Article

Effect of Sunscreen Application Under Maximal Use Conditions on Plasma Concentration of Sunscreen Active Ingredients: A Randomized Clinical Trial

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Abstract

Importance The US Food and Drug Administration (FDA) has provided guidance that sunscreen active ingredients with systemic absorption greater than 0.5 ng/mL or with safety concerns should undergo nonclinical toxicology assessment including systemic carcinogenicity and additional developmental and reproductive studies. Objective To determine whether the active ingredients (avobenzone, oxybenzone, octocrylene, and ecamsule) of 4 commercially available sunscreens are absorbed into systemic circulation. Design, Setting, and Participants Randomized clinical trial conducted at a phase 1 clinical pharmacology unit in the United States and enrolling 24 healthy volunteers. Enrollment started in July 2018 and ended in August 2018. Interventions Participants were randomized to 1 of 4 sunscreens: spray 1 (n = 6 participants), spray 2 (n = 6), a lotion (n = 6), and a cream (n = 6). Two milligrams of sunscreen per 1 cm² was applied to 75% of body surface area 4 times per day for 4 days, and 30 blood samples were collected over 7 days from each participant. Main Outcomes and Measures The primary outcome was the maximum plasma concentration of avobenzone. Secondary outcomes were the maximum plasma concentrations of oxybenzone, octocrylene, and ecamsule. Results Among 24 participants randomized (mean age, 35.5 [SD, 1.5] years; 12 (50%] women; 14 [58%] black or African American; 14 [58%]), 23 (96%) completed the trial. For avobenzone, geometric mean maximum plasma concentrations were 4.0 ng/mL (coefficient of variation, 6.9%) for spray 1; 3.4 ng/mL (coefficient of variation, 77.3%) for spray 2; 4.3 ng/mL (coefficient of variation, 46.1%) for lotion; and 1.8 ng/mL (coefficient of variation, 32.1%). For oxybenzone, the corresponding values were 209.6 ng/mL (66.8%) for spray 1, 194.9 ng/mL (52.4%) for spray 2, and 169.3 ng/mL (44.5%) for lotion; for octocrylene, 2.9 ng/mL (102%) for spray 1, 7.8 ng/mL (113.3%) for spray 2, 5.7 ng/mL (66.3%) for lotion, and 5.7 ng/mL (47.1%) for cream; and for ecamsule, 1.5 ng/mL (166.1%) for cream. Systemic concentrations greater than 0.5 ng/mL were reached for all 4 products after 4 applications on day 1. The most common adverse event was rash, which developed in 1 participant with each sunscreen. Conclusions and Relevance In this preliminary study involving healthy volunteers, application of 4 commercially available sunscreens under maximal use conditions resulted in plasma concentrations that exceeded the threshold established by the FDA for potentially waiving some nonclinical toxicology studies for sunscreens. The systemic absorption of sunscreen ingredients supports the need for further studies to determine the clinical significance of these findings. These results do not indicate that individuals should refrain from the use of sunscreen. Trial Registration ClinicalTrials.gov Identifier: NCT03582215

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... Benzophenone-3 provided higher plasma concentrations than others. According to Matta et al., using 2 mg/cm 2 of several sunscreen preparations (lotions and sprays) in 75% of the body (containing oxybenzone, avobenzone, octocrylene, homosalate, octisalate, octinoxate, ecamusla) showed plasma concentrations of oxybenzone 169 to 209 ng/ml, avobenzone 1.8 ng/ml, octocrylene 5.7 ng/ml, homosalate 23 ng / ml, octisalate 5.8 ng/ml octinoxate 7.9 ng/ml, and ecamusla 1.5 ng/ml [31]. In a comparison between lotion and spray formulations used in this study, the lotions yielded higher active ingredients' concentrations in plasma. ...
... In a comparison between lotion and spray formulations used in this study, the lotions yielded higher active ingredients' concentrations in plasma. Systemic exposures of all ingredients remained above 0.5 ng/mL for more than 50% of participants up to 7 days for avobenzone, octisalate, and octinoxate; 10 days for octocrylene; and 21 days for homosalate and oxybenzone [31]. following a single application; residual skin amounts during the wash-out phase; plasma concentrations up to 17 days after the last application; and the systemic exposure to additional commonly used sunscreen ingredients, including octisalate, homosalate, and octinoxate. ...
... Sunscreen lotion containing octyl methoxycinnamate (OMC), three times a day, caused irritation, immune system disorder, hormonal disruption, and significant stratum corneum DNA damage [40]. Sunscreens as a spray, lotion, and cream including avobenzone, oxybenzone, octocrylene, and ecamsule ingredients with different combinations applied on 75% of the body caused 17% rash [31]. In addition, 30% of participants using sunscreen containing polyethylene glycols, octyl salicylate, bemotrizinol, ensulizole, methyl methacrylate (MMA), homosalate, titanium dioxide, and avobenzone reported rash in a 90-day follow-up study in Thailand [41]. ...
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Sunscreen application is widespread and incorporated into daily life. Although FDA has approved 16 sunscreen ingredients, recent studies suggest a revaluation of their potential adverse effects. This systematic review assesses sunscreens’ percutaneous absorption, toxicity, and their ingredients concentration in urine and plasma. The search was conducted in Medline (PubMed), Scopus, Embase, and Cochrane until 05/08/2021. Data from 21 studies with related inclusion criteria were extracted. 18 studies reported sunscreen complications such as rash, irritation, immune system disorders, stratum corneum DNA damage, and hormonal disruption, 4 articles reported maximum concentration of sunscreen ingredients in plasma, and 4 articles reported urinary concentration of ingredients. In 2016, the FDA suggested a plasma concern level of 0.5 ng/mL for sunscreen ingredients. Sunscreen ingredients including avobenzone, octocrylene, ecamsule, homosalate, octisalate, enzacamene, octinoxate, and oxybenzone were detected more than 0.5 ng/mL after in blood 1-4 daily applications. Sunscreen application reduces the risk of sunlight harmful effects but could have advers effects related to their percutaneous penetration. Taken together, related data provide the impetus for detailed analysis of sunscreen toxicology. Also, highly adsorbed ingredients should be replaced with less adsorbed compounds to minimize body accumulation and the associated risks. Also, life time infant and children sunscreen exposure provide furthur impetus for in-depth toxicologic investigations
... Human PK data following single and repeated dermal exposure to products containing oxybenzone, homosalate, octisalate, octinoxate, avobenzone, octocrylene, and/or ecamsule have recently become available (data further described below) (Matta et al. 2019(Matta et al. , 2020. The case study uses a theoretical scenario of no systemic toxicity data for these chemicals (i.e., ignoring existing data for repeat dose toxicity, developmental toxicity, and reproductive toxicity). ...
... The intention is to demonstrate the possible use of iTTC as a tool that can be used to refine a TTC-based assessment for dermal exposure to a consumer product. Two constraints that will be applied to the case study are: (1) only PK data from the Matta et al. (2019Matta et al. ( , 2020 will be utilized; (2) no additional kinetic modeling (e.g., PBPK modeling) will be done. ...
... The systemic PK following dermal application of the 7 case study chemicals was evaluated by the US FDA in two separate clinical studies involving the use of commercially available sunscreen products (Matta et al. 2019(Matta et al. , 2020. The first clinical study (Matta et al. 2019) evaluated four products that contained avobenzone, oxybenzone, octocrylene, and/ or ecamsule in different concentrations, while the second clinical study (Matta et al. 2020) evaluated four products that contained homosalate, octisalate and/or octinoxate (note that one formulation was common between the two clinical studies). ...
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We present a case study that provides a practical step-by-step example of how the internal Threshold of Toxicological Concern (iTTC) can be used as a tool to refine a TTC-based assessment for dermal exposures to consumer products. The case study uses a theoretical scenario where there are no systemic toxicity data for the case study chemicals (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, octinoxate, and ecamsule). Human dermal pharmacokinetic data following single and repeat dermal exposure to products containing the case study chemicals were obtained from data published by the US FDA. The clinical studies utilized an application procedure that followed maximal use conditions (product applied as 2 mg/cm 2 to 75% of the body surface area, 4 times a day). The case study chemicals were first reviewed to determine if they were in the applicability domain of the iTTC, and then, the human plasma concentrations were compared to an iTTC limit of 1 µM. When assessed under maximum usage, the external exposure of all chemicals exceeded the external dose TTC limits. By contrast, the internal exposure to all chemicals, except oxybenzone, was an order of magnitude lower than the 1 µM interim iTTC threshold. This work highlights the importance of understanding internal exposure relative to external dose and how the iTTC can be a valuable tool for assessing low-level internal exposures; additionally, the work demonstrates how to use an iTTC, and highlights considerations and refinement opportunities for the approach.
... fects of octocrylene have been reported [6]. However, toxicokinetic studies concluded that after systemic absorption of octocrylene, its concentrations in plasma were found to be in the range of 25-100 nM [7,8]. Moreover, studies in zebrafish have already concluded that octocrylene may disrupt normal endocrine hemostasis [9,10]. ...
... The United States Food and Drug Administration has approved octocrylene for the use of sun protection factor (SPF). In addition, octocrylene is also used in other products such as shampoos, hair sprays, tannin oils, and conditioners, and octocrylene has become an environmental contaminant found in coastlines, rivers, and lakes all over the world [6][7][8]. However, the concertation of octocrylene in the rivers and waste water has been reported in the range of 5.2-38.0 ...
... mg/L, and in zebrafish, androgenic and estrogenic effects of octocrylene have been reported [6]. However, toxicokinetic studies concluded that after systemic absorption of octocrylene, its concentrations in plasma were found to be in the range of 25-100 nM [7,8]. Moreover, studies in zebrafish have already concluded that octocrylene may disrupt normal endocrine hemostasis [9,10]. ...
Article
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Octocrylene is a widely used ingredient in sunscreen products, and it has been observed that the use of sunscreen has been increasing over the last few decades. In this paper, we investigated the way in which sunscreen’s ingredient octocrylene may disrupt normal vitamin D synthesis pathway, resulting in an imbalance in vitamin D levels in the body. The key techniques used for this insilico investigation were molecular docking, molecular dynamic (MD) simulation, and MMPBSA-based assessment. Vitamin D abnormalities have become very common in human health. Unknown exposure to chemicals may be one of the important risk factors. In molecular docking analysis, octocrylene exhibited a binding energy of −11.52 kcal/mol with vitamin D binding protein (1KXP) and −11.71 for the calcitriol native ligand. Octocrylene had a binding potency of −11.152 kcal/mol with the vitamin D receptor (1DB1), and calcitriol had a binding potency of −8.73 kcal/mol. In addition, octocrylene has shown binding energy of −8.96 kcal/mol with CYP2R1, and the calcitriol binding energy was −10.36 kcal/mol. Regarding stability, the root-mean-square deviation (RMSD), the root-mean-square fluctuation (RMSF), the radius of gyration, hydrogen bonding, and the solvent-accessible surface area (SASA) exhibited that octocrylene has a stable binding pattern similar to calcitriol. These findings revealed that incessant exposure to octocrylene may disrupt normal vitamin D synthesis.
... In collaboration with FDA's Office of New Drugs, DARS led and conducted clinical research demonstrating that maximum usage sunscreen clinical trials are feasible, that sunscreen active ingredients are absorbed at levels that would trigger additional safety studies (Figure 1), and that further research is needed to fill in data gaps for sunscreen ingredients. Results from these studies were published in the Journal of the American Medical Association: JAMA (7,8), one of which was the most viewed JAMA article in 2019 (8). DARS also published the detailed bioanalytical method it developed (9) to enable further study and collaborated with FDA's Office of Pharmaceutical Quality staff on a study to assess sunscreen ingredient absorption with an in vitro model (10). ...
... In collaboration with FDA's Office of New Drugs, DARS led and conducted clinical research demonstrating that maximum usage sunscreen clinical trials are feasible, that sunscreen active ingredients are absorbed at levels that would trigger additional safety studies (Figure 1), and that further research is needed to fill in data gaps for sunscreen ingredients. Results from these studies were published in the Journal of the American Medical Association: JAMA (7,8), one of which was the most viewed JAMA article in 2019 (8). DARS also published the detailed bioanalytical method it developed (9) to enable further study and collaborated with FDA's Office of Pharmaceutical Quality staff on a study to assess sunscreen ingredient absorption with an in vitro model (10). ...
Article
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The U.S. Food and Drug Administration (FDA) Division of Applied Regulatory Science (DARS) moves new science into the drug review process and addresses emergent regulatory and public health questions for the Agency. By forming interdisciplinary teams, DARS conducts mission-critical research to provide answers to scientific questions and solutions to regulatory challenges. Staffed by experts across the translational research spectrum, DARS forms synergies by pulling together scientists and experts from diverse backgrounds to collaborate in tackling some of the most complex challenges facing FDA. This includes (but is not limited to) assessing the systemic absorption of sunscreens, evaluating whether certain drugs can convert to carcinogens in people, studying drug interactions with opioids, optimizing opioid antagonist dosing in community settings, removing barriers to biosimilar and generic drug development, and advancing therapeutic development for rare diseases. FDA tasks DARS with wide ranging issues that encompass regulatory science; DARS, in turn, helps the Agency solve these challenges. The impact of DARS research is felt by patients, the pharmaceutical industry, and fellow regulators. This article reviews applied research projects and initiatives led by DARS and conducts a deeper dive into select examples illustrating the impactful work of the Division.
... Conclusion: application of 3 commercially available sunscreens formulations containing BP-3 at concentrations of between 4-6% under maximal use conditions resulted in systemic absorption and associated plasma concentrations of 169.3 -209.6 ng/mL (Matta et al., 2019). ...
... Despite the detected levels being low in human samples, a study has detected BP-3 in 97% of the tested urine samples, with mean concentration of 22.9 ng/ml (95 th percentile of 1040 ng/ml) . A human volunteer study by Matta et al. (2019) has also indicated that application of 3 commercially available sunscreens formulations containing BP-3 at concentrations between 4-6%, under maximal use conditions, resulted in systemic absorption and associated plasma concentrations of 169.3 -209.6 ng/mL. In another study, Matta et al. (2020) found the systemic absorption and associated plasma concentrations of BP-3 to be between 180.1-258.1 ng/mL for aerosol spray and lotion respectively. ...
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SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) - SCCS/1625/20 - Final Opinion U. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads, M. Dusinska, J. Ezendam, E. Gaffet, C. L. Galli, B. Granum, E. Panteri, V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. Wijnhoven, A. Koutsodimou, W. Uter, N. von Goetz The SCCS adopted this document at its plenary meeting on 30-31 March 2021 (77 pages) Published:17 August 2022 Ed. Publications Office of the European Union, Luxembourg, Luxembourg (77 pages) ISSN : 1831-4767 ISBN : 978-92-76-54757-0 DOI : https://data.europa.eu/doi/10.2875/102562 Catalog Number : EW-AQ-22-007-EN-N https://op.europa.eu/fr/publication-detail/-/publication/a9917049-21c8-11ed-8fa0-01aa75ed71a1 https://op.europa.eu/fr/publication-detail/-/publication/a9917049-21c8-11ed-8fa0-01aa75ed71a1/language-en/format-PDF/source-264517698
... This study's findings sparked interest in comparing chemical sunscreens to those utilizing physical mineral blockers. 1 Currently, there are no known studies evaluating the interest on sunscreen selection among pregnant and/or nursing individuals. Thus, we completed an internet-based analysis to assess for changes in sunscreen recommendations for this demographic before and after May 2019. ...
... This has prompted the FDA to recommend additional research on organic ultraviolet filters to support further policy recommendations about sunscreen to support the health of this population. 1 Public interest in sunscreen safety is increasing and it would be helpful if the American Academy of Dermatology (AAD) provided guidance regarding which sunscreens are safe for use for pregnant and lactating women. An analysis of Google trends reveals that sunscreen recommendations are widely varied and not necessarily based on expert opinion. ...
... Concerns for greasiness may arise from the use of physical sunscreens based on inorganic filters (e.g., titanium dioxide, zinc oxide), which not only tend to be thick and oily but also leave white residue that may be cosmetically unacceptable for darker-skinned individuals [114,115]. Due to recent concerns that the application of sunscreen at recommended levels may lead to systemic absorption [116], titanium dioxide and zinc oxide are the only ingredients that are generally recognized as safe and effective (GRASE) by the US FDA [115]. Chemical sunscreens with organic filters and transparent formulations are often marketed to individuals with SOC [117], which may address some of the previously mentioned barriers to sunscreen use, but more studies are needed to verify their safety under current FDA provisions [118]. ...
... Patients seeking transparent formulations may consider using sunscreens with nanosized inorganic filters or organic filters, although these do not provide protection against visible light. Despite the possibility for systemic absorption and the need for additional safety data on chemical sunscreens based on organic filters, the FDA has cautioned against discontinuing their use [116,118]. ...
Article
Photoprotection behaviors can mitigate skin damage caused by ultraviolet radiation, and common methods include seeking shade, avoiding sun exposure during peak daylight hours, wearing sun-protective clothing, applying sunscreen, and using sunglasses. While the role of sun protection in preventing sunburns, photoaging, and skin cancer is well established in fair-skinned populations, individuals with skin of color (SOC) are presumed to suffer fewer negative effects from solar radiation. Thus, the importance of photoprotection in this population is understudied and may be underestimated. In SOC populations, sun exposure is known to cause pigmentary disorders, photoaging, and basal cell carcinoma (BCC), highlighting the potential benefits of photoprotection. Although SOC populations tend to practice photoprotection by seeking shade and wearing sun-protective clothing, survey and interview-based studies have consistently found relatively low use of sunscreen among these populations. Common motivators for photoprotection in individuals with SOC include preventing sunburn and pigmentation, with the prevention of skin cancer being a less important reason. As a skin cancer risk behavior, indoor tanning is relatively rare in SOC populations, but its use may increase with acculturation to US norms. While more studies are necessary to clarify whether photoprotection behaviors may decrease skin cancer-related mortality in SOC populations, regular dermatologic care and counseling on photoprotection remain essential in patients with SOC for overall skin health.
... Recent randomized control trials revealed that oxybenzone reaches and exceeds the US FDA's threshold of concern (0.5 ng/ml in blood) 2 hours after sunscreen application; these concentrations remained above the threshold for 23 h in all participants, and for 3 weeks in 96% of participants [11,12]. Based on these new findings, the U.S. FDA recently requested additional safety studies on oxybenzone and other sunscreen ingredients [13]. ...
... Yet, testing the 17 over-the-counter UV filters for safety (e.g., hazard identification) was previously not seen as necessary; the sunscreen ingredients, including oxybenzone, were considered by FDA to be "generally recognized as safe and effective" because it was assumed that their concentrations would not exceed a threshold of 0.5 ng/mL in systemic circulation after dermal application [13]. Now that this assumption has been shown to be wrong [11,12], the FDA has called for more data and possibly stricter regulation [13]. ...
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Background Technological advancements make lives safer and more convenient. Unfortunately, many of these advances come with costs to susceptible individuals and public health, the environment, and other species and ecosystems. Synthetic chemicals in consumer products represent a quintessential example of the complexity of both the benefits and burdens of modern living. How we navigate this complexity is a matter of a society’s values and corresponding principles. Objectives We aimed to develop a series of ethical principles to guide decision-making within the landscape of environmental health, and then apply these principles to a specific environmental chemical, oxybenzone. Oxybenzone is a widely used ultraviolet (UV) filter added to personal care products and other consumer goods to prevent UV damage, but potentially poses harm to humans, wildlife, and ecosystems. It provides an excellent example of a chemical that is widely used for the alleged purpose of protecting human health and product safety, but with costs to human health and the environment that are often ignored by stakeholders. Discussion We propose six ethical principles to guide environmental health decision-making: principles of sustainability, beneficence, non-maleficence, justice, community, and precautionary substitution. We apply these principles to the case of oxybenzone to demonstrate the complex but imperative decision-making required if we are to address the limits of the biosphere’s regenerative rates. We conclude that both ethical and practical considerations should be included in decisions about the commercial, pervasive application of synthetic compounds and that the current flawed practice of cost-benefit analysis be recognized for what it is: a technocratic approach to support corporate interests.
... 35 Recent studies have shown that many organic UV filters are readily absorbed through the skin, with detectable plasma levels even days after use. 36,37 Oxybenzone (benzophenone-3), which is present in two thirds of sunscreens in the United States, is a broad-spectrum UV filter that has significant transdermal absorption after topical use. This is of concern because oxybenzone has been reported to disrupt the endocrine system in humans and has been linked to female infertility and low birth weight; further study is needed to evaluate the causality of this association. ...
... [38][39][40] Significant transdermal penetration and detectable plasma levels after maximal usage sunscreen application (ie, to 75% of body surface area, at 2 mg/cm 2 ) have also been demonstrated for avobenzone, octocrylene, ecamsule, homosalate, octisalate, and octinoxate, even after a single application. 36,37 All 6 active ingredients were detectable in plasma for up to 21 days. 36 Again, additional study is necessary to determine the clinical significance of these results. ...
Article
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The effects of solar radiation on human skin differ based on skin phototype, the presence or absence of photodermatoses, biological capacity to repair DNA damage, wavelength, intensity of sun exposure, geographic latitude, and other factors, underscoring the need for a more tailored approach to photoprotection. To date, the focus of photoprotection guidelines has been to prevent sunburn and DNA damage induced by ultraviolet (UV) radiation, both UVB and UVA; however, several recent studies have shown that visible light (VL) also generates reactive oxygen and nitrogen species that can contribute to skin damage and pigmentation on the skin, particularly in people of color. Therefore, dark-skinned individuals, while naturally better protected against UVB radiation by virtue of high eumelanin content in melanocytes, may need additional protection from VL-induced skin damage. The current options for photoprotection products need to expand, and potential strategies against VL include the addition of iron oxide, titanium dioxide, and biologically relevant antioxidants to sunscreen formulations, as well as supplementation with orally active antioxidants.
... Hence, safe and effective moisturizers may represent an exciting new area for future research to reverse skin aging and to prevent intrinsic and extrinsic aging as well as skin cancer. Most importantly, compared to sunscreens they are much safer to human health and also environmentally friendly and may not require re-application every 2 hours recommended for use of current sunscreens [3,55]. Of note, the tissue regenerative property of propylene glycol can be usually demonstrated in a few days by applying an aqueous solution of about 30 to 70% to the cuticle area of big toenail 2 to 3 times a day [54]. ...
Article
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Currently the FDA adopts a zero-tolerance policy toward sun exposure in order to prevent skin cancer and premature skin aging (photoaging). This is apparently based on classical concept that damage from sunlight, a carcinogen, is cumulative and un-reparable. Such concept is apparently flawed both theoretically and in reality. The nature’s design to achieve genomic stability of body health and appearance for smooth passage of generations in our normal daily lives would require virtually complete repair of damages of DNA and other tissue components from daily Exposure to Non-Burning Sunlight (ENS). In other words, ENS is generally not expected to cause skin cancer and photoaging. Such notion is evidenced by, for example, low worldwide skin-cancer incidences, severe sunburn as overwhelming skin-cancer etiology, and intrinsic aging as overwhelming skin aging. Since ENS can provide numerous health benefits, such exposure can be regarded as healthy sun exposure and used to help prevent skin cancer. Due to unintended sunburn effect, use of sunscreens for intense intermittent exposure is strongly discouraged. As photoaging and skin cancer may be closely related, some questions related to conventional theories and practices in photoaging are also raised. They include the following: Schuster’s pioneering study in 1975; invalidation of accelerated aging theory; questionable theory on etiology of wrinkles and age spots; Fisher’s studies on metalloproteinases; bolus doing vs constant-rate dosing in irradiation; moisturizers as anti-photoaging/anti-cancer agents; inclusion of blood and water in skin-aging exosome; wind effect; differences in usage pattern between countries in sunscreen evaluation; replacement of UVA in tanning beds.
... After maximal use (4 times a day to 75% body surface area), increasing plasma concentrations above the FDA's safe threshold of 0.5 ng/mL were found between days 1-4 after application [86]. While concentrations for avobenzone, octocrylene, homosalate, octisalate, and octinoxate ranged from 7-50 times the FDA threshold, benzophenone-3 was detected at levels 500 times the FDA approval level [87]. ...
Article
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Photoprotection is a critical health prevention strategy to reduce the deleterious effects of ultraviolet radiation (UVR) and visible light (VL). Methods of photoprotection are reviewed in this paper, with an emphasis on sunscreen. The most appropriate sunscreen formulation for personal use depends on several factors. Active sunscreen ingredients vary in their protective effect over the UVR and VL spectrum. There are dermatologic diseases that cause photosensitivity or that are aggravated by a particular action spectrum. In these situations, sunscreen suggestions can address the specific concern. Sunscreen does not represent a single entity. Appropriate personalized sunscreen selection is critical to improve compliance and clinical outcomes. Health care providers can facilitate informed product selection with awareness of evolving sunscreen formulations and counseling patients on appropriate use. This review aims to summarize different forms of photoprotection, discuss absorption of sunscreen ingredients, possible adverse effects, and disease-specific preferences for chemical, physical or oral agents that may decrease UVR and VL harmful effects.
... Despite the proven advantages of regular sunscreen application (from reducing the effects of photoaging to protecting against skin cancer) [71,72], there are some concerns about the systematic and regular use of sunscreens and the effect on vitamin D synthesis, especially in older people; nonetheless, there is plenty of evidence that deny those claims and assure that the usage of sunscreens does not affect levels of vitamin D [73][74][75]. Another concern with sunscreens is the skin absorption of the most used active ingredients, such as avobenzone and oxybenzone, among others, resulting in high plasmatic levels [5,6]. In addition to these health concerns, the damage these organic ingredients cause to the environment has been studied [76,77]. ...
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The photolyase family consists of flavoproteins with enzyme activity able to repair ultraviolet light radiation damage by photoreactivation. DNA damage by the formation of a cyclobutane pyrimidine dimer (CPD) and a pyrimidine-pyrimidone (6-4) photoproduct can lead to multiple affections such as cellular apoptosis and mutagenesis that can evolve into skin cancer. The development of integrated applications to prevent the negative effects of prolonged sunlight exposure, usually during outdoor activities, is imperative. This study presents the functions, characteristics, and types of photolyases, their therapeutic and cosmetic applications, and additionally explores some photolyase-producing microorganisms and drug delivery systems.
... New data Matta et al. (2019) determined in healthy volunteers whether Octocrylene was absorbed into the systemic circulation. A randomized clinical trial, which was conducted at a phase 1 clinical pharmacology unit in the United States, enrolled 24 healthy volunteers. ...
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SCCS OPINION ON Octocrylene - SCCS/1627/21- Final Opinion U. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads, M. Dusinska, J. Ezendam, E. Gaffet, C. L. Galli, B. Granum, E. Panteri, V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. Wijnhoven, A. Koutsodimou, W. Uter, N. von Goetz The SCCS adopted this document at its plenary meeting on 30-31 March 2021 (49 pages) Published:30 December 2021 Ed. Publications Office of the European Union, Luxembourg, Luxembourg (49 pages) ISSN : 1831-4767 ISBN : 978-92-76-54695-5 DOI : https://data.europa.eu/doi/10.2875/955656 Catalog Number : EW-AQ-22-003-EN-N https://op.europa.eu/fr/publication-detail/-/publication/37fff3c6-21c8-11ed-8fa0-01aa75ed71a1 https://op.europa.eu/fr/publication-detail/-/publication/37fff3c6-21c8-11ed-8fa0-01aa75ed71a1/language-en/format-PDF/source-264520134
... Benzofenon-3 wydalany jest z organizmu głównie z moczem, po związaniu z kwasem glukuronowym [28]. Końcowy okres półtrwania jest długi, a sam związek w osoczu ulega akumulacji [31]. ...
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A ultraviolet filter is defined as a substance, mixture, or material that blocks or absorbs radiation in the UV range, and its key purpose is protect the skin from the harmful effects of the radiation. Consumer concern is mainly regarding organic filters and the frequent problems with their low photo-stability, which is highly undesirable in terms of safety. The aim of this work was to discuss the term “photo-stability” and to assess the safety of the three most popular compounds classified as ultraviolet filters. Cited studies and issued opinions by Scientific Committees on Customer Safety confirm the safety for human health of Avobenzone, Oxybenzone and Octinoxate in strictly defined maximum concentrations. Side effects of these filters, like accumulation in the bloodstream, may occur after prolonged use. In order to improve the level of photo-stability of Avobenzone and Octinoxate the following methods are used: the use of photo-stabilizers and excited state quenchers, encapsulation of the molecule in micelles or the addition of antioxidants such as vitamin C. Although these compounds do not pose a serious threat to human health, two of them (Oxybenzone and Octinoxate) have a negative impact on aquatic ecosystems.
... According to previous studies, in vitro and in vivo percutaneous absorption studies on common UV filters including benzophenone-3 (BP-3), octyl-methoxycinnamate (OMC) and 3-(4-methylbenzylidene) camphor (4-MBC) after topical application indicated skin permeability (Janjua et al., 2004;Montenegro et al., 2018). In this preliminary study reported by Matta et al. (2019Matta et al. ( , 2020, there was the presence of systemic absorption of sunscreen active ingredients (avobenzone, oxybenzone, octocrylene, ecamsule, octisalate, octinoxate, homosalate) under maximal use conditions resulted in adverse effects such as rash, milia, and pruritis. The study from Janjua et al. (2004) reported the substantial skin penetration, systemic uptake, and urinary excretion of UV filters both in plasma and urine after topical application. ...
Article
There is a risk of toxicological reactions due to systemic absorption and photo-instability of sunscreens. The study aimed to investigate the safety profile (cytotoxicity, phototoxicity, photostability, UV filter release profile, and skin irritation properties) of sunscreen (NLC-TRF sunscreen) produced from nanostructured lipid carriers (NLCs) and tocotrienol-rich fraction (TRF). The cytotoxicity and phototoxicity of the sunscreen were evaluated on normal human dermal fibroblast (NHDF) and skin irritation properties was tested on skin model. Besides, the photoprotection in pre- and post-UV irradiation were analysed to determine the photostability. Additionally, the release profile for UV filters (diethylamino hydroxybenzoyl hexyl benzoate (DHHB) and ethylhexyl triazone (EHT)) were evaluated. The NLC-TRF sunscreen demonstrated no cytotoxicity and skin irritation to cause cell death. It showed no phototoxic effect and high photostability up to 10 Minimal Erythema Dose (MED) to ensure high SPF value above 50 and broad-spectrum of UV absorption. The NLC-TRF sunscreen implies its safety for topical application with sustainable release profile for UV filter (cumulative release of 28% for DHHB and 40% for EHT after 8 h) due to the application of NLCs. The results suggest that the NLC-TRF sunscreen is an advanced formulation with improved stability and is safe for topical delivery.
... UV-filters are of interest in a wide range of applications either to directly protect the consumer against UV radiation exposure or to prevent degradation of goods caused by exposure to UV radiation. In recent years, several molecules widely used in sunscreen formulations have been subject to criticism, mainly due to their potential toxicity towards human (Matta et al., 2019;Matta et al., 2020) and environmental health (Schneider and Lim, 2019). As a consequence, the need to provide safe, bio-based and eco-friendly alternatives has grown exponentially. ...
Article
Full-text available
Although organic UV filters are extensively used in cosmetics to protect consumers from the deleterious effects of solar UV radiation-exposure, they suffer from some major drawbacks such as their fossil origin and their toxicity to both humans and the environment. Thus, finding sustainable and non-toxic UV filters is becoming a topic of great interest for the cosmetic industry. A few years ago, sinapoyl malate was shown to be a powerful naturally occurring UV filter. Building on these findings, we decided to design and optimize an entire value chain that goes from biomass to innovative biobased and non-toxic lignin-derived UV filters. This multidisciplinary approach relies on: (1) the production of phenolic synthons using either metabolite extraction from biomass or their bioproduction through synthetic biology/fermentation/in stream product recovery; (2) their functionalization using green chemistry to access sinapoyl malate and analogues; (3) the study of their UV-filtering activity, their photostability, their biological properties; and (4) their photodynamics. This mini-review aims at demonstrating that combining biotechnology, green chemistry, downstream process and photochemistry is a powerful approach to transform biomass and, in particular lignins, into high value-added innovative UV filters.
... Sunscreens offer the most diverse selection of marketed vehicle types all while being comparable in the active UV filters that are included. Currently the UV filter with the highest absorptive potential has been reported to be benzophenone-3 (oxybenzone) (45,46). It is included in over 600 marketed sunscreen formulations up to an allowable inclusion limit of 6% as set by the FDA (47). ...
Article
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Purpose It is often unclear how complex topical product formulation factors influence the transport kinetics through skin tissue layers, because of multiple confounding attributes. Environmental factors such as temperature effect are also poorly understood. In vitro permeation testing (IVPT) is frequently used to evaluate drug absorption across skin, but the flux results from these studies are from a combination of mechanistic processes. Method Two different commercially available formulations of oxybenzone-containing sunscreen cream and continuous spray were evaluated by IVPT in human skin. Temperature influence between typical skin surface temperature (32°C) and an elevated 37°C was also assessed. Furthermore, a multiphysics-based simulation model was developed and utilized to compute the flux of modeled formulations. Results Drug transport kinetics differed significantly between the two drug products. Flux was greatly influenced by the environmental temperature. The multiphysical simulation results could reproduce the experimental observations. The computation further indicated that the drug diffusion coefficient plays a dominant role in drug transport kinetics, influenced by the water content which is also affected by temperature. Conclusion The in vitro testing and bottom-up simulation shed insight into the mechanism of dermal absorption kinetics from dissimilar topical products.
... Moreover, given that these filters have a long half-life, usually greater than 48 h, repeated use means they can be detected in blood up to 17 days after the last application. 52,53 Similarly, although UV filters or their derivatives may reach humans via the food chain, to date, there have been no reports of toxic effects. ...
Article
Resumen Los filtros ultravioleta (UV) se han convertido en compuestos de uso diario para millones de personas. Sin embargo, algunos de ellos no son biodegradables al 100% y las plantas de tratamiento de aguas residuales muchas veces no son capaces de filtrarlos correctamente. Todo ello está llevando a su diseminación ambiental y a la detección de distintos filtros UV en el suelo, las aguas continentales, los océanos y en múltiples organismos (algas, corales, peces, mamíferos, incluso aves terrestres). Además, algunos filtros UV, especialmente la benzofenona-3 y el octocrileno se han mostrado tóxicos en estos organismos. Entre sus efectos tóxicos destacamos el blanqueamiento de los corales y problemas metabólicos, enzimáticos y de capacidad reproductiva en prácticamente cualquier organismo. Existen datos preliminares sobre la posible bioacumulación de estos filtros UV en humanos, al detectarse en muestras de orina y leche materna. Sin embargo, el estudio del impacto medioambiental de los filtros UV presenta muchas limitaciones.
... One of the main methods of eliminating BP-3 is excretion with urine, after bonding with glucuronic acid. Importantly, the most recent study by Matta et al. [17] highlighted a long terminal half-life of BP-3 and its accumulation by measuring the plasma concentration at constant intervals over 7 days after the first sunscreen application of products containing 6% of BP-3. ...
Article
Full-text available
Children and adolescents are particularly vulnerable to skin damage caused by ultraviolet radiation and require intensified photoprotection. Benzophenone-3 (BP-3) belongs to the organic sunscreens, which are widely used in personal care and cosmetic products. However, the impact of BP-3 on human health requires a careful assessment. This review focuses on potentially harmful effect of this compound in relation to the developing organism. Studies show that BP-3, after topical application, can penetrate into bloodstream, blood-brain barrier and blood-placental barrier and may induce the reproductive toxicity and abnormal development of the foetus, endocrine system disruption and neurotoxicity in experimental animal models. So far, human studies have been scarce and controversial, therefore the cosmetics containing BP-3 should be carefully used by the pregnant women, children and adolescents.
... Abb. 2 und 3 zeigen deutlich, dass unlösliche Filter -aufgrund ihrer Größe -kaum ins Stratum corneum eindringen können. » Unlösliche UV-Filter können das Stratum corneum nicht durchdringen Lösliche Filter hingegen sind in der Lage, das Stratum corneum in beträchtlichen Mengen zu überwinden, wie wiederholt nachgewiesen wurde[14,15]. Daher ist das Risiko negativer Auswirkungen infolge der Absorption (systemische Bioverfügbarkeit) bei löslichen Filtern höher als bei unlöslichen Filtern. Wie der Zauberlehrling in der gleichnamigen Ballade von Johann Wolfgang von Goethe haben alte und neue Science-Fiction-Geschichten sowie die Medien ein Gespenst geschaffen, von dem wir uns kaum befreien können. ...
Article
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Zusammenfassung Seit den 1950er-Jahren sind anorganische Sonnenschutzmittel mit mikronisiertem Titandioxid (TiO 2 ) und Zinkoxid (ZnO) erhältlich. Deren kosmetische Akzeptanz blieb beschränkt, da sie als weiße Paste auf der Haut zurückbleiben. Durch Verkleinerung der Partikel in den Nanobereich unter 100 nm wurde deren optische Eigenschaft, sichtbares Licht zu reflektieren, verringert. Nach 2000 wurden auch organische Filter in dieser Größenordnung entwickelt. Die damals herrschende Begeisterung für Nanotechnologie übertrug sich nicht auf Sonnenschutzmittel mit nanopartikulären Filtern. Verbraucher vermuten, dass die Partikel durch die Haut dringen, vom Blut aufgenommen werden, sich im Körper verteilen und Krankheiten verursachen. Nicht zuletzt aufgrund von Druck der Öffentlichkeit wurden Kosmetika – zu denen auch Sonnenschutzmittel gehören – das erste Produktsegment, in dem nanopartikuläre Stoffe strengen Regeln unterworfen wurden. Trotz fortschrittlicher Regulierung und strenger Zulassungsverfahren für nanopartikuläre Filter blieben Vorbehalte bestehen. Mögliche Gründe dafür sind mangelnde Kenntnisse über die geltenden Rechtsvorschriften oder Misstrauen gegenüber diesen, unklare Vorstellungen über das Verhalten von Nanopartikeln in Sonnenschutzmitteln und infolgedessen eine unklare Wahrnehmung von Gefahr, Risiko und Exposition. Vor diesem Hintergrund werden das Wesen und Verhalten von nanopartikulären Filtern in Sonnenschutzmitteln auf der Haut und potenziell in der Haut sowie der Regulierungsrahmen, der sicherstellt, dass nanopartikuläre Filter und die sie enthaltenden Sonnenschutzmittel sicher in der Anwendung sind, diskutiert.
... 47 Consequently, studies on the risks of systemic absorption and detection of plasma concentrations of UV filters have been published, which do not imply toxicity or that they are harmful to health. 59 In addition, the FDA has proposed increasing the maximum SPF value reported by manufacturers from 50+ to 60+ and adding a test to ensure broad and uniform protection against both UVB and UVA. 60 In Europe, sunscreens are classified as cosmetics; however, quality requirements are equally high; the allowed UV filters are regulated by Annex VI of the Cosmetics Regulation (EC N. 1223/2009), and the parameters established for labeling are: SPF with a maximum value of 50+ and UVAPF with a value of at least one-third of the UVB protection. ...
Article
Full-text available
The skin is regularly exposed to several environmental aggressions, including solar radiation, whose biological effects can induce sunburn, dyschromia, skin aging and cancer. Among the photoprotection measures, sunscreens comprise a relevant part of the strategy aimed to prevent solar radiation damage and, for effective action, the patient must adhere to the product use and the latter, in turn, must follow technical parameters to promote adequate protection. This review article brings together the most current and relevant concepts about photoprotection for dermatological use, including the challenges for their formulation, the risks of certain photoprotective active substances for individual and environmental safety and the importance of stringency in determining the product efficacy, considering the regulatory aspects, highlighting relevant differences between Brazil and other countries. Thus, when assessing a sunscreen, not only the visual aspects and sensory perception will be immediately evaluated, but also the quality and suitability of the vehicle, the chemical composition of the formulation, the environmental risks, the photostability of the screening system, and the measurement of its protection spectrum. Technical knowledge of sunscreens can help dermatologists in this important role of educating patients about the best photoprotective strategies in each situation.
... Our tests show that alcohol is not essential for photostabilization of UV filters in sunscreen products, especially since it is a penetration enhancer 22,23 . This is an unwanted phenomenon since UV filters, such as butylmethoxydibenzoylmethane, show increased transdermal penetration, known as passing the skin barrier 24 . ...
Article
Objective: Spray formulations are currently under development in the field of topical photoprotection. Such forms are characterized by their high fluidity, a property that is obtained by the presence of alcohol in the formula. The purpose of this work was to study the influence of ethanol in sunscreens on the photoprotective efficacy as well as the photostability of UV filters. Materials and methods: The filters tested were octyl methoxycinnamate (OMC), PEG-25 PABA, octyl salicylate and butyl methoxydibenzoylmethane (BMDBM) at their maximum concentration authorized by European regulations and in the presence of increasing amounts of alcohol, up to 15% (w/w). Results: The effect of the presence of alcohol on the efficacy of the filters and their photostability varies depending on the molecule considered. Alcohol has no effect on octyl salicylate, either on its efficacy or its photostability. However, filter stabilization is seen for BMDBM and PEG-25 PABA. Conclusions: Although these differences are significant, they are not great enough to justify large-scale use of ethanol in sunscreen products due to some of its properties, such as flammability.
... Because SS is known to be predominantly caused by intense UVB radiation and chronic nonburning sun exposure may not have significant adverse effects on skin aging, the need of using organic sunscreen ingredients in our daily lives for protection against UVA may need to be reconsidered, especially in view of their potential percutaneous absorption and long-term adverse effects [3,6,[12][13][14][15]. It is hoped that the present work may stimulate further debate and study on the need of using broad-spectrum sunscreens in our daily lives. ...
Article
Sun protection behavior can reduce skin cancer risk. This paper provides an overview of skin cancer risk and the complex behavioral options for sun protection, along with a narrative review of research on determinants of, and interventions to promote, sun protection. Gaps and opportunities for future research are also outlined. Evidence supports the effectiveness of sunscreen use, ultraviolet (UV) protection clothing, and shade seeking. However, these behaviors are complex and are often performed in ways that are inadequate for sun protection. Most research examining and targeting determinants of sun protection behavior has focused on sunscreen use, to the exclusion of other strategies, and has largely ignored the complexity of even sunscreen use. Most research and interventions are theory- driven, drawing on social cognitive constructs, but also considering self and social identity and emotion. Multilevel perspectives considering context, environment, policies, and other structural contexts have also been applied to sun protection behavior, but there is a need to combine psychological constructs with factors at other levels to optimize predictive models and intervention effectiveness. Effective sun protection effectively involves complex behaviors and perceived and actual tradeoffs that should be considered, in combination with multilevel determinants, in research predicting and promoting sun safety.
Article
Environmental chemicals are a persistent and pervasive part of everyday life. A subset of environmental chemicals are xenoestrogens, compounds that bind to the estrogen receptor (ER) and drive estrogen-related processes. One such chemical, benzophenone-3 (BP3), is a common chemical in sunscreen. It is a potent UV protectant but also is quickly absorbed through the skin. While it has been approved by the FDA, there is a renewed interest in the safety of BP3, particularly in relation to breast cancer. The focus of this study was to examine the impact that BP3 has on triple negative breast cancer (TNBC) through alterations to cells in the immune microenvironment. In this study, we exposed female mice to one of two doses of BP3 before injecting them with a TNBC cell line. Several immune endpoints were examined both in the primary tissues and from in vitro studies of T cell behavior. Our studies revealed that in the lung tumor microenvironment, exposure to BP3 not only increased the number of metastases, but also the total area of tumor coverage. We also found that BP3 caused alterations in immune populations in a tissue-dependent manner, particularly in T cells. Taken together, our data suggest that while BP3 may not directly affect the proliferation of TNBC, growth and metastasis of TNBC-derived tumors can be altered by BP3 exposures via the alterations in the immune populations of the tumor microenvironment.
Article
The purpose of the current investigation was to develop multifunctional TiO2-embedded mesoporous silica incorporating avobenzone to protect against environmental stress through pollutant adsorption and UVA protection. We sought to explore the effect of the mesoporous porosity on the capability of contaminant capture and the suppression of avobenzone skin penetration. The porosity of the mesoporous silica was tuned by adjusting the ratio of template triblock copolymers (Pluronic P123 and F68). The Pluronic P123:F68 ratios of 3:1, 2:2, and 1:3 produced mesoporous silica with pore volumes of 0.66 (TiO2/SBA-L), 0.47 (TiO2/SBA-M), and 0.25 (TiO2/SBA-S) cm³/g, respectively. X-ray scattering and electron microscopy confirmed the SBA-15 structure of the as-prepared material had a size of 3–5 μm. The maximum adsorbability of fluoranthene and methylene blue was found to be 43% and 53% for the TiO2/SBA-S under UVA light, respectively. The avobenzone loaded into the mesoporous silica demonstrated the synergistic effect of in vitro UVA protection, reaching an UVA/UVB absorbance ratio of near 1.5 (Boots star rating = 5). The encapsulation of avobenzone into the TiO2/SBA-S lessened cutaneous avobenzone absorption from 0.76 to 0.50 nmol/mg, whereas no reduction was detected for the TiO2/SBA-L. The avobenzone-loaded TiO2/SBA-S hydrogel exhibited a greater improvement in skin barrier recovery and proinflammatory mediator mitigation compared to the SBA-S hydrogel (without TiO2). The cytokines/chemokines in the photoaged skin were reduced by two- to three-fold after TiO2/SBA-S treatment compared to the non-treatment control. Our data suggested that the mesoporous formulation with low porosity and a specific surface area showed effective adsorbability and UVA protection, with reduced UVA filter absorption. The versatility of the developed mesoporous system indicated a promising potential for outdoor skin protection.
Article
Background: Availability of new UV filters in the United States lags behind the European Union (EU), partly due to differing approval processes. Objective: To review available human safety data of all US- and EU-approved UV filters. Methods: Data from Food and Drug Administration and EU regulatory guidelines, federal governmental documentation, databases, reviews, and opinions for approval and ongoing safety evaluation were analyzed. Results: Currently, there are 17 US UV filters and 29 EU UV filters (18 EU-approved only filters). Almost all US filters possessed sensitization data (94%, 16/17) with the majority (76%, 13/17) showing minimal skin sensitization. The minority of EU-approved only filters (33%, 6/18) possessed sensitization data, all showing no sensitization. Some filters possessed dermal absorption data (US: 76%, 13/17; EU: 44%, 8/18). Oxybenzone, octinoxate, octisalate, homosalate, and octocrylene, approved in the US and EU, were shown to have plasma levels exceeding the Food and Drug Administration exposure threshold. Limitations: Proprietary manufacturer human data were unavailable. Conclusions: Many new UV filters are available in the EU, but not yet in the United States. Rigorous US and EU guidelines ensure that UV filters provide adequate photoprotection assuming consumers follow American Academy of Dermatology SPF (sun protection factor) and broad-spectrum recommendations. Human data are limited, but known human risks of sunscreen appear minimal.
Article
Full-text available
The aim of this study was to evaluate in vitro skin permeation and deposition, in vivo toxicokinetics, percutaneous absorption and tissue distribution of benzophenone-3 (BP-3) in rats. Four transdermal formulations containing BP-3 were prepared and evaluated for in vitro skin permeation and deposition of BP-3 using Franz diffusion cells. A gel formulation was used in subsequent in vivo percutaneous absorption due to its high in vitro skin permeation and deposition. Compared to intravenous (i.v.) injection, the prolonged terminal t1/2 (3.1 ± 1.6 h for i.v. injection and 18.3 ± 5.8 h for topical application) was observed indicating occurrence of flip-flop kinetics after topical application. The bioavailability of BP-3 after topical application was 6.9 ± 1.8%. The tissue-to-plasma partition coefficient (kp) for testis, considered a toxic target for BP-3, was less than 1.. Overall, findings of this study may be useful for risk assessment of BP-3.
Article
Chronic exposure of skin to ultraviolet (UV) radiation is responsible for skin ageing, which includes degradation of the epidermal and dermal layers. Filtering UV light is key in the sunscreen industry. We studied the effects of organic UV filters on hyaluronan (HA) metabolism and skin hydration in human HaCaT keratinocytes. The gene expression of HA receptors, HA synthase (HAS), hyaluronidase (HYAL), and water channel aquaporin 3 (AQP3) was evaluated by quantitative RT–PCR. The state of oxidative stress was determined by measuring the intracellular levels of reactive oxygen species (ROS). The results showed that five organic UV filters reduced the extracellular contents of HA, and a phosphatidylinositol 3-kinase (PI3K) inhibitor partially restored the decreased HA levels after octinoxate, octocrylene, and oxybenzone treatment. The expression levels of HA receptors, including cluster of differentiation 44 (CD44), receptor for hyaluronic acid-mediated motility (RHAMM), and toll-like receptors (TLRs), were determined. Avobenzone, octinoxate, oxybenzone, and padimate O exerted inhibitory effects on RHAMM expression. Oxybenzone led to a significant increase in CD44 and AQP3 expression. Both octinoxate and octocrylene increased TLR4 expression but decreased ROS accumulation by activating the PI3K pathway. However, the organic UV filters differentially regulated the mRNA expression of HAS and HYAL. Taken together, these results suggest that certain organic UV filters regulate HA metabolism in human keratinocytes in a PI3K pathway-dependent manner.
Article
Calcium phosphates (CaPs) have been recently proposed as a bio- and eco-compatible alternative to UV filters in sunscreens, which are in the spotlight for being associated with health risks for both people and the environment. Here, natural CaPs extracted from fish bones have been tested as a booster of the sun protection factor (SPF), that is, as material working in synergy with UV filters to increase sunscreen UV-shielding efficiency, in combination with three of the most used UV filters, namely, octocrylene (OCR), octinoxate, and padimate-O, at different concentrations (10.0 and 20.0 wt %). The material obtained by calcination at 800 °C (CaP-N) was also enriched with Zn (CaP-Zn) or Mn (CaP-Mn) in an attempt to increase its SPF-boosting abilities. CaP-N and CaP-Zn consisted of a biphasic mixture of hydroxyapatite and beta tricalcium phosphate, while CaP-Mn presented a small quantity of Mn oxides. CaP-N was the most effective at increasing the SPF of the final emulsions, doubling the SPF of the formulation containing 20.0 wt % of OCR from 40.6 to 80.8. The results show that these CaPs, produced according to a circular economy approach, can be used as effective SPF boosters to decrease the concentration of UV filters used in sunscreen, while retaining high SPF values.
Article
One of organic ultraviolet (UV) filters, Octocrylene (OCL), is mainly used in various cosmetic products, which is being frequently detected in soil, sediment, aquatic systems and food chain. There is evidence confirmed the reproductive toxicity of OCL in Japanese medaka. However, less was known about the effects of OCL exposure on oocyte quality. Here, we investigated the impacts of OCL on mouse oocyte maturation and quality by exposing oocytes to OCL in vitro at concentrations of 8, 22, 30, 40 and 50 nM. The results showed that OCL markedly reduced mouse oocyte germinal vesicle breakdown (GVBD) at 50 nM and polar body extrusion (PBE) rates at 40 and 50 nM. OCL exposure further disrupted spindle assembly and chromosome alignment, finally inducing aneuploid. Mitochondrial function was also damaged by OCL exposure, leading to ROS overproduction and apoptosis in oocytes. Moreover, OCL treatment impaired the distribution of cortical granules and sperm binding ability of oocytes. In summary, these data demonstrated that OCL could disturb the oocyte meiotic maturation and reduce oocyte quality.
Article
Photoaging is a complex process of skin changes associated with chronic ultraviolet exposure. Prevention with photoprotection and treatment with topical retinoids are the core components of a topical antiaging regimen. Other topicals such as hydroquinone, vitamin C, niacinamide, and alpha hydroxyl acid can be added based on specific concerns. However, caution must be used with some of these products as the stability and absorption are major considerations. A simple topical regimen will reduce irritability and enhance compliance.
Article
Sunscreens provide excellent protection against erythema and against chronic damage such as photoaging and skin cancer. Today’s challenges concern safety of the products and improved methods for standardizing the evaluation of their efficacy. Other important topics are the further development of sunscreen products, as well as personalization of use. Personalized sun protection based on the phenotype, the genetic profiles and moreover the skin’s microbiome — all linked to the identification of certain consumer susceptibility factors — is an exciting new area of research. In particular, the expansion with innovative topical agents such as DNA repair liposomes in improved galenic formulations with UV filters tailored to the skin phototype and new topical antioxidants could in future provide even more comprehensive sun protection. New antioxidants and other agents such as nicotinamide could increase systemic photoprevention. Sustainability will also be an important aspect to protect consumers, but also the environment (i.e. especially marine wildlife) from toxic effects of sunscreens.
Article
UV filters are used daily by millions of people. Not all of these filters, however, are 100% biodegradable, and many wastewater treatments plants are ill-equipped to filter them properly. As a result, UV filters are increasingly reaching the environment. Various types have been detected in soil, continental water, oceans, and numerous organisms, including algae, corals, fish, mammals, and even land birds. In addition, some filters, benzophenone-3 and octocrylene in particular, are toxic to these organisms. Toxic effects include coral bleaching and interference with metabolic, enzymatic, and reproductive activities in practically all organisms. Preliminary data suggest that UV filters may be bioaccumulating in humans, as they have been detected in urine and breast milk. It should be noted, however, that research into the environmental impact of UV filters holds challenges and limitations.
Article
Due to high variability during clinical pharmacokinetic (PK) evaluation, the prediction of in vivo exposure from in vitro absorption testing of topical semisolid and liquid dermal products has historically proven difficult. Since absorption from unoccluded formulations can be influenced by environmental factors such as temperature and humidity, maximal effort must be placed on the harmonization of experimental parameters between in vitro and in vivo testing conditions to establish accurate in vitro/in vivo correlations (IVIVC). Using four different sunscreen formulations as a model, we performed in vitro permeation testing (IVPT) studies with excised human skin and maintained strict harmonization techniques to control application time, occlusion, temperature, and humidity during in vivo human serum PK evaluation. The goal was to investigate if increased control over experimental parameters would result in decreased inter-subject variability of common topical formulations leading to acceptable IVIVC establishment. Using a deconvolution-based approach, excellent point-to-point (Level A correlation) IVIVC for the entire 12-h study duration was achieved for all four sunscreen formulations with < 10% prediction error of both area under the curve (AUC) and peak concentration (Cmax) estimation. The low variability of in vivo absorption data presents a proof-of-concept protocol design for testing of complex semisolid and liquid topical formulations applied over a large surface area with reapplication in a reliable manner. This work also presents the opportunity for expanded development of testing for the impact of altered temperature and humidity conditions on product absorption in vivo with a high degree of precision.
Article
Accumulating evidence from numerous comprehensive studies has demonstrated that blue light, in particular high‐energy visible light, can exert a range of harmful effects on skin cells. These forms of radiation are now known to be able to trigger oxidation reactions, DNA damage, erythema and pigmentary changes, and may also be associated with photoaging. Sunscreens protecting the skin from only ultraviolet (UV)‐B and UVA rays can therefore no longer be regarded as sufficient to help prevent skin damage from sunlight, and products containing filters that can provide broad‐spectrum photoprotection are required. To meet this need, a new sunscreen formulation that provides photoprotection against solar radiation with wavelengths ranging from UV to visible light has been developed, using an innovative organic sun filter with unique optical properties: phenylene bis diphenyltriazine (TriAsorB™). This article outlines the development and characteristics of this innovative filter and describes new key results from studies performed to assess the effectiveness and safety of the filter and the new sunscreen product. The studies conducted so far demonstrate that the filter has a good human and environmental safety profile. In addition, the sunscreen, which contains TriAsorB in combination with three other UV filters to offer broad‐spectrum sun protection with a high sun protection factor (SPF50+), appears to effectively prevent multiple forms of cellular photodamage, in particular blue light‐induced oxidatively generated DNA lesions. Overall, the available data indicate that regular use of the TriAsorB‐containing sunscreen could help prevent solar radiation‐induced skin damage and the development of signs of premature skin aging, as well as photodermatoses caused or exacerbated by visible light.
Article
The direct use of naturally occurring, small molecular ingredients in bioinspired sunscreens has raised several concerns due to the instability, photocytotoxicity, and potential blood toxicity of those ingredients. In this work, we have employed natural ultraviolet (UV)-blocking molecule caffeic acid phenethyl ester (CAPE) from propolis to prepare poly(CAPE) nanoparticles (NPs) as the main bioactive ingredient to fabricate propolis-inspired hydrogel sunscreens. Compared with small molecular CAPE, poly(CAPE) NPs exhibited better dispersion and stability in water, as well as lower physiological toxicity and skin permeability. And the resulting composite hydrogels demonstrated promising properties including water-resistant whereas can be easily erased by warm water as well as safety when interacting with skin. More importantly, the hydrogel sunscreens showed excellent UV protection properties both in vitro and in vivo, and the positive effects in maintaining skin barrier functions. This work provides new strategies towards the facile construction of nature-inspired robust sunscreens in the future.
Article
The concentration of a formulation, defined as the mass of applied chemical per unit of skin surface area, is a key variable of skin absorption. Often only one concentration is available in the literature, hence a general evidence-based theory could allow prediction of how altering the concentration would produce a linear, increased, or decreased relative permeation. Here, we group topical chemicals into groups of how they permeate the skin when we increase or decrease their concentrations per unit area and discuss why we would like to predict their permeability in ranges of studied concentrations. Purpose Our research question is: How, if at all, do changes in surface chemical concentration affect percutaneous penetration/absorption in man? Specifically, as the drug concentration is relatively increased, is the rate or extent of absorption proportionally affected? And if so, how? Methods We searched PubMed, Google Scholar, the United States Food and Drug Administration, Scientific Committee on Consumer Safety, and the European Food Safety Authority for approved transdermal delivery systems from January 1965 to October 2020. Search terms included combinations of the following words: topical + [absorption/penetration] + cm + [human/man]. Results Of the nineteen chemicals identified, five (testosterone, hydrocortisone, benzoic acid, fluazifop-butyl and lindane) showed decreased percent absorbed with increased dose, one (2-butoxyethanol) showed decreased flux with increased concentration, and thirteen (Basic Brown 17, benzene in gasoline, benzophenone-3, benzoyl peroxide, boric acid, caffeine, climbazole, diclofenac, ethanolamines, ibuprofen, N-octylamine, 2-phenoxyethanol, 2-pyrrolidone) showed increased flux with increasing concentrations. Conclusion Dermal absorption depends on the interaction between the characteristics of the substance, the vehicle, and the skin. Without experiments investigating these characteristics, we cannot accurately predict the percent absorbed or flux of a formulation without in vitro or in vivo data. More experimental data, especially in vivo, is mandated before a highly efficient prediction model will be reached for validation.
Article
The benefits of sunscreen use have been well‐established. However, discussion of its risks remains on the internet. Given this point of controversy, a web search of 50 websites on children's sun safety was performed and indicated that the information online is variable and incomplete when informing parents on the benefits and risks of sunscreen use.
Article
Evaluating the dermal absorption of sunscreen UV filters requires the development of a bio-predictable in vitro permeation test (IVPT). This work describes the comparison of two IVPT methods and rank order correlations of in vitro absorption (skin permeation and retention) with the in vivo absorption (AUC and skin retention) of sunscreens. The IVPT was compared regarding the following elements: (1) application of a single finite dose vs. an infinite dose and (2) the use of heat-separated human epidermis vs. dermatomed skin models. The IVPT was used to evaluate dermal absorption of six UV filters (avobenzone, homosalate, octinoxate, octisalate, octocrylene, and oxybenzone) in commercial sunscreens. Both the in vivo and in vitro permeation studies demonstrated that all UV filters were absorbed following a single-dose application. Sunscreens were rank ordered by the amount of the UV filters absorbed. Data obtained from the IVPT method using a single finite dose and heat-separated human epidermis was found to correlate with the clinical data. Rank orders of the cumulative in vitro skin permeation and the in vivo AUC were found comparable for oxybenzone, homosalate, octisalate, and octinoxate. Rank orders of the in vitro and in vivo skin retention of oxybenzone and octinoxate were also comparable. Additional IVPT parameters may be optimized to enhance the discriminatory power for UV filters with low skin permeation potential (e.g., avobenzone and octocrylene).
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Polyphenols are a class of compounds widely existing in living species ranging from plants, fungi, bacteria to animals, and possess various interesting functions such as anti-inflammatory, immunomodulatory, anti-oxidative and anti-ultraviolet...
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Risk-benefit assessment of sunscreen use and risk assessment of UV filters using systematic approach methodology. Scripts (R) for exposure assessment of UV filters are available (https://vkm.no/english/riskassessments/allpublications/riskbenefitassessmentofuseofsunscreen.4.13dd6752161d1e853a116433.html).
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Sunscreens provide excellent protection against erythema and against chronic damage such as photoaging and skin cancer. Today's challenges concern safety of the products and improved methods for standardizing the evaluation of their efficacy. Other important topics are the further development of sunscreen products, as well as personalization of use. Personalized sun protection based on the phenotype, the genetic profiles and moreover the skin's microbiome - all linked to the identification of certain consumer susceptibility factors - is an exciting new area of research. In particular, the expansion with innovative topical agents such as DNA repair liposomes in improved galenic formulations with UV filters tailored to the skin phototype and new topical antioxidants could in future provide even more comprehensive sun protection. New antioxidants and other agents such as nicotinamide could increase systemic photoprevention. Sustainability will also be an important aspect to protect consumers, but also the environment (i.e. especially marine wildlife) from toxic effects of sunscreens.
Article
Rationale: Systemic absorption of UV filtering chemicals following topical application of sunscreens may present a safety concern. FDA had recommended an in vitro skin permeation test (IVPT) to evaluate the potential of this safety risk for the evaluation of sunscreens prior to clinical studies. Therefore, a sensitive and robust bioanalytical method(s) were required for IVPT studies of different topical sunscreen products. Methods: An analytical procedure to quantitate sunscreen UV filtering components and excipients in IVPT samples including avobenzone, octocrylene, oxybenzone, ecamsule, methylparaben and propylparaben was developed employing a RapidFire 360 robotic sample delivery system coupled with a tandem quadrupole mass spectrometer. The analytical procedure was developed and validated according to the requirements of the FDA Bioanalytical Method Validation Guidance for Industry (2018). Results: The analytical method provided a turnaround time of 12 seconds per sample and was determined to be accurate, precise, specific, and linear over the corresponding analytical ranges. The validated method was successfully applied for two IVPT studies for evaluating the skin permeation potential of UV filtering chemicals and assisting with the selection of the sunscreen products for the clinical study conducted by the FDA. Conclusions: This work highlights the first analytical procedure that has applied a non-chromatographic-MS/MS automation platform to an in vitro biopharmaceutics study. The analytical platform simultaneously quantitated four UV filters and two excipients in complex media to evaluate their permeation in IVPT studies. The sample throughput and analytical performance of advanced automation platforms indicate their analytical procedure has the potential to significantly advance the efficiency of IVPT studies to evaluate permeation of a wide variety of UV chemical filters and excipients for topical OTC sunscreen products.
Chapter
Chronic absorption of UV radiation leads to photoaging, sunburn, immunosuppression, and carcinogenesis. Photoaging is the most common form of skin damage caused by UV exposure, affecting connective tissue, melanocytes, and the microvasculature. In photoaged skin, the thickness of the epidermis can either increase or decrease, corresponding to areas of keratinocyte atypia. Changes in the dermis of photoaged skin can vary based on the amount of acquired UV damage. Substantial progress has been made to ascertain the molecular mechanisms accountable for photoaging in human skin. DNA damage and defective DNA repair mechanisms have been implicated in carcinogenesis as well as the intrinsic aging process. One of the histologic hallmarks of photoaging is elastolysis and an accumulation of abnormal elastin in the superficial dermis known as solar elastosis. The pathophysiology of photoaging stems from the ability of UV irradiation to exploit established molecular mechanisms that have evolved to maintain the internal milieu of human skin connective tissue.
Chapter
This chapter presents a basic skin regimen to protect from photodamage and to reverse the appearance of aging. The four necessary steps are cleansing, exfoliation, protection, and treatment. Proper cleansing is an essential component of skincare. The inclusion of medications as components of cleansers can be effective in actually treating the skin. Exfoliation is the rejuvenation treatment providing the most immediate improvement in appearance. The single most effective therapy for aging skin is sun protection. The ability of a sunscreen to prevent UVB‐mediated erythema is measured by the internationally accepted standard sun protection factor, the ratio of equivalent exposure by UVB in sunscreen‐protected compared with unprotected skin. Retinoids are the "gold standard" for reversing photoaging of the skin. The skin naturally uses nutritional antioxidants to protect itself from photodamage and topical application has been investigated. Ferulic acid is a potent antioxidant present in the cell walls of grains, fruits, and vegetables.
Article
Octocrylene (OC) is an extensively prescribed organic ultraviolet B filter used in sunscreen products. Due to its extensive use, a significant level of OC is detected in marine and freshwater environments. Notably, the bioaccumulation of OC in aquatic biota may affect human health. In this study, the effect of OC on metabolism was investigated using the adipogenesis model of human bone marrow mesenchymal stem cells (hBM-MSCs). OC promoted adiponectin production during adipogenesis in hBM-MSCs compared to the vehicle-treated control (EC50, 29.6 μM). In target identification, OC directly bound to peroxisome proliferator-activated receptor (PPAR) γ (Ki, 37.8 μM). OC-bound PPARγ also significantly recruited nuclear receptor coactivator proteins SRC-1 (EC50, 54.1 μM) and SRC-2 (EC50, 58.6 μM). In the molecular docking simulation study, the optimal ligand-binding mode of OC suggested that OC is a PPARγ partial agonist. A competitive analysis with a PPARγ full agonist pioglitazone revealed that OC acted as a PPARγ partial agonist. OC altered the gene transcription profile of lipid-metabolism associated enzymes in normal human keratinocytes, primarily exposed human cells after the application of sunscreens. In conclusion, OC is a potential metabolic disrupting obesogen.
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The potential human health risk of UV filters depends on their toxicity and the human systemic exposure which is a function of the extent of percutaneous absorption of the topically applied substance into the human organism. Using a 'mass balance' approach, a study was designed to investigate the systemically absorbed dose of [(14)C]-Mexoryl SX((R)) in humans after topical application of a typical sunscreen emulsion. In addition, to assess the correlation with in vitro experiments, the percutaneous absorption of this UVA filter through isolated human skin was measured under identical exposure conditions. When applied in vivo for a period of 4 h, 89-94% of the applied radioactivity was recovered from the wash-off samples. In urine samples, the radioactivity slightly exceeded background levels and corresponded maximally to 0.014% of the topically applied dose. No radioactivity was measured in blood or faeces sampled up to 120 h after application. In vitro, 24 h after a 4-hour application, [(14)C]-Mexoryl SX remained primarily on the skin surface. The mean in vitro absorption over 24 h, adding up the amounts found in the dermis and receptor fluid, was 0.16% of the applied dose. It is concluded from the in vivo pharmacokinetic results that the systemically absorbed dose of [(14)C]-Mexoryl SX is less than 0.1%. The order of magnitude of this value correlates well with the corresponding in vitro data which overestimate the in vivo results as previously observed with other hydrophilic compounds. This study demonstrates that, under realistic exposure conditions, the human systemic exposure to this UVA filter is negligible and poses no risk to human health.
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Sunscreens are regulated as over-the-counter drugs in the United States. Some sunscreen ingredients are absorbed into the systemic circulation, which raises concerns about the safety of these drugs. There is limited information on the systemic exposure for most sunscreen ingredients. This report estimates the systemic absorption of two sunscreen active ingredients, oxybenzone and enzacamene, by developing a pharmacokinetic model from published sunscreen absorption data and compares the results with safety thresholds proposed by the US Food and Drug Administration and in the literature. Our analysis indicates that systemic absorption can be substantial, and evaluation of the systemic exposure of sunscreen ingredients is warranted to better assess any long-term risks of use.
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The Food and Drug Administration (FDA) is issuing this document to address labeling and effectiveness testing for certain over-the counter (OTC) sunscreen products containing specified active ingredients and marketed without approved applications. This document addresses labeling and effectiveness testing issues raised by the nearly 2,900 submissions that we received in response to the sunscreen proposed rule of August 27, 2007 (2007 proposed rule). The document also identifies specific claims that render a product that is subject to this rule misbranded or would not be allowed on any OTC sunscreen product marketed without an approved application. The document does not address issues related to sunscreen active ingredients or certain other issues regarding the GRASE determination for sunscreen products. The document requires OTC sunscreen products to comply with the content and format requirements for OTC drug labeling contained in the 1999 Drug Facts final rule (published in the Federal Register of March 17, 1999, by lifting the delay of implementation date for that rule that we published on September 3, 2004).
Article
Due to health concerns about safety, three UV-filters (Benzophenone-3, BP3, 10%; Ethylhexyl Methoxycinnamate, EHMC, 10%; Butyl Methoxydibenzoylmethane, BMDBM; 5%) were examined in vitro for absorption on full-thickness pig-ear skin, mimicking human in-use conditions. Kinetic profiles confirmed the rapid permeation of BP3; after the first hour of skin (frozen-stored) exposure to 2 mg/cm(2) (W/O sunscreen; recommended but unrealistic amount), about 0.5% of the applied dose passed into the receptor fluid. The absorption rate of filters was higher from W/O than from O/W emulsions. The fresh/frozen-stored skin permeability coefficient (0.83-0.54) for each UV filter was taken into account. Systemic Exposure Dosage of BP3, EHMC, BMDBM for humans as a consequence of (i) whole-body and (ii) face treatment with 0.5 mg/cm(2) of W/O sunscreen for 6-h skin exposure followed by washing and subsequent 18-h permeation (a realistic scenario) were estimated to be (i) 4744, 1032 and 1036 μg/kg-bw/day, and (ii) 153, 33 and 34 μg/kg-bw/day, respectively. From Margin of Safety for BP3, EHMC and BMDBM (i) 42, 485 and 192 as well as (ii) 1307, 15151 and 5882, respectively, only the value of 42 (<100) for BP3 indicated a possible health risk. Escalation of a phobia towards all organic UV filters is undesirable. Copyright © 2015. Published by Elsevier Ltd.
Article
Dermatologic diseases can present in varying forms and severity, ranging from the individual lesion and up to almost total skin involvement. Pharmacokinetic assessment of topical drug products has previously been plagued by bioanalytical assay limitations and the lack of a standardized study design. Since the mid-1990’s the US Food and Drug Administration has developed and implemented a pharmacokinetic maximal usage trial (MUsT) design to help address these issues. The MUsT design takes into account the following elements: the enrollment of patients rather than normal volunteers, the frequency of dosing, duration of dosing, use of highest proposed strength, total involved surface area to be treated at one time, amount applied per square centimeter, application method and site preparation, product formulation, and use of a sensitive bioanalytical method that has been properly validated. This paper provides a perspective of pre-MUsT study designs and a discussion of the individual elements that make up a MUsT.
Article
Topical sunscreen products are widely used for protection of the skin against the harmful effects of exposure to ultraviolet radiation. Sunscreen agents are incorporated into many everyday-use cosmetics as well as so called 'beach' products. An ideal sunscreen product will provide effective protection against UV radiation with minimal skin absorption of the active ingredients. There is now clear evidence that a common sunscreen chemical, benzophenone-3, is absorbed systemically following topical application to the skin. Other more lipophilic sunscreens are absorbed into the skin, but penetration to deeper tissues and the cutaneous circulation appears to be limited. However, the extent to which sunscreens that are absorbed into the stratum corneum are absorbed to deeper tissues and the systemic circulation over time is currently unknown. The formulation vehicle in which the sunscreen is presented to the skin has a significant effect on absorption into and through the skin. Alcohol-based formulations appear to increase sunscreen absorption. In addition, some sunscreen chemicals may enhance the skin absorption of other sunscreens when applied in combination. Clearly, further research into the influence of sunscreen and formulation properties on skin absorption could lead to optimal design of sunscreen products with respect to efficacy and minimizing absorption. Despite the extensive use of sunscreen products, there have been few reports of adverse effects, and these tend to be limited to acute dermatitis and allergies. Some recent reports have raised concerns that sunscreen chemicals may damage tissues, particularly in the presence of UV radiation. Further research into the toxicity of sunscreens is urgently required. Given the information currently available and the importance of protecting the skin against sun damage, there is no clear justification for restricting the use of sunscreen products at this time.
Article
Today, topical application of sunscreens, containing ultraviolet-filters (UV-filters), is preferred protection against adverse effects of ultraviolet radiation. Evidently, use of sunscreens is effective in prevention of sunburns in various models. However, evidence for their protective effects against melanoma skin cancer is less conclusive. Three important observations prompted us to review the animal data and human studies on possible side effects of selected chemical UV-filters in cosmetics. (1) the utilization of sunscreens with UV-filters is increasing worldwide; (2) the incidence of the malignant disorder for which sunscreens should protect, malignant melanoma, is rapidly increasing and (3) an increasing number of experimental studies indicating that several UV-filters might have endocrine disruptive effects. The selected UV-filters we review in this article are benzophenone-3 (BP-3), 3-benzylidene camphor (3-BC), 3-(4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC), Homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate (OD-PABA) and 4-aminobenzoic acid (PABA). The potential adverse effects induced by UV-filters in experimental animals include reproductive/developmental toxicity and disturbance of hypothalamic-pituitary-thyroid axis (HPT). Few human studies have investigated potential side effects of UV-filters, although human exposure is high as UV-filters in sunscreens are rapidly absorbed from the skin. One of the UV-filters, BP-3, has been found in 96% of urine samples in the US and several UV-filters in 85% of Swiss breast milk samples. It seems pertinent to evaluate whether exposure to UV-filters contribute to possible adverse effects on the developing organs of foetuses and children.
Article
In order to assess potential risks of exposure to environmental chemicals, more information on concomitant exposure to different chemicals is needed. We present data on chemicals in human milk of a cohort study (2004, 2005, 2006) of 54 mother/child pairs, where for the first time, cosmetic UV filters, synthetic musks, parabens and phthalate metabolites were analyzed in the same sample along with persistent organochlor pollutants (POPs), i.e., organochlor pesticides and metabolites, polybrominated diphenylethers and polychlorinated biphenyls (PCBs). The two groups of chemicals exhibited different exposure patterns. Six out of seven PCB congeners and a majority of pesticides were present in all milk samples, with significant correlations between certain PCB congener and pesticide levels, whereas the cosmetic-derived compounds, UV filters, parabens and synthetic musks, exhibited a more variable exposure pattern with inter-individual differences. UV filters were present in 85.2% of milk samples, in the range of PCB levels. Comparison with a questionnaire revealed a significant correlation between use of products containing UV filters and their presence in milk for two frequently used and detected UV filters, 4-methylbenzylidene camphor and octocrylene, and for the whole group of UV filters. Concentrations of PCBs and organochlor pesticides were within ranges seen in Western and Southern European countries. For several POPs, mean and/or maximum daily intake calculated from individual concentrations was above recent US EPA reference dose values. Our data emphasize the need for analyses of complex mixtures to obtain more information on inter-individual and temporal variability of human exposure to different types of chemicals.
Article
Ultraviolet (UV) filters are the active ingredients in sunscreens. The concentration and combination of UV filters determine the efficacy of sunscreens as measured by sun protection factor. The safety of individual UV filters, and, more generally, sunscreen products, is a matter of a few related components: objective toxicologic evaluation, phototoxicologic potential, and human health consequences of using products that may reduce some but not all of the solar UV. Of 16 UV filters approved by the US Food and Drug Administration, 9 are used in different combinations in the most currently marketed sunscreens. Most of these compounds are considered safe and effective alone or in combination with other UV filters based on extensive toxicologic/phototoxicologic evaluations and market history. The benefits from proper use of sunscreens outweigh real or perceived human health concerns, establishing a favorable benefit-to-risk ratio. Future UV filters will require complete human safety evaluations alone and in combination with select benchmark ingredients.
Article
Benzophenone-3 (BZ-3; 2-hydroxy-4-methoxybenzophenone, oxybenzone) is commonly used to absorb ultraviolet (UV) radiation. BZ-3 penetrates the skin and can be found in the urine. The amount varies between 0.4% and 2%. This seems to be the main metabolic pathway in rats. To investigate the total amount of BZ-3 excreted in the urine after repeated topical whole-body applications of a sunscreen and to see if UV radiation has any effect on the amount excreted. Twenty-five volunteers applied a commercially available sunscreen containing 4% BZ-3 morning and night for 5 days. Their urine was measured during those 5 days and during a further 5 days after the last application. They were divided into groups A (unirradiated) and B. Group B received UV radiation according to skin type: UVA between 400 and 707 J cm(-2), and UVB between 0.46 and 2.0 J cm(-2). BZ-3 in urine was analysed with a high-performance liquid chromatography method. The volunteers excreted 1.2-8.7% (mean 3.7%) of the total amount of BZ-3 applied. There was no significant difference between the two groups (P < 0.99, t-test). We show that a large amount of BZ-3 is absorbed. BZ-3 is accumulated in the body as the volunteers excreted BZ-3 5 days after the last application.
Article
The three chemical ultraviolet absorbers benzophenone-3 (BP-3), octyl-methoxycinnamate (OMC) and 3-(4-methylbenzylidene) camphor (4-MBC) are commercially used in sunscreens worldwide. Apart from sun protection, they may possess endocrine-disrupting effects in animals and in vitro. For all three compounds, only sporadic measurements of percutaneous absorption and excretion after topical application in humans have been described. In this study, 32 healthy volunteers, 15 young males and 17 postmenopausal females, were exposed to daily whole-body topical application of 2 mg/cm(2) of sunscreen formulation at 10% (w/w) of each for 4 days. Blood concentrations were measured at 0, 1, 2, 3, 4, 24 and 96 h and urine concentrations at 0, 24, 48, 72 and 96 h. Almost all three sunscreens were undetectable in plasma and urine before the first application. One to 2 h after the first application, all three sunscreens were detectable in plasma. The maximum median plasma concentrations were 187 ng/mL BP-3, 16 ng/mL 4-MBC and 7 ng/mL OMC for females and 238 ng/mL BP-3, 18 ng/mL 4-MBC and 16 ng/mL OMC for men. In the females, urine levels of 44 ng/mL BP-3 and 4 ng/mL of 4-MBC and 6 ng/mL OMC were found, and in the males, urine levels of 81 ng/mL BP-3, 4 ng/mL of 4-MBC and OMC were found. In plasma, the 96-h median concentrations were higher compared with the 24-h concentrations for 4-MBC and OMC in men and for BP-3 and 4-MBC in females.
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Sunscreens: are they beneficial for health? an overview of endocrine disrupting properties of UV-filters
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