (FDA)–approved organic UV filters in use today, one of the most commonly manufactured and controversial agents is oxybenzone.10 Claims regarding the estrogenic and antiandrogenic effects of oxybenzone have been investigated with results refuting the claims or concluding that more sensitive studies are needed to determine if these organic ingredients pose such risks.10,19,20 One study demonstrated that nearly 300 years of daily sunscreen application would be needed to reach similar exposure levels of oxybenzone used and described in prior animal studies.21 Additionally, most of the studied adverse effects of UV filters have been evaluated based on oral exposure rather than actual dermal application.11 Although these compounds are absorbed systemically, studies have reported that the amounts are insignificant and noncumulative in the body.10,22-24 Furthermore, the binding affinity of oxybenzone for estrogen receptors has been shown to be much weaker and near insignificant compared to estrogen and estradiol.24,25 Although numerous important studies examining systemic absorption have not shown a clinically significant disruption of hormonal homeostasis or acute toxicity in humans by organic UV filters, further studies are needed.
Inorganic UV Filters
Used as the main active ingredients in sunscreen for decades, titanium dioxide (TiO2) and zinc oxide (ZnO) compounds generally are more photostable and less photoallergic than their organic counterparts.10 In recent years, the safety of these long-used photoprotectors has been questioned because of the development of nanoparticle (<100 nm) formulas that are less opaque on application. Although this formula provides a thin, transparent, and cosmetically appealing medium, there is concern that the metal oxides penetrate the skin and cause local and systemic toxicities.26-28 Several recent scientific studies have shown no percutaneous permeation of these particles in normal adult human skin and reported no causal damage to mammalian cells.10,29-31 Although skin penetration of TiO2 and ZnO has been described as insignificant, focus has shifted to health risks associated with inhaling TiO2 through the use of spray or powder products following statements made by the International Agency for Research on Cancer in 2006.32 Several studies investigating increased health risks, specifically lung cancer, in factory workers who were subjected to TiO2 and ZnO inhalation concluded that exposure was unlikely to pose substantial health risks or subchronic toxicity.33,34 Despite a relatively strong safety profile, a major concern of using these metal oxides as UV filters has been potential free radical formation.35-39 For this reason, the Scientific Committee on Emerging and Newly Identified Health Risks extensively researched and delivered opinions on the use of TiO2 and ZnO in cosmetics, concluding that topical application of either compound does not result in toxicity or other adverse effects.30,40-42 Additionally, an effort has been made by manufacturers to encapsulate nanoparticles with magnesium and other materials to quench the reactive oxygen species along with the human body’s own antioxidant defense system.10 In summary, it appears that the current weight of scientific evidence suggests that percutaneous absorption and toxicity by UV filters in humans may be overestimated and that the use of nanoparticles in sunscreens poses no or negligible potential risks to human health.43,44
Concerns Beyond Organic and Inorganic UV Filters
Beyond these concerns with organic and inorganic UV filters, there are several other claims regarding sunscreen safety that have stirred up controversy, including the side-effect profile of retinyl palmitate, vitamin D deficiency, phototoxicity, environmental effects, futility of sun protection factor levels greater than 50, and increased health risks in children. Although some studies report mixed results, the majority of scientific investigations have addressed and refuted several of these claims, again confirming the relative safety of sunscreen use. It is beyond the scope of this article to further discuss these topics specifically. However, it is worth mentioning that consumer studies report that the actual use of sunscreens is 0.5 mg/cm2 or less compared to the ideal application of 2 mg/cm2, thereby confounding many of the claims made about sunscreen use, such as vitamin D deficiency.45 Sunscreens often contain a combination of several UV filters. To date, only a few existing studies have shown that mixtures of the photoprotective agents discussed might interact and exhibit toxic activity when combined, even when there is no observed adverse toxic effect when used individually in products.46-48
The current FDA ruling on sunscreen labeling does not require manufacturers to state if inorganic UV filters have been formulated into nanoparticles; however, manufacturers are now required to include a statement on all sunscreen labels warning consumers to avoid using sunscreen on damaged or broken skin49 in an effort to prevent the active ingredients from getting under the skin, potentially causing inflammation and/or health risks, because available data do not provide conclusive evidence on increased penetration of open skin.50 Additional information regarding the 2011 FDA sunscreen ruling can be found in a prior Cutis Resident Corner column.51
Final Thoughts
As health care providers, we should take advantage of opportunities to educate our patients about other sun safety practices, such as avoiding excessive sun exposure during peak hours (10 am to 2 pm), seeking shade, and wearing photoprotective clothing (eg, wide-brimmed hats, sunglasses).
The research is quite clear: Using broadband sunscreens that absorb and/or block UV radiation results in reduced damage to the skin’s DNA, a fact that should be considered when taking into account the risks and benefits of sunscreen use.2,3 Although sunscreen use is highly recommended in addition to the other sun protection methods, it is ultimately the patient’s choice. If a patient is still concerned about the active ingredients of UV filters, even given the high probability of safety, there are products available on the market that do not include organic filters or nanoparticles. Given the established benefits of UV protection, the use of sunscreens remain one of the most important photoprotective methods, and with increased usage by the public, continuous monitoring of the overall safety and benefit profile of future products is prudent.
Skin cancer is the most common form of cancer in the United States and continues to rise in incidence and mortality each year.1 It is common knowledge that UV light plays a major role in the development of skin cancer.2,3 Studies have long demonstrated that using sunscreen on a daily basis can help prevent the development of skin cancer, premature aging, and exacerbation of photodermatoses.4-7 Although there are several photoprotective measures available, sunscreen remains the most popular and widely used among patients.8 Sunscreens that are on the market today contain either organic or inorganic UV filters or a combination of both based on their chemical composition and photoprotection mechanisms.9 Concerns about these ingredients causing cancer have created confusion among consumers. I will attempt to clarify these concerns by critically analyzing available evidence-based data on sunscreen use so that as dermatology residents we will be more knowledgeable about sunscreen safety topics and will be able to provide accurate and up-to-date information to our patients.
Organic UV Filters
Organic UV filters are classified as aromatic compounds that provide photoprotection by absorbing UV light.10 Aside from the photoallergic potential of organic UV filters, controversy has arisen in response to studies reporting their possible hormone disruptive effects.11-18 Although there are several US Food and Drug Administration (FDA)–approved organic UV filters in use today, one of the most commonly manufactured and controversial agents is oxybenzone.10 Claims regarding the estrogenic and antiandrogenic effects of oxybenzone have been investigated with results refuting the claims or concluding that more sensitive studies are needed to determine if these organic ingredients pose such risks.10,19,20 One study demonstrated that nearly 300 years of daily sunscreen application would be needed to reach similar exposure levels of oxybenzone used and described in prior animal studies.21 Additionally, most of the studied adverse effects of UV filters have been evaluated based on oral exposure rather than actual dermal application.11 Although these compounds are absorbed systemically, studies have reported that the amounts are insignificant and noncumulative in the body.10,22-24 Furthermore, the binding affinity of oxybenzone for estrogen receptors has been shown to be much weaker and near insignificant compared to estrogen and estradiol.24,25 Although numerous important studies examining systemic absorption have not shown a clinically significant disruption of hormonal homeostasis or acute toxicity in humans by organic UV filters, further studies are needed.
Inorganic UV Filters
Used as the main active ingredients in sunscreen for decades, titanium dioxide (TiO2) and zinc oxide (ZnO) compounds generally are more photostable and less photoallergic than their organic counterparts.10 In recent years, the safety of these long-used photoprotectors has been questioned because of the development of nanoparticle (<100 nm) formulas that are less opaque on application. Although this formula provides a thin, transparent, and cosmetically appealing medium, there is concern that the metal oxides penetrate the skin and cause local and systemic toxicities.26-28 Several recent scientific studies have shown no percutaneous permeation of these particles in normal adult human skin and reported no causal damage to mammalian cells.10,29-31 Although skin penetration of TiO2 and ZnO has been described as insignificant, focus has shifted to health risks associated with inhaling TiO2 through the use of spray or powder products following statements made by the International Agency for Research on Cancer in 2006.32 Several studies investigating increased health risks, specifically lung cancer, in factory workers who were subjected to TiO2 and ZnO inhalation concluded that exposure was unlikely to pose substantial health risks or subchronic toxicity.33,34 Despite a relatively strong safety profile, a major concern of using these metal oxides as UV filters has been potential free radical formation.35-39 For this reason, the Scientific Committee on Emerging and Newly Identified Health Risks extensively researched and delivered opinions on the use of TiO2 and ZnO in cosmetics, concluding that topical application of either compound does not result in toxicity or other adverse effects.30,40-42 Additionally, an effort has been made by manufacturers to encapsulate nanoparticles with magnesium and other materials to quench the reactive oxygen species along with the human body’s own antioxidant defense system.10 In summary, it appears that the current weight of scientific evidence suggests that percutaneous absorption and toxicity by UV filters in humans may be overestimated and that the use of nanoparticles in sunscreens poses no or negligible potential risks to human health.43,44
Concerns Beyond Organic and Inorganic UV Filters
Beyond these concerns with organic and inorganic UV filters, there are several other claims regarding sunscreen safety that have stirred up controversy, including the side-effect profile of retinyl palmitate, vitamin D deficiency, phototoxicity, environmental effects, futility of sun protection factor levels greater than 50, and increased health risks in children. Although some studies report mixed results, the majority of scientific investigations have addressed and refuted several of these claims, again confirming the relative safety of sunscreen use. It is beyond the scope of this article to further discuss these topics specifically. However, it is worth mentioning that consumer studies report that the actual use of sunscreens is 0.5 mg/cm2 or less compared to the ideal application of 2 mg/cm2, thereby confounding many of the claims made about sunscreen use, such as vitamin D deficiency.45 Sunscreens often contain a combination of several UV filters. To date, only a few existing studies have shown that mixtures of the photoprotective agents discussed might interact and exhibit toxic activity when combined, even when there is no observed adverse toxic effect when used individually in products.46-48
The current FDA ruling on sunscreen labeling does not require manufacturers to state if inorganic UV filters have been formulated into nanoparticles; however, manufacturers are now required to include a statement on all sunscreen labels warning consumers to avoid using sunscreen on damaged or broken skin49 in an effort to prevent the active ingredients from getting under the skin, potentially causing inflammation and/or health risks, because available data do not provide conclusive evidence on increased penetration of open skin.50 Additional information regarding the 2011 FDA sunscreen ruling can be found in a prior Cutis Resident Corner column.51
Final Thoughts
As health care providers, we should take advantage of opportunities to educate our patients about other sun safety practices, such as avoiding excessive sun exposure during peak hours (10 am to 2 pm), seeking shade, and wearing photoprotective clothing (eg, wide-brimmed hats, sunglasses).
The research is quite clear: Using broadband sunscreens that absorb and/or block UV radiation results in reduced damage to the skin’s DNA, a fact that should be considered when taking into account the risks and benefits of sunscreen use.2,3 Although sunscreen use is highly recommended in addition to the other sun protection methods, it is ultimately the patient’s choice. If a patient is still concerned about the active ingredients of UV filters, even given the high probability of safety, there are products available on the market that do not include organic filters or nanoparticles. Given the established benefits of UV protection, the use of sunscreens remain one of the most important photoprotective methods, and with increased usage by the public, continuous monitoring of the overall safety and benefit profile of future products is prudent.
1. Skin cancer statistics. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/cancer/skin/statistics/index.htm. Updated September 2, 2014. Accessed December 30, 2014.
2. World Health Organization, International Agency for Research on Cancer. Solar and ultraviolet radiation. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 55. Lyon, France: International Agency for Research on Cancer; 1992.
3. Green AC, Williams GM, Logan V, et al. Reduced melanoma after regular sunscreen use: randomized trial follow-up. J Clin Oncol. 2011;29:257-263.
4. Darlington S, Williams G, Neale R, et al. A randomized controlled trial to assess sunscreen application and beta carotene supplementation in the prevention of solar keratoses. Arch Dermatol. 2003;139:451-455.
5. Van der Pols JC, Williams GM, Pandeya N, et al. Prolonged prevention of squamous cell carcinoma of the skin by regular sunscreen use. Cancer Epidemiol Biomarkers Prev. 2006;15:2546-2548.
6. Hughes MC, Williams GM, Baker P, et al. Sunscreen and prevention of skin aging: a randomized trial. Ann Intern Med. 2013;158:781-790.
7. Bissonnette R, Nigen S, Bolduc C. Influence of the quantity of sunscreen applied on the ability to protect against ultraviolet-induced polymorphous light eruption. Photodermatol Photoimmunol Photomed. 2012;28:240-243.
8. Cancer trends progress report 2011/2012 update: sun protection. National Cancer Institute Web site. http://progressreport.cancer.gov/doc_detail.asp?pid¡1&did¡2009&chid¡91&coid¡911. Accessed December 30, 2014.
9. Sunscreen Drug Products for Over-the-counter Human Use, 21 CFR §352.10. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=352.10. Updated September 1, 2014. Accessed December 30, 2014.
10. Burnett ME, Wang SQ. Current sunscreen controversies: a critical review. Photodermatol Photoimmunol Photomed. 2011;27:58-67.
11. Krause M, Klit A, Blomberg Jensen M, et al. Sunscreens: are they beneficial for health? an overview of endocrine disrupting properties of UV-filters. Int J Androl. 2012;35:424-436.
12. Schlumpf M, Cotton B, Conscience M, et al. In vitro and in vivo estrogenicity of UV screens. Environ Health Perspect. 2001;109:239-244.
13. Schlumpf M, Schmid P, Durrer S, et al. Endocrine activity and developmental toxicity of cosmetic UV filters–an update. Toxicol. 2004;205:113-122.
14. Schlumpf M, Kypke K, Vökt C, et al. Endocrine active UV filters: developmental toxicity and exposure through breast milk. Chimia. 2008;62:345-351.
15. Nakagawa Y, Suzuki T. 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. 2002;139:115-128.
16. Ma R, Cotton B, Lichtensteiger W, et al. UV filters with antagonistic action at androgen receptors in the MDA-kb2 cell transcriptional-activation assay. Toxicol Sci. 2003;74:43-50.
17. Heneweer M, Muusse M, van den Berg M, et al. Additive estrogenic effects of mixtures of frequently used UV filters on pS2-gene transcription in MCF-7 cells. Toxicol Appl Pharmacol. 2005;208:170-177.
18. Knobler E, Almeida L, Ruzkowski AM, et al. Photoallergy to benzophenone. Arch Dermatol. 1989;125:801-804.
19. Draelos ZD. Are sunscreens safe? J Cosmet Dermatol. 2010;9:1-2.
20. Gilbert E, Pirot F, Bertholle V. Commonly used UV filter toxicity on biological functions: review of last decade studies. Int J of Cosmet Sci. 2013;35:208-219.
21. Wang SQ, Burnett ME, Lim HW. Safety of oxybenzone: putting numbers into perspective. Arch Dermatol. 2011;147:865-866.
22. Mancebo SE, Hu JY, Wang SQ. Sunscreens: a review of health benefits, regulations, and controversies. Dermatol Clin. 2014;32:427-438.
23. Jansen R, Osterwalder U, Wang SQ, et al. Photoprotection: part II. sunscreen: development, efficacy, and controversies. J Am Acad Dermatol. 2013;69:867.e1-867.e14.
24. Janjua NR, Mogensen B, Andersson AM, et al. Systemic absorption of the sunscreens benzo- phenone-3, octyl-methoxycinnamate, and 3-(4-methyl-benzy-lidene) camphor after whole-body topical application and reproductive hormone levels in humans. J Invest Dermatol. 2004;123:57-61.
25. Kadry AM, Chukwuemeka SO, Mohamed S, et al. Pharmacokinetics of benzophenone-3 after oral exposure in male rats. J Appl Toxicol. 1995;15:97-102.
26. Gulson B, McCall M, Korsch M, et al. Small amounts of zinc from zinc oxide particles in sunscreens applied outdoors are absorbed through human skin. Toxicol Sci. 2010;118:140-149.
27. Gulson B, Wong H, Korsch M, et al. Comparison of dermal absorption of zinc from different sunscreen formulations and differing UV exposure based on stable isotope tracing. Sci Total Environ. 2012:420:313-318.
28. Benech-Kieffer F, Meuling WJ, Leclerc C, et al. Percutaneous absorption of Mexoryl SX in human volunteers: comparison with in vitro data. Skin Pharmacol Appl Skin Physiol. 2003;16:343-355.
29. Nash JF. Human safety and efficacy of ultraviolet filters and sunscreen products. Dermatol Clin. 2006;24:35-51.
30. Nohynek GJ, Lademann J, Ribaud C, et al. Grey goo on the skin? nanotechnology, cosmetic and sunscreen safety. Crit Rev Toxicol. 2007;37:251-277.
31. Sadrieh N, Wokovich AM, Gopee NV, et al. Lack of significant dermal penetration of titanium dioxide from sunscreen formulations containing nano- and submicron-size TiO2 particles. Toxicol Sci. 2010;115:156-166.
32. International Agency for Research on Cancer. Carbon black, titanium dioxide, and talc. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 93. Lyon, France: International Agency for Research on Cancer; 2006.
33. Liao CM, Chiang YH, Chio CP. Model-based assessment for human inhalation exposure risk to airborne nano/fine titanium dioxide particles. Sci Total Environ. 2008:15;407:165-177.
34. Adamcakova-Dodd A, Stebounova LV, Kim JS, et al. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models. Part Fibre Toxicol. 2014;11:15.
35. Wamer WG, Yin JJ, Wei RR. Oxidative damage to nucleic acids photosensitized by titanium dioxide. Free Radic Biol Med. 1997;23:851-858.
36. Nakagawa Y, Wakuri S, Sakamoto K, et al. The photogenotoxicity of titanium dioxide particles. Mutat Res. 1997;394:125-132.
37. Dunford R, Salinaro A, Cai L, et al. Chemical oxidation and DNA damage catalysed by inorganic sunscreen ingredients. FEBS Lett. 1997;418:87-90, 99.
38. Hidaka H, Kobayashi H, Koike T, et al. DNA damage photoinduced by cosmetic pigments and sunscreen agents under solar exposure and artificial UV illumination. J Oleo Sci. 2006;55:249-261.
39. Dufour EK, Kumaravel T, Nohynek GJ, et al. Clastogenicity, photo-clastogenicity or pseudo-photo-clastogenicity: genotoxic effects of zinc oxide in the dark, in pre-irradiated or simultaneously irradiated Chinese hamster ovary cells [published online ahead of print June 21, 2006]. Mutat Res. 2006;607:215-224.
40. Opinion of the Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers concerning titanium dioxide. http://ec.europa.eu/health/archive/ph_risk/committees/sccp/documents/out135_en.pdf. Published October 24, 2000. Accessed December 30, 2014.
41. The Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers opinion concerning zinc oxide. http://ec.europa.eu/health/archive/ph_risk/committees/sccp/documents/out222_en.pdf. Published June 24-25, 2003. Accessed December 30, 2014.
42. Hackenberg S, Friehs G, Kessler M, et al. Nanosized titanium dioxide particles do not induce DNA damage in human peripheral blood lymphocytes. Environ Mol Mutagen. 2010;52:264-268.
43. Bach-Thomsen M, Wulf HC. Sunbather’s application of sunscreen is probably inadequate to obtain the sun protection factor assigned to the preparation. Photodermatol Photoimmunol Photomed. 1993:9;242-244.
44. Nohynek GJ, Antignac E, Re T, et al. Safety assessment of personal care products/cosmetics and their ingredients. Toxicol Appl Pharmacol. 2010:1;243:239-259.
45. Diffey BL. Sunscreens: use and misuse. In: Giacomoni PU, ed. Sun Protection in Man. Vol 3. Amsterdam, the Netherlands: Elsevier Science BV; 2001:521-534.
46. Heneweer M, Muusse M, Van den BM, et al. Additive estrogenic effects of mixtures of frequently used UV-filters on pS2-gene transcription in MCF-7 cells. Toxicol Appl Pharmacol. 2005;208:170-177.
47. Kunz PY, Galicia HF, Fent K. Comparison of in vitro and in vivo estrogenic activity of UV-filters in fish. Toxicol Sci. 2006;90:349-361.
48. Kortenkamp A, Faust M, Scholze M, et al. Low-level exposure to multiple chemicals: reason for human health concerns? Environ Health Perspect. 2007;115(suppl 1):106-114.
49. Labeling and effectiveness testing: sunscreen drug products for over-the-counter human use—small entity compliance guide. US Food and Drug Administration Web site. http://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/guidances/ucm330694.htm. Published December 2012. Updated May 13, 2014. Accessed December 30, 2014.
50. Schafer-Korting M, Korting HC, Ponce-Poschl E. Liposomal tretinoin for uncomplicated acne vulgaris. Clin Investig. 1994;72:1086-1091.
51. Bronfenbrener R. Simplifying sun safety: a guide to the new FDA sunscreen monograph. Cutis. 2014;93:e17-e19.
1. Skin cancer statistics. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/cancer/skin/statistics/index.htm. Updated September 2, 2014. Accessed December 30, 2014.
2. World Health Organization, International Agency for Research on Cancer. Solar and ultraviolet radiation. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 55. Lyon, France: International Agency for Research on Cancer; 1992.
3. Green AC, Williams GM, Logan V, et al. Reduced melanoma after regular sunscreen use: randomized trial follow-up. J Clin Oncol. 2011;29:257-263.
4. Darlington S, Williams G, Neale R, et al. A randomized controlled trial to assess sunscreen application and beta carotene supplementation in the prevention of solar keratoses. Arch Dermatol. 2003;139:451-455.
5. Van der Pols JC, Williams GM, Pandeya N, et al. Prolonged prevention of squamous cell carcinoma of the skin by regular sunscreen use. Cancer Epidemiol Biomarkers Prev. 2006;15:2546-2548.
6. Hughes MC, Williams GM, Baker P, et al. Sunscreen and prevention of skin aging: a randomized trial. Ann Intern Med. 2013;158:781-790.
7. Bissonnette R, Nigen S, Bolduc C. Influence of the quantity of sunscreen applied on the ability to protect against ultraviolet-induced polymorphous light eruption. Photodermatol Photoimmunol Photomed. 2012;28:240-243.
8. Cancer trends progress report 2011/2012 update: sun protection. National Cancer Institute Web site. http://progressreport.cancer.gov/doc_detail.asp?pid¡1&did¡2009&chid¡91&coid¡911. Accessed December 30, 2014.
9. Sunscreen Drug Products for Over-the-counter Human Use, 21 CFR §352.10. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=352.10. Updated September 1, 2014. Accessed December 30, 2014.
10. Burnett ME, Wang SQ. Current sunscreen controversies: a critical review. Photodermatol Photoimmunol Photomed. 2011;27:58-67.
11. Krause M, Klit A, Blomberg Jensen M, et al. Sunscreens: are they beneficial for health? an overview of endocrine disrupting properties of UV-filters. Int J Androl. 2012;35:424-436.
12. Schlumpf M, Cotton B, Conscience M, et al. In vitro and in vivo estrogenicity of UV screens. Environ Health Perspect. 2001;109:239-244.
13. Schlumpf M, Schmid P, Durrer S, et al. Endocrine activity and developmental toxicity of cosmetic UV filters–an update. Toxicol. 2004;205:113-122.
14. Schlumpf M, Kypke K, Vökt C, et al. Endocrine active UV filters: developmental toxicity and exposure through breast milk. Chimia. 2008;62:345-351.
15. Nakagawa Y, Suzuki T. 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. 2002;139:115-128.
16. Ma R, Cotton B, Lichtensteiger W, et al. UV filters with antagonistic action at androgen receptors in the MDA-kb2 cell transcriptional-activation assay. Toxicol Sci. 2003;74:43-50.
17. Heneweer M, Muusse M, van den Berg M, et al. Additive estrogenic effects of mixtures of frequently used UV filters on pS2-gene transcription in MCF-7 cells. Toxicol Appl Pharmacol. 2005;208:170-177.
18. Knobler E, Almeida L, Ruzkowski AM, et al. Photoallergy to benzophenone. Arch Dermatol. 1989;125:801-804.
19. Draelos ZD. Are sunscreens safe? J Cosmet Dermatol. 2010;9:1-2.
20. Gilbert E, Pirot F, Bertholle V. Commonly used UV filter toxicity on biological functions: review of last decade studies. Int J of Cosmet Sci. 2013;35:208-219.
21. Wang SQ, Burnett ME, Lim HW. Safety of oxybenzone: putting numbers into perspective. Arch Dermatol. 2011;147:865-866.
22. Mancebo SE, Hu JY, Wang SQ. Sunscreens: a review of health benefits, regulations, and controversies. Dermatol Clin. 2014;32:427-438.
23. Jansen R, Osterwalder U, Wang SQ, et al. Photoprotection: part II. sunscreen: development, efficacy, and controversies. J Am Acad Dermatol. 2013;69:867.e1-867.e14.
24. Janjua NR, Mogensen B, Andersson AM, et al. Systemic absorption of the sunscreens benzo- phenone-3, octyl-methoxycinnamate, and 3-(4-methyl-benzy-lidene) camphor after whole-body topical application and reproductive hormone levels in humans. J Invest Dermatol. 2004;123:57-61.
25. Kadry AM, Chukwuemeka SO, Mohamed S, et al. Pharmacokinetics of benzophenone-3 after oral exposure in male rats. J Appl Toxicol. 1995;15:97-102.
26. Gulson B, McCall M, Korsch M, et al. Small amounts of zinc from zinc oxide particles in sunscreens applied outdoors are absorbed through human skin. Toxicol Sci. 2010;118:140-149.
27. Gulson B, Wong H, Korsch M, et al. Comparison of dermal absorption of zinc from different sunscreen formulations and differing UV exposure based on stable isotope tracing. Sci Total Environ. 2012:420:313-318.
28. Benech-Kieffer F, Meuling WJ, Leclerc C, et al. Percutaneous absorption of Mexoryl SX in human volunteers: comparison with in vitro data. Skin Pharmacol Appl Skin Physiol. 2003;16:343-355.
29. Nash JF. Human safety and efficacy of ultraviolet filters and sunscreen products. Dermatol Clin. 2006;24:35-51.
30. Nohynek GJ, Lademann J, Ribaud C, et al. Grey goo on the skin? nanotechnology, cosmetic and sunscreen safety. Crit Rev Toxicol. 2007;37:251-277.
31. Sadrieh N, Wokovich AM, Gopee NV, et al. Lack of significant dermal penetration of titanium dioxide from sunscreen formulations containing nano- and submicron-size TiO2 particles. Toxicol Sci. 2010;115:156-166.
32. International Agency for Research on Cancer. Carbon black, titanium dioxide, and talc. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 93. Lyon, France: International Agency for Research on Cancer; 2006.
33. Liao CM, Chiang YH, Chio CP. Model-based assessment for human inhalation exposure risk to airborne nano/fine titanium dioxide particles. Sci Total Environ. 2008:15;407:165-177.
34. Adamcakova-Dodd A, Stebounova LV, Kim JS, et al. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models. Part Fibre Toxicol. 2014;11:15.
35. Wamer WG, Yin JJ, Wei RR. Oxidative damage to nucleic acids photosensitized by titanium dioxide. Free Radic Biol Med. 1997;23:851-858.
36. Nakagawa Y, Wakuri S, Sakamoto K, et al. The photogenotoxicity of titanium dioxide particles. Mutat Res. 1997;394:125-132.
37. Dunford R, Salinaro A, Cai L, et al. Chemical oxidation and DNA damage catalysed by inorganic sunscreen ingredients. FEBS Lett. 1997;418:87-90, 99.
38. Hidaka H, Kobayashi H, Koike T, et al. DNA damage photoinduced by cosmetic pigments and sunscreen agents under solar exposure and artificial UV illumination. J Oleo Sci. 2006;55:249-261.
39. Dufour EK, Kumaravel T, Nohynek GJ, et al. Clastogenicity, photo-clastogenicity or pseudo-photo-clastogenicity: genotoxic effects of zinc oxide in the dark, in pre-irradiated or simultaneously irradiated Chinese hamster ovary cells [published online ahead of print June 21, 2006]. Mutat Res. 2006;607:215-224.
40. Opinion of the Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers concerning titanium dioxide. http://ec.europa.eu/health/archive/ph_risk/committees/sccp/documents/out135_en.pdf. Published October 24, 2000. Accessed December 30, 2014.
41. The Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers opinion concerning zinc oxide. http://ec.europa.eu/health/archive/ph_risk/committees/sccp/documents/out222_en.pdf. Published June 24-25, 2003. Accessed December 30, 2014.
42. Hackenberg S, Friehs G, Kessler M, et al. Nanosized titanium dioxide particles do not induce DNA damage in human peripheral blood lymphocytes. Environ Mol Mutagen. 2010;52:264-268.
43. Bach-Thomsen M, Wulf HC. Sunbather’s application of sunscreen is probably inadequate to obtain the sun protection factor assigned to the preparation. Photodermatol Photoimmunol Photomed. 1993:9;242-244.
44. Nohynek GJ, Antignac E, Re T, et al. Safety assessment of personal care products/cosmetics and their ingredients. Toxicol Appl Pharmacol. 2010:1;243:239-259.
45. Diffey BL. Sunscreens: use and misuse. In: Giacomoni PU, ed. Sun Protection in Man. Vol 3. Amsterdam, the Netherlands: Elsevier Science BV; 2001:521-534.
46. Heneweer M, Muusse M, Van den BM, et al. Additive estrogenic effects of mixtures of frequently used UV-filters on pS2-gene transcription in MCF-7 cells. Toxicol Appl Pharmacol. 2005;208:170-177.
47. Kunz PY, Galicia HF, Fent K. Comparison of in vitro and in vivo estrogenic activity of UV-filters in fish. Toxicol Sci. 2006;90:349-361.
48. Kortenkamp A, Faust M, Scholze M, et al. Low-level exposure to multiple chemicals: reason for human health concerns? Environ Health Perspect. 2007;115(suppl 1):106-114.
49. Labeling and effectiveness testing: sunscreen drug products for over-the-counter human use—small entity compliance guide. US Food and Drug Administration Web site. http://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/guidances/ucm330694.htm. Published December 2012. Updated May 13, 2014. Accessed December 30, 2014.
50. Schafer-Korting M, Korting HC, Ponce-Poschl E. Liposomal tretinoin for uncomplicated acne vulgaris. Clin Investig. 1994;72:1086-1091.
51. Bronfenbrener R. Simplifying sun safety: a guide to the new FDA sunscreen monograph. Cutis. 2014;93:e17-e19.
