[Characterization of sun protection performance: Quo vadis?] / Charakterisierung von Sonnenschutzleistung: Quo vadis?

The task of the first sunscreens was to prevent the development of sunburn and, following the spirit of the 1950/1960s, to not impair the tanning of the skin. The need to quantify the protective performance soon arose. Originally with the help of natural-nowadays artificial-sunlight, a method was developed to determine a sun protection factor (SPF). It is formally defined as a ratio between minimum erythema-effective UV dose on sunscreen-protected skin and minimum erythema-effective UV dose on unprotected skin (ISO 24444:2019). Three observations question the suitability of the method. (1) Interlaboratory variability: Despite strict standardization, results of SPF determinations from different laboratories are subject to large variations. (2) Natural vs. artificial sunlight: The radiation spectrum of artificial sunlight differs from that of natural sunlight. SPFs determined with artificial sunlight (as depicted on all sunscreens currently on the market) are significantly too high compared to SPF determination with natural sunlight. (3) Erythema burden: When determining SPF, subjects are exposed to potentially harmful radiation. Against this background alternative methods-in vitro SPF, hybrid diffuse reflectance spectroscopy (HDRS) and in silico calculations-are presented. These have the potential to replace the current method. As an immediate measure, it is recommended to return to the comprehensible description of low, medium, high, and very high protection and in the future to take into account the spectrum of natural sunlight.

[Nano is big! : Facts and myths about nanoparticulate UV filters]. / Nano ist groß! : Fakten und Mythen über nanopartikuläre UV-Filter.

Sunscreen products containing inorganic micronized titanium dioxide (TiO2) and zinc oxide (ZnO) have been available since the 1950s. Their cosmetic acceptance remained limited as they persist as a white paste on the skin. By reducing the size of the particles into the nano-range below 100 nm, their optical property of reflecting visible light is reduced. After the year 2000, organic filters of this size range were developed. The enthusiasm for nanotechnology that prevailed at the time did not transfer to sunscreen products with nanoparticulate filters. Consumers suspect that the particles permeate the skin, are absorbed by the blood, and spread throughout the body causing illness. Not least due to public pressure, cosmetics-which include sunscreen products-became the first product segment in which accordingly manufactured substances were subjected to strict regulations. Despite advanced regulation and strict approval procedures for nanoparticulate filters, public reservations remained. Possible reasons for this are lack of knowledge or mistrust of the applicable legislation, unclear perception of the behavior of nanoparticles in sunscreen products and as a result unclear perceptions of hazard, risk, and exposure. Against this background, the nature and behavior of nanoparticulate filters in sunscreens on the skin and potentially in the skin, as well as the regulatory framework that ensure that nanoparticulate filters and the products containing them are safe to use are discussed.

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.

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.

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.

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.

Labelled sunscreen SPFs may overestimate protection in natural sunlight.

Limited evidence exists to indicate that sunscreen protection factors determined in the laboratory are higher than those in natural sunlight. In this article we propose an explanation for this difference and estimate the expected SPFs of sunscreen products in natural sunlight and those expected from laboratory testing. Our results indicate that the labelled SPF, determined by in vivo assay using a UV solar simulator, overestimates the SPF that would be expected in natural sunlight to the extent that for products labelled SPF50+, it may not be possible to achieve a protection against sunlight of more than 25-fold. The popular interpretation of the SPF that it can be thought of as how much longer skin covered with sunscreen takes to burn in sunlight compared with unprotected skin, can no longer be defended.

Comparison of ultraviolet A light protection standards in the United States and European Union through in vitro measurements of commercially available sunscreens.

BACKGROUND: The importance of adequate ultraviolet A light (UVA) protection has become apparent in recent years. The United States and Europe have different standards for assessing UVA protection in sunscreen products. OBJECTIVE: We sought to measure the in vitro critical wavelength (CW) and UVA protection factor (PF) of commercially available US sunscreen products and see if they meet standards set by the United States and the European Union. METHODS: Twenty sunscreen products with sun protection factors ranging from 15 to 100+ were analyzed. Two in vitro UVA protection tests were conducted in accordance with the 2011 US Food and Drug Administration final rule and the 2012 International Organization for Standardization method for sunscreen effectiveness testing. RESULTS: The CW of the tested sunscreens ranged from 367 to 382 nm, and the UVA PF of the products ranged from 6.1 to 32. Nineteen of 20 sunscreens (95%) met the US requirement of CW >370 nm. Eleven of 20 sunscreens (55%) met the EU desired ratio of UVA PF/SPF > 1:3. LIMITATIONS: The study only evaluated a small number of sunscreen products. CONCLUSION: The majority of tested sunscreens offered adequate UVA protection according to US Food and Drug Administration guidelines for broad-spectrum status, but almost half of the sunscreens tested did not pass standards set in the European Union.

Calculation of the sun protection factor of sunscreens with different vehicles using measured film thickness distribution - Comparison with the SPF in vitro.

The sun protection factor (SPF) depends on UV filter composition, and amount and type of vehicle of the applied sunscreen. In an earlier work, we showed that the vehicle affected the average thickness of sunscreen film that is formed upon application to a skin substrate and that film thickness correlated significantly with SPF in vitro. In the present study, we quantitatively assess the role for sunscreen efficacy of the complete film thickness frequency distribution of sunscreen measured with an oil-in-water cream, an oil-in-water spray, a gel, a water-in-oil, and an alcoholic spray formulation. A computational method is employed to determine SPF in silico from calculated UV transmittance based on experimental film thickness and thickness distribution, and concentration and spectral properties of the UV filters. The investigated formulations exhibited different SPFs in vitro and different film thickness distributions especially in the small thickness range. We found a very good agreement between SPF in silico and SPF in vitro for all sunscreens. This result establishes the relationship between sun protection and the film thickness distribution actually formed by the applied sunscreen and demonstrates that variation in SPF between formulations is primarily due to their film forming properties. It also opens the possibility to integrate the influence of vehicle into tools for in silico prediction of the performance of sunscreen formulations. For this, the use of the Gamma distribution was found to be appropriate for describing film thickness distribution.

Suntanning with sunscreens: a comparison with sunbed tanning.

BACKGROUND/PURPOSE: Acquiring a tanned skin, either by sunbathing, sunbed use, or a combination of both, is a desirable objective for many people. The objective here was to compare the ultraviolet (UV) exposure resulting from a 2-week vacation spent sunbathing with sunscreen-protected skin, with that from a typical course of 10 sessions on a sunbed. METHODS: A numerical analysis combining data on sunlight and sunbed UV levels, time spent tanning and spectral absorption properties of different types of sunscreen. RESULTS: The analysis showed that unless a sunscreen provides optimal broad-spectrum protection, a 2-week sunbathing vacation that avoids sunburn on sunscreen-protected skin can result in a higher cumulative UV exposure than a typical 10-session sunbed course. The lowest exposures for a given sun protection factor (SPF) are obtained when sunscreen delivers broad-spectrum protection that approaches the ideal of uniform absorption at all wavelengths throughout the UV spectrum. CONCLUSION: In extreme cases of recreational sun exposure where sunscreens providing suboptimal broad-spectrum protection are used, the UV insult to the skin is likely to result in higher cumulative exposures than commonly employed sunbed practices.

Global state of sunscreens.

The use of sunscreen is embedded in a hierarchy of sun protection strategies consisting primarily of sun avoidance by seeking shade and covering up with clothing. Sunscreens are, however, important means of protection; thus, understanding how they work and knowing their limitations are crucial. This review explains the role of ultraviolet (UV) filters, emollients, emulsifier systems and other components in a sunscreen, as well as trends in formulations in Europe, North America, Latin America, and Asia Pacific. Furthermore, it explains how sunscreen performance in terms of sun protection factor, UVA protection, and other metrics can be simulated. The role of sensory characteristics in assessing and improving compliance is also discussed.In the final chapter, Facts and Fiction, five of the most common myths about sun exposure and sun protection by sunscreen are debunked.

Photoprotection: part I. Photoprotection by naturally occurring, physical, and systemic agents.

The acute and chronic consequences of ultraviolet radiation on human skin are reviewed. An awareness of variations in naturally occurring photoprotective agents and the use of glass, sunglasses, and fabric can lead to effective protection from the deleterious effects of ultraviolet radiation. New systemic agents, including Polypodium leucotomos, afamelanotide, and antioxidants have potential as photoprotective agents.

Photoprotection: part II. Sunscreen: development, efficacy, and controversies.

In addition to the naturally occurring, physical, and systemic photoprotective agents reviewed in part I, topical ultraviolet radiation filters are an important cornerstone of photoprotection. Sunscreen development, efficacy, testing, and controversies are reviewed in part II of this continuing medical education article.

Ex vivo evaluation of radical sun protection factor in popular sunscreens with antioxidants.

BACKGROUND: UVA induces tissue damage via the production of radical oxygen species. Adding antioxidants to UV filters in sunscreens is a novel photoprotective strategy. The topical application of antioxidants in sunscreen can potentially neutralize the UVA-induced free radicals. OBJECTIVES: We sought to assess the degree of free radical protection offered by sunscreens with antioxidants and attempted to differentiate the contribution of free radical protection from that of the UV filters. METHOD: Twelve sunscreen products were purchased. The degree of UVA protection (UVA-PF) was measured via an in vitro assay according to a European guideline (Colipa). In addition, an electron spin resonance (ESR) spectroscopy-based assay was used to measure the radical skin protection factor (RSF) and antioxidant power (AP) of each product. RESULTS: The sun protection factor (SPF) values of the sunscreens ranged from 15 to 55, and the UVA-PF values ranged from 2.4 to 28.2. The RSF values ranged from 2.4 to 27.1. There is a high correlation between RSF and UVA-PF. The AP values for nearly all the products were 0, and two products (#4 and #9) had very low AP values of 16 and 12, respectively. LIMITATIONS: The study only evaluated a small number of sunscreen products, and only ex vivo and in vitro methods were used to assess the products. CONCLUSIONS: The idea of combining UV filters with antioxidants is appealing. Current sunscreen products on the market offer free radical protection, but the majority of the radical protection is from UV filters rather than antioxidants.