Influence of sunscreen formulation on the transfer of mineral and organic ultraviolet filters from skin to seawater in simulated ocean bathing tests.

OBJECTIVE: Significant research and regulatory attention have been focussed on the potential for some ultraviolet filters (UVFs) to rinse off from beachgoers' skin into seawater leading to exposure to sea life, especially coral reefs. The amount of UVFs potentially rinsed from skin during recreational beach activities has not been well studied, leading to uncertainty about the potential magnitude of aquatic UVF exposure due to changes in sunscreen use patterns. This study quantifies rinse-off of UVFs in sunscreen from skin into synthetic seawater and identifies differences in rinse-off quantity due to formulation type with a goal of informing future modelling efforts aimed at estimating UVF exposure to sea life associated with recreational activities at the beach. METHODS: UVF rinse-off from skin during recreation in seawater was simulated by applying eight different sunscreen products to porcine skin samples followed by three periods of shaking in synthetic seawater totalling 40 min. The rinsed mass of six UVFs - zinc oxide, titanium dioxide, avobenzone, homosalate, octisalate, and octocrylene - was determined analytically in synthetic seawater and in extractant rinsate from glassware for organic UVFs and compared among formulas. RESULTS: Among the 22 UVF-formulation combinations tested, 19 resulted in less than 10% of the applied UVF rinsed from skin. All formulation-UVF combinations where the formula types were water-in-oil (reverse phase) emulsions or anhydrous resulted in 5% or less of the applied UVF rinsed to synthetic seawater. Sunscreens formulated as oil-in-water emulsions yielded higher rinse-off percentages for all UVFs tested, with a maximum of 20% rinse-off of avobenzone in one lotion. CONCLUSION: The potential for sunscreen UVF rinse-off is significantly influenced by formulation and is generally well below the prior assumed rinse-off levels used to estimate risk. Formulation consideration is therefore essential for accurate exposure models used in environmental risk assessment. Anhydrous and reverse phase (water-in-oil) sunscreen formulations tested resulted in lower UVF transfer from skin to synthetic seawater in simulated ocean bathing tests and as a result, are expected to yield lower UVF exposures to sea life. This approach can be used in predictive environmental exposure models to support ecologically safe sunscreen formulation design.

OBJECTIF: Des recherches importantes ont été effectuées et l'attention réglementaire a été portée sur le potentiel de certains filtres ultraviolets (UVF) à être rincés de la peau de baigneurs par l'eau de mer à la plage, entraînant une exposition à la vie marine, en particulier aux récifs coralliens. La quantité d'UVF potentiellement rincée de la peau pendant les activités récréatives sur la plage n'a pas été étudiée de manière approfondie, ce qui entraîne une incertitude quant à l'ampleur potentielle de l'exposition aux UVF dans l'eau en raison des changements dans les habitudes d'utilisation de la crème solaire. Cette étude quantifie le rinçage des UVF contenus dans la crème solaire appliquée sur la peau par de l'eau de mer reconstituée et identifie les différences dans la quantité UVF rinçés selon le type de formulation afin d'éclairer les futurs efforts de modélisation visant à estimer l'exposition des UVF à la vie marine associée aux activités récréatives à la plage. MÉTHODES: Le rinçage des UVF pendant les loisirs en eau de mer a été simulé en appliquant huit produits de protection solaire différents sur des échantillons de peau porcine, suivis de trois périodes d'agitation dans de l'eau de mer reconstituée d'une durée totale de 40 min. La masse rincée de six UVF - oxyde de zinc, dioxyde de titane, avobenzone, homosalate, octisalate et octocrylène - a été déterminée analytiquement dans l'eau de mer reconstituée et en solution pour les UVF organiques, et une comparaison entre les formules a été effectuée. RÉSULTATS: Parmi les 22 combinaisons de formulations UVF testées, 19 ont entraîné le rinçage de moins de 10 % des UVF appliqués sur la peau. Toutes les combinaisons de formulations UVF où les types de formule étaient des émulsions eau dans huile (phase inverse) ou anhydres ont entraîné 5 % ou moins de rinçage des UVF appliquées dans l'eau de mer reconstituée. Les écrans solaires formulés sous forme d'émulsions huile dans l'eau ont produit des pourcentages de rinçage plus élevés pour tous les UVF testés, avec un maximum de 20 % de rinçage pour l'avobenzone pour une lotion. CONCLUSION: Le potentiel de rinçage des UVF de l'écran solaire est significativement influencé par la formulation et est généralement bien inférieur aux niveaux de rinçage précédemment supposés, utilisés pour estimer le risque. La prise en compte de la formulation est donc essentielle pour obtenir des modèles d'exposition exacts utilisés dans l'évaluation des risques environnementaux. Les formulations de crème solaire anhydre et en phase inverse (eau dans l'huile) testées ont entraîné un transfert plus faible des UVF dans l'eau de mer reconstituée dans des tests de simulation de bain de mer et, par conséquent, devraient entrainer une exposition plus faible des UVF à la vie marine. Cette approche peut être utilisée dans des modèles prédictifs d'exposition environnementale pour soutenir une conception de crème solaire écologiquement sûre.

Development of a novel rinse-off method for improved sunscreen exposure assessment.

Recent legislative measures restricting the sale of sunscreens containing certain ultraviolet light filtering ingredients (UVFs) have been based on a perception of risk to aquatic life despite the lack of a robust data set to support these decisions. Concerns were focused on the potential for recreational swimmers' and divers' sunscreen use to result in exposures to coral already stressed due to climate change, disease, and other local conditions. In published environmental risk assessments for UVFs, exposure estimates were based on episodic environmental monitoring or estimates of typical sunscreen use, arbitrarily assuming the portion rinsed off from skin in seawater. To improve the accuracy of exposure estimates and thereby develop more robust risk assessments, we measured the amount of the UVFs, avobenzone, homosalate, octisalate, octocrylene, and oxybenzone released to seawater from four sunscreen products (two lotions, one spray, one stick) in a novel porcine skin model of typical human sunscreen use. Sunscreen was applied to porcine skin, allowed to briefly dry, then exposed to four rinse cycles in artificial seawater. The mass of each UVF in seawater, partitioned from seawater onto glassware, and extractable from skin after rinsing were determined. The proportion rinsed from skin varied by UVF, by formula type, and by application rate. Less than 1.4% of applied octisalate, homosalate, and octocrylene was detected in seawater samples (independent of formula) increasing to an average of 4% and 8% for avobenzone in stick and lotion forms, and to 24% for oxybenzone in lotions. The initial data show substantial differences in rinse-off among formulation types and sunscreen application rates, and stress the importance of using UVF-specific rinse-off values rather than a single value for all UVFs. This new method provides a tool for more robust exposure estimates, with initial data supporting lower rinse-off values than adopted in published risk assessments. Integr Environ Assess Manag 2021;17:961-966. © 2021 Johnson & Johnson Consumer Companies Inc. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Colloidal Oatmeal (Avena Sativa) Improves Skin Barrier Through Multi-Therapy Activity.

Oats (Avena sativa) are a centuries-old topical treatment for a variety of skin barrier conditions, including dry skin, skin rashes, and eczema; however, few studies have investigated the actual mechanism of action for the skin barrier strengthening activity of colloidal oatmeal. Four extracts of colloidal oatmeal were prepared with various solvents and tested in vitro for skin barrier related gene expression and activity. Extracts of colloidal oatmeal were found to induce the expression of genes related to epidermal differentiation, tight junctions and lipid regulation in skin, and provide pH-buffering capacity. Colloidal oatmeal boosted the expression of multiple target genes related to skin barrier, and resulted in recovery of barrier damage in an in vitro model of atopic dermatitis. In addition, an investigator-blinded study was performed with 50 healthy female subjects who exhibited bilateral moderate to severe dry skin on their lower legs. Subjects were treated with a colloidal oatmeal skin protectant lotion. Clinically, the colloidal oatmeal lotion showed significant clinical improvements in skin dryness, moisturization, and barrier. Taken together, these results demonstrate that colloidal oatmeal can provide clinically effective benefits for dry and compromised skin by strengthening skin barrier.

J Drugs Dermatol. 2016;15(6):684-690.

Anti-inflammatory activities of colloidal oatmeal (Avena sativa) contribute to the effectiveness of oats in treatment of itch associated with dry, irritated skin.

BACKGROUND: Oat (Avena sativa) in colloidal form is a centuries-old topical treatment for a variety of skin conditions, including skin rashes, erythema, burns, itch, and eczema; however, few studies have investigated the exact mechanism of action for the anti-inflammatory activity of colloidal oatmeal. METHODS: Four extracts of colloidal oatmeal were made with various solvents and tested in anti-inflammatory and antioxidant assays. In addition, an investigator blind study was performed with twenty-nine healthy female subjects who exhibited bilateral mild to moderate itch with moderate to severe dry skin on their lower legs. Subjects were treated with a colloidal oatmeal skin protectant lotion. RESULTS: Extracts of colloidal oatmeal diminished pro-inflammatory cytokines in vitro and the colloidal oat skin protectant lotion showed significant clinical improvements in skin dryness, scaling, roughness, and itch intensity. CONCLUSIONS: These results demonstrate that colloidal oat extracts exhibit direct anti-oxidant and anti-inflammatory activities, which may provide the mechanisms for observed dermatological benefits while using the colloidal oatmeal skin protectant lotion.

Phenolic-rich extract from the Costa Rican guava (Psidium friedrichsthalianum) pulp with antioxidant and anti-inflammatory activity. Potential for COPD therapy.

The potential therapeutic effects of Costa Rican guava (Psidium friedrichsthalianum) extracts for chronic obstructive pulmonary disease were examined. The ethyl acetate fraction displayed the highest antioxidant activity, as compared to the hexane, chloroform, and n-butanol fractions, as well as the crude extract. This fraction was evaluated for its anti-inflammatory activity response relationship against interleukin-8 (IL-8) and inhibition of matrix metalloproteinase-1 (MMP-1) expression before and after treatment with cigarette smoke. The ethyl acetate fraction exhibited inhibitory activity against IL-8 production and MMP-1 expression, showing the most potent inhibitory activities in both assays at 100µg/mL, and nine compounds (1-9) were found. Phenolic compounds 1-O-trans-cinnamoyl-ß-d-glucopyranose (2), ellagic acid (3), myricetin (4), quercitrin (7), and quercetin (9) were identified using standard compounds or literature reports from related species. Compounds 1, 5, 6, and 8 were tentatively identified as 1,5-dimethyl citrate (1), sinapic aldehyde 4-O-ß-d-glucopyranose (5), 3,3',4-tri-O-methylellagic acid-4'-O-d-glucopyranoside (6), and 1,3-O-diferuloylglycerol (8), All nine compounds are reported for the first time in Costa Rican guava.

Edible Myrciaria vexator fruits: bioactive phenolics for potential COPD therapy.

The edible fruits of Myrciaria vexator McVaugh (Myrtaceae), from northern South America, are eaten in certain locales, either fresh or processed into jellies and drinks. Activity-guided fractionation of M. vexator resulted in identification of ellagic acid (1), cyanidin-3-O-glucoside (2), delphinidin-3-O-glucoside (3), 2-O-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxyphenylacetic acid (4), and jaboticabin (5), and latter two compounds are being reported for the first time in this species. Ellagic acid was further examined, and found to inhibit cigarette smoke extract induced MMP-1 expression in vitro, and may be of significance in the treatment of chronic obstructive pulmonary (COPD). Other compounds identified for the first time from M. vexator include cyanidin-3-O-galactoside (6), cyanidin-3-O-arabinoside (7), cyanidin-3-O-rutionoside (8), petunidin (9), peonidin-3-O-galactoside (10) malvidin (11), hyperoside (12), querecetin-3-O-glucoside (13), and guajaverin (14), methyl protocatechuate (15), and protocatechuic acid (16).

Anthocyanins from Eugenia brasiliensis edible fruits as potential therapeutics for COPD treatment.

Nine anthocyanins (1-9) from the edible fruits of Eugenia brasiliensis were identified by HPLC-PDA and LC-MS, and seven of these are described for the first time in this Brazilian fruit. Two of the major anthocyanins, delphinidin (8) and cyanidin (9), were studied for their inhibitory activity against chemokine interleukin-8 (IL-8) production before and after cigarette smoke extract (CSE) treatment of cells. In non-treated cells the amount of IL-8 was unchanged following treatment with cyanidin and delphinidin in concentrations 0.1-10 µM. Both delphinidin (8) and cyanidin (9) decreased the production of IL-8 in treated cells, at 1 and 10 µM, respectively. Delphinidin (8) demonstrated IL-8 inhibition in the CSE treated cells in a dose-dependent manner.

Induction of murine embryonic stem cell differentiation by medicinal plant extracts.

Epidemiological evidence indicates that diets high in fruits and vegetables provide a measure of cancer chemoprevention due to phytochemical constituents. Natural products are a rich source of cancer chemotherapy drugs, and primarily target rapidly cycling tumor cells. Increasing evidence indicates that many cancers contain small populations of resistant, stem-like cells that have the capacity to regenerate tumors following chemotherapy and radiation, and have been linked to the initiation of metastases. Our goal is to discover natural product-based clinical or dietary interventions that selectively target cancer stem cells, inducing differentiation. We adapted an alkaline phosphatase (AP) stain to assay plant extracts for the capacity to induce differentiation in embryonic stem (ES) cells. AP is a characteristic marker of undifferentiated ES cells, and this represents a novel approach to screening medicinal plant extracts. Following a survey of approximately 100 fractions obtained from 12 species of ethnomedically utilized plants, we found fractions from 3 species that induced differentiation, decreasing AP and transcript levels of pluripotency markers (Nanog, Oct-4, Rex-1). These fractions affected proliferation of murine ES, and human embryonal, prostate, and breast carcinoma cells in a dose-dependent manner. Several phytochemical constituents were isolated; the antioxidant phytochemicals ellagic acid and gallic acid were shown to affect viability of cultured breast carcinoma cells.

Stability evaluation of selected polyphenols and triterpene glycosides in black cohosh.

Black cohosh ( Actaea racemosa L., syn. Cimicifuga racemosa L.) is rich in both triterpene glycosides and polyphenols, which have various biological activities that may be important to its medical use. To evaluate the stability of the polyphenolic constituents and triterpene glycosides of black cohosh, experiments were conducted using three sample types: plant material, extracts of black cohosh, and encapsulated commercial extract. The samples were stored at various temperatures and humidity conditions. Three triterpene glycosides and six major polyphenols in black cohosh were quantitatively measured with an HPLC-PDA method at 0, 3, 6, and 9 weeks. The triterpene glycosides were stable at the tested conditions, whereas the polyphenols were stable only at room temperature and low humidity and not stable at higher temperature and/or humidity due to hydrolysis and/or oxidation. The rate of compound decomposition depended upon the chemical structure of the individual polyphenols. Polyphenols in the extracts decomposed more readily than those in plant material.

Quantitative analysis of antiradical phenolic constituents from fourteen edible Myrtaceae fruits.

Many species of Myrtaceae are cultivated in home gardens throughout the tropics for their edible fruit, and have been used in traditional medicine to treat several inflammatory conditions. Fruit phenolics are important dietary antioxidant and anti-inflammatory constituents. We have investigated the antiradical activity, total phenolic content (TPC), and total anthocyanin content (TAC) of 14 underutilized Myrtaceae fruits, namely Eugenia aggregata, E. brasiliensis, E. luschnathiana, E. reinwardtiana, Myrciaria cauliflora, M. dubia, M. vexator, Syzygium cumini, S. curranii, S. jambos, S. javanicum, S. malaccense, S. samarangense, and S. samarangense var. Taiwan pink. An HPLC-PDA method was developed to quantify the amounts of cyanidin 3-glucoside (1), delphinidin 3-glucoside (2), ellagic acid (3), kaempferol (4), myricetin (5), quercetin (6), quercitrin (7), and rutin (8) present in MeOH extracts of the fruit. TPC ranged from 3.57 to 101 mg/g, TAC ranged from undetectable to 12.1 mg/g, and antiradical activity, measured as DPPH˙ IC(50), ranged from very active (19.4 µg/ml) to inactive (389 µg/ml).

Cytotoxic chalcones and antioxidants from the fruits of a Syzygium samarangense (Wax Jambu).

Bioassay-guided fractionation of the methanolic extracts of the pulp and seeds of the fruits of Syzygium samarangense Merr. & Perry (Blume) led to the identification of four cytotoxic compounds and eight antioxidants on the basis of HPLC-PDA analysis, MS, and various NMR spectroscopic techniques. Three C-methylated chalcones, 2',4'-dihydroxy-3',5'-dimethyl-6'-methoxychalcone (1), 2',4'-dihydroxy-3'-methyl-6'-methoxychalcone (stercurensin, 2), and 2',4'-dihydroxy-6'-methoxychalcone (cardamonin, 3), were isolated and displayed cytotoxic activity (IC(50) = 10, 35, and 35 µM, respectively) against the SW-480 human colon cancer cell line. Also a number of known antioxidants were obtained including six quercetin glycosides: reynoutrin (4), hyperin (5), myricitrin (6), quercitrin (7), quercetin (9), and guaijaverin (10), one flavanone: (S)-pinocembrin (8), and two phenolic acids: gallic acid (11) and ellagic acid (12).

Bioactive depsides and anthocyanins from jaboticaba (Myrciaria cauliflora).

A new depside, jaboticabin (1), together with 17 known compounds were isolated from the fruit of jaboticaba (Myrciaria cauliflora). The structure of 1 was elucidated by spectroscopic data interpretation. Known compounds were identified by comparison of their spectroscopic data with literature values or by comparison to authentic standards. Compound 1 and the related depside 2-O-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxyphenylacetic acid (2) significantly inhibited chemokine interleukin (IL)-8 production before and after cigarette smoke treatment of cells. Compound 1 was cytotoxic in the HT29 colon cancer cell line (IC50 = 65 microM), and 2 was active against HCT116 colon cancer cells (IC50 = 30 microM). Compounds 1 and 2 also exhibited antiradical activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay (IC50 = 51.4 and 61.8 microM, respectively). Two anthocyanins, cyanidin 3-glucoside (3) and delphinidin 3-glucoside (4), also showed good activity in these assays.

Comparative analyses of bioactive Mammea coumarins from seven parts of Mammea americana by HPLC-PDA with LC-MS.

Mammea americana L. is tropical plant in the Clusiaceae family that bears edible fruit. Mammea coumarins are isoprenylated derivatives of the lactones of the 2-hydroxy-Z-cinnamic acids that are bioactive and have limited distribution in three Clusiaceae genera. Qualitative and quantitative analyses were performed to determine the distribution of mammea coumarins in the seed nucleus, seed coat, fruit flesh, fruit skin, leaf, stem, and root of M. americana using high-performance liquid chromatography-photodiode array detector (HPLC-PDA) and liquid chromatography-mass spectrometry (LC-MS). Ten major mammea coumarins, mammea E/BD (1), mammea E/BC (2), mammea E/BA (3), mammea E/BB (4), mammea B/BA hydroxycyclo F (5), mammea B/BD (6), mammea B/BC (7), mammea B/BA (8), mammea B/BB (9), and mammea B/BA cyclo F (10), were isolated and identified from the seed nucleus of M. americana and employed as standards. The HPLC-PDA method was validated with respect to sensitivity, linearity, recovery, accuracy, and precision. The total content (w/w %) of the 10 major mammea coumarins in M. americana was determined to be highest in the root (0.75%), followed by the leaf (0.64%), seed nucleus (0.48%), fruit skin (0.11%), stem (0.08%), seed coat (0.02%), and fruit flesh (<0.01%). The leaf and seed nucleus are rich and sustainable natural sources of mammea coumarins. Additionally, the described HPLC-PDA and LC-MS methods are sensitive and accurate and can be applied to the analysis of mammea coumarins in other samples.

Antioxidant and cytotoxic isoprenylated coumarins from Mammea americana.

Antioxidant-guided fractionation of Mammea americana L. seeds resulted in the identification of three new isoprenylated coumarins, mammea B/BA hydroxycyclo F (1), mammea E/BC (2), and mammea E/BD (3). In addition, twelve known isoprenylated coumarins, mammea A/AA (4), mammea A/AA cyclo D (5), mammea A/AA cyclo F (6), mammea A/AC cyclo D (7), mammea A/AD cyclo D (8), mammea B/BA (9), mammea B/BA cyclo F (10), mammea B/BB (11), mammea B/BC (12), mammea B/BD (13), mammea E/BA (14), and mammea E/BB (15), as well as two known flavanols, (+)-catechin (16) and (-)-epicatechin (17) were identified. The fifteen isoprenylated coumarins were screened for their cytotoxicity in the SW-480, HT-29, and HCT-116 human colon cancer cell lines and antioxidant capacities in the DPPH (1,1-diphenyl-2-picrylhydrazyl) free-radical assay. Compounds 1 - 15 exhibited significant cytotoxic activities in the SW-480, HT-29, and HCT-116 human colon cancer cell lines (IC50 ranges 13.9 - 88.1, 11.2 - 85.3, and 10.7 - 76.7 microM, in the three cell lines, respectively) at concentrations comparable to 5-fluorouracil (IC50 = 53.0, 46.1, and 45.1 microM), a drug frequently used for human colon cancer treatment. Compounds 2 - 4, 9, and 11 - 15 displayed high antioxidant activity in the DPPH assay (IC50 range 86 - 135 microM), compounds 1, 5 - 8, and 10, however, had no antioxidant activity (IC50 > 200 microg/mL) in the DPPH assay. The results of these assays were used to study the structure-activity relationships for this class of compounds. In the SW-480 cell line, the three new coumarins, 1 - 3, also exhibited dose-dependent increases in sub-diploid cells by flow cytometry, indicating that they induce apoptosis.

A traditional method of Cinnamomum carolinense preparation eliminates safrole from a therapeutic Pohnpean tea.

Cinnamomum carolinense, locally known as madeu, is a tree endemic to the volcanic mountains of the Island of Pohnpei in the Eastern Carolines of the South Pacific. The bark is harvested from trees and brewed to make a medicinal tea and hot beverage that is regularly consumed. Many species of Cinnamomum contain the known hepatocarcinogen safrole, sparking concern regarding habitual consumption of this beverage. HPLC-PDA analysis confirmed the presence of the carcinogen in alcoholic extracts of Cinnamomum carolinense bark shavings (0.435%, w/w), but safrole was not detected in the tea. The limit of detection and limit of quantitation of safrole were determined to be 1.25 and 3.75 microg/mL, respectively. The traditional preparation method, which boils the bark shavings, degrades the safrole.