Bis-ethylhexyloxyphenol Methoxyphenyl Triazine Research Articles

A Survey of UV Filters Used in Sunscreen Cosmetics

The aim of this study was to determine the types of UV filters used in adult and children’s sunscreen products sold in Poland (part of the EU market) and their frequency of use. The INCI compositions of sunscreen products were collected and analyzed for the presence of UV filters. The study included 150 randomly selected preparations for adults (from 71 brands) and 50 for children (from 33 brands). The survey concerned the UV filters listed in Annex VI to Regulation (EC) No 1223/2009 of the European Parliament and Council of 30 November 2009 on cosmetic products. The most frequently used UV filters in the child sunscreens were triazine derivatives: bis-ethylhexyloxyphenol methoxyphenyl triazine (60.0%) and ethylhexyl triazone (52.0%), and ethylhexyl salicylate (46.0%), a derivative of salicylic acid. The most common in adult sunscreens were butyl methoxydibenzoylmethane (56.0%), a dibenzoylmethane derivative, followed by the salicylic acid derivative ethylhexyl salicylate (54.7%) and the triazine derivatives bis-ethylhexyloxyphenol methoxyphenyl triazine (54.7%) and ethylhexyl triazone (50.0%). Physical filters, including their nano and non-nano forms, were more popular in sunscreens for children, i.e., 50.0% (TiO2) and 22.0% (ZnO), than for adults: 21.3% (TiO2) and 6.7% (ZnO). For both adults and children, many cosmetic products contained four or five UV filters per preparation; however, the child preparations often used two UV filters. To summarize, the following UV filters dominate in photoprotectors for both adults and children: butyl methoxydibenzoylmethane, bis-ethylhexyloxyphenol methoxyphenyl triazine, ethylhexyl triazone, ethylhexyl salicylate, and diethylamino hydroxybenzoyl hexyl benzoate.

Recent Trends on UV filters

UV filters are the shield ingredients of sunscreens against the negative effects of solar radiation. Since the discovery of the first UV filter, nearly 30 filters have become commercially available. Over the years, innovation and regulatory updates have driven their use by the cosmetic industry. This work aimed to characterize commercial sunscreens and unveil the main trends by analyzing the labels of 444 sunscreen formulations that are currently being marketed. Avobenzone, octocrylene, and bis-ethylhexyloxyphenol methoxyphenyl triazine were the three UV filters with the highest usage frequencies (>40%). Emulsified preparations and sprays were the preferred forms, while the most frequent SPF was 50+. Differences were noted between adult and children’s sunscreens, namely the higher usage of inorganic filters for the latter. Over the past few years, the five most used UV filters remained the same, but octocrylene, ethylhexyl salicylate, and nano methylene bis-benzotriazolyl tetramethylbutylphenol had decreased usage. An increasing tendency towards the use of the inorganic UV filter titanium oxide was also observed. Overall, this study characterized the true market impact of approved UV filters and how the market has evolved over recent years. This insight can help pave the way for the design of new UV filters and is helpful for the assessment of environmental risks.

Assessing the eco-compatibility of new generation sunscreen products through a combined microscopic-molecular approach

There is now unequivocal evidence that sunscreen can severely affect marine ecosystems. However, so far, most studies have focused on the impact of single sunscreen ingredients rather than on the whole sunscreen products, which are released into the marine environment. In the present work, we investigated the ecological impact of six formulations, which represent the “new generation” organic UV filters such as diethylamino hydroxybenzoyl hexyl benzoate (DHHB), methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT), ethylhexyl triazone (EHT), and bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT), which are progressively replacing the “old generation” organic UV filters (e.g., oxybenzone, octinoxate) banned in several countries of the world. The six formulations tested were characterized by a different combination of ingredients, on a model species particularly sensitive to environmental alterations: the sea urchin, Paracentrotus lividus. We investigated the sea urchin responses both in terms of gene expression and anomalies in embryonic development. We found that all sunscreen products containing only MBBT, DHHB, BEMT, and EHT as UV filters, are more eco-compatible than those also containing also ES, or other ingredients such as emollients and texturizing compounds, which may act synergistically causing molecular stress, morphological anomalies, and ultimately possible death. Overall, the results presented here provide new insights on the effects of sunscreen products based on “new generation” UV filters, and highlights the urgency of testing complete formulations, rather than just specific UV filters to ascertain the eco-compatibility of sunscreen products, to effectively minimize their impact on marine ecosystems.

Widening the Lens on UV Filters: Newfound Ubiquity of Triazine UV Filters in Breast Milk from South China and Implications for Augmented “Cocktail” Exposure in Infants

Our previous work demonstrated triazine UV filters (TA-UVFs) as an emerging class of abundant, ubiquitous pollutants in the indoor environment; however, information about human exposure to these novel chemicals remains unknown. In this study, 17 TA-UVFs as well as 9 benzotriazole (BTR)-UVFs and 6 benzophenone (BP)-UVFs were included in a comprehensive, dedicated screening in breast milk from South China. In addition to some previously unrecognized BTR- and BP-UVFs, 11 of the 17 TA-UVFs were detected for the first time in breast milk, with ethylhexyl triazone (EHT) and bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT) as the predominant, omnipresent pollutants in humans. The median total concentration of TA-UVFs reached 1350 pg/mL, which is nearly half that of BTR-UVFs (3080 pg/mL) or BP-UVFs (3220 pg/mL). More daily use of personal care products (≥5 types) significantly elevated breast milk levels for all three classes of UVFs (p < 0.05) in the studied population. The overall daily intake of UVFs for infants via breast-feeding will substantially increase by 28% under the median exposure scenario if TA-UVFs are included in an integrative assessment. The current breast milk levels of TA-UVFs indicate a demand for additional monitoring and actions to reduce maternal and infant exposure to these emerging contaminants.

Identification of Triazine UV Filters as an Emerging Class of Abundant, Ubiquitous Pollutants in Indoor Dust and Air from South China: Call for More Concerns on Their Occurrence and Human Exposure.

Triazine UV filters are an important class of UV filters, but knowledge on their environmental occurrence and human exposure remains largely unknown. In this study, we performed a targeted analysis of 17 emerging triazine UV filters in indoor dust and indoor air from South China based on a newly developed LC-MS/MS method. A total of 12 of the 17 emerging triazine UV filters were first positively detected in the dust and air samples. Ethylhexyl triazone (EHT) and bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT) were identified as the most abundant compounds. The median total concentrations of triazine UV filters reached 3860 ng/g in indoor dust and 1590 pg/m3 in indoor air. Gas-particle partitioning analysis showed that triazine UV filters were predominant in the particle phase in ambient air. Significant concentration correlations were observed among most triazine UV filters. The estimated daily intake of triazine UV filters through dust ingestion and air inhalation for toddlers under high-end exposure scenarios was up to 839 ng/kg bw/day, but a lack of toxic thresholds hampers accurate risk assessment. Our work highlights another emerging class of UV filters that significantly contribute to indoor chemical mixtures and expresses concerns over their occurrence and human exposure.

Evaluation of the degradation capacity of WWTP sludge enrichment cultures towards several organic UV filters and the isolation of octocrylene-degrading microorganisms

Organic UV filters are present in wastewater treatment plants (WWTPs) due to the use of these compounds in many personal care products (PCPs) and their subsequent release into the wastewater system from showering/bathing. Once in the wastewater system, organic UV filters generally partition into the solid phase but might also undergo other processes, such as degradation by microorganisms. To further understand the fate of organic UV filters in WWTPs, the degradation of 7 UV filters by WWTP sludge was investigated The UV filters 2-ethylhexyl salicylate (ES), homosalate (HS), butyl methoxydibenzoylmethane (BM) and octocrylene (OC) were degraded after 20–60 days. The rest of the filters tested, namely, bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT), methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT) and diethylhexyl butamido triazone (DBT), did not degrade even after 120 days of incubation. The microbial community from the microcosms degrading ES, HS, OC and BM was transferred every 30 days into new microcosms to enrich for microorganisms capable of utilizing the individual UV filters for growth. The enrichment cultures continued to degrade throughout 20 transfers. The microbial community was clearly different between the enrichments degrading ES, HS, OC and BM, meaning that the microbial community was strongly influenced by the UV filter present. Furthermore, several strains were isolated from OC-degrading cultures and two of these strains, Gordonia sp. strain OC_S5 and Sphingopyxis sp. strain OC_4D, degraded OC with and without other carbon sources present. These experiments show that several organic UV filters can be degraded by a specific set of microorganisms. The lack of degradation observed for BEMT, MBBT and DBT is probably due to limited bioavailability. Indeed, this is the first biodegradation study of these filters, in addition to being the first description of ES and HS degradation in microcosm experiments.

Transfer of 7 Organic UV Filters from Sediment to the Ragworm Hediste diversicolor: Bioaccumulation of Benzophenone-3 and Further Proof of Octocrylene Metabolism

Organic UV filters are continuously released in aquatic ecosystems due to their widespread use, especially in touristic coastal environments. Generally, organic UV filters are poorly soluble in water and tend to accumulate in the sediment compartment. This represents a conceivable risk for sediment-dwelling organisms and a potential for transfer of the UV filters up the food chain. This study aimed to assess the potential transfer of seven UV filters including benzophenone-3 (BP3), bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT), butyl methoxydibenzoylmethane (BM), methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT), 2-ethylhexyl salicylate (ES), diethylhexyl butamido triazone (DBT), and octocrylene (OC) from artificial spiked sediment (10 µg.g−1 dry weight) to sediment-dwelling worms. All UV filters were detected in the worms after 28 days of exposure, but only BP3 was apparently bioaccumulated, with a biota sediment accumulation factor (BSAF) of 12.38 ± 4.65. However, metabolomic profiling revealed that OC was metabolized by the worms into 11 fatty acid conjugates, demonstrating that OC did also accumulate in the worms in the form of OC–fatty acid conjugates. Here, the sole quantification of the parent organic UV filter underestimated the accumulation factor and the exposure of organisms. In general, it is therefore important to pair the conventional method (BSAF calculus) with other techniques, such as metabolomics, to assess the actual potential for bioaccumulation of xenobiotics including transformed xenobiotics.

Photokinetics of oil soluble 1,3,5-Triazine UV filters in combination with Butyl Methoxydibenzoylmethane or with Diethylamino Hydroxybenzoyl Hexyl Benzoate

Bis-ethylhexyloxyphenol Methoxyphenyl Triazine (BEMT) was previously shown to efficiently quench the excited state of Butyl Methoxydibenzoylmethane (BMDBM) and to prevent its photodegradation. However, little is known on the consequences for the quenching molecule in this process. In this study we examined the impact of BMDBM on the photokinetics of the quencher BEMT by HPLC measurements and determination of the rate constant. We extended the investigation to Ethylhexyl Triazone (EHT) and Diethylhexyl Butamido Triazone (DBT), two 1,3,5-Triazine filters that became standardly used UVB filters in systems with BMDBM and without Octocrylene (OCR). We performed DFT computations on each studied UV filter to identify possible photostabilization mechanisms within the binary systems. Additionally, we evaluated the number of free radicals formed in formulations containing the studied mixtures. The same investigation was carried out with Diethylamino Hydroxybenzoyl Hexyl Benzoate (DHHB) as an alternative UVA filter to BMDBM. Our experiments showed that EHT and DBT own no capability in photostabilizing BMDBM but confirmed the photostabilization effect of BEMT on BMDBM. At the same time, our work revealed a photodestabilization effect of BMDBM on BEMT, EHT and DBT as well as an increased UV-induced number of free radicals in the formulations containing the binary mixture of the 1,3,5-Triazine UV filters and BMDBM. This is hypothesized to be the consequence of chain reactions following the production of free radicals of destabilized BMDBM. In contrary to BMDBM, DHHB photostabilized the three 1,3,5-Triazine filters BEMT, EHT and DBT completely. Corresponding results of quantum computations predicted efficient triplet-triplet energy transfer to DHHB. No free radicals could be detected after UV exposure in the formulations containing the binary combination of BEMT, EHT, DBT with DHHB in contrast to formulations containing binary combinations with BMDBM.

Lignosulfonate is an efficient SPF booster: Application to eco-friendly sunscreen formulations

Sunscreen oil-in-water emulsions containing few ingredients and two EU-authorized organic filters had been developed in an eco-friendly approach. Based on their photostability, spectroscopic features, and the lack of data on toxicity, BEMT (UVA/B range; bis-ethylhexyloxyphenol methoxyphenyl triazine) and DHHB (UVA; diethylamino hydroxybenzoylhexyl benzoate) were selected and incorporated at minimal concentrations to reduce the risk of impact on human health and coastal marine ecosystems. Despite the inconclusive results previously reported, the use of the w-soluble and largely available Na-lignosulfonate (LiS) had been reconsidered with success. Since BEMT and DHHB alone or in combination were not able to higher the sun protection factor (SPF) value at 50, results showed that it becomes possible by supplementing with LiS at 5% (w/w), ensuring stability, antiradical property, and a non-toxicity of the sun emulsion. After defining the range doses for the three components, minimizing concentrations was achieved by experimental design studies using a response surface methodology in which SPF values before and after irradiation has been considered. Consequently, an SPF30 and SPF50 emulsions containing only 9 and 12% total filter respectively and 5% LiS each had been developed. This high boosting effect led to discussions on how LiS interacts, suggesting the involvement of J aggregation, the formation of LiS micelles that would partly encapsulate the o-soluble filters, and the mode of adsorption at the solid-liquid interface of the poly(methyl-methacrylate) plate or the skin.

Simultaneous determination of 22 sunscreen agents in cosmetics by ultra-high-performance liquid chromatography using diode array detector

建立了一种超高效液相色谱-二极管阵列检测法同时测定不同种类化妆品中22种防晒剂的方法。样品首先加入少量四氢呋喃,涡旋、分散、混匀(蜡质化妆品可于50 ℃超声,以便分散完全),然后加入0.1%(v/v)甲酸乙醇溶液振摇、超声提取,稀释、过滤后经Poroshell 120 EC-C18(100 mm×4.6 mm, 2.7 μm)分离,乙腈-异丙醇-50 mmol/L乙酸铵水溶液(含0.05%(v/v)甲酸)梯度洗脱,二极管阵列检测器检测,检测波长311 nm,外标法定量。结果表明,22种防晒剂在各自的范围内线性关系良好,相关系数(r)均在0.998以上。选取两种不同基质类型的样品,在低、中、高3个不同添加水平下的平均回收率为85.2%~112.3%,相对标准偏差(RSD)在0.5%~6.5%之间,方法的检出限和定量限分别为0.7~64 mg/kg和2.4~215 mg/kg。在2、10、50 mg/L3个水平的混合标准溶液的稳定性试验中,甲酚曲唑三硅氧烷组分12 h内稳定,其余组分36 h内稳定。采用该方法测定市售16份化妆品中的防晒剂,其中5份样品检测结果与厂家提供的配方值匹配良好。与《化妆品安全技术规范》(2015年版)收载方法相比,该方法在流动相组成和提取溶剂选择方面,摒弃了四氢呋喃和高氯酸等腐蚀性溶剂的使用,改善了弱极性组分的提取效率,同时增加了检测组分二苯酮-2,被测物稳定性更好,实验操作更便利高效,分离效果更好,结果更准确,兼顾绿色环保,可用于化妆品防晒剂的日常检测。

Exposure to four chemical UV filters through contaminated sediment: impact on survival, hatching success, cardiac frequency, and aerobic metabolic scope in embryo-larval stage of zebrafish

UV filters are widely used in many pharmaceutical and personal care products such as sunscreen and cosmetics to protect from UV irradiation. Due to their hydrophobic properties and relative stability, they have a high capacity to accumulate in sediment. Little information is available on their ecotoxicity on fish. In aquatic ecosystems, fish eggs could be directly affected by UV filters through contact with contaminated sediment. The aim of this study was to investigate the individual toxicity of four UV filters: benzophenone-3 (BP3), butyl methoxydibenzoylmethane (BM), bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT), and methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT), in embryo-larval stages of zebrafish Danio rerio. Fish eggs were exposed to single UV filters by contact with spiked sediment during 96 h at a concentration of 10 μg g-1. Among the four UV filters tested, BP3 was the more toxic, reducing cardiac frequency and increasing standard metabolic rate of larvae.

Ultraviolet filters in sunscreens and cosmetic products-A market survey.

As several reports have raised a variety of environmental, health, and safety issues related to ultraviolet (UV) filters, it is crucial to understand the trends in the exposure of the population to UV filters. To determine the frequency of UV filter usage in sunscreens and other cosmetic products in Thai market. We surveyed the UV filter labelling on sunscreens and cosmetic products sold in the Thai market. In all, 312 sunscreens and 1350 other cosmetic products were investigated. Titanium dioxide was the most frequently used UV filter in both sunscreens (66.7%) and other cosmetic products (68.4%). Ethylhexyl methoxycinnamate was the most common organic UVB filter, whereas butyl methoxydibenzoylmethane was the most common organic UVA filter. In sunscreens aimed at children, bis-ethylhexyloxyphenol methoxyphenyl triazine was the most commonly used UV filter. The most frequent co-occurrence of UV filters was titanium dioxide and ethylhexyl methoxycinnamate. Titanium dioxide was the most commonly used UV filter, which differs from the findings of previous surveys. Knowing the availability and frequency of each UV filter provides valuable information about consumer exposure levels, facilitates refinements of the allergen series in patch testing, and enhances the monitoring of adverse effects of UV filters.

Modeling an in silico platform to predict chromatographic profiles of UV filters using ChromSimulator

The use of Analytical Quality by Design (AQbD) concepts is increasing for rational development of analytical methods of liquid chromatography. To facilitate the use of the AQbD approach, we developed an in silico tool capable of predicting the chromatographic profile of organic UV filters based on theoretical retention and separation predictions, in absence of experimentation, with sufficient assertiveness to support analytical development. For this purpose, we used Design of Experiments (DoE) in conjunction with chemical understanding offered by Quantitative Structure – Retention Relationship (QSRR), combined with Monte Carlo method (MCM). Seven analytes were used to establish the prediction model: benzophenone-3, butyl methoxydibenzoilmethane, ethylhexyl triazone, ethylhexyl dimetyl PABA, ethylhexyl methoxycinnamate, bis-ethylhexyloxyphenol methoxyphenyl triazine, and octocrylene. The model generated by multiple regression analysis, using Minitab 19 software, obtained a determination coefficient (R2) of 99.82% and an adjusted determination coefficient (R2 adj) of 99.80%, in addition, residual values had normal distribution, homoscedasticity, and independence. From the results obtained, the predictors considered in the model were the proportion of ethanol in the mobile phase, mobile phase pH, mobile phase flow rate, column temperature, and molecular descriptors (Wlambda3.unity, ATSc5, and geomShape). The model exhibited high performance in internal and external validation, obtaining coefficients of prediction (R2 pred) and determination (R2) of 99.71% and 99.79%, respectively. The in silico platform demonstrated great potential for predicting profile and chromatographic parameters of organic UV filters, allowing, without experimentation, an overview of the retention behavior of compounds under various chromatographic conditions.

Effect of 10 UV Filters on the Brine Shrimp Artemia salina and the Marine Microalga Tetraselmis sp.

The presence of pharmaceutical and personal care product (PPCP) residues in the aquatic environment is an emerging issue due to their uncontrolled release through gray water, and accumulation in the environment that may affect living organisms, ecosystems and public health. The aim of this study is to assess the toxicity of benzophenone-3 (BP-3), bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT), butyl methoxydibenzoylmethane (BM), methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT), 2-ethylhexyl salicylate (ES), diethylaminohydroxybenzoyl hexyl benzoate (DHHB), diethylhexyl butamido triazone (DBT), ethylhexyl triazone (ET), homosalate (HS) and octocrylene (OC) on marine organisms from two major trophic levels, including autotrophs (Tetraselmis sp.) and heterotrophs (Artemia salina). In general, results showed that both HS and OC were the most toxic UV filters for our tested species, followed by a significant effect of BM on Artemia salina due to BM—but only at high concentrations (1 mg/L). ES, BP3 and DHHB affected the metabolic activity of the microalgae at 100 µg/L. BEMT, DBT, ET, MBBT had no effect on the tested organisms, even at high concentrations (2 mg/L). OC toxicity represents a risk for those species, since concentrations used in this study are 15–90 times greater than those reported in occurrence studies for aquatic environments. For the first time in the literature, we report HS toxicity on a microalgae species at concentrations complementing those found in aquatic environments. These preliminary results could represent a risk in the future if concentrations of OC and HS continue to increase.

Effect of emollients on UV filter absorbance and sunscreen efficiency

The idea of increasing the performance of sunscreens without adding more UV-filters is very attractive. Early studies reported an influence of solvents on the absorbing properties of UV-absorbers which was shown to be connected to the solvent polarity. However, the polarity differed a lot between tested solvents and most were unsuitable UV-filter solubilizers. The aim of the present study was to focus exclusively on emollients pertinent for sunscreens and investigate their impact on the performance of UV-filter combinations. The UV absorbance of Bis-ethylhexyloxyphenol Methoxyphenyl Triazine, Ethylhexyl Triazone, Diethylamino Hydroxybenzoyl Hexyl Benzoate, and Ethylhexyl Methoxycinnamate was measured in suncare relevant emollients comprising C12–15 Alkyl Benzoate, Dibutyl Adipate, Caprylic/Capric Triglyceride, Coco-caprylate, Isopropyl Myristate, Dicaprylyl Carbonate. The wavelength of maximum absorbance (λmax) and specific extinction at λmax (E1,1 (λmax)) were assessed for each UV-filter – emollient system. The performance of market relevant UV-filter combinations based on the studied UV-filters was simulated for each emollient with a computational method using the absorbance values measured for each UV-filter - emollient system. The difference in polarity of emollients led to a 2-3 nm bathochromic shift and a variation of the E1,1 (λmax) ranging from 4 to 20% for tested UV-filters. The emollient type showed nearly no influence on the sun protection factor (SPF) of market relevant UV-filter combinations probably due to a different influence an emollient shows on the UVB filters resulting in cancelling of the corresponding effect. Conversely, for all UV-filter combinations the UVA protection decreased with a decrease in the emollient polarity. Whilst the SPF was not impacted by standardly used cosmetic oils, the results advocate to use polar emollients to optimize the UVA protection. This is of advantage since polar emollients better dissolve crystalline UV-filters. From tested emollients, Dibutyl Adipate performed the best for both SPF and PPD factors.

Occurrence and Environmental Distribution of 5 UV Filters During the Summer Season in Different Water Bodies

Organic UV filters are used worldwide in various personal care products as well as textiles, paints, plastic, food, and adhesives. They are main ingredients in sunscreen lotions that are used heavily by beachgoers in the summer season. There is thus an increasing concern regarding the fate of organic UV filters in the environment and their impact on living organisms. Many of the UV filters in use are hydrophobic and are expected to accumulate in the sediment phase in aquatic systems, but this has yet to be validated in situ. We targeted the UV filters benzophenone 3 (BP3), butyl methoxydibenzoylmethane (BMDBM), diethylhexyl butamido triazone (DBT), bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT), and methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT) in a freshwater lake and in a coastal bay in order to understand their distribution during summer 2016. Further, we examined their environmental partitioning by collecting samples from the surface water, the sediment phase, and water surface microlayer (SML). We show for the first time the presence of DBT, BEMT, and MBBT in environmental matrices (water, SML, and sediment). Notably, these UV filters were detected at low amounts in surface waters with maximum concentrations of 9.9 ng/L for DBT, 18.4 ng/L for BEMT, and below detection limits for MBBT and somewhat higher concentrations in the SML, with maximum concentrations of 43.3 ng/L for DBT, 5625.4 ng/L for BEMT, and 45.6 ng/L for MBBT. These filters were detected at even greater concentrations in the sediments, with maximum concentrations of 652.6 ng/g for DBT, 115.0 ng/g for BEMT, and 75.2 ng/g for MBBT (dry weight sediment). We also performed controlled laboratory experiments to determine their partitioning behavior, and we verified the actual solubility of many of the filters. This will help in determining the environmental fate and finally lead to a better risk assessment of these compounds. Together, these results corroborate the hypothesis that hydrophobic UV filters accumulate in the sediment phase and highlight the importance of discerning whether these UV filters impact the benthic community and their potential for bioaccumulation.

Ferulic acid photoprotective properties in association with UV filters: multifunctional sunscreen with improved SPF and UVA-PF

Ultraviolet (UV) radiation stimulates several injurious biological effects on cutaneous tissue, causing, for instance, photocarcinogenesis. Sunscreens are topical products designed to protect the skin against these harmful effects and their use must be encouraged. The addition of antioxidants, as ferulic acid (FA), a phenolic compound from the class of the hydroxycinnamic acids, in sunscreens could improve their sun protection factor (SPF) and prevent inflammatory reactions. Here, the clinical safety and efficacy of an association of ethylhexyl triazone and bis-ethylhexyloxyphenol methoxyphenyl triazine (UV filters) with ferulic acid were assessed. Samples had good skin biocompatibility and presented satisfactory safety profile, even in a sun-exposed condition. A synergic effect between the natural polyphenol and the UV filters was evidenced, as well as, FA increased in vivo SPF in 37% and the UVA protection factor (UVA-PF) in 26%. The in vivo data indicated that FA reinforced the broad-spectrum characteristic of the photoprotective formulations. Additionally, according to the results from the ex vivo antioxidant test, it is plausible to recommend adjustments on the ex vivo protocol to explicitly determine the positive effects of topical antioxidant ingredients applied over the skin. These results provided a new perspective for the development of multifunctional bioactive sunscreens using FA as a new platform.

Risk assessment of bis-ethylhexyloxyphenol methoxyphenyl triazine in cosmetic products

Animal toxins are natural resources for pharmacological studies. The venom of Crotalus durissus cascavella (C.d. cascavella) may be a source in the bio-prospecting of new anti-hypertensive agents. The aim of this study was to investigate vascular effects of the venom of C.d. cascavella in normotensive rats. Studies were performed using isolated mesenteric artery segments and aortic endothelial cells. The cumulative administration of the venom of C.d. cascavella (0.001–30 μg/mL) on phenylephrine (Phe; 10 μM) pre-contracted rings induced a concentration-dependent vasorelaxation in the presence of vascular endothelium (Emax = 47.9 ± 5.0% n = 8), and its effect was almost abolished in the absence of endothelium (Emax = 5.8± 2.4% n = 5 (∗∗∗p < 0.001)). Tissue viability was maintained as there was no difference in the contractile capacity of rings before and after the administration of venom. The vasorelaxant effect of the venom was also abolished when arteries were pre-contracted with potassium chloride (KCl; 80 mM) (Emax = 6.4± 0.9% n = 5, ∗∗∗p < 0.001). When assessing the participation of endothelium-derived relaxing factors, it was noted that non-selective COX inhibition with indomethacin (10 μM) caused a significant reduction in the vasorelaxant effect of C.d. cascavella (*p < 0.05). When investigating the participation of NO released by endothelium, there was a significant reduction of the vasorelaxant effect of venom in rings treated with L-NAME (100 μM; Emax = 17.5± 2.2% n = 6; **p < 0.01). Similar results were noted in the presence of ODQ (10 μM), an inhibitor of soluble guanylyl cyclase (Emax = 11.2± 3.5%, n = 6) and PTIO (100 μM), a stable radical scavenger for nitric oxide (Emax = 10.77± 3.6%, n = 6). Moreover, the venom induced the release of NO by isolated aortic endothelial cells through amperometric studies. When assessing the participation of K+ channels on the vasodilatory response of the venom, tyrode solution with 20 mM of KCl caused a significant reduction in the relaxation response (p < 0.001) (Emax = 21.3 ± 8%, n = 7), as did inhibitor of delayed rectifier K+ channels (4-amynopiridine 1 mM; Emax = 9.5 ± 1.3, %, n = 5, ***p < 0.001), and vasorelaxation was almost abolished in the presence of Iberiotoxin (IbTx 100 nM). Therefore, these results suggest that the venom of C.d. cascavella induces vasorelaxation in superior mesenteric artery rings of normotensive rats in an endothelium-dependent manner. Specifically, the venom stimulates the generation of endothelium-derived relaxing factors, especially NO, and activates vascular smooth muscle hyperpolarization through K+ channels. These data illustrate that C.d. cascavella is a source of bioactive molecules and therefore has therapeutic potential in the treatment of cardiovascular diseases such as hypertension.

Development of a HPLC method for determination of four UV filters in sunscreen and its application to skin penetration studies.

This study describes the development, validation and application of a high-performance liquid chromatography (HPLC) method for the simultaneous determination of the in vitro skin penetration profile of four UV filters on porcine skin. Experiments were carried out on a gel-cream formulation containing the following UV filters: diethylamino hydroxybenzoyl hexyl benzoate (DHHB), bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT), methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT) and ethylhexyl triazone (EHT). The HPLC method demonstrated suitable selectivity, linearity (10.0-50.0 μg/mL), precision, accuracy and recovery from porcine skin and sunscreen formulation. The in vitro skin penetration profile was evaluated using Franz vertical diffusion cells for 24 h after application on porcine ear skin. None of the UV filters penetrated the porcine skin. Most of them stayed on the skin surface (>90%) and only BEMT, EHT and DHHB reached the dermis plus epidermis layer. These results are in agreement with previous results in the literature. Therefore, the analytical method was useful to evaluate the in vitro skin penetration of the UV filters and may help the development of safer and effective sunscreen products.

Advanced UV Absorbers for the Protection of Human Skin.

The increasing awareness of the damaging effects of UV radiation to human skin triggered the market introduction of new cosmetic UV absorbers. This article summarizes the outcome of a multi-year research program, in which the author contributed to the development of different new UV filters. First of all, the molecular design and the basic properties of bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT) will be presented. This oil-soluble filter, which today is widely used in both beach products and skin care products, exhibits inherent photostability and strong broad-spectrum UV-A+B absorbance. Based on the concept of micronized organic UV absorbers, the UV-B filter tris biphenyl triazine (TBPT) will be introduced. At present TBPT exhibits the highest efficacy of all cosmetic UV absorbers in the market (measured by area under the UV spectrum). Finally, the concept of liposomogenic UV absorbers will be featured. This approach was developed to create water-resistant UV filters, as liposomogenic structures are thought to integrate into the lipids of the horny layer. Due to prohibitively high costs, this technology did not result in a commercial product so far.