ETHYLHEXYL SALICYLATE

With increasing awareness regarding the risks of sunburn, photoaging, and skin cancer, the use of sunscreens has increased. Organic and inorganic filters are used in sunscreen products worldwide. Concerns have been raised regarding the environmental effects of commonly used organic ultraviolet (UV) filters, including oxybenzone (benzophenone-3), 4-methylbenzylidene camphor, octocrylene, and octinoxate (ethylhexyl methoxycinnamate). Studies have identified UV filters such as oxybenzone, octocrylene, octinoxate, and ethylhexyl salicylate in almost all water sources around the world and have commented that these filters are not easily removed by common wastewater treatment plant techniques. Additionally, in laboratory settings, oxybenzone has been implicated specifically as a possible contributor to coral reef bleaching. Furthermore, UV filters such as 4-methylbenzylidene camphor, oxybenzone, octocrylene, and octinoxate have been identified in various species of fish worldwide, which has possible consequences for the food chain. As dermatologists, it is important for us to continue to emphasize the public health impact of excessive sun exposure and advise our patients about proper photoprotection practice, which consists of seeking shade, wearing photoprotective clothing (including hats and sunglasses), and applying appropriate sunscreens.

Acne is a multifactorial inflammatory disease with a robust microbial component and numerous correlations with dysbiosis states. Furthermore, various factors are recognized as triggers for skin dysbiosis, including the use of certain cosmetics. Based on these arguments, we hypothesized that using photoprotective formulations could trigger dysbiosis and the occurrence of acne manifestations. To verify this assumption, six volunteers between 19 and 23 years of age, meeting all the inclusion criteria, received two applications a day of a non-commercial sunscreen formulation developed with the sun filters ethylhexyl methoxycinnamate, ethylhexyl salicylate, methyl anthranilate, and octocrylene dispersed in a base gel, with an estimated protection factor of 28.8. The pure base gel was used as a control. The samples were applied to an area delimited by a standard template (15 cm 2 ) in an amount corresponding to 30 mg (2 mg cm 2 ) for ten days. At two points in time, pre- and post-sample applications, the facial skin surface was swabbed to collect extracted DNA and processed to verify divergent degrees of 16 S RNA coding sequences. The data obtained allowed us to determine the abundance of different bacterial entities at the genus and species levels. The results showed that critical species of the acne process, such as Cutibacterium acnes and Staphylococcus epidermidis, seem to tolerate the evaluated formulation well and are not significantly affected by the formulation, suggesting no interference of its use concerning dysbiosis induction. These findings refute the idea that photoprotectors may cause skin dysbiosis in men.

Organic ultraviolet (UV) filters mitigate radiation transmission through the skin; however, uncertainties persist regarding their ability to cross the skin barrier and induce toxicity. Our aim was to use published in vitro skin permeation studies to predict UV-filter concentrations in blood and skin. In our review, we identified 35 papers reporting in vitro skin permeation of the 12 most used organic UV-filters. We estimated the UV-filters' theoretical concentrations in blood and skin layers for two case scenarios and compared them with in vivo data. Five of the UV-filters penetrated skin as the parent compound, among these the highest estimated blood concentration was for benzophenone 4 (419 mg/L). These were overestimated (up to 100 times) compared to the reported in vivo results. Ten of the UV-filters permeated skin, among these ethylhexyl salicylate had the highest estimated skin concentration (15.99 g/cm 3 ). Results from literature were inconsistent, likely due to different experimental in vitro methods. Although skin can metabolize chemicals, none of the included studies quantified potential UV-filter metabolites. We recommend future in vitro skin permeation studies to standardize the methods according to existing guidelines (including quantification of the metabolites) and screen UV-filters for possible skin absorption followed by a risk evaluation.

As emerging global environmental contaminants, organic ultraviolet absorbers (OUVAs) are widely used in personal care formulations and exhibit environmental persistence and potential bioaccumulation. Among these compounds, 2-ethylhexyl salicylate (EHS) and homosalate (HMS) are the most frequently used salicylate-type UV filters in cosmetic formulations. Although an increasing number of studies have demonstrated their environmental hazards, little is known about the molecular mechanisms underlying their cytotoxicity in mammalian systems, a fundamental knowledge gap for both human health protection and the development of more environmentally friendly consumer goods. In this study, we used mouse embryonic fibroblasts (MEFs, 3T6) and zebrafish as models to assess the toxicological phenotypes of EHS and HMS in vitro and in vivo, respectively. We found that both EHS and HMS induced cellular damage characterized by oxidative stress, disrupted intracellular calcium homeostasis, mitochondrial impairment, and DNA damage. Importantly, molecular analyses further suggested the concurrent activation of two distinct regulated cell death programs: pyroptosis, as suggested by Caspase-11 -mediated GSDMD cleavage, and necroptosis, as suggested by ZBP1-RIPK3-Caspase-8 -mediated MLKL phosphorylation. The in vitro data have been partially validated at the level of gene expression and in developmental toxicity in the zebrafish model, providing some in vivo phenotypic and molecular correlates. While the upstream events were experimentally verified, the causal links among them remain to be further elucidated. Taken together, this work suggested that OUVA-induced toxicity is not limited to isolated oxidative damage, but may also involve the activation of two different cell death programs. These findings provide important molecular clues to understanding the potential health and ecological risks of widely used UV filters and offer a scientific basis for their more environmentally friendly safety evaluation and regulatory management, which are crucial for advancing more sustainable chemistry and safer consumer goods.

Sea salt increasingly harbors organic contaminants from personal care products, yet current monitoring methods lack spatial resolution and require destructive sampling. This study introduces an innovative analytical framework integrating Laser-Induced Fluorescence (LIF) Hyperspectral Imaging (HSI) with machine learning for the rapid, non-destructive detection of sunscreen residues on salt crystals. To simulate contamination, seawater from the Mediterranean coast (Alexandria, Egypt) was spiked to achieve a 10 mg/L sunscreen concentration within the seawater matrix prior to crystallization; this formulation contained Ethylhexyl Methoxycinnamate, Homosalate, and Ethylhexyl Salicylate. A SOC710 HS camera (128 bands) acquired fluorescence data under 450 nm laser excitation. Raw data underwent preprocessing and dimensionality reduction via Sparse Principal Component Analysis (Sparse PCA, λ = 0.5, k = 4 components, 73.4% sparsity). A Support Vector Machine (SVM) with an RBF kernel was trained on these sparse features. Performance evaluation employed tenfold stratified cross-validation, an 80-20 holdout test on ROI-based spectra, and independent sample validation against manually annotated pixel-wise ground-truth masks. While ROI-based tests yielded near-perfect accuracy under ideal conditions, full-image evaluation achieved ≈96% pixel-wise accuracy (precision ≈ 0.99, recall ≈ 0.95, F1 ≈ 0.97), providing a realistic estimate under heterogeneous conditions. Full-image classification mapped widespread contamination (57.8% of pixels), whereas an independently prepared clean salt sample produced zero false positives. The integrated Sparse PCA-SVM framework transforms fluorescence-imaging data into spatio-chemical maps, simultaneously revealing contaminant presence and spatial distribution on salt surfaces, thereby offering a powerful paradigm for the interpretable monitoring of organic pollutants in food materials.

UV filters used in personal care products are increasingly recognised as emerging contaminants due to their persistence and ecological risks. Detected in aquatic systems at concentrations from ng L -1 to μg L -1 , their monitoring is essential for environmental risk assessment but challenging because of their diverse physicochemical properties, requiring sensitive analytical methods. This study optimised a solid-phase extraction gas chromatography-tandem mass spectrometry (SPE-GC-MS/MS) method for the simultaneous determination of twelve UV filters in marine waters. The method showed suitable linearity, precision, and recoveries, with detection limits below 1 ng L -1 . Seawater samples collected along the Adriatic coast (Rimini and Riccione, Italy) during peak recreational activity were analysed. All twelve UV filters were detected, with octocrylene (up to 23,100 ng L -1 ), homosalate (up to 16,400 ng L -1 ), and ethylhexyl salicylate (up to 10,900 ng L -1 ) being most abundant. Trans-2-Ethylhexyl methoxycinnamate (E-EHMC, the trans isomer of octinoxate, 13-1474 ng L -1 ) occurred consistently with its isomer Z-EHMC (cis-octinoxate), contributing 18-64 % of total (E + Z)-EHMC, suggesting in situ photochemical conversion, since the cis form is negligible in cosmetic products. Benzophenone, ethylhexyl dimethyl PABA, 4-methylbenzylidene camphor, benzyl salicylate, and isoamyl methoxycinnamate were found at lower yet relevant concentrations. UV filters banned under European regulations, such as menthyl anthranilate and etocrylene, were absent or barely detected. This work provides the first data on sunscreen UV filters in Adriatic coastal waters and the first quantitative evidence of Z-EHMC in environmental waters, highlighting its in situ formation and contributing to understanding their environmental fate and risks.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of Salicylic Acid and 17 salicylates; 15 of these ingredients were previously reviewed by the Panel, and 3 are reviewed herein for the first time. Some of the reported functions in cosmetics for ingredients in this group are hair and skin conditioning agents, and, less frequently, preservatives and fragrance ingredients. Upon review of relevant new data, including frequency and concentration of use, and consideration of data from the previous CIR report, the Panel concluded that these ingredients are safe in cosmetics in the present practices of use and concentration described in the safety assessment when formulated to be non-irritating and non-sensitizing, which may be based on a quantitative risk assessment (QRA).

Ultraviolet filters (UVFs), widely used in industrial and personal care products, are emerging environmental contaminants of great concern because of their persistence, bioaccumulation and toxicity. Sediments are generally considered the reservoir and secondary source of UVFs, yet knowledge of the occurrence of these emerging contaminants in coastal sediments on a large geographical scale remains unknown. In this study, 31 out of 37 target UVFs were detected in 91 sediment samples collected from 43 coastal cities of China. Benzophenone UVFs exhibited the highest mean total concentration of 5374.8 pg/g, followed by benzotriazole (3298.3 pg/g), salicylate (3094.1 pg/g) and triazin UVFs (61.2 pg/g), respectively. Spatial analysis revealed significantly higher UVF concentrations ranging from 1839 pg/g to 82,308 pg/g in coastal sediments from the Yellow Sea compared with those of the South China Sea, the East China Sea and the Bohai Sea (p < 0.05). Source apportionment indicated that the emissions from industrial productions, cosmetics and personal care products are major contributors to UVF contamination. A nationwide mass inventory identified the Liaodong Peninsula, Yangtze River Estuary, Pearl River Estuary, and north-east Hainan Province as UVF accumulation hotspots, influenced by tourism, industrial activities, and ocean currents. Ecological risk assessment showed that seven UVFs, including Benzophenone-7 (BP-7), 2-(benzotriazol-2-yl)-4-tert-butylphenol (UV-PS), 2-tert-butyl-6-(5-chlorobenzotriazol-2-yl)-4-methylphenol (UV-326), 2,4-ditert-butyl-6-(5-chlorobenzotriazol-2-yl) phenol (UV-327), 2-(benzotriazol-2-yl)-4-(2,4,4-trimethylpentan-2-yl) phenol (UV-329), 2-Ethylhexyl salicylate (EHS) and Homosalate (HMS), posed significant ecological risks (RQ > 0.1) in coastal sediments. This work delivers the first nationwide assessment of four classes of UVFs contamination in coastal sediments of China, providing critical data for their environmental mitigation and management.

Understanding the processes that organic UV filters undergo in coastal and marine environments is crucial for assessing their long-term environmental risks. One key process is degradation by microorganisms in sediments. This study aimed to determine whether coastal marine sediments harbor microorganisms capable of degrading organic UV filters. Sediment from Toulon Harbor was tested for its degradation potential with respect to 12 different organic UV filters. Sediment microcosms showed degradation activity towards benzophenone-3 (BP3), 2-ethylhexyl salicylate (ES), and homosalate (HS) after 12 days. However, no degradation was observed for butyl methoxydibenzoylmethane (BM), octocrylene (OC), diethylamino hydroxybenzoyl hexyl benzoate (DHHB), drometrizole trisiloxane (DTS), phenylene bis-diphenyltriazine (TriAsorB), bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT), methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT), diethylhexyl butamido triazone (DBT), or ethylhexyl triazone (ET), even after 100 days of incubation. Two degrading strains were isolated from the microcosms: a Rhodococcus strain degrading ES and a Microbacterium strain capable of degrading HS. Despite substantial efforts, the microorganism thought to be responsible for BP3 degradation could not be isolated. This work demonstrates that microorganisms in coastal sediments can degrade a limited range of organic UV filters.

The increasing use of personal care products has led to the widespread of organic UV filters (oUVFs) in marine ecosystems, yet their occurrence and potential impacts on pelagic and deep-sea environments remain unclear. This study assessed oUVFs contamination in the blubber of two deep-diving cetacean species -the short-finned pilot whale (Globicephala macrorhynchus) and the sperm whale (Physeter macrocephalus)-off Madeira Island, Eastern North Atlantic. Using microwave-assisted extraction and UHPLC-MS/MS, four of eleven targeted oUVFs were detected in blubber: homosalate, 2-ethylhexyl salicylate, octocrylene, and methylene bis-benzotriazole (UV-360). Concentrations reached up to 352.3 ng/g wet weight (w.w.) in pilot whales and 1505 ng/g w.w. in sperm whales. Detection frequencies were higher in pilot whales (60-100 %) than in sperm whales (30-50 %). This study provides the first evidence of UV-360 concentration in cetaceans. These findings suggest that pilot whales' higher site fidelity in Madeiran waters may increase exposure to oUVF, while sperm whales may accumulate oUVFs through benthopelagic feeding at higher trophic levels. These results highlight the potential for oUVF to disperse into deep marine ecosystems and underscore the importance of monitoring emerging contaminants in oceanic apex predators.

Ultraviolet (UV) filters are emerging contaminants of great concern that are widely used in personal care products (PCPs). In this study, the concentrations of 15 UV filters in six types of PCP marketed in China were analyzed and the health risks posed by their internal and external exposure were evaluated. 2-ethylhexyl-4-methoxycinnamate (EHMC) presented the highest median concentration of 3150 ng/g in PCPs, followed by 2-ethylhexyl salicylate (109 ng/g) and octocrylene (OC, 95.1 ng/g). The total UV filter concentrations were considerably higher in sunscreens than other PCPs. Total external dermal exposure to UV filters in sunscreen was higher than the total estimated daily dietary intake of UV filters. A physiologically based toxicokinetic model to predict internal UV filter concentrations after sunscreen application for 1 d showed that EHMC had the highest predicted maximum concentration in venous blood at 0.0770 ng/mL, only one order of magnitude lower than the reference dose. The predicted maximum UV filter concentrations were higher for high-lipid-content tissues than venous blood, consistent with UV filters being lipophilic. OC, EHMC and homosalate made large contributions to the toxic activity assay results, and thus should receive more attention than other UV filters.

Ultraviolet (UV) filters, the active ingredients in sunscreens, have been used for several decades to reduce the risk of acute and chronic damage to the skin from solar UV radiation, which can lead to skin cancer. Based on recent clinical studies showing that certain UV filters are absorbed systemically at low levels in humans, the US Food and Drug Administration (FDA) has requested supplementing existing safety data with preclinical studies including oral and dermal 2-year rodent carcinogenicity studies. Although the conduct of 2-year rodent carcinogenicity studies has been the standard approach for evaluating the carcinogenic potential of chemicals and new drugs for approximately 6 decades, there are multiple examples showing that such studies are not predictive of human cancer risk. Given these concerns with 2-year rodent carcinogenicity studies, we have developed and applied an alternative approach for supplementing existing data related to carcinogenic potential for six of the most commonly used UV filters in sunscreen products (i.e. avobenzone, ensulizole, homosalate, octinoxate, octisalate, and octocrylene). This approach evaluates their mode of action (MOA) based on in vivo , in vitro , and in silico data combined with an assessment of exposure margins. This approach is based on the substantial progress in understanding the MOAs that are responsible for tumor induction in humans. It is consistent with those being developed by the International Council for Harmonization (ICH) and other health authorities to replace 2-year carcinogenicity studies given their limitations and questionable biological relevance to humans. The available data for the six UV filters show that they are not genotoxic and show no evidence of biologically relevant carcinogenic MOAs. Furthermore, their systemic exposure levels in humans fall well below concentrations at which they have biologic activity. In conclusion, these data support the continued safe use of these six filters in sunscreen products.

Sunscreen products, essential for photoprotection, introduce organic UV filters into aquatic environments, raising concerns about their ecotoxicological impacts. This study evaluates the sensitivity of seven marine microalgae species spanning diverse taxonomic groups to six organic UV filters (benzophenone-3, butyl methoxydibenzoylmethane, ethylhexyl triazone, homosalate, 2-ethylhexyl salicylate, and octocrylene). Growth rate and chlorophyll a fluorescence were analyzed after 72 hr exposures at concentrations of 10, 100, and 1,000 µg/L. Growth rate was revealed to be the most sensitive indicator, with significant interspecies variability in response to UV filters. Results revealed that Tisochrysis lutea exhibited better sensitivity than the commonly used Phaeodactylum tricornutum, which demonstrated low sensitivity across endpoints. Among UV filters, 2-ethylhexyl salicylate and homosalate were the most toxic, significantly affecting growth and fluorescence in multiple species. Interestingly, growth inhibition often coincided with increased fluorescence, suggesting species-specific compensatory mechanisms. These findings underscore the limitations of relying solely on P. tricornutum in standardized toxicity tests and advocate for the inclusion of sensitive species to improve ecological relevance. Integrating growth and fluorescence metrics in high-throughput assays could advance risk assessment methodologies for emerging contaminants like UV filters.

Exposure to ultraviolet (UV) radiation is a major contributor to skin injury, including sunburn, photoaging, and augmented risk of skin cancer, primarily through the generation of reactive oxygen species (ROS) that induce oxidative stress. Rosmarinic acid (RA), a natural phenolic compound with antioxidant and several other biological properties, has shown promise in mitigating such damage when incorporated into sunscreens. We evaluated RA's possible interactions and potential to enhance the efficacy of three worldwide known UVB filters-ethylhexyl methoxycinnamate (EHMC), octocrylene (OCT), and ethylhexyl salicylate (EHS). The performance of sunscreens with and without RA (0.1% w / w ) was analyzed through in vitro and in vivo photoprotective assessments. The HPLC-TBARS-EVSC (high-performance liquid chromatography-thiobarbituric acid reactive substances-ex vivo stratum corneum) protocol, which quantified oxidative stress reduction in the human stratum corneum, was also used. The in vitro photoprotective assays showed that RA had distinct levels of interactions with the UVB filters. When associated with EHMC, RA exclusively acted in the UVB range (SPF-enhancing effect). Remarkably, for EHS, RA contributed to a higher efficacy profile in the total UV spectrum. OCT-RA was the sample that reached the highest critical wavelength value parallelly to OCT, boosting the in vivo SPF by more than 157% in comparison to OCT. However, its in vitro SPF performance was not affected by the RA addition, being comparable to OCT, EHS, and EHS-RA. Furthermore, the HPLC-TBARS-EVSC protocol highlighted RA's ability to reduce lipid peroxidation, with OCT-RA exhibiting the most notable protective effect. These findings underscore RA's potential as a multifunctional additive in sunscreen systems, enhancing both photoprotection and oxidative stress mitigation.