salicylates and avobenzone

A prior pilot study demonstrated the systemic absorption of 4 sunscreen active ingredients; additional studies are needed to determine the systemic absorption of additional active ingredients and how quickly systemic exposure exceeds 0.5 ng/mL as recommended by the US Food and Drug Administration (FDA).. To assess the systemic absorption and pharmacokinetics of the 6 active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate) in 4 sunscreen products under single- and maximal-use conditions.. Randomized clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) was conducted in 48 healthy participants. The study was conducted between January and February 2019.. Participants were randomized to 1 of 4 sunscreen products, formulated as lotion (n = 12), aerosol spray (n = 12), nonaerosol spray (n = 12), and pump spray (n = 12). Sunscreen product was applied at 2 mg/cm2 to 75% of body surface area at 0 hours on day 1 and 4 times on day 2 through day 4 at 2-hour intervals, and 34 blood samples were collected over 21 days from each participant.. The primary outcome was the maximum plasma concentration of avobenzone over days 1 through 21. Secondary outcomes were the maximum plasma concentrations of oxybenzone, octocrylene, homosalate, octisalate, and octinoxate over days 1 through 21.. Among 48 randomized participants (mean [SD] age, 38.7 [13.2] years; 24 women [50%]; 23 white [48%], 23 African American [48%], 1 Asian [2%], and 1 of unknown race/ethnicity [2%]), 44 (92%) completed the trial. Geometric mean maximum plasma concentrations of all 6 active ingredients were greater than 0.5 ng/mL, and this threshold was surpassed on day 1 after a single application for all active ingredients. For avobenzone, the overall maximum plasma concentrations were 7.1 ng/mL (coefficient of variation [CV], 73.9%) for lotion, 3.5 ng/mL (CV, 70.9%) for aerosol spray, 3.5 ng/mL (CV, 73.0%) for nonaerosol spray, and 3.3 ng/mL (CV, 47.8%) for pump spray. For oxybenzone, the concentrations were 258.1 ng/mL (CV, 53.0%) for lotion and 180.1 ng/mL (CV, 57.3%) for aerosol spray. For octocrylene, the concentrations were 7.8 ng/mL (CV, 87.1%) for lotion, 6.6 ng/mL (CV, 78.1%) for aerosol spray, and 6.6 ng/mL (CV, 103.9%) for nonaerosol spray. For homosalate, concentrations were 23.1 ng/mL (CV, 68.0%) for aerosol spray, 17.9 ng/mL (CV, 61.7%) for nonaerosol spray, and 13.9 ng/mL (CV, 70.2%) for pump spray. For octisalate, concentrations were 5.1 ng/mL (CV, 81.6%) for aerosol spray, 5.8 ng/mL (CV, 77.4%) for nonaerosol spray, and 4.6 ng/mL (CV, 97.6%) for pump spray. For octinoxate, concentrations were 7.9 ng/mL (CV, 86.5%) for nonaerosol spray and 5.2 ng/mL (CV, 68.2%) for pump spray. The most common adverse event was rash, which developed in 14 participants.. In this study conducted in a clinical pharmacology unit and examining sunscreen application among healthy participants, all 6 of the tested active ingredients administered in 4 different sunscreen formulations were systemically absorbed and had plasma concentrations that surpassed the FDA threshold for potentially waiving some of the additional safety studies for sunscreens. These findings do not indicate that individuals should refrain from the use of sunscreen.. ClinicalTrials.gov Identifier: NCT03582215.

Topics: Acrylates; Adult; Benzophenones; Cinnamates; Female; Humans; Male; Middle Aged; Propiophenones; Salicylates; Skin Absorption; Sunscreening Agents

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.. 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).. 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.. 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.

Topics: 4-Aminobenzoic Acid; Cinnamates; Drug Compounding; Drug Stability; Ethanol; Photolysis; Polyethylene Glycols; Propiophenones; Salicylates; Sunscreening Agents

The uptake, translocation and transformation of three UV-blockers commonly employed in sunscreens, namely avobenzone, octocrylene and octisalate from water by Lemna gibba and Cyperus alternifolius was investigated. Reversed phase high performance liquid chromatography coupled to drift-tube ion-mobility quadrupole time-of-flight mass spectrometry was used for analyzing the extracts from the selected plants after incubation with the UV-blockers for one week. For avobenzone several transformation products resulting from hydroxylation, demethylation and oxidation of the parent molecule could be identified by measuring accurate mass, performing MS/MS experiments and by determining their drift-tube collision cross sections employing nitrogen as drift gas. In addition, the plants were subjected to two commercially available sunscreens, providing similar results to those obtained for the standard solutions of the UV-blockers. Finally, a kinetic study on the uptake and transformation of avobenzone, octocrylene and octisalate was conducted over a period of 216 h, revealing that the UV-filters were mostly present in their parent form and only to a smaller part converted into transformation products.

Topics: Acrylates; Araceae; Biotransformation; Chromatography, High Pressure Liquid; Cyperus; Ion Mobility Spectrometry; Propiophenones; Salicylates; Sunscreening Agents; Tandem Mass Spectrometry

Monitoring human exposure to chemical UV filters is essential for an accurate assessment of the health risk caused by the resorbed compounds. We developed different procedures for the determination of the prominent UV filters octocrylene (OC), avobenzone (AVO) and 2-ethylhexyl salicylate (EHS) as well as for two OC and EHS metabolites in human urine and OC, AVO and 2-cyano-3,3-diphenylacrylic acid (CDAA) in plasma samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Since the development of a multi-method for all analytes proved to be difficult, three different procedures were established for the determination of AVO, OC and its metabolite CDAA in urine and plasma as well as for EHS and its metabolite 5-hydroxy-EHS in urine. The methods have been validated with good sensitivity, precision and accuracy. The procedures were satisfactorily applied to the determination of the target compounds in human samples collected from volunteers after sunscreen application. These new analytical procedures can provide information on the internal exposure to the UV filters OC, AVO and EHS, which has been little studied.

Topics: Acrylates; Chromatography, High Pressure Liquid; Humans; Propiophenones; Salicylates; Sunscreening Agents; Tandem Mass Spectrometry; Urine

Development of photostable sunscreens is extremely important to preserve the UV protective capacity and to prevent the reactive intermediates of photounstable filter substances behaving as photo-oxidants when coming into direct contact with the skin. Thus, the objective of this study was to evaluate the photostability of four different UV filter combinations in a sunscreen by using HPLC analysis and spectrophotometry. The formulations that were investigated included four different UV filter combinations often used in SPF 15 sunscreens. The UV filter combinations were: octyl methoxycinnamate (OMC), benzophenone-3 (BP-3) and octyl salicylate (OS) (formulation 1); OMC, avobenzone (AVB) and 4-methylbenzilidene camphor (MBC) (formulation 2); OMC, BP-3 and octocrylene (OC) (formulation 3); OMC, AVB and OC (formulation 4). In the photostability studies, 40 mg of each formulation were spread onto a glass plate and left to dry before exposure to different UVA/UVB irradiation. Exposed samples were then immersed in isopropanol and the dried film dissolved ultrasonically. The filter components in the resulting solution were quantified by HPLC analysis with detection at 325 nm and by spectrophotometry. In this study, the four UV filter combinations showed different photostability profiles and the best one was formulation 3 (OMC, BP-3 and OC), followed by formulations 4, 1 and 2. In addition, OC improved the photostability of OMC, AVB and BP-3.

Topics: Acrylates; Benzophenones; Camphor; Chalcones; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Cinnamates; Drug Stability; Photochemistry; Propiophenones; Salicylates; Spectrophotometry; Sunscreening Agents; Time Factors; Ultraviolet Rays

This paper reports the development of a reversed-phase high-performance liquid chromatographic assay for quantifying five of the most common sunscreen agents, namely 2-ethylhexyl-p-dimethyl aminobenzoate (Escalol 507), 2-ethylhexyl-p-methoxycinnamate (Parsol MCX); 4-tert.-butyl-4'-methoxydibenzoylmethane (Parsol 1789), 2-hydroxy-4-methoxybenzophenone-3 (oxybenzone) and 2-ethylhexyl-salicylate (octylsalicylate). The assay permits analysis of the sunscreen agents in formulations and in biological fluids, including bovine serum albumin (BSA) solution, a common additive to in vitro skin diffusion cell receptor fluids, as well as human plasma. Separation was achieved using an ODS C154 column with a methanol-water (88:12) mobile phase. The analytes were detected by ultraviolet light absorption at a wavelength of 315 nm. The assay was linear with minimum detectable limits, calculated as greater than 3-times the baseline noise level: for oxybenzone and Escalol 507, 0.05 microgram/ml; for Parsol 1789 and Parsol MCX, 0.1 microgram/ml; for octylsalicylate, 1 microgram/ml. Recoveries from both plasma and 2% BSA were within the range 89-107%. The inter- and intra-day coefficients of variation for the five agents were not more than 4% at the upper end of the linear range and not more than 10% at the lower end. Preliminary stability studies of the sunscreen agents in a commercial product and in two diffusion cell receptor fluids were also conducted.

Topics: 4-Aminobenzoic Acid; Animals; Benzoates; Benzophenones; Calibration; Cattle; Chalcones; Chromatography, High Pressure Liquid; Cinnamates; Circadian Rhythm; Cosmetics; Drug Stability; Ethanol; Humans; Linear Models; para-Aminobenzoates; Propiophenones; Reproducibility of Results; Salicylates; Sensitivity and Specificity; Serum Albumin, Bovine; Spectrophotometry, Ultraviolet; Sunlight; Sunscreening Agents; Time Factors