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1.
Environ Sci Technol ; 58(12): 5472-5482, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38466321

RESUMO

The fate of selected UV filters (UVFs) was investigated in two soil aquifer treatment (SAT) systems, one supplemented with a reactive barrier containing clay and vegetable compost and the other as a traditional SAT reference system. We monitored benzophenone-3 (BP-3) and its transformation products (TPs), including benzophenone-1 (BP-1), 4,4'-dihydroxybenzophenone (4DHB), 4-hydroxybenzophenone (4HB), and 2,2'-dihydroxy-4-methoxybenzophenone (DHMB), along with benzophenone-4 (BP-4) and avobenzone (AVO) in all involved compartments (water, aquifer sediments, and biofilm). The reactive barrier, which enhances biochemical activity and biofilm development, improved the removal of all detected UVFs in water samples. Among monitored UVFs, only 4HB, BP-4, and AVO were detected in sediment and biofilm samples. But the overall retained amounts were several orders of magnitude larger than those dissolved. These amounts were quantitatively reproduced with a specifically developed simple analytical model that consists of a mobile compartment and an immobile compartment. Retention and degradation are restricted to the immobile water compartment, where biofilm absorption was simulated with well-known compound-specific Kow values. The fact that the model reproduced observations, including metabolites detected in the biofilm but not in the (mobile) water samples, supports its validity. The results imply that accumulation ensures significant biodegradation even if the degradation rates are very low and suggest that our experimental findings for UVFs and TPs can be extended to other hydrophobic compounds. Biofilms act as accumulators and biodegraders of hydrophobic compounds.


Assuntos
Solo , Poluentes Químicos da Água , Porosidade , Protetores Solares/análise , Benzofenonas/química , Água/química , Poluentes Químicos da Água/análise
2.
J Am Acad Dermatol ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38777185

RESUMO

The second part of this CME article discusses sunscreen regulation and safety considerations for humans and the environment. First, we provide an overview of the history of the United States Food and Drug Administration's regulation of sunscreen. Recent Food and Drug Administration studies clearly demonstrate that organic ultraviolet filters are systemically absorbed during routine sunscreen use, but to date there is no evidence of associated negative health effects. We also review the current evidence of sunscreen's association with vitamin D levels and frontal fibrosing alopecia, and recent concerns regarding benzene contamination. Finally, we review the possible environmental effects of ultraviolet filters, particularly coral bleaching. While climate change has been shown to be the primary driver of coral bleaching, laboratory-based studies suggest that organic ultraviolet filters represent an additional contributing factor, which led several localities to ban certain organic filters.

3.
J Toxicol Environ Health A ; 87(17): 687-700, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38836411

RESUMO

The increasing use of UV filters, such as benzophenone-3 (BP-3) and titanium dioxide nanoparticles (TiO2 NPs), has raised concerns regarding their ecotoxicological effects on the aquatic environment. The aim of the present study was to examine the embryo-larval toxicity attributed to BP-3 or TiO2 NPs, either alone or in a mixture, utilizing zebrafish (Danio rerio) as a model after exposure to environmentally relevant concentrations of these compounds. Zebrafish embryos were exposed to BP-3 (10, 100, or 1000 ng/L) or TiO2 NPs (1000 ng/L) alone or in a mixture (BP-3 10, 100, or 1000 ng/L plus 1000 ng/L of TiO2 NPs) under static conditions for 144 hr. After exposure, BP-3 levels were determined by high-performance liquid chromatography (HPLC). BP-3 levels increased in the presence of TiO2 NPs, indicating that the BP-3 degradation decreased in the presence of the NPs. In addition, in the presence of zebrafish, BP-3 levels in water decreased, indicating that zebrafish embryos and larvae might absorb BP-3. Data demonstrated that, in general, environmentally relevant concentrations of BP-3 and TiO2 NPs, either alone or in a mixture, did not significantly induce changes in heart and spontaneous contractions frequencies, levels of reactive oxygen species (ROS), morphological and morphometric parameters as well as mortality rates during 144 hr exposure. However, the groups exposed to TiO2 NPs alone and in a mixture with BP-3 at 10 ng/L exhibited an earlier significant hatching rate than the controls. Altogether, the data indicates that a potential ecotoxicological impact on the aquatic environment exists.


Assuntos
Benzofenonas , Embrião não Mamífero , Protetores Solares , Titânio , Poluentes Químicos da Água , Peixe-Zebra , Animais , Titânio/toxicidade , Titânio/química , Benzofenonas/toxicidade , Protetores Solares/toxicidade , Protetores Solares/química , Embrião não Mamífero/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Nanopartículas/toxicidade , Nanopartículas Metálicas/toxicidade , Ecotoxicologia , Larva/efeitos dos fármacos
4.
Skin Res Technol ; 30(5): e13744, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38771547

RESUMO

BACKGROUND: Evidence from animal models suggests a role for the organic ultraviolet filter benzophenone-3's (BP-3) on white blood cells (WBCs). However, BP-3's effect on WBCs in humans is unknown. MATERIALS AND METHODS: We used National Health and Nutrition Examination Survey data from 2003 to 2016. We included participants >6 years with data on urinary BP-3, urinary creatinine, and WBC count. Quintiles of urinary creatinine-normalized BP-3 (CnBP-3) levels were used in linear regression models adjusting for age, gender, race, body mass index (BMI), smoking status, education level, family income to poverty threshold ratio, survey cycle, and season. RESULTS: Of the 16 959 participants, 8564 (50.5%) were females, 6602 (38.9%) were White, and 3870 (22.8%) were Black. The mean (standard deviation) age was 37.6 (22.7) years, BMI was 26.8 (7.40) kg/m2, WBC count was 7.22 (2.53) × 109/L, neutrophil count was 4.15 (1.86) × 109/L, and lymphocyte count was 2.25 (1.33) × 109/L and median (interquartile range) of CnBP-3 was 12.1 (44.9) µg/gm. The highest quintile of CnBP-3 was associated with significantly lower WBC and neutrophil counts compared to the lowest quintile of CnBP-3 (Δ quintiles = -137 × 106/L, 95% CI: -249 to -24, p = 0.02 and = -177 × 106/L, 95% CI: -323 to -30, p = 0.02, respectively). In contrast, we did not observe a difference in lymphocyte count between the lowest and highest quintiles of CnBP-3 in unadjusted or adjusted analyses. CONCLUSION: We found an inverse relationship between BP-3 levels and WBC and neutrophil counts, and not with lymphocyte count. Further research is needed to confirm our findings.


Assuntos
Benzofenonas , Inquéritos Nutricionais , Protetores Solares , Humanos , Feminino , Masculino , Contagem de Leucócitos , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Creatinina/sangue , Creatinina/urina , Adolescente
5.
Ecotoxicol Environ Saf ; 278: 116441, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38733805

RESUMO

Oxybenzone (OBZ; benzophenone-3, CAS# 131-57-7), as a new pollutant and ultraviolet absorbent, shows a significant threat to the survival of phytoplankton. This study aims to explore the acute toxic effects of OBZ on the growth of the microalga Selenastrum capricornutum, as well as the mechanisms for its damage to the primary metabolic pathways of photosynthesis and respiration. The results demonstrated that the concentrations for 50 % of maximal effect (EC50) of OBZ for S. capricornutum were 9.07 mg L-1 and 8.54 mg L-1 at 72 h and 96 h, respectively. A dosage of 4.56 mg L-1 OBZ significantly lowered the photosynthetic oxygen evolution rate of S. capricornutum in both light and dark conditions for a duration of 2 h, while it had no effect on the respiratory oxygen consumption rate under darkness. OBZ caused a significant decline in the efficiency of photosynthetic electron transport due to its damage to photosystem II (PSII), thereby decreasing the photosynthetic oxygen evolution rate. Over-accumulated H2O2 was produced under light due to the damage caused by OBZ to the donor and acceptor sides of PSII, resulting in increased peroxidation of cytomembranes and inhibition of algal respiration. OBZ's damage to photosynthesis and respiration will hinder the conversion and reuse of energy in algal cells, which is an important reason that OBZ has toxic effects on S. capricornutum. The present study indicated that OBZ has an acute toxic effect on the microalga S. capricornutum. In the two most important primary metabolic pathways in algae, photosynthesis is more sensitive to the toxicity of OBZ than respiration, especially in the dark.


Assuntos
Benzofenonas , Microalgas , Fotossíntese , Protetores Solares , Fotossíntese/efeitos dos fármacos , Benzofenonas/toxicidade , Microalgas/efeitos dos fármacos , Protetores Solares/toxicidade , Poluentes Químicos da Água/toxicidade , Peróxido de Hidrogênio/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Complexo de Proteína do Fotossistema II/efeitos dos fármacos , Raios Ultravioleta , Transporte de Elétrons/efeitos dos fármacos
6.
Environ Monit Assess ; 196(7): 599, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38844615

RESUMO

This research was carried out in order to assess a baseline occurrence in Biscayne National Park, Florida, of four organic contaminants: the UV filters oxybenzone, dioxybenzone, and benzophenone, as well as the topical pain reliever benzocaine. A total of 35 samples were taken from five locations within the park, four near barrier islands, and one at a coral reef. Analyses were carried out using liquid chromatography coupled to high-resolution mass spectrometry. Oxybenzone was detected in 26% of samples from the park at concentrations up to 31 ng/L. Benzophenone was detected in 49% of samples from the park at concentrations up to 131 ng/L. Benzocaine and dioxybenzone were not detected in any of the samples.


Assuntos
Benzofenonas , Monitoramento Ambiental , Parques Recreativos , Protetores Solares , Poluentes Químicos da Água , Florida , Benzofenonas/análise , Poluentes Químicos da Água/análise , Protetores Solares/análise , Benzocaína/análise
7.
Environ Sci Technol ; 57(44): 17110-17122, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37851929

RESUMO

Organic ultraviolet filters (OUVFs) are extensively released into aquatic environments, where they undergo complex phototransformation. However, there is little knowledge regarding their transformation products (TPs) and associated endocrine disruption potentials. In the present study, we characterized the chemical and toxicological profiles of TPs for two common OUVFs, oxybenzone (BP3) and ethylhexyl methoxycinnamate (EHMC), by photooxidation under environmentally relevant conditions. It is hypothesized that TPs of the tested OUVFs will show varied estrogenicity at different reaction times. High-resolution liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) identified 17 TPs of 7 m/z for BP-3 and 13 TPs of 8 m/z for EHMC at confidence levels ≤2. Five novel TPs of 2 m/z were reported for the first time with structure-diagnostic MS/MS spectra. Estrogenicity assessment using the MCF-7-luc cell line showed discrepant estrogenic activities exhibited by OUVF-TPs over time. Specifically, BP3-TPs exhibited significantly greater estrogenicity than the parent at several reaction times, whereas EHMC-TPs displayed fluctuating estrogenicity with a declining trend. Correlation analysis coupled with molecular docking simulations further suggested several TPs of BP3 as potential endocrine disruptive compounds. These findings underscore the necessity of considering mixtures during chemical testing and risk assessment and highlight the potentially greater risks associated with post-transformation cocktails.


Assuntos
Espectrometria de Massas em Tandem , Poluentes Químicos da Água , Espectrometria de Massas em Tandem/métodos , Raios Ultravioleta , Simulação de Acoplamento Molecular , Poluentes Químicos da Água/análise
8.
Xenobiotica ; 53(4): 309-319, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37476967

RESUMO

Personal care products, such as UV filters, are frequently present in aquatic ecosystems, but studies on their impact on marine organisms are still scarce. Here we addressed the effects of benzophenone-3 (BP-3) on the antioxidant status of Perna perna mussels exposed to concentrations of 0.1 and 3 µg.L-1 for 72 h and 7 days. Glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), glucose-6-phosphate dehydrogenase (G6PDH) activity and lipoperoxidation (MDA) were evaluated in the gills. A significant reduction (p < 0.05) in the activity of G6PDH and GPx was observed after exposure for 7 days to 0.1 µg.L-1. However, no significant differences were observed in GST activity and MDA levels, independently of the exposure time. Principal component analysis (PCA) showed an association of BP-3 highest concentration with GR and MDA at 72 h and only with GR at 7 days of exposure. Similarly, the integrated biomarker response (IBR) demonstrated GR and MDA alterations. In conclusion, environmentally relevant concentrations of BP-3 altered antioxidant and auxiliary enzymes, which could cause long-term damage to P.perna mussels. The need to implement more efficient techniques in wastewater treatment systems is pointed out, especially in summer, when UV filters are used more frequently and abundantly.


Assuntos
Perna (Organismo) , Poluentes Químicos da Água , Animais , Antioxidantes , Perna (Organismo)/fisiologia , Ecossistema , Catalase , Glutationa Transferase , Glutationa Redutase/farmacologia , Glutationa Peroxidase/farmacologia , Poluentes Químicos da Água/toxicidade , Biomarcadores
9.
Photodermatol Photoimmunol Photomed ; 39(6): 642-647, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37749909

RESUMO

BACKGROUND: Photopatch testing represents the gold standard for the diagnosis of photoallergic contact dermatitis (PACD). We aimed to identify common photoallergens in our tertiary dermatological referral centre from 2012 to 2021, to compare this to the preceding period studied, and data from other communities. METHODS: We conducted a retrospective review of all 90 patients who underwent photopatch testing at the National Skin Centre, Singapore, between 2012 and 2021. RESULTS: Of 90 patients, 19 (21.1%) were male, and the mean age was 41.6 years. Eighty-four (93.3%) underwent testing to our standard sunscreen series, 10 (11.1%) to our extended series, and 73 (81.1%) to their own items. Seventeen (18.9%) were diagnosed with PACD (i.e., photocontact allergy with present or past relevance), 12 (13.3%) with ACD, and 4 (4.4%) with photoaugmented ACD. Relevant reactions were commonest to oxybenzone (8, 9.5%) and mexenone (3, 3.6%). Eleven (15.1%) had PACD to their own items, with 3 of 4 (75%) tested to ketoprofen diagnosed with PACD and the remaining 1 (25%) with photoaugmented ACD. Age, race, sex, atopy, and site of involvement were not associated with photocontact allergy. Compared to the preceding time period, the overall frequency of photocontact allergy and PACD decreased, but rates of photoallergic reactions to individual photoallergens were not significantly different. CONCLUSION: Organic ultraviolet absorbers such as oxybenzone and mexenone remained the most relevant photoallergens. Personal item testing was valuable, and testing to ketoprofen should be considered.


Assuntos
Dermatite Fotoalérgica , Cetoprofeno , Humanos , Masculino , Adulto , Feminino , Estudos Retrospectivos , Singapura , Testes do Emplastro , Dermatite Fotoalérgica/diagnóstico , Dermatite Fotoalérgica/epidemiologia , Dermatite Fotoalérgica/etiologia , Protetores Solares
10.
Environ Sci Technol ; 56(17): 12473-12482, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-35951380

RESUMO

Benzophenone (BP)-type ultraviolet (UV) filters are estrogenic chemicals used extensively in sunscreen products, leading to concerns over human exposure. To assess exposure to BP derivatives in sunscreens, we tested 14 BP UV filters in 50 products representing 44 brands marketed in the United States in 2021, finding BP, 2-hydroxy-4-methoxybenzophenone (BP-3 or oxybenzone), 2,2'-dihydroxy-4-methoxybenzophenone (BP-8), 2-hydroxy-4-methoxy-4'-methylbenzophenone (BP-10), 2,3,4-trihydroxybenzophenone (2,3,4-OH-BP), and 4-methylbenzophenone (4-Me-BP) in ≥70% of the samples. The geometric mean (GM) concentration of the sum of these BPs (∑14BPs) in the 50 products was 6600 ng/g. BP-3 was the predominant BP in oxybenzone-containing products (accounting for >99% of the total concentration), with a concentration 5-6 orders of magnitude higher than that in "oxybenzone-free" products (GM: 35 600 000 vs 113 ng/g). BP was present in >90% of products analyzed, including those labeled "oxybenzone-free" (GM: 2100 ng/g). BP concentrations were ∼100-fold higher in octocrylene-containing vs "octocrylene-free" products (GM: 15900 vs 151 ng/g). Dermal exposure doses of BP-3 from oxybenzone-containing products (GM: 4140 000 ng/kg body weight (BW)/day) and of BP in some (24%) octocrylene-containing products (GM: 12 200 ng/kg BW/day) were above reference values (2 000 000 and 30 000 ng/kg BW/day for BP-3 and BP, respectively). This study provides evidence that BP and BP-3 concentrations in sunscreen products vary widely and may be noteworthy even in products labeled oxybenzone- or octocrylene-free, making dermal exposure a continuing concern.


Assuntos
Benzofenonas , Protetores Solares , Humanos , Estados Unidos
11.
Environ Res ; 213: 113689, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35718163

RESUMO

A preponderance of recent evidence indicates that oxybenzone and other personal-care product chemicals threaten the biota inhabiting various ecological niches. What is understudied is the ecotoxicological impact of oxybenzone, a UV filter in sunscreens and anti-aging products, to terrestrial/soil organisms that are keystone species in these habitats. In the present study, acute exposure (14-day) to oxybenzone resulted in earthworm mortality (LC50 of 364 mg/kg) and growth rate inhibition. Environmentally relevant concentration of oxybenzone (3.64, 7.28 and 36.4 mg/kg) at exposures of 7-day, 14-day, 28-day induced oxidative stress and neurotoxicity followed by perturbations in reproduction processes and changes in vital organs. Decreased levels of superoxide dismutase (SOD) and catalase (CAT) activity were statistically lower than controls (p < 0.05) on day 14 for all three concentrations, while glutathione-s-transferase (GST) activity was significantly elevated from controls on days 7 and 14. On day 28, SOD and CAT activities were either not significantly different from the control or were higher, demonstrating a temporal multiphasic response of anti-oxidant enzymes. GST activity on day 28 was significantly reduced compared to controls. Acetylcholinesterase levels across the three-time points exhibited a complicated behaviour, with every exposure concentration being significantly different from the control. Chronic exposure negatively influences earthworm health status with elevated biomarker values analysed using IBRv2 index. This, in turn, impacted higher levels of hierarchical organization, significantly impairing reproduction and organismal homeostasis at the histological level and manifesting as decreasing cocoon formation and successful hatching events. Thus, the overall findings demonstrate that oxybenzone is toxic to Eisenia fetida at low-level, long-term exposure. Based on the concentration verification analysis and application of the EPA PestDF tool, oxybenzone undergoes single first-order kinetics degradation in OECD soil with DT50 and DT90 as 8.7-28.9 days, respectively.


Assuntos
Oligoquetos , Poluentes do Solo , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/metabolismo , Benzofenonas , Catalase/metabolismo , Oligoquetos/metabolismo , Estresse Oxidativo , Solo/química , Poluentes do Solo/metabolismo , Poluentes do Solo/toxicidade , Superóxido Dismutase/metabolismo
12.
Int J Environ Health Res ; 32(10): 2135-2148, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34313174

RESUMO

Experimental studies have suggested benzophenone-3 (BP-3), a sunscreen ingredient, may have endocrine-disrupting properties. A cohort of girls were recruited at ages 6-7 years and returned semi-annually for pubertal maturation staging, provided blood for serum hormone analyses [estradiol, estrone, testosterone, dehydroepiandrosterone-sulfate (DHEA-S)], and urine to measure BP-3 concentrations. We found a significant negative linear association between amount of reported sunscreen use and testosterone levels at the onset of puberty (N = 157, adjusted ß = -0.0163, 97.5% CI:-0.0300,-0.0026). The 2nd quartile of the BP-3 biomarker had earlier thelarche compared to the 1st quartile (N = 282, adjusted HR = 1.584, 97.5% CI:1.038,2.415). Results suggest that higher report of sunscreen use may be associated with lower testosterone levels at thelarche and a non-linear relationship between the BP-3 urinary biomarker and onset of puberty, although the clinical significance of the finding is limited and may be a random effect. Improved methods of BP-3 exposure characterization are needed.


Assuntos
Estrona , Protetores Solares , Benzofenonas , Biomarcadores , Criança , Desidroepiandrosterona , Estradiol , Feminino , Hormônios Esteroides Gonadais , Humanos , Estudos Longitudinais , Sulfatos , Inquéritos e Questionários , Testosterona
13.
AAPS PharmSciTech ; 23(2): 73, 2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35149892

RESUMO

Although there are several methods for assessing the sun protection factor (SPF) of sunscreen products, there is no standard and reliable in vitro method. Each test entails limitations and drawbacks. Therefore, this study aimed to assess the employability of FTIR as an alternative and quick method to evaluate the efficacy of various sunscreen formulations, their concentrations, and the timing of their application. Infrared radiation has longer wavelengths than ultraviolet, penetrates deeply into the skin, and hence enables the understanding of sunscreens' ability to block the transmission of radiation. The FTIR transmission using synthetic skin to study the effect of sunscreen agents (oxybenzone, octyl methoxycinnamate, titanium dioxide (TiO2), and zinc oxide (ZnO)) was conducted in the range 450-4000cm-1. Comparison studies were made at the peak of 805cm-1. After 2 h of sunscreen application, using the maximum concentrations, the FTIR peak at wavenumber 805cm-1 demonstrated a significant reduction of transmission from 96.55 to 60.09%, 57.59%, 32.02%, and 37.1% for oxybenzone, octyl methoxycinnamate, TiO2, and ZnO respectively (P<0.05). A significant reduction in transmission was observed (P<0.05) with increasing sunscreen concentrations after 2 h of application. Nevertheless, the upper limit of concentration showed no appreciable change from the middle level of concentration, and hence it is cost-effective to employ the middle concentration. Inorganic sunscreens showed a higher protection level than organic. Fixed-dose combinations of sunscreens showed an enhanced effect yet were not synergistic. In conclusion, the use of FTIR spectroscopy with synthetic skin is a quick and user-friendly technique that enables the assessment of the efficacy of sunscreen formulations.


Assuntos
Pele Artificial , Protetores Solares , Análise de Fourier , Pele , Espectroscopia de Infravermelho com Transformada de Fourier , Raios Ultravioleta
14.
Environ Monit Assess ; 193(12): 840, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34822005

RESUMO

UV-filters are widely used in cosmetics and personal care products to protect users' skin from redamage caused by ultraviolet (UV) radiation from the sun. Globally, an estimated 16,000 to 25,000 tonnes of products containing UV-filters were used in 2014 with modern consumption likely to be much higher. Beyond this use in cosmetics and personal care products, UV-filters are also widely used to provide UV-stability in industrial products such as paints and plastics. This review discusses the main routes by which UV-filters enter aquatic environments and summarises the conclusions of studies from the past 10 years that have investigated the effects of UV-filters on environmentally relevant species including corals, microalgae, fish, and marine mammals. Safety data regarding the potential impact of UV-filters on human health are also discussed. Finally, we explore the challenges surrounding UV-filter removal and research on more environmentally friendly alternatives to current UV-filters.


Assuntos
Cosméticos , Protetores Solares , Animais , Monitoramento Ambiental , Peixes , Humanos , Protetores Solares/análise , Protetores Solares/toxicidade , Raios Ultravioleta/efeitos adversos
15.
Immunol Cell Biol ; 98(10): 883-896, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32713010

RESUMO

Ex vivo mammary explant systems are an excellent model to study interactions between epithelium and stromal cell types because they contain physiologically relevant heterotypic interactions in the background of genetically diverse patients. The intact human mammary tissue, termed patient-derived explant (PDE), can be used to investigate cellular responses to a wide variety of external stimuli in situ. For this study, we examined the impact of cytokines or environmental chemicals on macrophage phenotypes. We demonstrate that we can polarize macrophages within human breast tissue PDEs toward M1 or M2 through the addition of interferon-γ (IFNγ) + lipopolysaccharide (LPS) or interleukin (IL)-4 + IL-13, respectively. Elevated expression levels of M(IFNγ + LPS) markers (HLADRA and CXCL10) or M(IL-4 + IL-13) markers (CD209 and CCL18) were observed in cytokine-treated tissues. We also examined the impact of the endocrine-disrupting chemical, benzophenone-3, on PDEs and measured significant, yet varying effects on macrophage polarization. Furthermore, a subset of the PDEs respond to IL-4 + IL-13 through downregulation of E-cadherin and upregulation of vimentin which is reminiscent of epithelial-to-mesenchymal transition (EMT) changes. Finally, we were able to show immortalized nonmalignant breast epithelial cells can exhibit EMT characteristics when exposed to growth factors secreted by M(IL-4 + IL-13) macrophages. Taken together, the PDE model system is an outstanding preclinical model to study early tissue-resident immune responses and effects on epithelial and stromal responses to stimuli found both endogenously in the breast and exogenously as a result of exposures.


Assuntos
Mama/imunologia , Exposição Ambiental , Ativação de Macrófagos , Benzofenonas/efeitos adversos , Mama/efeitos dos fármacos , Polaridade Celular , Disruptores Endócrinos/efeitos adversos , Feminino , Humanos , Macrófagos/citologia , Técnicas de Cultura de Tecidos
16.
Xenobiotica ; 50(6): 689-704, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31613170

RESUMO

2-Hydroxy-4-methoxybenzophenone (HMB) is a common ingredient in personal care products and used as an UV stabilizer. In these studies, disposition and metabolism of [14C]HMB in rats and mice was assessed following single gavage administration (10, 100, or 500 mg/kg), single IV administration (10 mg/kg), or dermal application (0.1, 1, 10, or 15 mg/kg).Following gavage administration, [14C]HMB was well absorbed and excreted mainly in urine (39-57%) and feces (24-42%) with no apparent difference between doses, species or sexes. Distribution of HMB in tissues was minimal in rats (0.36%) and mice (<0.55%).Distribution of HMB following dermal application was comparable to that following gavage administration; no differences between doses, sexes, or species were observed but absorption varied between dose vehicles. Light paraffin oil had the highest absorption and excretion (98% of the HMB dose absorbed).In rats, HMB slowly appeared in the systemic circulation (Tmax ∼2-6 h) and had poor bioavailability (F%<1).Urine metabolites for both species and all routes included HMB, HMB-glucuronide, 2,4-dihydroxybenzophenone (DHB), DHB-glucuronide, and DHB-sulfates, and novel minor dihydroxy metabolites including 2,5-dihydroxy-4-methoxybenzophenone.In vitro hepatic metabolism in mice differed from human and in vivo metabolism especially for phase II conjugates.


Assuntos
Benzofenonas/metabolismo , Protetores Solares/metabolismo , Animais , Humanos , Camundongos , Camundongos Endogâmicos , Ratos , Ratos Sprague-Dawley
17.
Drug Chem Toxicol ; 43(4): 361-368, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305169

RESUMO

A skin irritation test using in vitro reconstructed human epidermis (RhE) models was established for hazard identification of irritant chemicals in accordance with UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) category. In this study, EpiDerm™ was used to assess skin irritation by oxybenzone and N,N-diethyl-m-toluamide (DEET), which are widely used sunscreen and insect repellent components, respectively. EpiDerm™ was applied with oxybenzone and DEET, combined and sequentially with each single dose. Epidermal morphology and differentiation/proliferation were examined microscopically. Oxybenzone and sequential administration groups were determined as nonirritant with cell viability >50% and the morphology was comparable to the human epidermis. Contrastingly, the DEET and coadministration groups exhibited cell viability <50% and poor epidermal morphology. Interleukin (IL)-1α release from substance-treated EpiDerm™ increased inversely to cell viability, suggesting the pro-inflammatory reaction was initiated by DEET. CK-10, E-cadherin, Ki-67, laminin, and ceramide were identified as relevant markers to assess oxybenzone- or DEET-induced epidermal injury. In conclusion, these results may indicate to be aware of the possible skin irritation by indiscriminate use of oxybenzone and DEET without animal testing.


Assuntos
Benzofenonas/toxicidade , DEET/toxicidade , Epiderme/efeitos dos fármacos , Repelentes de Insetos/toxicidade , Irritantes/toxicidade , Testes de Irritação da Pele , Protetores Solares/toxicidade , Sobrevivência Celular , Dermatite Irritante/etiologia , Epiderme/patologia , Humanos
18.
J Am Acad Dermatol ; 80(1): 266-271, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29981751

RESUMO

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.


Assuntos
Benzofenonas , Poluição Ambiental , Protetores Solares , Benzofenonas/efeitos adversos , Meio Ambiente , Protetores Solares/efeitos adversos
19.
J Clin Pharm Ther ; 44(1): 134-139, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30484882

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Hawaii will ban two major ingredients of sunscreens. This article reviews the reasons and future directions. Hawaii recently enacted legislation that will ban the use of two major ingredients of the majority of commonly used sunscreens. The reason for the ban is the ingredients' putative deleterious impact on marine ecosystems, particularly coral reefs. But sunscreens also save lives by decreasing the risk of UV-induced skin cancers. We review both sides of the issue and potential implications for the healthcare system. COMMENT: Coral reefs consist of organisms in delicate equilibria that are susceptible to small changes in their surroundings. Recent natural and man-made disruptions, direct or indirect, such as changes in ocean temperature and chemistry, ingress of invasive species, pathogens, pollution and deleterious fishing practices, have been blamed for the poor health, or even the outright destruction, of some coral reefs. The most popular sunscreen products contain two ingredients-oxybenzone and octinoxate-that have also been implicated in coral toxicity and will be banned. This creates a healthcare dilemma: Will the protection of coral reefs result in an increase in human skin cancers? WHAT IS NEW AND CONCLUSION: Concentration estimates and mechanism studies support an association-direct or indirect (via promotion of viral infection)-of sunscreens with bleaching of coral reefs. A ban on the two most common sunscreen ingredients goes into effect in Hawaii on January 1, 2021. Proponents suggest that this is a trend, just the first of many such bans worldwide; opponents warn of a dire increase in human skin cancers. As a result, alternative sunscreen compounds are being sought.


Assuntos
Antozoários/efeitos dos fármacos , Benzofenonas/toxicidade , Cinamatos/toxicidade , Protetores Solares/toxicidade , Animais , Benzofenonas/administração & dosagem , Cinamatos/administração & dosagem , Qualidade de Produtos para o Consumidor/legislação & jurisprudência , Recifes de Corais , Havaí , Humanos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/prevenção & controle , Protetores Solares/administração & dosagem , Protetores Solares/química
20.
J Am Acad Dermatol ; 76(3S1): S91-S99, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28038886

RESUMO

Electromagnetic radiation in the ultraviolet, visible, and infrared ranges all produce biologic effects. Ultraviolet filters are the most well-studied photoprotective measure for the adverse effects of ultraviolet radiation. Because of the reported endocrinologic effects of oxybenzone in animal studies, its effects on coral reefs, and its photocontact allergy potential, its use has been minimized in many countries worldwide. New developments in topical antioxidants and oral and subcutaneous agents (eg, Polypodium leucotomos extract, afamelanotide, nicotinamide) with photoprotective and antiphotocarcinogenic properties could potentially provide addition modalities for protection against the effects of visible light and infrared radiation.


Assuntos
Roupa de Proteção , Proteção Radiológica/métodos , Protetores Solares/uso terapêutico , Animais , Antioxidantes/uso terapêutico , Humanos , Nanopartículas/uso terapêutico , Extratos Vegetais/uso terapêutico , Pele/efeitos da radiação , Neoplasias Cutâneas/prevenção & controle , Luz Solar/efeitos adversos , Protetores Solares/efeitos adversos , Raios Ultravioleta/efeitos adversos , Deficiência de Vitamina D/prevenção & controle
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