salicylates and octylmethoxycinnamate

Today, topical application of sunscreens, containing ultraviolet-filters (UV-filters), is preferred protection against adverse effects of ultraviolet radiation. Evidently, use of sunscreens is effective in prevention of sunburns in various models. However, evidence for their protective effects against melanoma skin cancer is less conclusive. Three important observations prompted us to review the animal data and human studies on possible side effects of selected chemical UV-filters in cosmetics. (1) the utilization of sunscreens with UV-filters is increasing worldwide; (2) the incidence of the malignant disorder for which sunscreens should protect, malignant melanoma, is rapidly increasing and (3) an increasing number of experimental studies indicating that several UV-filters might have endocrine disruptive effects. The selected UV-filters we review in this article are benzophenone-3 (BP-3), 3-benzylidene camphor (3-BC), 3-(4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC), Homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate (OD-PABA) and 4-aminobenzoic acid (PABA). The potential adverse effects induced by UV-filters in experimental animals include reproductive/developmental toxicity and disturbance of hypothalamic-pituitary-thyroid axis (HPT). Few human studies have investigated potential side effects of UV-filters, although human exposure is high as UV-filters in sunscreens are rapidly absorbed from the skin. One of the UV-filters, BP-3, has been found in 96% of urine samples in the US and several UV-filters in 85% of Swiss breast milk samples. It seems pertinent to evaluate whether exposure to UV-filters contribute to possible adverse effects on the developing organs of foetuses and children.

Topics: 4-Aminobenzoic Acid; Animals; Benzyl Compounds; Camphor; Cinnamates; Endocrine Disruptors; Humans; Hypothalamo-Hypophyseal System; Melanoma; para-Aminobenzoates; Receptors, Estrogen; Salicylates; Skin Neoplasms; Sunburn; Sunscreening Agents; Thyroid Gland; Ultraviolet Rays

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

The aim of the present study was to objectively quantify and predict bioavailability of three sunscreen agents (i.e., benzophenone-3, 2-ethylhexylsalicylate, and 2 ethylhexyl-4-methoxycinnamate) in epidermis treated by petrolatum and emulsion-based formulations for 7 and 30min on four human volunteers. Profiles of sunscreen agents through stratum corneum (SC), derived from the assessment of chemical amounts in SC layers collected by successive adhesive tape-stripping, were successfully fitted to Fick's second law of diffusion. Therefore, permeability coefficients of sunscreen agents were found lower with petrolatum than with emulsion based formulations confirming the crucial role of vehicle in topical delivery. Furthermore, the robustness of that methodology was confirmed by the linear relationship between the chemical absorption measured after 30min and that predicted from the 7-min exposure experiment. Interestingly, in this dermatopharmacokinetic method, the deconvolution of permeability coefficients in their respective partition coefficients and absorption constants allowed a better understanding of vehicle effects upon topical bioavailability mechanisms and bioequivalence of skin products.

Topics: Administration, Topical; Adult; Aged; Benzophenones; Biological Availability; Cinnamates; Humans; Middle Aged; Salicylates; Skin; Skin Absorption; Sunscreening Agents

Dispersive liquid-liquid microextraction (DLLME) using a floating organic drop has been optimized and used for the sample preparation of four commonly used ultraviolet filter (UVF) substances in sunscreens. Plackett-Burman experimental design was used to screen 10 variables in DLLME. The most significant variables were then optimized by using a response surface method with a Box-Behnken design. DLLME followed by an optimized HPLC identified octocrylene, 2-ethylhexyl-4-methoxycinnamate, ethylhexyl salicylate, and homosalate as the frequently found UVFs in commercial sunscreens. The systemic exposure dosage and margin of safety (MoS) for the identified UVFs were estimated using in-use concentrations and application patterns. The average systemic exposure dosage values for octocrylene, 2-ethylhexyl-4-methoxycinnamate, ethylhexyl salicylate, and homosalate were 0.52, 0.61, 0.020, and 0.079 mg/kg body weight per day, respectively. Whereas the average MoS values for individual UVFs ranging from 296 to 3160 were all significantly higher than the limit value of 100, the combined exposure risks were slightly above the limit. The probabilistic health risk assessment using Monte Carlo simulation revealed that the combined MoS values were (mean, 10‰, 90‰) 342, 119, and 441, respectively. Regarding the usage of sunscreen cosmetics containing the UVFs studied, these results indicate a safety concern for those who apply multiple UVF products.

Topics: Liquid Phase Microextraction; Monte Carlo Method; Salicylates; 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 human population is widely exposed to benzophenone-3 (BP-3), octylmethoxycinnamate (OMC), 4-methylbenzilidenecamphor (4-MBC) and homosalate from their use in consumer goods to absorb ultraviolet (UV) light. Their oestrogenic activity and presence in human milk suggest a potential to influence breast cancer development. In this study, high-performance liquid chromatography-tandem mass spectrometry was used to measure concentrations of these UV filters in human breast tissue from three serial locations across the breast from 40 women undergoing mastectomy for primary breast cancer. One or more of these UV filters were quantifiable in 101 of 120 (84%) of the tissue samples and at least one breast region for 38 of 40 women. BP-3 was measured in 83 of 120 (69%) tissue samples and at least one breast region for 33 of 40 women (range 0-26.0 ng g

Topics: Benzophenones; Breast; Breast Neoplasms; Camphor; Cinnamates; Female; Humans; Mastectomy; Salicylates; Sunscreening Agents

Topical commercial formulations containing diclofenac (DC) were submitted to photostability tests, according to the international rules, showing a clear degradation of the drug. The degradation process was monitored by applying the multivariate curve resolution technique to the UV spectral data from samples exposed to stressing irradiation. This method was able to estimate the number of components evolved as well as to draw their spectra and concentration profiles. Three photoproducts (PhPs) were resolved by the analysis of photodegradation kinetics, according to two consecutive reactions with a mechanism postulated as DC>PhP₁>PhP₂ and PhP₃. Photodegradation rate of DC in gel was found to be very fast, with a residual content of 90% only after 3.90 min under a radiant exposure of 450 Wm(-2). Because of a very slow skin uptake of DC, a prolonged time of exposure to light could lead to a significant decrease of drug available or the uptake of undesired photoproducts. New gel formulations were designed to increase the photostability of DC by incorporating chemical light-absorbers or entrapping the drug into cyclodextrin. Drug photostability resulted increased significantly in comparison with that of the commercial formulations. The gel containing the light-absorbers such as octisilate, octyl methoxycinnamate and a combination thereof showed a residual DC of 90% up to 12.22 min, 13.75 min and 15.71 min, respectively, under the same irradiation power. The best results were obtained by incorporating the drug in β-cyclodextrin with a degradation of 10% after 25.01 min of light exposure.

Topics: Absorption, Radiation; Administration, Cutaneous; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Chemistry, Pharmaceutical; Cinnamates; Diclofenac; Drug Stability; Excipients; Gels; Kinetics; Least-Squares Analysis; Models, Chemical; Multivariate Analysis; Photolysis; Salicylates; Technology, Pharmaceutical

A novel TiO2-nanosheets coated fiber for solid-phase microextraction (SPME) was fabricated by anodization of Ti wire substrates in ethylene glycol with concentrated NH4F. The in situ fabricated TiO2-nanosheets were densely embedded into Ti substrates with about 1μm long, 300nm wide and 80nm thick. The as-fabricated TiO2-nanosheets coating was employed to extract polycyclic aromatic hydrocarbons, phthalates and ultraviolet (UV) filters in combination with high performance liquid chromatography-UV detection (HPLC-UV). It was found that the TiO2-nanosheets coating exhibited high extraction capability and good selectivity for some UV filters frequently used in cosmetic sunscreen formulations. The main parameters affecting extraction performance were investigated and optimized. Under the optimized conditions, the calibration graphs were linear in the range of 0.1-400μgL(-1). The limits of detection of the proposed method were between 0.026μgL(-1) and 0.089μgL(-1) (S/N=3). The single fiber repeatability varied from 4.50% to 8.76% and the fiber-to-fiber reproducibility ranged from 7.75% to 9.64% for the extraction of spiked water with 50μgL(-1) UV filters (n=5). The SPME-HPLC-UV method was successfully established for the selective preconcentration and sensitive detection of target UV filters from real environmental water samples. Recovery of UV filters spiked at 10μgL(-1) and 25μgL(-1) ranged from 88.8% to 107% and the relative standard deviations were less than 9.8%. Furthermore the in situ growth of the TiO2-nanosheets coating was performed in a highly reproducible manner and the TiO2-nanosheets coated fiber has high mechanical strength, good stability and long service life.

Topics: Acrylic Resins; Adsorption; Chromatography, High Pressure Liquid; Cinnamates; Dimethylpolysiloxanes; Electrochemical Techniques; Nanostructures; para-Aminobenzoates; Phthalic Acids; Reproducibility of Results; Rivers; Salicylates; Solid Phase Microextraction; Surface Properties; Titanium; Water Pollutants, Chemical

Melatonin has attracted attention because of their high antioxidant and anticarcinogenic activity. Otherwise, the use of sunscreens is recommended for patients after chemotherapy and radiotherapy treatments or to prevent UV radiation-induced skin damages that may result in pre-cancerous and cancerous skin lesions.. To evaluate the beneficial influence of melatonin in topical sunscreen emulsions combined with three common ultraviolet filters.. After the formulation characterization in terms of rheology, stability studies were performed. Release studies let us to evaluate its mechanism of delivery and ex vivo permeation study through human skin, the amount of melatonin retained. The antioxidant activity assay was also carried out, and finally the in vivo photoprotective effect in rats was tested as transepidermal water loss and erythema formation.. The rheological behaviour of formulations was pseudoplastic fluid, all emulsions had good physical stability. Release studies showed a trend of enhancement in melatonin release from emulsions incorporating UV filters and followed a Weibull model. Melatonin permeation was higher from the emulsion containing melatonin combined with a mixture of three ultraviolet filters (MMIX) formulation. Equally this formulation exhibited the highest radical scavenging activity. Finally the photoprotective assay showed that only skin areas treated with this formulation were statistically equivalent to the unirradiated control area.. MMIX formulation would be a promising formulation for preventing the undesirable adverse effects of UV skin irradiation because melatonin not only acts as a potent antioxidant itself, but also is capable of activating an endogenous enzymatic protective system against oxidative stress.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Benzophenones; Cinnamates; Emulsions; Erythema; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Melatonin; Permeability; Rats; Rats, Wistar; Rheology; Salicylates; Skin; Stress, Mechanical; Sunburn; Sunscreening Agents; Temperature; Ultraviolet Rays

Organic sunscreens may decrease their protective capability and also behave as photo-oxidants upon ultraviolet radiation (UVR) exposure. The present study investigated the effect of a cream gel formulation containing the UV filters benzophenone-3, octyl methoxycinnamate, and octyl salicylate on skin superoxide dismutase (SOD) after a single dose of UVR (2.87 J/cm(2)). The retention of these UV filters was first evaluated in vivo using hairless mice to guarantee the presence of the filters in the skin layers at the moment of irradiation. The in vivo effect of the UV filters on skin SOD was then assayed spectrophotometrically via the reduction of cytochrome c. The cream gel formulation promoted the penetration of the three UV filters into the epidermis and the dermis at one hour post-application. A significant decrease in SOD activity was observed in irradiated animals treated with sunscreen formulation. However, no effect on SOD activity in skin was observed by the isolated presence of the sunscreens, the formulation components, or the exposure to UVR. The sunscreens may have formed degradation products under UVR that may have either inhibited the enzyme or generated reactive species in the skin.

Topics: Administration, Cutaneous; Animals; Benzophenones; Cinnamates; Cytochromes c; Drug Combinations; Female; Male; Mice; Mice, Hairless; Permeability; Salicylates; Skin; Spectrophotometry; Sunscreening Agents; Superoxide Dismutase; Ultraviolet Rays

A simple, inexpensive sample preparation procedure, based on the matrix solid-phase dispersion (MSPD) technique, for the determination of six UV filters: 2-ethylhexyl salicylate (EHS), 3,3,5-trimethylcyclohexyl salicylate (Homosalate, HMS), 3-(4-methylbenzylidene) camphor (4-MBC), isoamyl-p-methoxycinnamate (IAMC), 2-ethylhexyl-p-methoxycinnamate (EHMC) and octocrylene (OCR), in dust from indoor environments is presented and the influence of several operational parameters on the extraction performance discussed. Under the final working conditions, sieved samples (0.5 g) were mixed with the same amount of anhydrous sodium sulphate and dispersed with 2 g of octadecyl bonded silica (C18) in a mortar with a pestle. This blend was transferred to a polypropylene solid-phase extraction cartridge containing 2 g of activated silica, as the clean-up co-sorbent. The cartridge was first rinsed with 5 mL of n-hexane and the analytes were then recovered with 4 mL of acetonitrile. This extract was adjusted to 1 mL, filtered and the compounds were determined by gas chromatography combined with tandem mass spectrometry (GC-MS/MS). Recoveries for samples spiked at two different concentrations ranged between 77% and 99%, and the limits of quantification (LOQs) of the method between 10 and 40 ng g(-1). Analysis of settled dust from different indoor areas, including private flats, public buildings and vehicle cabins, showed that EHMC and OCR were ubiquitous in this matrix, with maximum concentrations of 15 and 41 microg g(-1), respectively. Both UV filters were also quantified in dust reference material SRM 2585 for first time. EHS, 4-MBC and IAMC were detected in some of the analyzed samples, although at lower concentrations than EHMC and OCR.

Topics: Acetonitriles; Acrylates; Air Pollution, Indoor; Camphor; Cinnamates; Dust; Gas Chromatography-Mass Spectrometry; Salicylates; Sensitivity and Specificity; Solid Phase Extraction; Sunscreening Agents; Tandem Mass Spectrometry

Polarity of the surrounding medium affects the excited states of UV-B sunscreens. Therefore understanding excited state processes in a mixed polarity model system similar to skin is essential. We report the excited state lifetimes, quantum yields, radiative and non-radiative rates of three sunscreens. Among the three UV-B sunscreens studied, octyl salicylate emits from a single excited state, while padimate O and octyl methoxy cinnamate show multiple states. The radiative rates of salicylate and cinnamate are approximately constant, while that of padimate O depends strongly on solvent. The non-radiative rates of all sunscreens vary with solvent polarity. Compared to salicylate and cinnamate, padimate O is complex to analyze because of its two emission peaks and one peak's strong dependence on the dielectric constant. High absorbance, broad absorption peak with small fluorescence quantum yield, and low radiative rate make octyl methoxy cinnamate a superior UV-B sunscreen ingredient. The complexity in excited-state analysis shows that the lifetimes of the sunscreens are critical parameters, in addition to absorbance and quantum yield. Fluorescence lifetime substantiates the use of polystyrene nanospheres as a model host to study the photo-physical properties of sunscreen in a heterogeneous environment.

Topics: 4-Aminobenzoic Acid; Cinnamates; Fluorescence; Fluorescent Dyes; para-Aminobenzoates; Photochemistry; Salicylates; Solvents; Spectrometry, Fluorescence; Sunscreening Agents; Ultraviolet Rays

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

Fluorescence and absorption spectra of hydrophobic sunscreens, weakly fluorescent octyl methoxycinnamate, moderately fluorescent octyl salicylate and highly fluorescent 2-ethylhexyl-4-(dimethylamino)benzoate (padimate O) adsorbed to dielectric microspheres in aqueous suspension, have been compared with spectra in organic solution. The fluorescence of adsorbed salicylate and padimate is enhanced compared with fluorescence in methanol: about a factor of 6 and 30 in terms of fluorescence yield per molecule of salicylate and padimate, respectively. Cinnamate, which has a low fluorescence yield, does not show a comparable fluorescence enhancement. The fluorescence amplification is independent of sphere diameter from 30 to 1500 nm, at least for salicylate. The enhancement, as well as the location of absorption spectral peaks, is consistent with a low-dielectric constant environment of the molecules, in spite of the presumed location near the interface between polystyrene (epsilon = 2.4-3.8) and water (epsilon = 78). The adsorbed state of these sunscreens represents a proposed improved in vitro model for the environment of sunscreens in vivo, as well as a general model for chromophores in heterogeneous environments.

Topics: 4-Aminobenzoic Acid; Absorption; Adsorption; Cinnamates; Hydrophobic and Hydrophilic Interactions; Microspheres; Molecular Structure; Nanotechnology; para-Aminobenzoates; Particle Size; Salicylates; Solutions; Spectrometry, Fluorescence; Sunscreening Agents; Water

Temperature influences the stratum corneum adsorption of several topically applied compounds. This study was designed to evaluate the influence of the temperature on the stratum corneum adsorption of 3 UV filters. The UV filters were solubilized in two vehicles, an emulsion gel and petroleum jelly and applied at respectively, 31 and 40 degrees C during 30 min. In vivo stratum corneum UV filter content was measured using the tape stripping method. Similar amounts of UV filter were detected in the stratum corneum when comparing applications at the different temperatures. Application of the UV filters in the emulsion gel resulted in higher stratum corneum UV filter concentrations compared with application in the petroleum jelly. The application temperature did not influence the stratum corneum adsorption of the tested UV filters while the nature of the vehicle significantly influenced the amount of UV filters recovered from the stratum corneum.

Topics: Adult; Benzophenones; Cinnamates; Emulsions; Gels; Humans; Humidity; Petrolatum; Reproducibility of Results; Salicylates; Skin; Skin Physiological Phenomena; Sunscreening Agents; Temperature; Ultraviolet Rays

Topics: Administration, Oral; Administration, Topical; Age Factors; Animals; Benzophenones; Cinnamates; Cosmetics; Environmental Exposure; Estradiol Congeners; Ethinyl Estradiol; Female; Guidelines as Topic; Humans; No-Observed-Adverse-Effect Level; Rats; Rats, Long-Evans; Rats, Sprague-Dawley; Rats, Wistar; Research Design; Risk Assessment; Salicylates; Sunscreening Agents; Toxicity Tests; Ultraviolet Rays; Uterus

Topical application of alpha-tocopherol (alphaTH), the most prominent naturally occurring form of vitamin E, inhibits ultraviolet (UV) B-induced photocarcinogenesis and DNA photodamage in C3H mice in vivo. In this study, we compared alphaTH with other vitamin E compounds and with three commercial sunscreen compounds for their ability to inhibit DNA photodamage in C3H mouse skin in vivo. When applied in a 5% dispersion in a neutral cream vehicle, alpha-tocopherol (alphaTH), gamma-tocopherol (gammaTH), and delta-tocopherol (deltaTH) each produced a statistically significant inhibition of thymine dimer formation, whereas alpha-tocopherol acetate (alphaTAc) and alpha-tocopherol methyl ether (alphaTOMe) did not. Application of 5% dispersions of the commercial sunscreen agent octylmethoxycinnamate also inhibited dimer formation, whereas ethylhexyl salicylate and oxybenzone did not, despite their considerably greater UVB absorbances than alphaTH. To test the hypothesis that cellular uptake and distribution are necessary for optimal photoprotection by tocopherols, photoprotection was studied in mouse 308 keratinocyte cells in vitro. Preincubation of 308 cells with 1 microM alphaTH for at least 2 h before exposure to 2.5 J/m2/s UVB for 10 min significantly (P < 0.05) attenuated thymine dimer formation. Pre-incubation with 1 microM gammaTH, deltaTH, alphaTAc, or alphaTOMe for 2 h did not inhibit thymine dimer formation significantly. Uptake of alphaTH was measured after incubation with 1 microM [2H3]alphaTH (d3-alphaTH) and resulted in a time-dependent increase in alphaTH levels. Use of d3-alphaTH allowed separate, simultaneous measurement of added d3-alphaTH and unlabeled endogenous alphaTH by gas chromatography-mass spectrometry. Accumulation of 167 +/- 62 pmol d3-alphaTH/mg protein was measured within 1 h in whole-cell fractions. d3-AlphaTH in the nuclear fraction reached levels of 15 +/- 4 pmol d3-alphaTH/mg protein at 2 h. Accumulation of alphaTH in the whole cell and nuclei corresponded temporally with significant protection against DNA photodamage. The kinetics of accumulation of the three tocopherols in whole cells and in nuclei were similar. Although only alphaTH conferred significant protection compared with irradiated controls at 2 h, the differences between individual tocopherols were not statistically significant. This work suggests that incorporation of tocopherol compounds into sunscreen products confers protection against procarcinogenic DNA photoda

Topics: Administration, Cutaneous; alpha-Tocopherol; Animals; Anticarcinogenic Agents; Benzophenones; Biological Transport; Cell Nucleus; Cells, Cultured; Cinnamates; DNA Damage; Ethers; Female; Keratinocytes; Mice; Mice, Inbred C3H; Neoplasms, Radiation-Induced; Photochemistry; Pyrimidine Dimers; Radiation Tolerance; Radiation-Protective Agents; Salicylates; Skin; Skin Neoplasms; Sunscreening Agents; Tocopherols; Ultraviolet Rays; Vitamin E

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