Challenges in Sun Protection.

Since time immemorial, people protected themselves from solar radiation. Limiting time in the sun by seeking shade or wearing clothing was a matter of course. In the early 20th century, tanned skin - a result of exposure to sunlight - was associated with good health. At the same time, however, one also had to protect oneself against the potential of excessive exposure to avoid sunburns. Around 1945, the first sunscreen products for protection against solar radiation became available. In the years to follow and up to the recent past, a vast number of different sunscreen filters were developed and incorporated into a wide variety of product formats. Frameworks regulating filter substances and preparations and methods to characterize sunscreen products' performance parameters were developed. Over the past 50-70 years, the perception regarding the tasks of sunscreen products changed several times. It was initially promoted as a lifestyle product and had the task of preventing sun-related erythema (tan without burn). Later, the prevention of skin cancer was added. Only in recent times, sunscreen products have been increasingly advertised and perceived as beauty and lifestyle products again. Also, the use of sunscreen products for antiaging purposes is now commonplace. The different intended purposes (averting harm and prevention) and the widespread use of topical sunscreen products have promoted many investigations and generated a vast and ongoing need for consumer and patient information and education. In the following review, we analyze and discuss current topics from conflicting areas, such as sun protection products (e.g., ideal sun protection products, sun protection metrics), product safety (e.g., nanoparticulate sunscreen filters, regulatory issues), application in everyday life (e.g., wish to tan, vulnerable cohorts), as well as controversies and future challenges (e.g., risks and benefits of UV radiation).

Spectral Homeostasis - The Fundamental Requirement for an Ideal Sunscreen.

Sunscreen application to UV-exposed skin is promoted to prevent skin cancer and sun damage, within a comprehensive photoprotection strategy that also includes sun avoidance and wearing UV protective clothing. The benefits of sunscreen are verified in preventing sunburn but appear to be largely presumptive in skin cancer prevention. Contemporary science establishes UVA as a primary driver of melanoma and photoaging. Consequentially, the traditional UVB-skewed protection of sunscreens provides an intellectual and logical explanation for rising skin cancer rates and, in particular, their failure to protect against melanoma. Better protection could be achieved with more balanced UVB/UVA sunscreens, toward spectral homeostasis protection. Greater balanced protection has another advantage of attenuating fewer UVB rays, which aid synthesis of vitamin D and nitric oxide. Percutaneous absorption of Soluble Organic UV Filters leads to systemic exposure, which becomes the relevant safety consideration. It is minimized by selecting Insoluble UV Filters with low absorption potential from a molecular weight above 500 Da. The filters must also be very hydrophilic, very lipophilic, or consist of particles. The risk-benefit ratio is a medical imperative, more so for cosmetics or sunscreens, since in principle there should be no risk from their use. The production of ideal sunscreens that mimic the effective, balanced UVB/UVA attenuation of textiles and shade is now possible, while maintaining an acceptable therapeutic margin of safety in humans and a favorable ecologic profile. Sunscreens with a favorable risk-benefit ratio and good esthetic properties or other consumer-friendly attributes will improve compliance and may achieve substantial clinical benefits.

Percutaneous Absorption of Sunscreen Filters: Review of Issues and Challenges.

Although skin is a vital barrier to the outside world, it is permeable to certain substances used in topical pharmacotherapy. It is therefore not surprising that other xenobiotics intentionally or accidentally coming in contact with skin can cross the skin barrier. Long before the turn of the millennium, it became clear that sunscreen filters from sunscreen products can be systemically absorbed and detected in urine and plasma. Against this background, we review issues and challenges with safety assessments related to the possible percutaneous absorption of the sunscreen filters. A reference is made to the Regulation (EC) No. 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products (version 1 August 2018) and the concepts of the Maximal Usage Trial (MUsT) and Generally Recognized As Safe and Effective (GRASE), currently discussed in the United States.

Performance Metrics of Sunscreen Formulations: In Vitro and In Vivo Techniques.

Effective skin protection of consumers by sunscreens can only be achieved when meaningful and reliable test methods are available to objectively measure the protection of sunscreen products. Quantitative, scientifically sound, and valid methods to detect UVB and UVA light protection as well as methods to assess sunscreen substantivity to water are required. Continuous improvement and, if necessary, extension of the test methods are important to provide optimum protection from harmful sun rays to the consumer. This work documents the historical background of the development of sunscreen test methods and provides the actual worldwide status of applied methods. Future developments and trends are discussed as far as they actually become apparent.

Challenges in Formulating Sunscreen Products.

Developing efficient sunscreen products with an acceptable sensory feel after application on skin, that meet current regulatory market and consumer requirements, is a major challenge, exacerbated by new restrictions limiting the use of certain ingredients previously considered crucial. This paper outlines a development strategy for -formulating sunscreens along a generic professional development pathway. Each galenic system will be different and must be customized. Development starts with benchmarking, followed by UVA/UVB filter platform selection and in silico calculation/optimization of photoprotection performance for the desired SPF, UVA-PF, and other requested endpoints. Next comes the selection of the emulsifier system and other key formulation ingredients, such as oil components, triplet quenchers, and antioxidants, with sensory, rheological, and film formation functions. Preliminary cost estimation is then performed to -complete the conceptual process before the start of the practical galenic development. The successful development of modern sunscreen products is based on -comprehensive expertise in chemistry, galenic methodology, regulation, and patenting, as well as specific -market and consumer requirements. The selection of the UV filters is the first key decision and constrains later choices. Other properties, such as water resistance and preservation or active ingredients, may need to be considered. The 4 basic requirements of efficacy, safety, registration, and patent freedom become checklist items to ensure that after development, a sunscreen product has a chance of success.

Natural and Simulated Solar Radiation.

The extra-terrestrial solar spectrum corresponds approximately to a black body of temperature about 5,800 K, with the ultraviolet region accounting for almost 8% of the total solar energy. Terrestrial solar spectral irradiance peaks at around 500 nm in the blue-green region, whereas the diffuse component peaks in the UVAI-blue region of the spectrum, with the infrared component comprising almost entirely direct radiation. Several factors impact on the magnitude and spectral profile of terrestrial solar spectral irradiance, and these include solar elevation, reflection from land and sea, air pollution, altitude above sea level and cloud cover. Measurements of erythemal UV from a number of ground-based networks around the world indicate an approximate 4-fold difference in ambient annual exposure between Australia and countries in northern Europe. In the absence of measured data, models to compute solar UV irradiance are a useful tool for studying the impact of variables on the UV climate. Simulated sources of sunlight based on a xenon arc lamp can be configured to give a close match to the spectral output of natural sunlight at wavelengths less than about 350 nm, and these are invaluable in the laboratory determination of sunscreen performance, notably the Sun Protection Factor (SPF). However, the divergence -between natural and simulated solar spectra at longer wavelengths may explain why SPFs measured in natural sunlight are less than those determined in the laboratory.

Regulation of Sun Protection Products in the EU.

Unlike more "traditional" cosmetic products, sunscreens do not sit inertly on the skin, providing a simple decorative effect. Their recognized and important contribution to public health has led many regions in the world to treat them as drugs or special cosmetics. Against the trend at that time, in 1976, the EU legislator already took a conscious decision to treat and regulate sunscreens as fast-moving consumer products. Since then, the EU Cosmetics Directive/Regulation balances the need for strict safety and efficacy requirements, with need for rapid innovation and easy consumer availability. Whilst the EU Regulation considers that "all cosmetic products are equal," sunscreens are clearly "more equal." In several areas of the legislation, specific requirements or guidance for sunscreen products have been introduced over the years. Whilst staying in the overall spirit of the legislation, these requirements take into account the specificity of sunscreens with regard to ingredient safety (positive list for UV filters), product safety assessment (photostability, deliberate exposure to UV light), minimum efficacy (UVA/UVB), efficacy testing (standardized test methods) and labelling (clear use instructions, non-misleading information to consumers). The article presents the history of the EU Cosmetics Regulation, its main requirements, where applicable, and specific considerations relating to sunscreens are highlighted and explained.

Size Matters! Issues and Challenges with Nanoparticulate UV Filters.

Preparations containing pigments have been used since ancient times to protect against negative effects of solar radiation. Since the 1950s, sunscreen products containing micronized TiO2 and ZnO have been marketed. These products were soon regarded as cosmetically unattrac-tive due to their property of remaining as a white paste on the skin, a result of particle sizes. In order to eliminate these unfavourable properties, particle size distribution was lowered into a range below 100 nm, a size threshold for decreasing the particle's optical property to reflect visible light. After 2000, new nanoparticulate organic filters were developed. Effects of both the inorganic and organic nanoparticulate substances - alone or in combination - with non-particulate UV filters were well documented and had shown great effectiveness. At the time, nanotechnology fuelled great hope in the progress of science and technology, including the health sector and cosmetics industry. Instead, influenced by images from the science fiction literature of self-replicating nanorobots destroying all living matter or health and environmental disasters caused by asbestos, fear of this new unknown amongst the general population has hindered acceptance and progress of nano-enabled products. Consumers have started to suspect that the particles permeate through skin, are absorbed by the blood and are distributed throughout the body, causing disease. Not least because of public pressure, cosmetics - which include sunscreen products - became the first product segment in which appropriately manufactured substances were subject to stringent rules. Despite advanced regulation and rigorous approval procedures for nanoparticulate UV filters, widespread reservations remain. Possible reasons could be a lack of knowledge of current legislation and unclear ideas about nature and behaviour of nanoparticles. Against this background, we discuss the nature and behaviour of nanoparticulate UV filters within finished products, on the skin and potentially in the skin, and the regulatory framework that ensures that nanoparticulate UV filters and the sunscreen products containing them are safe to use.

Sunscreen Secondary Claims: Market Differentiation or Market Confusion?

This chapter is focused on those products that are sold primarily as sun protection products and considers the additional claims made for these that are intended to differentiate and imply additional benefits. It is essentially an overview, as each claim would require an individual chapter to deal with in detail. We do not consider products with another intended primary use, such as moisturizer or colour comments, which are, in themselves "secondary sunscreens," defined specifically in Australia [AS/NZS 2604:2012 Sunscreen products - Evaluation and classification] or Canada. Primarily, the chapter serves as a reference guide. An argument is presented for the potential negative impact on the credibility of the whole product category brought about by the marketing strategy of attempting to segment on the basis of either criticism of competitor products and/or targeting niche groups of consumers. The European Union (EU) Regulation 655/2013 [Commission Regulation (EU) No 655/2013 laying down common criteria for the justification of claims used in relation to cosmetic products] states 6 criteria for representation of products. These are Legal Compliance, Truthfulness, Evidential Support, Honesty, Fairness and Informed Decision Making. More specifically to sunscreens, the EU Synthesis Document makes recommendation on efficacy and related claims [European Union Synthesis Document - Commission recommendation on the efficacy of sunscreen products and claims related thereto]. This chapter does not consider or test these criteria but does include a table of claims and suggested ways to substantiate these.

Assessment of Natural Sunlight Protection Provided by 10 High-SPF Broad-Spectrum Sunscreens and Sun-Protective Fabrics.

In 1978, the FDA Advisory Panel proposed both indoor and natural sunlight SPF testing methods but reverted to indoor testing only in 1993. Today's sunscreen sun protection and broad-spectrum claims are based on mandated clinical tests using solar simulators and in vitro spectrophotometers. This research evaluated the protection of 10 high-SPF (30-110), broad-spectrum sunscreen products, as well as 6 sun-protective fabrics against natural sunlight in Arequipa, Peru. Each of the 17 subjects was exposed to natural sunlight for 1 h and 59 min under clear skies, with temperatures and humidity similar to those in an indoor clinical laboratory. Test sites were photographed 16-24 h later. Four dermatologists evaluated the photographs for erythema and persistent pigment darkening (PPD). Perceptible sun-induced skin injury (sunburn and/or pigmentation) was detected at 97% of the sunscreen-protected scores. The most sun-sensitive subjects obtained the least erythema protection. The higher the SPF was, the higher the erythema protection, but the intensity of PPD was also higher. The 2 sunscreens using only FDA-approved sunscreen filters rated 30 SPF and 45+ SPF performed poorly: Eighty-one percent of the 136 scores were graded 1 minimal erythema dose or higher erythema, achieving, at a maximum, SPF of 5-7 in natural sunlight. Sun-protective fabrics tested provided excellent sun protection. The erythema and PPD observed through the sunscreens in less than 2 h are incongruous with the broad-spectrum, high-SPF sunscreen claims. Reapplying these sunscreens and staying in the sun longer, as stated on the product labels, would have subjected the subjects to even more UV exposure. High-SPF, broad-spectrum sunscreen claims based on indoor solar simulator testing do not agree with the natural sunlight protection test results.

HDRS - Hybrid Diffuse Reflectance Spectroscopy: Non-Erythemal In Vivo Driven SPF and UVA-PF Testing.

BACKGROUND/AIMS: In order to define a label SPF of topically applied sunscreens, in vivo test methods like ISO 24444, FDA Guideline, and the Australian Standard are used worldwide. The basis of all these methods is to induce an erythemal skin reaction by UV irradiation to find the level of MEDu and MEDp (Minimal Erythmal Dose unprotected and protected). In vitro methods replacing the human skin by any kind of nonhuman material are still not available. Thus, offering the new hybrid diffuse reflectance spectroscopy (HDRS) technique that can maintain an in vivo level for SPF testing while neglecting the UV-dose-related erythemal skin reaction is a perfect combination to take care of sun protection and any ethical concerns in SPF testing nowadays. METHODS: HDRS is a combination of in vivo diffuse reflectance spectroscopy measurements on the skin and in vitro transmission measurements of a sunscreen on a roughened polymethylmethacrylate plate. By this technique, the in vivo behavior of the investigated sunscreen on the skin is measured as well as the UVB absorption, which is still nonvisible in the reflectance technique. In order to establish an alternative method for in vivo SPF and UVA-PF testing, a huge number of sunscreens (250 samples) were measured by HDRS and compared with the worldwide accepted standards ISO 24444, ISO 24442, and ISO 24443. The variety of sunscreens measured reflect a wide range of different types of formulations as well as a wide range of SPFs (5-120) to validate this new alternative SPF testing procedure. RESULTS: Far-reaching statistical data analyses show an excellent link between the new nonerythemal-driven HDRS-SPF technique and ISO 24444 results. In the same way, HDRS-UVA-PF results can be correlated with UVA-PF values calculated from ISO 24442 as well as from ISO 24443. The importance of the inclusion of a spectral ratio of photodegradation is shown in the comparison of photostable and photounstable products. CONCLUSION: Owing to the elimination of any erythemal-relevant UVB and UVA doses, absolutely no skin reaction occurs during the HDRS experiment. Consequently, there is no need to define an MED anymore. For the first time, an alternative way to arriving at SPF and UVA-PF values is shown, without any ethical concerns of SPF testing in vivo and/or any restriction of SPF testing in vitro. Regardless of the type of formulation or the level of protection, an excellent correlation between SPFHDRSand SPF24444as for sunscreen labeling could be found. By this new alternative nonerythemal technique, not only SPF values can be measured but also UVA-PF values can be calculated with a linear correlation to ISO 24442 as well as to ISO 24443 from the same set of data. By this a robust alternative test method of SPF and UVA-PF values is described, taking into account the interaction of sunscreen formulation and skin.

Environmental Effects of Ultraviolet (UV) Filters.

Organic and inorganic ultraviolet (UV) filters are used in topical sunscreens and other applications to prevent or limit damage following exposure to UV light. Increasing use of UV filters has contributed to a growing number of investigations examining potential effects on human health and the environment. Worldwide environmental monitoring data demonstrate that UV filters reach aquatic environments through two main input sources - direct (i.e., washoff from swimmers/bathers) and indirect (i.e., incomplete wastewater treatment removal) - and can be taken up by various algal, plant, and animal species and sediments. In areas where industrial wastewater sources or significant recreational activities result in a greater input load, levels may be elevated and could impart an increased risk on native species health. In vitro, at higher levels typically not measured in the environment, effects on growth and reproduction are observed in different species, including fish, coral reef, and plants. Despite this, predicted no-effect concentrations for UV filters are generally above measured environmental concentrations. Recent legislative activity banning the use of certain UV filters has heightened awareness of their environmental ubiquity and precipitated a need for a thorough examination of evidence linking their ecological presence with adverse outcomes. In order to gauge the true potential risk to native ecosystems associated with UV filters, future studies should consider factors inherent both to finished sunscreen products (e.g., metabolic fate/transport and effect of inactive ingredients) and to the sampled environment (e.g., species sensitivity, presence of other contaminants, water flow, and photodegradation).

Past, Present, and Future of Sun Protection Metrics.

Since the beginning of the development of sunscreen products, efforts have been made to measure and quantify the protection performance of such products. Early on an in vivo method was established that allowed statements on the sun protection performance in humans. Later, by establishing defined basic and experimental conditions, the method became internationally standardized delivering the well-known sun protection factor (SPF). The method was widely used and is nowadays regarded as a gold-standard method. Further standardized methods were added shortly thereafter. However, shortcomings such as the confined radiation spectra used by the methods, the invasiveness, the complexity in their application, as well as their time- and cost-intensity promoted the development of alternative methods. The shortcomings were recently followed by another, namely, the large interlaboratory variances of the sun protection metrics SPFISO 24444. This all together shows that there is a justifiable need to explore the potential of alternative methods, to complement the existing methods, to serve as equivalents, or even to replace it in the future. Based on the work of Uhlig and coworkers, the authors propose to test the suitability of the alternative methods and their possible equivalency to the reference methods in a broad-based investigation, taking into account possible interlaboratory variances. A research program - developed by a consortium - is in public planning where stakeholders from research, industry, authorities, and the public can come together to facilitate and further advance standardization of the measurement of the sun protection performance. The authors give an insight into historical, technical--conceptual, and future developments of methods for -determining the protective performance of sun protection products.

Attack on Sunscreens Continues.

The Food and Drug Administration (FDA) was required to issue and put into effect a final sunscreen monograph by November 26, 2019. On March 27, 2020, President Donald Trump signed into effect H.R. 748, the "Coronavirus Aid, Relief, and Economic Security Act" (CARES). This bill eliminated the November 2019 requirement. The CARES Act includes legislative reforms that modernize the way over-the-counter (OTC) monograph drugs are regulated in the United States. Under this Act, sunscreens will be considered generally recognized as safe and effective (GRASE), if they meet conditions newly defined by the FDA. In addition, the FDA is required to issue a proposal to revise the sun-screen requirements for GRASE not later than 18 months after enactment and will sunset by the end of the fiscal year 2022. The CARES Act also addresses the requirement for a new drug application (NDA).1-7.

Sunscreens and Photoaging: A Review of Current Literature.

Sunscreens have been on the market for many decades as a means of protection against ultraviolet-induced erythema. Over the years, evidence has also shown their efficacy in the prevention of photoaging, dyspigmentation, DNA damage, and photocarcinogenesis. In the USA, most broad-spectrum sunscreens provide protection against ultraviolet B (UVB) radiation and short-wavelength ultraviolet A (UVA) radiation. Evidence suggests that visible light and infrared light may play a role in photoaging and should be considered when choosing a sunscreen. Currently, there is a paucity of US FDA-approved filters that provide protection against long UVA (> 370 nm) and none against visible light. Additionally, various sunscreen additives such as antioxidants and photolyases have also been reported to protect against and possibly reverse signs of photoaging. This literature review evaluates the utility of sunscreen in protecting against photoaging and further explores the requirements for an ideal sunscreen.

Sunscreens in the United States: Current Status and Future Outlook.

Incidence rates of nonmelanoma skin cancer and melanoma have been on the rise in the USA for the past 25 years. UV radiation (UVR) exposure remains the most preventable environmental risk factor for these cancers. Aside from sun avoidance, sunscreens continue to provide the best alternative protection. UVR directly damages DNA and causes indirect cellular damage through the creation of reactive oxygen species, the sum of which leads to cutaneous immunosuppression and a tumorigenic milieu. The current generation of sunscreens protect from UVR through two main mechanisms: absorption and deflection. In the USA, the Food and Drug Association (FDA) regulates sunscreen products which are considered over-the-counter drugs. With the release of new FDA testing and labeling requirements in 2011 and the enactment of the Sunscreen Innovation Act in 2014, sunscreen manufacturers are now required to evaluate their products not only on the sun protection factor (SPF) but also on broad-spectrum UVA protection. The American Academy of Dermatology Association and the American Academy of Pediatrics have provided specific recommendations for proper sun protection and sunscreen usage with the continual goal of increasing public awareness and compliance with appropriate sun protective measures. Antioxidants, photolyases, and plant polyphenols remain an interesting avenue of research as additives to sunscreens or stand-alone topical or oral products that appear to modulate the immunosuppressive effects of UVR on the skin. Additionally, although UVR induces endogenous cutaneous production of vitamin D, its damaging effects overshadow this positive benefit, especially in light of the ease of achieving recommended amounts of vitamin D through diet and supplementation.

Photoprotection With Mineral-Based Sunscreens.

BACKGROUND: Although chemical sunscreens have traditionally been at the forefront of sun protection, safety concerns and increasing awareness of the environmental impact of personal-care products have led to greater interest in the use of mineral blockers as photoprotective agents. OBJECTIVE: To examine the safety and efficacy of mineral-based sunscreens to allow patients to make informed choices about ultraviolet (UV) protection. MATERIALS AND METHODS: A review of the literature was performed using the PubMed database. RESULTS: This article provides an overview of physical blockers and focuses on the efficacy of mineral sunscreens in offering broad-spectrum UV protection and safety concerns, including the controversy surrounding the use of nanoparticles. Practical tips for application are also reviewed. CONCLUSION: Mineral sunscreens are an attractive, efficacious option for consumers who prefer alternative choices in sun protection.