ArticleLiterature Review

Sunscreens: Are they beneficial for health? An overview of endocrine disrupting properties of UV-filters

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Abstract

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.

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... Depuis les années 1970, les crèmes de protection solaire contiennent des filtres ultraviolets UV A et UV B pour la prévention de la brûlure cutanée suite à exposition solaire, de la kératose solaire, et du cancer de la peau non-mélanome. Un nombre grandissant d'études expérimentales chez l'animal, et in vitro, indique que certains filtres organiques anti-UV pourraient avoir des effets indésirables de perturbation du système hypothalamo-hypophyso-gonadique, incluant des perturbations du développement de l'appareil reproducteur détecté chez l'animal, et notamment la benzophenone-3 (BP-3), le 4-methyl-benzylidène-camphre (4-MBC), et le 2-ethylhexyl-4-methoxy-cinnamate (OMC) [40]. La plupart des études réalisées chez l'animal ont choisi une exposition par voie orale à ces substances, or l'exposition primaire à ces trois filtres organiques relève de la voie cutanée, dénuée d'effet de premier passage hépatique [40]. ...
... Un nombre grandissant d'études expérimentales chez l'animal, et in vitro, indique que certains filtres organiques anti-UV pourraient avoir des effets indésirables de perturbation du système hypothalamo-hypophyso-gonadique, incluant des perturbations du développement de l'appareil reproducteur détecté chez l'animal, et notamment la benzophenone-3 (BP-3), le 4-methyl-benzylidène-camphre (4-MBC), et le 2-ethylhexyl-4-methoxy-cinnamate (OMC) [40]. La plupart des études réalisées chez l'animal ont choisi une exposition par voie orale à ces substances, or l'exposition primaire à ces trois filtres organiques relève de la voie cutanée, dénuée d'effet de premier passage hépatique [40]. Les effets mesurés sont alors probablement sousévalués par rapport à l'exposition réelle par voie cutanée. ...
... Les effets mesurés sont alors probablement sousévalués par rapport à l'exposition réelle par voie cutanée. Malgré l'abondance de données in vitro, et en dépit des études d'exposition humaine aux filtres UV, peu d'études ont examiné les effets des filtres UV sur l'humain [40][41][42][43][44][45][46][47] [41,42]. Une augmentation importante de l'inhibine B (hormone peptidique gonadique avec action inhibitrice sur la synthèse de FSH) a été observée, ainsi qu'une forte diminution des concentrations plasmatiques en hormones thyroïdiennes (T3L, T4L), thyroxin-binding-globulin et testostérone. ...
... Body care products and cosmetics contribute considerably to the exposure of humans to exogenous chemicals. Many of these products contain several paraben and UV-filter chemicals and their potential endocrine disrupting effects are of broad concern, widely studied but controversially discussed (Darbre and Harvey, 2014;Krause et al., 2012;Matwiejczuk et al., 2020;Nowak et al., 2018;Wang et al., 2016). In contrast, less is known on potential immune disrupting effects and xenobiotics-induced RORγ activation may disrupt immune responses. ...
... Additionally, UV-filters are additives in multiple cosmetic products such as hair spray, shampoo, make-up, perfumes, and skin care products to protect ingredients from the effects of UV-radiation and consequently enhance product stability and durability (Liao and Kannan, 2014). An increasing number of human cell-and yeast-based in vitro studies and animal investigations suggest that some organic UV-filters can cause endocrine disrupting effects, including estrogenic and androgenic disturbances, as well as disturbances of thyroid hormone-and progesterone receptor-mediated signaling (reviewed in Krause et al., 2012;Kunz and Fent, 2006;Schlecht et al., 2004;Wang et al., 2016). Similar to parabens, the main route of human exposure to UV-filters is via dermal uptake after topical application of sunscreens and cosmetics, allowing direct entrance to the systemic circulation without first-pass effect in the liver (Krause et al., 2012;Sarveiya et al., 2004). ...
... An increasing number of human cell-and yeast-based in vitro studies and animal investigations suggest that some organic UV-filters can cause endocrine disrupting effects, including estrogenic and androgenic disturbances, as well as disturbances of thyroid hormone-and progesterone receptor-mediated signaling (reviewed in Krause et al., 2012;Kunz and Fent, 2006;Schlecht et al., 2004;Wang et al., 2016). Similar to parabens, the main route of human exposure to UV-filters is via dermal uptake after topical application of sunscreens and cosmetics, allowing direct entrance to the systemic circulation without first-pass effect in the liver (Krause et al., 2012;Sarveiya et al., 2004). Importantly, human exposure to UV-filters is not limited to summer and usage of sun cream, suggesting that a substantial exposure derives from other body care products (Calafat et al., 2008). ...
Article
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Retinoic acid-related orphan receptor γt (RORγt) regulates immune responses and its impaired function contributes to inflammatory and autoimmune diseases and may promote skin cancer. Synthetic inverse RORγt agonists block the production of Th17-associated cytokines including interleukin (IL)-17A and IL-22 and are under investigation for treatment of such pathologies. Unintentional RORγt activation in skin, following exposure to environmental chemicals, may promote inflammatory skin disease. Parabens and UV-filters, frequently used as additives in cosmetics and body care products, are intensively inspected for endocrine disrupting properties. This study assessed whether such compounds can interfere with RORγ activity using a previously established tetracycline-inducible reporter gene assay in CHO cells. These transactivation experiments revealed hexylparaben, benzylparaben and benzophenone-10 as RORγ agonists (EC50 values: 144 ± 97 nM, 3.39 ± 1.74 µM and 1.67 ± 1.04 µM, respectively), and they could restore RORγ activity after suppression by an inverse agonist. Furthermore, they enhanced RORγt-dependent transcription of the pro-inflammatory IL-17A and/or IL-22 genes in the murine T-cell model EL4. Virtual screening of a cosmetics database for structurally similar chemicals and in vitro testing of the most promising hits revealed benzylbenzoate, benzylsalicylate and 4-methylphenylbenzoate as RORγ agonists (low micromolar EC50 values). Moreover, an analysis of mixtures of the newly identified RORγ agonists suggested additive effects. This study presents novel RORγ(t) agonistic structural scaffolds. By activating RORγ(t) the identified parabens and UV-filters may potentially aggravate pathophysiological conditions, especially skin diseases where highest exposure of such chemicals can be expected. Follow-up studies should assess whether such compounds, either alone or as mixtures, can reach relevant concentrations in tissues and target cells to activate RORγ(t) in vivo.
... Several organic UVFs have been associated with endocrine disruption [37][38][39][40][41][42]. Benzophenone-3 (BP-3) seems to have systemic effects on sex and thyroid hormone pathways in animal models [40,41,43,44] and can be absorbed at a rate of 1% to 9% with topical application in some models [45]. ...
... Several organic UVFs have been associated with endocrine disruption [37][38][39][40][41][42]. Benzophenone-3 (BP-3) seems to have systemic effects on sex and thyroid hormone pathways in animal models [40,41,43,44] and can be absorbed at a rate of 1% to 9% with topical application in some models [45]. ...
Article
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Some chemical components in sun cream filters have endocrine-disrupting activity or can be carcinogenic, neurotoxic, bioaccumulative, allergens, or be toxic for human reproduction. It is important that sunscreens have safety requirements. The objective of this work is to compare sun cream filters used in conventional commercial sunscreens and those that are considered natural products, especially focused on endocrine-disrupting effects. In order to achieve the above objective, the compositions of different conventional and natural sun cream filters were evaluated and compared, taking into account the presence of the different sun cream filters whose effects were evaluated on the website specialized in safety and cosmetics, Environmental Working Group (EWG), and in the Register of chemical substances and mixtures in the EU Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) Regulation. The currently available evidence of each sun cream filter and their degree of safety has been summarized. Several organic sun cream filters present a potential risk to health and the environment; however, inorganic sun cream filters such as titanium dioxide and zinc oxide (ZnO and TiO2) show a very low risk in humans as they are not absorbed through intact or damaged tissues. The legislation does not oblige manufacturers to specify the concentration of each substance, which provides qualitative but not quantitative information for the consumer.
... Further phenolic substances of EDC potential, whose use in consumer products implicates a significant exposure of the population, are triclosan (TCS) and several esters of parahydroxybenzoic acid, so called parabens, which are frequently used as biocides in cosmetics and personal care products [8][9][10][11]. Other prominent phenolic substances with a comparable exposure pathway are benzophenones, which are used as UV filters and thus are ingredients of sunscreens but also cosmetics [12,13]. A human exposure to relevant phenolic substances can also result from the degradation or metabolism of xenobiotics. ...
... Usually, human urine is the matrix of choice for the preparation of calibration and control material to monitor the renal excretion of analytes in human biomonitoring. However, since the here investigated analytes of interest are used in various applications, such as cosmetics (MHB, EHB, PHB, BHB), nail polishes, sun protection products or perfumes (BP1, BP3), and biocides (TCS) as well as food (DAI, GEN), humans are exposed to these chemicals through their daily routines [8][9][10][11][12][13][39][40][41]. Thus, background levels of the investigated analytes in collected pooled human urine samples are often observed which specifically concerns the phytoestrogens genistein and daidzein [23]. ...
Article
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Many xenobiotics were identified as possible endocrine disruptors during the last decades. Structural analogy of these substances to natural hormones may lead to agonists or antagonists of hormone receptors. For a comprehensive human biomonitoring of such substances, we developed a simple, reliable, and highly sensitive method for the simultaneous monitoring of the parameters bisphenol A, triclosan, methylparaben, ethylparaben, propylparaben, butylparaben, benzophenone-1, benzophenone-3, 3,5,6-trichloropyridin-2-ol, p -nitrophenol, genistein, and daidzein in urine. Thereby, optimization of the enzymatic hydrolysis and the use of β-glucuronidase from E. coli K12 as well as sulfatase from Aerobacter aerogenes ensures the acquisition of intact analytes without cleavage of ester bonds among parabens. Validation of the method revealed limits of detection between 0.02 and 0.25 µg/L as well as limits of quantification between 0.08 and 0.83 µg/L. Thereby, the use of analyte-free surrogate matrix for calibration and control material influenced the sensitivity of the procedure positively. Furthermore, excellent precision in and between series was observed. Good absolute and relative recoveries additionally proved the robustness of the multimethod. Thus, the procedure can be applied for exploring the exposome to these prominent endocrine disruptors in the general population. Graphical Abstract
... Recent studies indicate that BP-3 exposure may occur from sources other than sunscreens or Personal Care Products (Krause et al., 2012). Frederiksen et al. (2013b) reported BP-3 in almost all urine samples (97-98%) that were collected during seasons when sunscreens are not generally used. ...
... FDA considered that inadequate data on BP-3's developmental and reproductive toxicity were reported. The literature suggests that BP-3 may have endocrine activity (see, e.g., Schlumpf et al., 2001;Schlumpf et al., 2004;Krause et al., 2012). ...
Book
SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) - SCCS/1625/20 - Final Opinion U. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads, M. Dusinska, J. Ezendam, E. Gaffet, C. L. Galli, B. Granum, E. Panteri, V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. Wijnhoven, A. Koutsodimou, W. Uter, N. von Goetz The SCCS adopted this document at its plenary meeting on 30-31 March 2021 (77 pages) Published:17 August 2022 Ed. Publications Office of the European Union, Luxembourg, Luxembourg (77 pages) ISSN : 1831-4767 ISBN : 978-92-76-54757-0 DOI : https://data.europa.eu/doi/10.2875/102562 Catalog Number : EW-AQ-22-007-EN-N https://op.europa.eu/fr/publication-detail/-/publication/a9917049-21c8-11ed-8fa0-01aa75ed71a1 https://op.europa.eu/fr/publication-detail/-/publication/a9917049-21c8-11ed-8fa0-01aa75ed71a1/language-en/format-PDF/source-264517698
... Asterisks indicate significant correlations (*p < 0.05; **p < 0.01). f stands for 1st and t sands for 3rd trimester UV index, which increases the need for sunscreen use, and health care products with high BP-3 (Krause et al. 2012). In such regions, exposure to a high level of BPs can reduce the duration of pregnancy and affect infant birth outcomes. ...
... Although the estrogenic activity of this metabolite and its binding to estrogen receptors such as α and β, as well as its association with inflammatory markers, may affect the duration of pregnancy, any differences between the findings of various studies can be attributed to the dose-dependent hormonal effects of this metabolite. So the hormonal activity of BP-3 depends on its level of exposure and received doses (Krause et al. 2012;Aung et al. 2019). Furthermore, it should be noted that apart from exposure to EDCs, preterm birth can be influenced by different factors such as infection, cervical pathology, uterine overdistension, progesterone disorders, vascular alterations, pregnancy stress, allergic phenomena, and perhaps other several unknown factors (Di Renzo et al. 2018). ...
Article
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In recent decades, emerging environmental pollutants such as endocrine-disrupting chemicals (EDCs) have become a particular concern. This study examined the association of maternal exposure to benzophenones as one of the EDCs with gestational age and evaluated their effects on birth outcomes including birth weight, birth length, head circumference, and Ponderal Index. We assessed 166 pregnant mothers of the PERSIAN cohort population of Isfahan, Iran, in the 1st and 3rd trimesters of pregnancy and their infants at birth. Four common benzophenones (BPs) including 2,4-dihydroxy benzophenone (BP-1), 2-hydroxy-4-methoxy benzophenone (BP-3), 4-hydroxy benzophenone (4-OH-BP), and 2,2′-dihydroxy-4-methoxy benzophenone (BP-8) were measured in maternal urine samples. The median urinary concentrations of 4-OH-BP, BP-3, BP-1, and BP-8 in the 1st trimester were 6.62, 7.5, 4.39, and 1.32 µg/g creatinine and those in the 3rd trimester were 3.15, 16.98, 9.95, and 1.04 µg/g creatinine, respectively. BP-3 was the predominant metabolite in both trimesters. There was a significant correlation between BP-3, BP-1, and 4-OH-BP levels (p < 0.05) but not BP-8. BP-1 showed a significant positive association with gestational age (GA) in all infants in the 1st trimester, but a negative association was observed between BP-3 and BP-1 levels and GA in girls. Classification of infants’ birth weight for different GAs represented that the majority of them were appropriate for GA. However, boys’ weights were heavier than girls. Also, birth outcomes of preterm (< 37 weeks) infants were noticeably lower than term infants (37–42 weeks). This study demonstrated that benzophenone derivatives especially BP-3 can affect the duration of pregnancy and consequently fetal growth in the early and late stages of pregnancy. This is more pronounced in girls; however, more investigations in a different population are needed to prove the results. Therefore, the application of these compounds as a UV protector requires precise regulation to reduce exposure, especially in pregnant women.
... The adverse reactions to sunscreens include subjective irritation (stinging, burning), contact dermatitis and comedogenicity. The potential adverse effects induced by UV filters in experimental animals include reproductive/developmental toxicity and disturbance of hypothalamic-pituitarythyroid axis (HPT) [81,82]. ...
Article
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Due to the rapid growth of the cosmetic industry in recent years, the development of new, reliable, cost-effective, ease of use and rapid methods to assay cosmetics’ quality is of particular importance. Modern electrochemistry provides powerful analytical techniques with excellent sensitivity, instrumental simplicity and portability, providing reliable alter­natives to conventional analytical methods. This review aims to give readers a clear view of advances in areas of electrode modification, successful strategies for signal amplification, and miniaturization techniques used in electro­analytical devices for cosmetics control and safety. We have summarized recent trends in the nonenzymatic electrochemical sensor sys­tems applied in the analysis of cosmetic products revealing that there are a variety of ef­ficient sensors for whitening agents, preservatives, UV filters, heavy metals, etc. In con­clu­sion, current challenges related to the sensors design and future perspectives are outlined.
... The SPF of the hydrogel is lower than SPF30 P*** is a positive control due to the chemical SPF. There are Ethyl hexyl methoxycinnamate and 4-Methylbenzylidene Camphor as sunscreens against UVB [26], and Butyl Methoxy dibenzoyl methane, a sunscreen agent that provides proper UVA protection [27]. Formula 3 has an SPF value of 6.65 is the highest, meaning effective as sunscreen for 66.5 minutes. ...
Article
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Solar UV radiation can inactivate the SARS-CoV-2 virus and indirectly accelerate the recovery rate of Covid-19 patients by converting pro-vitamin D3 in the skin into pre-vitamin D. On the other hand, prolonged exposure to UV radiation might be harmful to skin health, making it necessary to use sunscreen. Synthetic chemical sunscreens can have adverse side effects, and alternatives utilizing natural ingredients are needed. The peel of the black pomegranate has strong antioxidant properties and it also has the potential as a sunscreen by making it into a topical hydrogel preparation. The purpose of this study was to examine the characteristics, antioxidant activity, and sun protection factor (SPF) capacity of the ethanol extract of black pomegranate peel hydrogel preparations. Hydrogel was created containing black pomegranate peel ethanolic extract at concentrations of 0.5%, 1.0%, and 1.5%. Then, the characteristic properties were determined, the antioxidant power was examined using DPPH (2,2′-diphenyl-1-picrylhydrazyl radical) assay, and the SPF was investigated by the spectrophotometry method. The hydrogel containing extracts of 0.5%, 1.0%, and 1.5% had characteristics that fulfilled the specified requirements, having an inhibition percentage of 27.39%, 54.90%, and 83.91%, respectively, at the sample concentration of 600 ppm, and the SPF of this hydrogel was 2.67, 4.36, and 6.65, respectively. Therefore, according to the findings, hydrogel of black pomegranate peel ethanolic extract is good as a topical antioxidant but is less effective as SPF sunscreen. Keywords: antioxidant, hydrogel, SPF, black pomegranate peel ethanolic extarct
... The relationship of BP-3 with ANA could be mediated by hormone-disrupting effects (e.g., estrogenic, androgenic) either directly or through its metabolites (29)(30)(31). Experimental studies of other phenols (e.g., BPA), suggest potential effects on the development of T-cells, including regulatory T-cells. Other nonendocrine mediated effects may include BP-3 phototoxicity, or through other pathways (e.g., retinoid-X receptor) (32,33). ...
Article
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Background Between 1988 and 2012, prevalence of antinuclear antibodies (ANA) increased in the U.S., especially in adolescents and non-Hispanic Whites. Female predominance of ANA suggests a role for hormonal factors, including xenobiotic exposures that may disrupt endocrine signaling. Benzophenone-3 (BP-3) is one such chemical with increasing exposure through sunscreen use. We investigated whether urinary BP-3 levels were related to ANA in adolescents and young adults. Methods In a sample of 1,785 individuals ages 12-39 years in the National Health and Nutrition Examination Survey (NHANES; 2003-4, 2011-12), we examined cross-sectional associations of ANA (N=192; 3+ or 4+ at the 1:80 dilution, measured by HEp-2 immunofluorescence) with urinary BP-3, and other phenols bisphenol-A, triclosan, and parabens. Adjusted prevalence odds ratios (POR) were calculated in season-stratified models [winter (November-April) and summer (May-October)], given differences in sunscreen use and BP-3 concentrations. Results BP-3 concentrations (detected in >98.5% of individuals) did not differ by ANA positivity in the summer (geometric mean, GM 30.6 ng/ml ANA-positive vs. 35.3 ANA-negative; GM ratio 1.15), but in winter were higher among ANA-positives (50.2 vs. 20.1 ANA-negative; GM ratio 2.50). ANA was associated with log 10 BP-3 in winter (POR 1.57; 95%CI 1.07-2.30 per unit increase) but not summer (0.94; 0.61, 1.44; interaction p=0.09). Triclosan, parabens, and bisphenol-A levels were unrelated to ANA overall or by season (ORs 0.64 to 1.33). Conclusions The association of urinary BP-3 with ANA in the winter may reflect different exposure patterns or unmeasured confounders. Findings warrant replication in prospective studies and including past and year-round exposures.
... Perfluorinated compounds (PFCs) such as perfluoro octane sulfonate (PFO) cause liver adenomas, cancer, Leydig cell adenomas, and pancreatic adenocarcinoma (Chang et al., 2014). Personal care products (PCPs) primarily damage the reproductive and hypothalamus-pituitary-thyroid axis, further leading to infertility, a decrease in fecundity, and reproductive complications (Krause et al., 2012;Shrestha et al., 2015). Paliya et al. (2021a) reviewed the neurotoxic, genotoxic, and reproductive-endocrine disruptions by polybrominated diphenyl ethers (PBDEs) in humans, leading to alterations in the thyroid system and harming the brain and developmental growth in humans (Paliya et al., 2021a). ...
... Chemical or organic filters are a heterogeneous group of organic molecules ( Figure 1, Tables 1 and 2) which, due to the effect of photochemical excitation, can modify their structure, resulting in a loss of activity. In some cases, the formation of degradation products has been shown to cause potential local and systemic toxicity, up to the involvement of the immune and endocrine systems [1][2][3][4]. [6,14] Some chemical filters, such as PABA and some of its derivatives, have been banned in the European Union and in other countries around the world. The problems associated with protective lotions are related not only to the interaction of their organic filter with solar radiation but also specifically to the contact of the organic filter with water, depending on its pH and composition, or with agents that are used for the disinfection of the water itself. ...
Article
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The development of any commercial product should also be aimed at reducing the risk associated with it, according to the safe-by-design concept; that is, risk assessment should always be at the center of the design, and the impact on human and environmental health should be assessed and eliminated during the product development phase and not afterwards. Unfortunately, even today, most operators in any production sector implement the philosophy of “risk management” or rather of managing the problem when it occurs, using spot interventions instead of changing the approach. This argument is also valid in the production of solar filters, which have reached a satisfactory degree of efficiency in the face of a substantial underestimation of the risks associated with their possible environmental fate. In fact, solar filters have been found in bathing waters and their environmental fate may depend on various factors such as the pH of the water, the presence of organic material, metal ions and light, and, above all, the chemical agents used in the disinfection of the water itself. Thus, during disinfection processes, the generation of dozens of products with a lower molecular weight and generally of an aromatic nature has been tested, where some of them did not receive an exact structural definition and a precise evaluation of their precise toxicological profile. Therefore, it is interesting to draw a complete picture of organic sunscreens and of the byproducts obtained under different conditions and their related ecotoxicological profile.
... Homosalate is an anti-inflammatory drug commonly used as a chemical UV-screen in sun lotions (Couteau, Chauvet, Paparis, & Coiffard, 2012;Wang, Marling, Plum, & Deluca, 2017). However, it displays estrogen-like properties and is suspected to be a potential endocrine disruptor dangerous for health (Krause et al., 2012). Here we identified an unsuspected action of Homosalate, that is, increasing EV release from different tumour cell lines. ...
Article
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Eukaryotic cells, including cancer cells, secrete highly heterogeneous populations of extracellular vesicles (EVs). EVs could have different subcellular origin, composition and functional properties, but tools to distinguish between EV subtypes are scarce. Here, we tagged CD63‐ or CD9‐positive EVs secreted by triple negative breast cancer cells with Nanoluciferase enzyme, to set‐up a miniaturized method to quantify secretion of these two EV subtypes directly in the supernatant of cells. We performed a cell‐based high‐content screening to identify clinically‐approved drugs able to affect EV secretion. One of the identified hits is Homosalate, an anti‐inflammatory drug found in sunscreens which robustly increased EVs’ release. Comparing EVs induced by Homosalate with those induced by Bafilomycin A1, we demonstrate that: (1) the two drugs act on EVs generated in distinct subcellular compartments, and (2) EVs released by Homosalate‐, but not by Bafilomycin A1‐treated cells enhance resistance to anchorage loss in another recipient epithelial tumour cell line. In conclusion, we identified a new drug modifying EV release and demonstrated that under influence of different drugs, triple negative breast cancer cells release EV subpopulations from different subcellular origins harbouring distinct functional properties.
... In particular, the inorganic absorbers generate reactive oxygen species (ROS) that are the potential to damage DNA or tissues; the organic ones can penetrate the skin, which not only limits their effectiveness in protecting the skin from UV rays but also causes potential health damage. These conventional UV filters with poor durability under dynamic physiological conditions, and poor biocompatibility have limitations in practical use (Krause et al., 2012;Li et al., 2020;Lu et al., 2021). Therefore, the use of UV-resistant natural extracts loaded into chitosan hydrogels is being investigated as they can become a new type of sunscreen product owning safety, eco-friendliness, and high effectiveness in protecting our skin from harmful external influences. ...
Article
Chitosan hydrogel is a smart and highly applicable drug delivery carrier because of its nature, biocompatibility, biodegradability, and ability to encapsulate, carry and release the drug to the desired target flexibly depending on the conditions of the patient. Not only developing delivery systems but natural compounds are also increasingly being studied in supporting the treatment of diseases. However, the physicochemical and pharmacokinetic issues of the phytochemicals are remaining. This review summarizes the remarkable properties of chitosan hydrogel; approaches to loading natural extracts on the hydrogels to overcome the susceptibility of the phytochemicals to degradation; and their applications in biomedical fields. The drug loading efficiency, release profile, in vitro and in vivo results of the chitosan hydrogels carrying natural compounds are discussed to point out the remaining challenges of combining the extracts with chitosan hydrogels and controlling the release of the carried substances.
... However, not all UV-filters that appear oestrogenic in vitro were also oestrogenic in acute in vivo models. [30] . ...
Article
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For over 75 years, the use of UV filters in the composition of sunscreen and some products of cosmetics has been continuing for the purpose of the protection of the skin from acquiring damaging frequencies and wavelengths of sunlight. Even before 1500 BC, people were already conscious of the results of UV rays on the application of skin in which they used clothing for their protection against its harmful effects. In today's time, modern sunscreens are commonly used for the same purpose, mainly for protecting the skin from sunburn-inducing UV radiation. Moreover, sunscreens contain UV filters that could help lessen such occurrences. Reports indicated in this review are the common effects of UV filters that are used for the cosmetics available in market, its solubility and absorption, factors linked to the usage of sunscreen, reasons of the consumers on sunscreen usage, and those reasons of why consumers do not use sunscreens. Also, the paper will be discussing the health concerns and toxicities that UV filters might cause as it will be utilised as skin protectors in sunscreen formulation.
... Specifically, some widely used UVFs are known to have toxic effects on protozoa, microalgae, and crustaceans [15]. Also, identification of harmful side-effects of UV-filters, such as endocrine disruption and breast cancer risk, has increased the interest to controlling and monitoring the dose of organic UVFs in PCPs and their environmental fate and transport [16,17]. Therefore, use of the advanced technologies to remove or reduce PCPs released into the environment and their subsequent impacts has become a necessity. ...
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In this study, simultaneous photocatalytic degradation of different parabens (methyl-, ethyl-, propyl-, and butyl paraben) and UV filters (benzophenone-3, 4-methylbenzylidene camphor, 2-ethylhexyl 4-(dimethylamino) benzoate, ethylhexyl methoxycinnamate and octocrylene) in water matrices was performed under visible light irradiation using novel double plasmonic Ag@Ag3PO4/Ag@AgCl nanophotocatalyst, synthesized by an easy and fast photochemical conversion and photo-reduction. It was found that the nanophotocatalyst with appropriate mole ratio of Ag@Ag3PO4/Ag@AgCl (1:3) showed superior photocatalytic activity than individual plasmonic nanoparticles. This is because there are two simultaneous surface plasmon resonances (SPR) generated by the metallic Ag nanoparticles, in addition to the hetero-junction structure formed at the interface between Ag@Ag3PO4 and Ag@AgCl. The structures of the synthesized photocatalysts were characterized, and the principal reactive oxygen species in the photocatalytic process were identified via a trapping experiment, confirming superoxide radicals (∙O2-) as the key reactive species of the photocatalytic system. The process of photodegradation of the target pollutants was monitored using an optimized method that incorporated solid-phase extraction in combination with gas chromatography-mass spectrometry. The simultaneous photodegradation process was modeled and optimized using central composite design. The kinetic study revealed that the degradation process over Ag@Ag3PO4 (30%)/Ag@AgCl (70%) under visible light followed a pseudo-first-order kinetic model. The simultaneous degradation of target compounds was further investigated in sewage treatment plant effluent as well as tap water. It was found that the matrix constituents can reduce the photodegradation efficiency, especially in the case of highly contaminated samples.
... Due to their frequent use, it is not surprising that UV filters have been detected in many tissues (Krause et al., 2012). Humans are potentially also exposed to the halogenation transformation products of UV filters. ...
Article
The everyday use of household and personal care products (HPCPs) generates an enormous amount of chemicals, of which several groups warrant additional attention, including: (i) parabens, which are widely used as preservatives; (ii) bisphenols, which are used in the manufacture of plastics; (iii) UV filters, which are essential components of many cosmetic products; and (iv) alkylphenol ethoxylates, which are used extensively as non-ionic surfactants. These chemicals are released continuously into the environment, thus contaminating soil, water, plants and animals. Wastewater treatment and water disinfection procedures can convert these chemicals into halogenated transformation products, which end up in the environment and pose a potential threat to humans and wildlife. Indeed, while certain parent HPCP ingredients have been confirmed as endocrine disruptors, less is known about the endocrine activities of their halogenated derivatives. The aim of this review is first to examine the sources and occurrence of halogenated transformation products in the environment, and second to compare their endocrine-disrupting properties to those of their parent compounds (i.e., parabens, bisphenols, UV filters, alkylphenol ethoxylates). Albeit previous reports have focused individually on selected classes of such substances, none have considered the problem of their halogenated transformation products. This review therefore summarizes the available research on these halogenated compounds, highlights the potential exposure pathways, and underlines the existing knowledge gaps within their toxicological profiles.
... In 1970, sunscreen that could block both UV-A and UV-B was developed. 4 There are two categories of sunscreen materials. One is inorganic sunscreen generally known as physical sunscreen. ...
Article
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Sunscreen can protect human skin from sunlight by decreasing exposure to ultraviolet (UV) light, specifically UV-B and UV-A. In this study, a new type of UV screen system is proposed using cholesteric liquid crystal (CLC) capable of selectively reflecting UV-A within the human skin temperature range of 32-36 °C. Polycaprolactone (PCL) capsules with CLC mixture which had a helical chiral pitch corresponding to the wavelength of UV light were made by a solvent evaporation method. The average diameter of the capsules was about 34 μm. Consequently, it was confirmed that the CLC mixture (COC : CN = 80 : 20) could reflect UV-A light over 350-380 nm within the human skin temperature range. Also, it was confirmed that the CLC/PCL microcapsules could block UV light over 290-400 nm by about 6%.
... Benzophenone derivatives also induce disturbance of hypothalamic-pituitary-thyroid axis. Dermal exposure to low dose of benzophenone-3 during early pregnancy in mice induces sex ratio alterations and modification in the growth curve of male mice (Schlumpf et al., 2004;Krause et al., 2012;Santamaria et al., 2020). ...
Article
Endocrine disrupting chemicals (EDCs) act on peripheral endocrine organs or interfere with general endocrine pathways. Several EDCs alter the central regulation of neuroendocrine pathways, and affect neurological functions, and as such can be classified as neurotoxic molecules. Environmental pollutants classified as EDCs and affecting the central nervous system include perfluoroalcanes, parabens, phthalates, organotins, bisphenols, benzophenones, polychlorinated biphenyls, and dioxins. In this review we provide a brief description of these families of EDCs. We report and compare the EDC concentrations measured in the brain of humans and wild animals naturally exposed to these molecules, as well as in the brain of laboratory animals experimentally exposed to EDCs. The importance of using sophisticated analytical tools to detect EDCs in the brain is pointed out. The ability of blood-brain interfaces to reduce the brain exposition to EDCs in adult and during development is discussed in relation with the specific morphological, transport and metabolic properties of these cellular layers. Finally, we review the evidence that blood-brain interfaces neuroprotective functions can be altered by EDCs, a process that may participate to the central toxic action of these molecules. Overall this analysis points to the implication of blood-brain interfaces in setting the extent of central EDCs toxicity, although most evidences are indirect. Therefore, more specific blood-brain interface-oriented studies are called for in this field of EDC neurotoxicology.
... The constituent elements and concentrations of the materials used in the formulation are presented in Table 1 (Total = 100 g). Chemical filters for protection against UVR are recommended at the concentration of 2-10% (Krause et al. 2012;Sabzevari et al. 2021). The ethyl acetate fraction (as a biological filter) was used at the concentration of 5% (Surget et al. 2015;Pratama et al. 2019). ...
Article
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Phlorotannins are polyphenolic compounds in brown algae and can be used as a natural UV filter in sunscreen formulations. The aim of the present study was to characterize the biological activities of phlorotannins-rich fractions from the brown alga Polycladia myrica and to validate the protective effect as well as stability of cream formulation with phlorotannins against UVR. With respect to antioxidant properties, the ethyl acetate fraction (EF) possessed the highest DPPH radical scavenging (65 ± 0.2%), and the highest antioxidant activity (11.2 ± 0.2 μg ASA mg⁻¹). The EF was active against Gram-positive bacteria with EF effectively reducing UVB-induced cytotoxicity in HaCaT keratinocytes. The cream formulation with 5% EF revealed a high sun protective factor (31.79 ± 4.73), UVA/PF (24.67 ± 4.03), critical wavelength (383.2 ± 0.1 nm), and UVA/UVB ratio (0.98 ± 0.01). The cream formulation was completely homogeneous and had a pH close to human skin pH. The cream was stable in the cooling-heating cycle and the DPPH scavenging activity of the cream was not altered for 30 days of storage at temperatures of 4–40 °C. These findings are promising for the use of brown alga P. myrica extract as a valuable source of sunscreen protective substance for pharmaceutical and cosmetic applications.
... The adverse effects of organic UVFs on aquatic organisms have been reviewed in recent literature [21], but studies on the ecological risk of inorganic UVFs are limited. Although studies have found that inorganic UVFs do not cause more damage to humans than organic UVFs [34,[99][100][101], notably, the potential environmental effects of UVFs on aquatic organisms are not taken into consideration during their production, and even worse, few specific recommendations for the environmentally friendly use of sunscreens have been offered by agencies or governments worldwide. ...
Article
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An increasing number of inorganic ultraviolet filters (UVFs), such as nanosized zinc oxide (nZnO) and titanium dioxide (nTiO2), are formulated in sunscreens because of their broad UV spectrum sunlight protection and because they limit skin damage. However, sunscreen-derived inorganic UVFs are considered to be emerging contaminants; in particular, nZnO and nTiO2 UVFs have been shown to undergo absorption and bioaccumulation, release metal ions, and generate reactive oxygen species, which cause negative effects on aquatic organisms. We comprehensively reviewed the current study status of the environmental sources, occurrences, behaviors, and impacts of sunscreen-derived inorganic UVFs in aquatic environments. We find that the associated primary nanoparticle characteristics and coating materials significantly affect the environmental behavior and fate of inorganic UVFs. The consequential ecotoxicological risks and underlying mechanisms are discussed at the individual and trophic transfer levels. Due to their persistence and bioaccumulation, more attention and efforts should be redirected to investigating the sources, fate, and trophic transfer of inorganic UVFs in ecosystems.
... UV filters, including benzophenones (BPs), octyl methoxycinnamate (OMC), and 3-(4-methylbenzylidene)-camphor (4-MBC), are widely used in many PCPs such as lotions, creams, lipsticks, hairspray, and sunscreens (reviewed in Witorsch and Thomas, 2010). Although studies have shown that UV filters protect against sunburn, solar keratosis, and nonmelanoma skin cancer, some UV filters might have adverse effects on reproduction (Krause et al., 2012). ...
Chapter
This chapter discusses the known effects of chemicals that are commonly used in personal care products and cosmetics on reproduction. Specifically, this chapter focuses on phthalates, parabens, and triclosan. For each category of chemicals, the chapter describes the effects of the chemicals on female and male reproductive endpoints. The reproductive endpoints that are of interest include the developing and mature sex organs, steroidogenic capacity and regulation, puberty, reproductive diseases and complications, fertility, pregnancy, and birth outcomes. Both human and animal studies are discussed in this chapter.
... For example, the sale and use of BP-3 containing sunscreens was prohibited by the republic of Palau and the U.S. state Hawaii as this compound threatens the health of coral reefs by promoting viral infections (Danovaro et al., 2008) and is assumed to act as endocrine disruptor (Republic of Palau, 2018; The Senate Twenty-ninth legislature and State of Hawaii, 2018). In this context the structure-dependent endocrine activity is considered alarming (Kawamura et al., 2003) and was reviewed for BP-2 and BP-3 in Krause et al. (2012). However, an overview of possible changes in endocrine activity, caused by the biotic and abiotic decomposition of BPs, is still lacking. ...
Article
Benzophenone-type UV filters (BPs) represent a very diverse group of chemicals that are used across a range of industrial sectors around the world. They are found within different environmental compartments (e.g. surface water, groundwater, wastewater, sediments and biota) at concentrations ranging from ng/L to mg/L. Some are known as endocrine disruptors and are currently within the scope of international regulations. A structural alert for high potential of endocrine disrupting activity was assigned to 11 BP derivatives. Due to the widespread use, distribution and disruptive effects of some BPs, knowledge of their elimination pathways is required. This review demonstrates that biodegradation and photolytic decomposition are the major elimination processes for BP-type UV filters in the environment. Under aerobic conditions, transformation pathways have only been reported for BP, BP-3 and BP-4, which are also the most common derivatives. Primary biodegradation mainly results in the formation of hydroxylated BPs, which exhibit a structure-related increase in endocrine activity when compared to their parent substances. By combining 76 literature-based transformation products (TPs) with in silico results relating to their receptor activity, it is demonstrated that 32 TPs may retain activity and that further knowledge of the degradation of BPs in the environment is needed.
... Detrimental effects of UV radiation are not limited to living tissues, application of sunscreens are necessary for the longevity of the day-to-day materials ranging from packaging to furniture and clothing. 183 Nontoxic and sustainable alternatives to the commonly used sunscreens compounds used in these materials such as oxybenzone and octinoxate are needed as much as the biodegradable eco-friendly material alternatives. 184À187 Scytonemins and MAAs are large families of UV filtering compounds. ...
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Cyanobacteria depend on solar radiation for photosynthesis and have, since ancient times, developed different strategies to cope with the damaging radiation in the UV range. Among these, the production of small molecules that act as UV filters has been thoroughly investigated for these organisms. Two major families of UV filters are produced by cyanobacteria—scytonemins and mycosporine-like amino acids. Here, we present an overview of the diversity, distribution, structural features, and UV protective properties of these metabolites. We also provide an account of their associated biological activities and biotechnological potential. Finally, we look into how these valuable small molecules can be accessed, namely, their biological sources, their biosynthesis and heterologous expression, as well as synthetic routes that have been developed to access these scaffolds. Finally, we briefly cover additional cyanobacterial compounds that have unique UV-radiation absorbing chromophores.
... The sunscreen sample consists nanoparticles of titanium dioxide and zinc oxide dispersed in an emulsion of water and oil (Fig 5A) [24,25]. Therefore, it was used in this study for evaluation for our 8-frequency IP-SEM system. ...
Article
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Nanometre-scale observation of specimens in water is indispensable in many scientific fields like biology, chemistry, material science and nanotechnology. Scanning electron microscopy (SEM) allows high-resolution images of biological samples to be obtained under high vacuum conditions but requires specific sample-preparation protocols. Therefore, there is a need for convenient and minimally invasive methods of observing samples in solution. We have developed a new type of impedance microscopy, namely multi-frequency impedance SEM (IP-SEM), which allows nanoscale imaging of various specimens in water while minimising radiation damage. By varying the frequency of the input voltage signal of the sine wave, the present system can detect dielectric properties of the sample’s composition at nanometre resolution. It also enables examination of unstained biological specimens and material samples in water. Furthermore, it can be used for diverse samples in liquids across a broad range of scientific subjects such as nanoparticles, nanotubes and organic and catalytic materials.
... Other adverse effects of PFCs on human health include infertility, decreased sperm production, and thyroid tissue difficulties (Corsini et al., 2014;Shrestha et al., 2015;Webster et al., 2014). The disturbance of developmental activities, the hypothalamus pituitary thyroid axis, and reproductive systems in humans and animals is the most serious health concern associated with PPCPs (Corsini et al., 2014;Krause et al., 2012). A common gasoline additive, methyl tertbutyl ether (MTBE), has the potential to be a hazardous emergent environmental pollutant. ...
Article
Wastewater is contaminated water that must be treated before it may be transferred into other rivers and lakes in order to prevent further groundwater pollution. Over the last decade, research has been conducted on a wide variety of contaminants, but the emerging contaminants are those caused primarily by micropollutants, endocrine disruptors (EDs), pesticides, pharmaceuticals, hormones, and toxins, as well as industrially-related synthetic dyes and dye-containing hazardous pollutants. Most emerging pollutants did not have established guidelines, but even at low concentrations they could have harmful effects on humans and aquatic organisms. In order to combat the above ecological threats, huge efforts have been done with a view to boosting the effectiveness of remediation procedures or developing new techniques for the detection, quantification and efficiency of the samples. The increase of interest in biotechnology and environmental engineering gives an opportunity for the development of more innovative ways to water treatment remediation. The purpose of this article is to provide an overview of emerging sources of contaminants, detection technologies, and treatment strategies. The goal of this review is to evaluate adsorption as a method for treating emerging pollutants, as well as sophisticated and cost-effective approaches for treating emerging contaminants.
... Given the growing controversies surrounding the safety of approved organic UV filters (Krause, 2012, Lindqvist, 2014, Planta, 2011, we asked whether the natural optical features of xanthommatin could be applied as a UV filter-booster for low (< 0.2 mM) concentrations of organic UV filters. To test this hypothesis, we evaluated xanthommatin's absorbance capabilities J o u r n a l P r e -p r o o f alone in solution ( Figure 3A) and in combination with FDA approved organic UV filters ( Figure 3B-C) over a spectral range of 280-500 nm. ...
Article
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We describe the investigation of an organic natural product, ammonium xanthommatin (Xanthochrome®), in a series of studies designed to not only assess its impact on endocrine receptor function in vitro but also interrogate its mutagenic potential using bacterial reverse mutation assays. As a multifunctional raw material, ammonium xanthommatin functions as an antioxidant with a broad absorption profile spanning the ultraviolet through visible spectrum, making it an interesting target for cosmetic applications. In solution, ammonium xanthommatin contributes to <30% inhibition of hormonal activities, indicating that it is not an endocrine disruptor. Furthermore, the compound does not cause gene mutations in the bacterial strains used, indicating it is non-mutagenic. Applications are also described, highlighting xanthommatin’s ability to boost the UVA and UVB absorptive properties of traditional chemical UV filters by >50% across all filters tested. In addition to these features, xanthommatin exhibited no phototoxic hazards in vitro when irradiated with UVA and visible light, demonstrating its utility as a multifunctional cosmetic ingredient. While these findings encourage the use of xanthommatin in cosmetics, they represent only the beginning of the complete in vitro and in vivo data package needed to support safety and efficacy claims for future applications in skin health.
... It is known that sun lotions guarantee only a partial protection and could induce toxicity with a frequent use [95,99]. As reported by Jansen et al. (2013) [100], oxybenzone induces a low rate of photo-allergenicity and is harmful for the environment (i.e. ...
Article
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Xeroderma Pigmentosum (XP) is a rare genetic syndrome with a defective DNA nucleotide excision repair. It is characterized by (i) an extreme sensitivity to ultraviolet (UV)-induced damages in the skin and eyes; (ii) high risk to develop multiple skin tumours; and (iii) neurologic alterations in the most severe form. To date, the management of XP patients consists of (i) early diagnosis; (ii) a long-life protection from ultraviolet radiation, including avoidance of unnecessary UV exposure, wearing UV blocking clothing, and use of topical sunscreens; and (iii) surgical resections of skin cancers. No curative treatment is available at present. Thus, in the last decade, in order to prevent or delay the progression of the clinical signs of XP, numerous strategies have been proposed and tested, in some cases, with adverse effects. The present review provides an overview of the molecular mechanisms featuring the development of XP and highlights both advantages and disadvantages of the clinical approaches developed throughout the years. The intention of the authors is to sensitize scientists to the crucial aspects of the pathology that could be differently targeted. In this context, the exploration of the process underlining the conception of liposomal nanocarriers is reported to focus the attention on the potentialities of liposomal technology to optimize the administration of chemoprotective agents in XP patients.
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Contaminants of emergent concern (CECs) in aquatic ecosystems entail a potential risk for the environment, due to their persistent behavior and adverse effect on living organisms during a long-term exposition, even at residual concentrations. Conventional Wastewater Treatment Plants (WWTPs) are not designed to eliminate CECs properly because the treatment technologies are not enough to remove these contaminants, which generates environmental and technological challenges. In this review, the sources of CEC contaminants to aquatic environments have been discussed in detail. Understanding the occurrences and pathways of CECs, their adverse effects on the environment, and removal techniques is a valuable key for the proper maintenance of global ecological health. This scenario was more explored through the harmful impacts of CECs on the environment, including their toxic effects and permissible limits. This review gathers information about CECs occurrences from a global perspective compiling information about their ecotoxicological effects, conventional and advanced treatment methods towards their mitigation. Advanced hybrid treatment techniques such as membrane bioreactor with ozonation, reverse osmosis, and ultrafiltration have shown to be a promising alternative for CECs removal. New advanced oxidation processes with assisted and non-assisted UVC/H2O2 systems with TiO2 photocatalysis were also demonstrated as a good approach to be implemented in the CECs mitigation strategies.
Article
Environmental chemicals are a persistent and pervasive part of everyday life. A subset of environmental chemicals are xenoestrogens, compounds that bind to the estrogen receptor (ER) and drive estrogen-related processes. One such chemical, benzophenone-3 (BP3), is a common chemical in sunscreen. It is a potent UV protectant but also is quickly absorbed through the skin. While it has been approved by the FDA, there is a renewed interest in the safety of BP3, particularly in relation to breast cancer. The focus of this study was to examine the impact that BP3 has on triple negative breast cancer (TNBC) through alterations to cells in the immune microenvironment. In this study, we exposed female mice to one of two doses of BP3 before injecting them with a TNBC cell line. Several immune endpoints were examined both in the primary tissues and from in vitro studies of T cell behavior. Our studies revealed that in the lung tumor microenvironment, exposure to BP3 not only increased the number of metastases, but also the total area of tumor coverage. We also found that BP3 caused alterations in immune populations in a tissue-dependent manner, particularly in T cells. Taken together, our data suggest that while BP3 may not directly affect the proliferation of TNBC, growth and metastasis of TNBC-derived tumors can be altered by BP3 exposures via the alterations in the immune populations of the tumor microenvironment.
Article
It has been demonstrated that benzophenone-3 is one of the endocrine-disrupting compounds which are considered as potential risk factors of adverse health effects. However, whether benzophenone-3 exposure can influence the sex steroid hormones levels remains unknown. We used data from the National Health and Nutrition Examination Survey, which is a cross-sectional dataset, from 2013 to 2016. A total of 1690 male US participants aged 18 or above were included. Urinary benzophenone-3, serum total testosterone, serum estradiol, serum sex hormone-binding globulin were measured. Confounders including age, body mass index, race, education level, urinary creatinine, ratio of family income to poverty, alcohol use, time of venipuncture, cardiac arterial diabetic score, energy intake, bisphenol A, triclosan and total parabens were controlled. After full adjustment (Model III), the upper benzophenone-3 quintiles had odds ratios (95% confidence intervals) of testosterone deficiency of 1.75 (1.03, 2.99), 2.47 (1.53, 3.98), 2.08 (1.13, 3.84) and 1.74 (0.94, 3.23) compared with quintile 1. Compared with quintile 1, percent changes (95% confidence intervals) in testosterone were -12% (-19%, -5%) and -9% (-17%, -1%) for quintile 3 and quintile 5 in Model III. Estradiol and sex hormone-binding globulin were generally similar to total testosterone in the associations with benzophenone-3. In conclusion, our results demonstrated that adult men in the US with higher urinary benzophenone-3 had a higher risk of testosterone deficiency and had inverse associations with total testosterone, estradiol and sex hormone-binding globulin. To confirm the causal links between benzophenone-3 and sex steroid hormones, prospective studies are needed.
Article
Microplastics can be considered potential carriers of emerging organic ultraviolet (UV) filters due to their considerable adsorption capacity in wastewater treatment. The adsorption behavior of organic UV filters, which are commonly contained in personal care products to preserve the skin against UV radiation, onto polyethylene (PE) microplastics were systematically studied to investigate their combined effects. Kinetics and isotherm analyses revealed that the adsorption of organic UV filters onto PE microplastic surfaces followed a multi-rate and a heterogeneous multi-layer pattern. Several factors including salinity, microplastic size, and dosage also influenced the adsorption efficiency due to hydrophobic interactions. A bench-scale cross-flow ceramic membrane filtration experiment was investigated to evaluate the role of PE microplastics on the retention performance of organic UV filters. The retentions for organic UV filters were 34.2%–37.8% in the non-existence of PE microplastics. Conversely, organic UV filter retentions were significantly increased up to 82.2%–97.9% when they were adsorbed onto the PE microplastics, which were almost completely retained by the ceramic membrane. Therefore, organic UV filters can likely migrate and eventually be carried by PE microplastics, thus increasing the retention of both emerging organic UV filters and microplastics prior to discharge from wastewater treatment facilities.
Article
Background Humans are widely exposed to chemicals with known or suspected endocrine disrupting effects. Among those are several benzophenones, bisphenols and other phenols commonly used in consumer products. Objectives To provide human biomonitoring data from young families including infants and their parents as well as longitudinal data of infants exclusively breastfed versus on mixed diet. Method Twenty-two benzophenones, bisphenols and other phenols, were measured in urine sample sets collected from more than 100 infants and their parents (the TRIO study) and in paired samples from 61 infants when exclusively breastfed and after introduction of mixed diet (the FOOD study). Results Twelve out of 22 substances were detectable in more than half of the urine samples from infants, mothers or fathers. Large variation in excreted levels of almost all the substances were observed. The TRIO study showed that infants had comparable or even significantly higher daily urinary excretion (DUE) of benzophenone, 4-hydroxy-benzophenone, bisphenol A, bisphenol S, triclosan and 2-phenylphenol than their parents. In the FOOD study, exclusively breastfed infants had higher or similar DUE of triclosan and benzophenones compared to when they received mixed diet. Urinary levels of triclosan and the benzophenones, BP-1 and BP-3 were significantly correlated between all trio members, indicating exposure from the same sources at home. For triclosan, BP-1 and BP-3, the within family variation was lower than between families in the TRIO study. Many substances were positively correlated both within infants and parents, indicating that some families were exposed to several of these substances concurrently. Conclusion Participants in this study excreted relatively low chemical levels, however, simultaneous exposure to several chemicals with endocrine disrupting abilities is of concern due to the dose-additive effects of these substances in combination with other chemicals.
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This book examines a wide range of emerging sources off water pollution. It consists of thirteen chapters dedicated to the topic, giving readers comprehensive information about the types of materials involved and the solution for their removal. The first five chapters present an analysis of the emerging water pollutants, their toxicities, legislations available to monitor and regulate their emissions. This introduction is followed by 3 chapters that cover risk assessment of emerging pollutants, their fate and life cycle assessment. The last section of the book goes through the details of remediation technologies for wastewater treatment. This reference is equally suitable for academia, industry professionals and students, presenting state-of-the-art learnings on emerging water pollutants and their remediation methods.
Article
The photoprotective properties of ethanol extracts from fruiting bodies of cultivated macromycetes Hericium erinaceus, Lentinula edodes, Ganoderma lucidum, and Pleurotus ostreatus, and wild-growing Inonotus obliquus, Fomes fomentarius, Trichaptum biforme, and Ganoderma applanatum, were evaluated. The yield of extracts was 29.2%; 25.0%; 11.5% and 9.1% for H. erinaceus, L. edodes, G. lucidum and P. ostreatus, respectively; 16.5%; 2.6%; 2.3% and 5.1% for I. obliquus, F. fomentarius, T. biforme and G. applanatum, respectively. Ethanol extracts from the fruiting bodies of cultivated mushrooms had a low level of photoprotection in terms of SPF, with a score of λcrit = 3÷4, were excellent and most effective in terms of UV-A/UV-B. Extracts from the fruiting bodies of T. biforme and G. applanatum are not photoprotective: the first according to the criterion λcrit < 370 nm; the second is SPF < 15.0. The extract from F. fomentarius is photoprotective, the extract from I. obliquus is close to being photoprotective.
Article
Benzophenone-type ultraviolet filters (BP-UVFs) are a group of emerging contaminants, which found in various environmental aqueous samples raising potential risks for public health concern and could bioaccumulate in the food chain. This study describes a simple and “green” method to rapidly analyze five BP-UVFs that are frequently found in surface water and in seawater samples. Dispersive solid-phase extraction (DSPE) using a zeolitic imidazolate framework‑8 (ZIF-8) as the sorbent was applied to efficiently extract the BP-UVFs from aqueous samples, and they were then detected and quantified by UHPLC-electrospray ionization (+)-quadrupole time-of-flight mass spectrometry (UHPLC-ESI (+)-QTOF-MS). The ZIF-8 sorbent was synthesized by a green one-step mechanochemical process using water-assisted grinding and a stoichiometric reaction. The Box-Behnken Design coupled with the response surface method was applied to optimize the main DSPE extraction factors. The developed method was fully validated, showing low limits of quantification (LOQs; 0.3−20 ng L⁻¹), satisfactory mean spiked recoveries (72−105%), and a high level of precision (3−9%). A preliminary analysis of the surface water and seawater samples revealed that 2-hydroxy-4-methoxybenzophenone (BP-3) was the most common BP-UVF present in our aquatic environment, likely due to its widespread applications and slow rate of degradation.
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Bionanotechnology is an effective amalgamation of biological sciences and engineering, with applications in a wide range of scientific and technological fields such as the environment, health, energy, medicine, electronics, and so on. The most prominent question affecting people all over the world is a lack of access to safe drinking water and sanitation. The treatment of wastewater in order to return it to a reusable state is crucial in order to meet current and future demands. Water treatment methods have been the focus of many environmentalists, scientists, research organizations, and governmental agencies over the last few decades. To treat the wastewater, various methods have been used. However, an advanced nanotechnology-oriented approach combined with traditional methods has yielded intriguing results. Being green and biodegradable in nature, bionanocomposites are the most promising materials for the remediation of pollutants such as microorganisms, organic pollutants, and inorganic pollutants from contaminated water. The small sizes and dimensions of the materials render them unique characteristics with potential capacities for environmental depollution. This chapter discusses the classification, preparation, characterization, and applications of bionanocomposites pertaining to the sector of water/wastewater treatment. The performance of bionanocomposites as adsorbents and membranes, and regeneration studies in water treatment are also mentioned.
Article
Throughout human life, an extensive and varied range of emerging environmental contaminants, called endocrine disruptors (EDCs), cause adverse health effects, including in the cardiovascular (CV) system. Cardiovascular diseases (CVD) are worryingly one of the leading causes of all mortality and mobility worldwide. The UV-B filter octylmethoxycinnamate (also designated octinoxate, or ethylhexyl methoxycinnamate (CAS number: 5466-77-3)) is an EDC widely present in all personal care products. However, to date, there are no studies evaluating the OMC-induced effects on vasculature using animal models to improve human cardiovascular health. This work analysed the effects of OMC on rat aorta vasculature and explored the modes of action implicated in these effects. Our results indicated that OMC relaxes the rat aorta by endothelium-dependent mechanisms through the signaling pathways of cyclic nucleotides and by endothelium-independent mechanisms involving inhibition of L-Type voltage-operated Ca²⁺ channels (L-Type VOCC). Overall, OMC toxicity on rat aorta may produce hypotension via vasodilation due to excessive NO release and blockade of L-Type VOCC. Moreover, the OMC-induced endothelial dysfunction may also occur by promoting the endothelial release of endothelin-1. Therefore, our findings demonstrate that exposure to OMC alters the reactivity of the rat aorta and highlight that long-term OMC exposure may increase the risk of human CV diseases.
Article
Growing awareness of the harmful effects derived from sunlight overexposure has led to a regular use of sunscreens. Nonetheless, major environmental side-effects have been concurrently originated due to the increasing concentration of related pollutants. Considering the advantages that microrobots offer for water remediation tasks, magnetically-driven photoactive microrobots (i.e., MG-µROSES) are here developed as a pioneering response from the field to face this global threat. Particularly, photoactive bismuth oxyiodide (i.e., BiOI) flower-like microparticles (i.e., µROSES) have been prepared and modified with tailored Fe3O4 nanoparticles through a mild surface functionalization. Therefore, static µROSES acquired an appealing magnetic steering motion and an easy retrieval without sacrificing large BiOI surface areas. The performance of MG-µROSES against the main organic UV-filter in suntan lotions (i.e., oxybenzone, BP-3) has been analyzed. An effective photocatalytic removal —in pure water and under visible light— have been observed and attributed to the synergistic combination of adsorption and photocatalytic activity provided by this appropriate design. Moreover, the noticeable enhancement of the photocatalytic removal of MG-µROSES has been linked to their magnetically-driven navigation, favoring an on-the-fly: (i) adsorption of BP-3; and (ii) distribution of the photogenerated reactive oxygen species, in particular hydroxyl radicals (OH·)). All in all, an efficient strategy based on photoresponsive magnetic microrobot against sunscreens residues is presented. Hence, a potential contender to beat alternative traditional methodologies is offered.
Article
Unlike the environmental pollutants or industrial chemicals, the chemicals in consumer products may pose higher levels of risks, depending on how the chemicals are used in the products and how humans interact with the products. Recently, endocrine disrupting chemicals in cosmetics, personal care products, cleaners, sunscreens, and vinyl products were analytically quantified and many active chemicals including phthalates, parabens and bisphenols were detected. This indicates a wide range of exposures from common products. In this study, 35 chemicals known to be ingredients of consumer products were selected and screened for the transactivation of estrogen receptors and androgen receptors. From the results of individual chemicals, the activity of binary/ternary mixture prepared from the agonists for the ER transcription activity was measured, and compared to the predicted values obtained by the full logistic model. The measured and the predicted values were found to be very similar. This study may suggest that prediction of mixture activity by proper models would be one of the supportive tools for the risk assessment and sound regulation of chemical mixtures which have potential endocrine disrupting effects in consumer products.
Article
Taro mucilage, a hydrocolloid present in the rhizome of Colocasia esculenta (L.) Schott, was extracted and characterized by infrared spectroscopy, X-ray diffraction, scanning electron microscopy, thermal analysis, and proximal composition. In addition, cosmetic formulations based on extracted mucilage were developed and studied. The mucilage presented a semicrystalline structure with high thermal stability, the presence of granules along its surface area, and good emulsifying activity. High physical-chemical stability was also found in the mucilage and the cosmetic formulations during storage. All cream samples presented pseudoplastic behavior, with a flow behavior index lower than 1, which is a desirable characteristic for cosmetics, as it improves its applicability. The mucilage demonstrates potential for application in cosmetic products, and its commercial use as an ingredient in cosmetics could be a strategic tool for the creation of a new product chain and adding value to the culture of Colocasia0 esculenta.
Article
The active chemicals in sunscreen formulations are released into the environment from human skin, and found in recreational-use waters like seawater, but can also be washed into fresh water from bathing and showering. The level of sunscreen chemicals found in samples varies considerably between regions, time of year (higher in summer months), and time of day. Average typical concentrations are only in the nanograms per litre (ng L−1) range in marine and fresh water systems, and typically, the highest levels are in waste-water sludge because of a concentrating effect during the treatment process. From numerous studies, it is known that the active chemicals in sunscreens can have potential hormonal/oestrogenic activity and non-hormonal effects, including: acting as teratogens, altering gene regulation, inducing changes in antioxidant and free radical production, and inducing coral bleaching. However, the effects of sunscreens on aquatic life under laboratory conditions typically occur only at concentrations (µg or mg L−1) that far exceed (10–10 000-fold) levels found in the environment. As such, when damage does occur to reefs and animal life, there are often other causes that are more likely impacting the aquatic life including changes in water temperature, water turbidity, elevated nutrient levels, and the presence of pesticides and medicines used for human and animal health.
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Today, the negative effects of ultraviolet radiation on the skin are well known, so we know we should use protection whenever we are exposed to the sun. Sun protection products, therefore, form part of an overall strategy against photo-induced cancers. However, over several years, controversies have led to consumer mistrust of certain sun protection products containing organic filters, said to be allergens, endocrine disrupters or even responsible for coral bleaching. Taking advantage of the dismay this has caused in some consumers, internet sites have promoted plant oils and essential oils as natural solar filters to replace pharmaceutical sun creams. Using an in vitro method, we studied 15 fixed oils, one oily macerate, one butter, eight essential oils, and an essential wax, chosen among the substances most commonly mentioned on the internet. For each substance, we determined the sun protection factor (SPF) and UVA protection factor (PF-UVA), the universal references for protection level in the ultraviolet range. We demonstrated that these fixed oils and essential oils, for which we found SPF and PF-UVA values of only around 1, are totally devoid of any photoprotective properties. So as to avoid potential users suffering serious consequences, therefore, they should not be considered as sunscreens.
Chapter
Emerging contaminants (ECs) have huge impacts on all living beings, and conventional treatment processes like coagulation, precipitation, and chlorination have limited capability for removal. So, a tertiary and combined treatment process is required. Alternative treatment technologies include adsorption, chemical treatment, and membrane filtration. However, the associated operating cost, ECs rejection, fouling propensity, and by-product formation are some of the drawbacks. Membrane distillation (MD) is one of the promising membrane technologies for emerging contaminants removal. In MD, The vapor pressure difference between the hot feed and cold permeate is a driving force. MD technology has some added advantages like low-pressure requirements, less fouling susceptibility, low-temperature requirements, and only vapor mass transfer, i.e., 100% non-volatile compounds retention. MD employs a low temperature and pressure so fouling is less compact and is easily cleanable. MD technology has been studied for desalination, hypersaline brine treatment, chemical separation and can potentially remove emerging contaminants. The MD technology does not require very high-quality heat; solar heat, waste heat, or cogeneration-based heat utilization is possible. This way, MD can be operated on renewable energy and becomes sustainable and carbon neutral. MD technology has also been integrated with other efficient treatment technologies like Forward Osmosis (FO), Reverse osmosis (RO), and Nanofiltration (NF), providing a leading edge compared to other treatment methods. This chapter elaborates on various available MD technologies, possible materials, configurations, operating parameters, and energy requirements. We have also highlighted future research trends and challenges for MD treatment technology’s sustainable and commercial application.
Chapter
In the present world scenario, emerging contaminants (ECs) are found widespread in groundwater resources. They include different types of pharmaceuticals, personal care products, lifestyle products, surfactants, pesticides, and many industrial compounds. These chemicals may end up in subsurface through various pathways after being discharged by domestic, agricultural, and industrial areas. In this chapter, these contaminants are comprehensively addressed by describing their occurrence, source, and fate in the groundwater, and their effects on humans and the environment. The methods used to detect and analyze the contaminants’ concentrations in laboratory are also described, followed by the review of remediation technologies, and the risks associated with their exposure to human bodies. Additionally, the important physicochemical properties of the ECs are discussed, and the challenges arising due to their increasing presence in the environment are presented.
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Photophysics and photochemistry are basic subjects in the study of light-matter interactions and are ubiquitous in diverse fields such as biology, energy, materials, and environment. A full understanding of mechanistic photophysics and photochemistry underpins many recent advances and applications. This contribution first provides a short discussion on the theoretical calculation methods we have used in relevant studies, then we introduce our latest progress on the mechanistic photophysics and photochemistry of two classes of molecular systems, namely unnatural bases and sunscreens. For unnatural bases, we disclose the intrinsic driving forces for the ultrafast population to reactive triplet states, impacts of the position and degree of chalcogen substitutions, and the effects of complex environments. For sunscreen molecules, we reveal the photoprotection mechanisms that dissipate excess photon energy to the surroundings by ultrafast internal conversion to the ground state. Finally, relevant theoretical challenges and outlooks are discussed.
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Octylmethoxycinnamate (OMC) is a filter for ultraviolet B radiation used in sunscreens to protect skin. There is some evidence about the OMC activity as endocrine disruptor concerning a possible estrogenic activity, but its vascular effects were not still analyzed. The objective was to evaluate the non-genomic effects of the OMC on human umbilical artery (HUA) without endothelium. By mean of an organ bath system, HUA rings without endothelium were contracted by 5-hydroxytryptamine (5HT; 1µM) or by depolarization with KCl (60mM), and the effect of different concentrations of OMC was analyzed. The OMC elicits vasodilator effect on HUA without endothelium contracted by 5-HT (1μM) and by KCl (60mM). The effect was similar for the two contractile agents used. Here, we established that the OMC causes vasodilation of human arteries. This effect is analogous to the non-genomic effect caused by estradiol (E2), which occurs also by and endothelial-independent mechanism.
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Several UV filters exhibit endocrine activity. Evidence for transdermal passage and presence in the food chain (fish) suggests potential exposure of humans during development. Developmental toxicity was studied in rats for the estrogenic UV filters 4-methylbenzylidene camphor (4-MBC, 0.7, 7, 24, 47 mg/kg/day) and 3-benzylidene camphor (3-BC, 0.07, 0.24, 0.7, 2.4, 7 mg/kg/day) administered in chow to the parent generation before mating, during pregnancy and lactation, and to the offspring until adulthood. Neonates exhibited enhanced prostate growth after 4-MBC and altered uterine gene expression after both filters. 4-MBC and 3-BC delayed male puberty and affected reproductive organ weights of adult offspring. Interactions with the thyroid were noted. Expression and estrogen sensitivity of target genes and nuclear receptor coregulators were altered at mRNA and protein levels in adult uterus, prostate and brain. Female sexual behavior was affected by 4-MBC and 3-BC, estrous cycles by 3-BC. Classical endpoints exhibited LOAELs/NOAELs of 7/0.7 mg/kg/day for 4-MBC and 0.24/0.07 mg/kg/day for 3-BC. Molecular endpoints were affected by the lowest doses. In order to obtain information on human exposure, we conducted a monitoring study on human milk with three series of mother-child pairs (2004, 2005, 2006), with focus on cosmetic UV filters in relation to other endocrine disrupters. Methods for UV filter analysis followed the principles of European standardized methods for pesticide residue analysis (EN 15289). In cohorts 2004 and 2005, 78.8% of women reported use of product(s) containing cosmetic UV filters in a questionnaire, and 76.5% of milk samples contained these filters. Use of UV filters and concentration in human milk were significantly correlated. The results agree with the idea of transdermal passage of UV filters. They also indicate that it may be possible to reduce human exposure during critical periods such as pregnancy and lactation by transiently abstaining from use.
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Data concerning the effects of prenatal exposures to phthalates and phenols on fetal growth are limited in humans. Previous findings suggest possible effects of some phenols on male birth weight. Our aim was to assess the relationships between prenatal exposures to phthalates and phenols and fetal growth among male newborns. We conducted a case-control study on male malformations of the genitalia nested in two French mother-child cohorts with recruitment between 2002 and 2006. We measured, in maternal urinary samples collected between 6 and 30 gestational weeks, the concentrations (micrograms per liter) of 9 phenol (n = 191 pregnant women) and 11 phthalate metabolites (n = 287). Weight, length, and head circumference at birth were collected from maternity records. Statistical analyses were corrected for the oversampling of malformation cases. Adjusted birth weight decreased by 77 g [95% confidence interval (CI): -129, -25] and by 49 g (95% CI: -86, -13) in association with a 1-unit increase in ln-transformed 2,4-dichlorophenol (DCP) and 2,5-DCP urinary concentrations, respectively. Benzophenone-3 (BP3) ln-transformed concentrations were positively associated with weight (26 g; 95% CI: -2, 54) and head circumference at birth (0.1 cm; 95% CI: 0.0, 0.2). Head circumference increased by 0.3 cm (95% CI: 0.0, 0.7) in association with a 1-unit increase in ln-transformed BPA concentration. For phthalate metabolites there was no evidence of monotonic associations with birth weight. Consistent with findings of a previous study, we observed evidence of an inverse association of 2,5-DCP and a positive association of BP3 with male birth weight.
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The capability of benzophenone-3 (BP-3) to absorb and dissipate ultraviolet radiation facilitates its use as a sunscreen agent. BP-3 has other uses in many consumer products (e.g., as fragrance and flavor enhancer, photoinitiator, ultraviolet curing agent, polymerization inhibitor). Our goal was to assess exposure to BP-3 in a representative sample of the U.S. general population > or = 6 years of age. Using automated solid-phase extraction coupled to high-performance liquid chromatography-tandem mass spectrometry, we analyzed 2,517 urine samples collected as part of the 2003--2004 National Health and Nutrition Examination Survey. We detected BP-3 in 96.8% of the samples. The geometric mean and 95th percentile concentrations were 22.9 microg/L (22.2 microg/g creatinine) and 1,040 microg/L (1,070 microg/g creatinine), respectively. Least-square geometric mean (LSGM) concentrations were significantly higher (p < or = 0.04) for females than for males, regardless of age. LSGM concentrations were significantly higher for non-Hispanic whites than for non-Hispanic blacks (p < or = 0.01), regardless of age. Females were more likely than males [adjusted odds ratio (OR) = 3.5; 95% confidence interval (95% CI), 1.9-6.5], and non-Hispanic whites were more likely than non-Hispanic blacks (adjusted OR = 6.8; 95% CI, 2.9-16.2) to have concentrations above the 95th percentile. Exposure to BP-3 was prevalent in the general U.S. population during 2003--2004. Differences by sex and race/ethnicity probably reflect differences in use of personal care products containing BP-3.
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Exposure to environmental endocrine disruptors is a potential risk factor for humans. Many of these chemicals have been shown to exhibit disruption of normal cellular and developmental processes in animal models. Ultraviolet (UV) filters used as sunscreens in cosmetics have previously been shown to exhibit estrogenic activity in in vitro and in vivo assays. We examined the effects of two UV filters, 4-methylbenzylidene camphor (4-MBC) and 3-benzylidene camphor (3-BC), in the developing prostate of the fetal rat. Pregnant Long Evans rats were fed diets containing doses of 4-MBC and 3-BC that resulted in average daily intakes of these chemicals corresponding to the lowest observed adverse effects level (LOAEL) and the no observed adverse effects level (NOAEL) doses in prior developmental toxicity studies. Using digital photographs of serial sections from postnatal day 1 animals, we identified, contoured, and aligned the epithelial ducts from specific regions of the developing prostate, plus the accessory sex glands and calculated the total volume for each region from three-dimensional, surface-rendered models. Fetal exposure to 4-MBC (7.0 mg/kg body weight/day) resulted in a significant increase (p < 0.05) in tissue volume in the prostate and accessory sex glands. Treated males exhibited a 62% increase in the number of ducts in the caudal dorsal prostate. Increased distal branching morphogenesis appears to be a consequence of exposure in the ventral region, resulting in a 106% increase in ductal volume. 4-MBC exposure during development of the male reproductive accessory sex glands exhibited classical growth effects associated with estrogenic endocrine disruptors. The different regional responses suggest that the two developmental processes of ductal outgrowth and branching morphogenesis are affected independently by exposure to the environmental chemicals.
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Prostaglandins (PGs) play key roles in development and maintenance of homeostasis of the adult body. Despite these important roles, it remains unclear whether the PG pathway is a target for endocrine disruption. However, several known endocrine-disrupting compounds (EDCs) share a high degree of structural similarity with mild analgesics. Using cell-based transfection and transduction experiments, mass spectrometry, and organotypic assays together with molecular modeling, we investigated whether inhibition of the PG pathway by known EDCs could be a novel point of endocrine disruption. We found that many known EDCs inhibit the PG pathway in a mouse Sertoli cell line and in human primary mast cells. The EDCs also reduced PG synthesis in ex vivo rat testis, and this reduction was correlated with a reduced testosterone production. The inhibition of PG synthesis occurred without involvement of canonical PG receptors or the peroxisome proliferator-activated receptors (PPARs), which have previously been described as targets of EDCs. Instead, our results suggest that the compounds may bind directly into the active site of the cyclooxygenase (COX) enzymes, thereby obstructing the conversion of arachidonic acid to PG precursors without interfering with the expression of the COX enzymes. A common feature of the PG inhibitory EDCs is the presence of aromatic groups that may stabilize binding in the hydrophobic active site of the COX enzymes. Our findings suggest a hitherto unknown mode of action by EDCs through inhibition of the PG pathway and suggest new avenues to investigate effects of EDCs on reproductive and immunological disorders that have become increasingly common in recent decades.
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Many phthalates and phenols are hormonally active and are suspected to alter the course of development. We investigated prenatal exposures to phthalate and phenol metabolites and their associations with body size measures of the infants at birth. We measured 5 phenol and 10 phthalate urinary metabolites in a multiethnic cohort of 404 women in New York City during their third trimester of pregnancy and recorded size of infants at birth. Median urinary concentrations were > 10 microg/L for 2 of 5 phenols and 6 of 10 phthalate monoester metabolites. Concentrations of low-molecular-weight phthalate monoesters (low-MWP) were approximately 5-fold greater than those of high-molecular-weight metabolites. Low-MWP metabolites had a positive association with gestational age [0.97 day gestational age per ln-biomarker; 95% confidence interval (CI), 0.07-1.9 days, multivariate adjusted] and with head circumference. Higher prenatal exposures to 2,5-dichlorophenol (2,5-DCP) predicted lower birth weight in boys (-210 g average birth weight difference between the third tertile and first tertile of 2,5-DCP; 95% CI, 71-348 g). Higher maternal benzophenone-3 (BP3) concentrations were associated with a similar decrease in birth weight among girls but with greater birth weight in boys. We observed a range of phthalate and phenol exposures during pregnancy in our population, but few were associated with birth size. The association of 2,5-DCP and BP3 with reduced or increased birth weight could be important in very early or small-size births. In addition, positive associations of urinary metabolites with some outcomes may be attributable partly to unresolved confounding with maternal anthropometric factors.
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The incidence of and mortality from skin cancer are increasing in many countries. In view of the added concern about ozone depletion, many organizations are promoting the regular use of sunscreens to prevent skin cancer, despite the absence of evidence that these products have this effect. Solar (actinic) keratosis is a precursor of squamous-cell carcinoma of the skin. We conducted a randomized, controlled trial of the effect on solar keratoses of daily use of a broad-spectrum sunscreen cream with a sun-protection factor of 17 in 588 people 40 years of age or older in Australia during one summer (September 1991 to March 1992). The subjects applied either a sunscreen cream or the base cream minus the active ingredients of the sunscreen to the head, neck, forearms, and hands. The mean number of solar keratoses increased by 1.0 per subject in the base-cream group and decreased by 0.6 in the sunscreen group (difference, 1.53; 95 percent confidence interval, 0.81 to 2.25). The sunscreen group had fewer new lesions (rate ratio, 0.62; 95 percent confidence interval, 0.54 to 0.71) and more remissions (odds ratio, 1.53; 95 percent confidence interval, 1.29 to 1.80) than the base-cream group. There was a dose-response relation: the amount of sunscreen cream used was related to both the development of new lesions and the remission of existing ones. Regular use of sunscreens prevents the development of solar keratoses and, by implication, possibly reduces the risk of skin cancer in the long-term.
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Ultraviolet (UV) screens are increasingly used as a result of growing concern about UV radiation and skin cancer; they are also added to cosmetics and other products for light stability. Recent data on bioaccumulation in wildlife and humans point to a need for in-depth analyses of systemic toxicology, in particular with respect to reproduction and ontogeny. We examined six frequently used UVA and UVB screens for estrogenicity in vitro and in vivo. In MCF-7 breast cancer cells, five out of six chemicals, that is, benzophenone-3 (Bp-3), homosalate (HMS), 4-methyl-benzylidene camphor (4-MBC), octyl-methoxycinnamate (OMC), and octyl-dimethyl-PABA (OD-PABA), increased cell proliferation with median effective concentrations (EC(50)) values between 1.56 and 3.73 microM, whereas butyl-methoxydibenzoylmethane (B-MDM) was inactive. Further evidence for estrogenic activity was the induction of pS2 protein in MCF-7 cells and the blockade of the proliferative effect of 4-MBC by the estrogen antagonist ICI 182,780. In the uterotrophic assay using immature Long-Evans rats that received the chemicals for 4 days in powdered feed, uterine weight was dose-dependently increased by 4-MBC (ED(50 )309mg/kg/day), OMC (ED(50) 935 mg/kg/day), and weakly by Bp-3 (active at 1,525 mg/kg/day). Three compounds were inactive by the oral route in the doses tested. Dermal application of 4-MBC to immature hairless (hr/hr) rats also increased uterine weight at concentrations of 5 and 7.5% in olive oil. Our findings indicate that UV screens should be tested for endocrine activity, in view of possible long-term effects in humans and wildlife.
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In this study we found that the ultraviolet sunscreen component 3-(4-methylbenzylidine)camphor (4MBC) is uterotrophic in immature rats when administered by either subcutaneous injection or oral gavage. These data confirm earlier reports of uterotrophic activity for this agent when administered to immature rats in the diet or by whole-body immersion; however, they are in contrast to negative unpublished immature rat uterotrophic assay results. Data also indicate that 4MBC binds to isolated rat uterine estrogen receptors and shows activity in a human estrogen receptor yeast transactivation assay; however, we considered both of these effects equivocal. In this study, we confirmed the original observation that 4MBC was active as a mitogen to MCF-7 breast cancer cells. We evaluated and discounted the possibility that the estrogenic activity of 4MBC is related to its bulky camphor group, which is of similar molecular dimensions to that of the weak estrogen kepone. Uncertainty remains regarding the mechanism of the uterotrophic activity of 4MBC.
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In the past decade the list of chemicals in the environment that are able to mimic the natural hormone estrogen, thereby disrupting endocrine function, has grown rapidly. These chemicals are able to bind to estrogen receptors (ERs) and influence estrogen signalling pathways, although several of them have structures that differ substantially from the endogenous hormone 17beta-estradiol. In this study, six extensively used ultraviolet (UV) filters were assessed for transcriptional activation of estrogen receptors. Because of their high lipophilicity, these UV filters tend to bioaccumulate in the environment. They have been found in surface waters, fish, and in human milk fat. Using a sensitive in vitro reporter gene assay, we found that all six compounds induce estrogenic activity towards ERalpha, while four out of six compounds induced transcriptional activity of ERbeta. Zebrafish, in which an estrogen responsive luciferase reporter gene has been stably introduced, were used for in vivo testing. In this transgenic zebrafish assay none of the compounds showed estrogenic activity. Our findings suggest that one should be aware of over-interpretation when predicting in vivo effects from weak in vitro data. However, it can not be ruled out that these UV filters have long-term effects in the environment.
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Bisphenol A (BPA), an endocrine disruptor, is employed in the manufacture of a wide range of consumer products. The suggestion that BPA, at amounts to which we are exposed, alters the reproductive organs of developing rodents has caused concern. At present, no information exists concerning the exposure of human pregnant women and their fetuses to BPA. We therefore investigated blood samples from mothers (n = 37) between weeks 32 and 41 of gestation. Afer the births, we also analyzed placental tissue and umbilical cord blood from the same subjects. We developed a novel chemical derivatization-gas chromatography/mass spectrometry method to analyze parent BPA at concentrations < 1 micro g/mL in plasma and tissues. Concentrations of BPA ranged from 0.3 to 18.9 ng/mL (median = 3.1 ng/mL) in maternal plasma, from 0.2 to 9.2 ng/mL (median = 2.3 ng/mL) in fetal plasma, and from 1.0 to 104.9 ng/g (median = 12.7 ng/g) in placental tissue. BPA blood concentrations were higher in male than in female fetuses. Here we demonstrate parent BPA in pregnant women and their fetuses. Exposure levels of parent BPA were found within a range typical of those used in recent animal studies and were shown to be toxic to reproductive organs of male and female offspring. We suggest that the range of BPA concentrations we measured may be related to sex differences in metabolization of parent BPA or variable maternal use of consumer products leaching BPA.
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Because the estrogen receptor (ER) ligand type influences transactivation, it is important to obtain information on molecular actions of nonclassical ER agonists. UV filters from cosmetics represent new classes of endocrine active chemicals, including the preferential ER beta ligands 4-methylbenzylidene camphor (4-MBC) and 3-benzylidene camphor. We studied estrogen target gene expression in uterus of Long Evans rats after developmental exposure to 4-MBC (0.7, 7, 24, and 47 mg/kg x d) administered in feed to the parent generation before mating, during pregnancy and lactation, and to the offspring until adulthood. 4-MBC altered steady-state levels of mRNAs encoding for ER alpha, ER beta, progesterone receptor (PR), IGF-I, androgen receptor, determined by real-time RT-PCR in uterus of 12-wk-old offspring. Western-blot analyses of the same tissue homogenates indicated changes in ER alpha and PR but not ER beta proteins. To assess sensitivity to estradiol (E2), offspring were ovariectomized on d 70, injected with E2 (10 or 50 microg/kg sc) on d 84, and killed 6 h later. Acute up-regulation of PR and IGF-I and down-regulation of ER alpha and androgen receptor by E2 were dose-dependently reduced in 4-MBC-exposed rats. The reduced response to E2 was accompanied by reduced coactivator SRC-1 mRNA and protein levels. Our data indicate that developmental exposure to 4-MBC affects the regulation of estrogen target genes and the expression of nuclear receptor coregulators in uterus at mRNA and protein levels.
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In order to protect consumers from ultraviolet (UV) radiation and enhance light stability of the product, three to eight UV filters are usually added to consumer sunscreen products. High lipophilicity of the UV filters has been shown to cause bioaccumulation in fish and humans, leading to environmental levels of UV filters that are similar to those of PCBs and DDT. In this paper, estrogen-regulated pS2 gene transcription in the human mammary tumor cell line MCF-7 was used as a measure of estrogenicity of four individual UV filters. Since humans are exposed to more than one UV filter at a time, an equipotent binary mixture of 2-hydroxy-4-methoxy-benzophenone (BP-3) and its metabolite 2,4-dihydroxy benzophenone (BP-1), as well as an equipotent multi-component mixture of BP-1, BP-3, octyl methoxy cinnamate (OMC) and 3-(4-methylbenzylidene) camphor (4-MBC), were also evaluated for their ability to induce pS2 gene transcription in order to examine additivity. An estrogen receptor-mediated mechanism of action was expected for all UV filters. Therefore, our null-hypothesis was that combined estrogenic responses, measured as increased pS2 gene transcription in MCF-7 cells after exposure to mixtures of UV filters, are additive, according to a concentration-addition model.
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In this work, we evaluate whether in vitro systems are good predictors for in vivo estrogenic activity in fish. We focus on UV filters being used in sunscreens and in UV stabilization of materials. First, we determined the estrogenic activity of 23 UV filters and one UV filter metabolite employing a recombinant yeast carrying the estrogen receptor of rainbow trout (rtERalpha) and made comparisons with yeast carrying the human hERalpha for receptor specificity. Benzophenone-1 (BP1), benzophenone-2 (BP2), 4,4-dihydroxybenzophenone, 4-hydroxybenzophenone, 2,4,4-trihydroxy-benzophenone, and phenylsalicylate showed full dose-response curves with maximal responses of 81-115%, whereas 3-benzylidene camphor (3BC), octylsalicylate, benzylsalicylate, benzophenone-3, and benzophenone-4 displayed lower maximal responses of 15-74%. Whereas the activity of 17beta-estradiol was lower in the rtERalpha than the hERalpha assay, the activities of UV filters were similar or relatively higher in rtERalpha, indicating different relative binding activities of both ER. Subsequently, we analyzed whether the in vitro estrogenicity of eight UV filters is also displayed in vivo in fathead minnows by the induction potential of vitellogenin after 14 days of aqueous exposure. Of the three active compounds in vivo, 3BC induced vitellogenin at lower concentrations (435 microg/l) than BP1 (4919 microg/l) and BP2 (8783 microg/l). The study shows, for the first time, estrogenic activities of UV filters in fish both in vitro and in vivo. Thus we propose that receptor-based assays should be used for in vitro screening prior to in vivo testing, leading to environmental risk assessments based on combined, complementary, and appropriate species-related assays for hormonal activity.
Article
: Chemical UV-filters are used in sun protection products and various kinds of cosmetics. The lipophilic chemical UV-filter 3-benzylidene camphor was investigated for its capability to cause vitellogenin induction, possibly via oestrogen receptor binding, in a well-established in vivo fish assay (juvenile rainbow trout, Oncorhynchus mykiss, vitellogenin ELISA). A clear relationship was demonstrated between the dose of injected 3-benzylidene camphor and the concentration of plasma vitellogenin with a 105-times induction from 68 mg 3-benzylidene camphor /kg/injection and above compared to the control vitellogenin level. The relationship between the injected dose of 3-benzylidene camphor and the percent of responding fish (vitellogenin) was evaluated by logistic regression analysis and effective dose-values (ED-values) were determined. ED10, ED50 and ED90 of 3-benzylidene camphor after 6 days (2 injections) were 6.4, 16 and 26 mg/kg/injection, respectively. These ED-values place 3-benzylidene camphor among the more potent xenooestrogens discovered to date and necessitates investigations on the distribution, concentration, persistence and bioaccumulation of 3-benzylidene camphor and other UV-filters in nature.
Article
4-Methylbenzylidene-camphor (4-MBC) is an organic sunscreen that protects against UV radiation and may therefore help in the prevention of skin cancer. Recent results on the estrogenicity of 4-MBC have raised concerns about a potential of 4-MBC to act as an endocrine disruptor. Here, we investigated the direct interaction of 4-MBC with estrogen receptor (ER) α and ERβ in a series of studies including receptor binding, ER transactivation and functional tests in human and rat cells. 4-MBC induced alkaline phosphatase activity, a surrogate marker for estrogenic activity, in human endometrial Ishikawa cells. Interestingly, 4-MBC induced weakly ERα and with a higher potency ERβ mediated transactivation in Ishikawa cells at doses more than 1 μM, but showed no distinct binding affinity to ERα or ERβ. In addition, 4-MBC was an effective antagonist for ERα and ERβ. In an attempt to put 4-MBC's estrogenic activity into perspective we compared binding affinity and potency to activate ER with phyto- and xenoestrogens. 4-MBC showed lower estrogenic potency than genistein, coumestrol, resveratrol, bisphenol A and also camphor. Analysis of a potential metabolic activation of 4-MBC that could account for 4-MBC's more distinct estrogenic effects observed in vivo revealed that no estrogenic metabolites of 4-MBC are formed in primary rat or human hepatocytes. In conclusion, we were able to show that 4-MBC is able to induce ERα and ERβ activity. However, for a hazard assessment of 4-MBC's estrogenic effects, the very high doses of 4-MBC required to elicit the reported effects, its anti-estrogenic properties as well as its low estrogenic potency compared to phytoestrogens and camphor has to be taken into account.
Article
Bisphenol A (BPA) is a well-known endocrine disrupter used widely. Despite the potential risk of human exposure to BPA, little information exists concerning maternal and fetal exposure to BPA during pregnancy in Korea. This study purposed to evaluate the correlation between maternal and fetal exposure, and to determine exposure levels to BPA in Korean pregnant women and their fetuses. Maternal blood and umbilical cord blood were collected from 300 subjects, and total BPA levels were measured. Blood BPA concentrations ranged from non-detectable to 66.48 μg/L in pregnant women and from non-detectable to 8.86 μg/L in umbilical cords. Serum BPA levels in most pregnant women were higher than in corresponding fetal umbilical cords and a positive correlation was found between in maternal and fetal BPA concentrations (p < 0.05).
Article
Recently, we reported on in vitro and in vivo estrogenic activity of UV filters and on developmental toxicity of 4-methylbenzylidene (4-MBC) camphor [Schlumpf, M., Cotton, B., Conscience, M., Haller, V., Steinmann, B., Lichtensteiger, W., 2001a. In vitro and in vivo estrogenicity of UV screens. Environ. Health Perspect. 109, 239; Schlumpf, M., Berger, L., Cotton, B., Conscience-Egli, M., Durrer, S., Fleischmann, I., Haller, V., Maerkel, K., Lichtensteiger, W., 2001b. Estrogen active UV screens. SÖFW-J. 7, 10]. 4-MBC (7, 24, 47mg/(kgday)) was administered in chow to long Evans rats from 10 weeks before mating of the parent (F0) generation until adulthood of the F1 generation. Peripheral reproductive organs and central nervous system were studied in adult offspring. mRNA expression of progesterone receptor (PR), an estrogen-regulated gene, was investigated in medial preoptic area (MPO) and ventromedial hypothalamic nucleus (VMH) by real-time RT-PCR. We analyzed intact 12-week-old male and female offspring under steady state conditions and adult gonadectomized offspring 6h after a single s.c. injection of estradiol-17β (E2) (10 or 50μg/kg) in order to assess estrogen sensitivity. At steady state conditions we observed significantly higher PR mRNA expression in VMH of control females versus control males. 4-MBC exposed females exhibited a decrease in PR mRNA to levels of control males. The increase in PR mRNA in response to E2 was higher in VMH of males of both 4-MBC groups as compared to control males. PR mRNA levels were similar in MPO of control males and females. Developmental 4-MBC exposure increased PR mRNA levels in male MPO, but did not significantly change female levels. The acute response to the lower E2 dose was decreased in MPO of 4-MBC-exposed males, whereas females of the 7mg/kg dose group exhibited an increased reaction to 50μg/kg of E2. Our data indicate that developmental exposure to endocrine active chemicals such as the UV filter 4-MBC can interfere with sexually dimorphic gene expression in brain in a sex- and region-specific manner.
Article
Regular sunscreen use prevents cutaneous squamous cell carcinoma long term, but the effect on melanoma is highly controversial. We evaluated whether long-term application of sunscreen decreases risk of cutaneous melanoma. Participants and In 1992, 1,621 randomly selected residents of Nambour, a township in Queensland, Australia, age 25 to 75 years, were randomly assigned to daily or discretionary sunscreen application to head and arms in combination with 30 mg beta carotene or placebo supplements until 1996. Participants were observed until 2006 with questionnaires and/or through pathology laboratories and the cancer registry to ascertain primary melanoma occurrence. Ten years after trial cessation, 11 new primary melanomas had been identified in the daily sunscreen group, and 22 had been identified in the discretionary group, which represented a reduction of the observed rate in those randomly assigned to daily sunscreen use (hazard ratio [HR], 0.50; 95% CI, 0.24 to 1.02; P = .051). The reduction in invasive melanomas was substantial (n = 3 in active v 11 in control group; HR, 0.27; 95% CI, 0.08 to 0.97) compared with that for preinvasive melanomas (HR, 0.73; 95% CI, 0.29 to 1.81). Melanoma may be preventable by regular sunscreen use in adults.
Article
Octyl Methoxycinnamate (OMC) is a frequently used UV-filter in sunscreens and other cosmetics. The aim of the present study was to address the potential endocrine disrupting properties of OMC, and to investigate how OMC induced changes in thyroid hormone levels would be related to the neurological development of treated offspring. Groups of 14-18 pregnant Wistar rats were dosed with 0, 500, 750 or 1000 mg OMC/kg bw/day during gestation and lactation. Serum thyroxine (T(4)), testosterone, estradiol and progesterone levels were measured in dams and offspring. Anogenital distance, nipple retention, postnatal growth and timing of sexual maturation were assessed. On postnatal day 16, gene expression in prostate and testes, and weight and histopathology of the thyroid gland, liver, adrenals, prostate, testes, epididymis and ovaries were measured. After weaning, offspring were evaluated in a battery of behavioral and neurophysiological tests, including tests of activity, startle response, cognitive and auditory function. In adult animals, reproductive organ weights and semen quality were investigated. Thyroxine (T(4)) levels showed a very marked decrease during the dosing period in all dosed dams, but were less severely affected in the offspring. On postnatal day 16, high dose male offspring showed reduced relative prostate and testis weights, and a dose-dependent decrease in testosterone levels. In OMC exposed female offspring, motor activity levels were decreased, while low and high dose males showed improved spatial learning abilities. The observed behavioral changes were probably not mediated solely by early T(4) deficiencies, as the observed effects differed from those seen in other studies of developmental hypothyroxinemia. At eight months of age, sperm counts were reduced in all three OMC-dosed groups, and prostate weights were reduced in the highest dose group. Taken together, these results indicate that perinatal OMC-exposure can affect both the reproductive and neurological development of rat offspring, which may be a cause of concern, as humans are systematically exposed to the compound through usage of sunscreens and other cosmetics.
Article
In order to assess potential risks of exposure to environmental chemicals, more information on concomitant exposure to different chemicals is needed. We present data on chemicals in human milk of a cohort study (2004, 2005, 2006) of 54 mother/child pairs, where for the first time, cosmetic UV filters, synthetic musks, parabens and phthalate metabolites were analyzed in the same sample along with persistent organochlor pollutants (POPs), i.e., organochlor pesticides and metabolites, polybrominated diphenylethers and polychlorinated biphenyls (PCBs). The two groups of chemicals exhibited different exposure patterns. Six out of seven PCB congeners and a majority of pesticides were present in all milk samples, with significant correlations between certain PCB congener and pesticide levels, whereas the cosmetic-derived compounds, UV filters, parabens and synthetic musks, exhibited a more variable exposure pattern with inter-individual differences. UV filters were present in 85.2% of milk samples, in the range of PCB levels. Comparison with a questionnaire revealed a significant correlation between use of products containing UV filters and their presence in milk for two frequently used and detected UV filters, 4-methylbenzylidene camphor and octocrylene, and for the whole group of UV filters. Concentrations of PCBs and organochlor pesticides were within ranges seen in Western and Southern European countries. For several POPs, mean and/or maximum daily intake calculated from individual concentrations was above recent US EPA reference dose values. Our data emphasize the need for analyses of complex mixtures to obtain more information on inter-individual and temporal variability of human exposure to different types of chemicals.
Article
The developing female brain represents a potential target for estrogenic environmental chemicals because it depends on estrogen but is exposed to low endogenous estrogen levels, thus facilitating competition by exogenous estrogen receptor (ER) agonists. We investigated effects of two estrogenic UV filters, 4-methylbenzylidene camphor (4-MBC) and 3-benzylidene camphor (3-BC). 4-MBC has been detected in human milk, indicating potential exposure of fetus and infant. The two chemicals were administered in chow to rats of the parent generation before mating, during pregnancy and lactation, and to their offspring until adulthood. Female sexual behavior was recorded on videotape in adult female offspring on proestrus evening at the beginning of the dark phase. 4-MBC (7 and 24mg/kg bw/day) and 3-BC (2.4 and 7mg/kg bw/day) reduced proceptive behavior (jump and ear wiggling) and receptive behavior (lordosis quotient), and increased rejection behavior towards the male. Estrous cycles were not affected by 4-MBC but disturbed by 3-BC. mRNAs encoding for genes involved in female sexual behavior, ERalpha, ERbeta, progesterone receptor (PR) and steroid receptor coactivator-1 (SRC-1), were measured by real-time RT-PCR in ventromedial hypothalamic nucleus (VMH) and medial preoptic area of adult male and female offspring (studied in diestrus) after pre- and postnatal exposure to 3-BC (0.24, 0.7, 2.4 and 7mg/kg bw/day). Gene expression was affected in a sex- and region-specific manner. PR mRNA in female VMH was reduced to male levels at dose levels of 2.4 and 7mg/kg bw/day 3-BC. Our data demonstrate that female sexual behavior represents a sensitive target of endocrine disrupters and point to an involvement of PR in VMH.
Article
The use of sunscreens on the skin can prevent sunburn but whether long-term use can prevent skin cancer is not known. Also, there is evidence that oral betacarotene supplementation lowers skin-cancer rates in animals, but there is limited evidence of its effect in human beings. In a community-based randomised trial with a 2 by 2 factorial design, individuals were assigned to four treatment groups: daily application of a sun protection factor 15-plus sunscreen to the head, neck, arms, and hands, and betacarotene supplementation (30 mg per day); sunscreen plus placebo tablets; betacarotene only; or placebo only. Participants were 1621 residents of Nambour in southeast Queensland, Australia. The endpoints after 4.5 years of follow-up were the incidence of basal-cell and squamous-cell carcinomas both in terms of people treated for newly diagnosed disease and in terms of the numbers of tumours that occurred. Analysis of the effect of sunscreen was based only on skin cancers that developed on sites of daily application. All analyses were by intention to treat. 1383 participants underwent full skin examination by a dermatologist in the follow-up period. 250 of them developed 758 new skin cancers during the follow-up period. There were no significant differences in the incidence of first new skin cancers between groups randomly assigned daily sunscreen and no daily sunscreen (basal-cell carcinoma 2588 vs 2509 per 100,000; rate ratio 1.03 [95% CI 0.73-1.46]; squamous-cell carcinoma 876 vs 996 per 100,000; rate ratio 0.88 [0.50-1.56]). Similarly, there was no significant difference between the betacarotene and placebo groups in incidence of either cancer (basal-cell carcinoma 3954 vs 3806 per 100,000; 1.04 [0.73-1.27]; squamous-cell carcinoma 1508 vs 1146 per 100,000; 1.35 [0.84-2.19]). In terms of the number of tumours, there was no effect on incidence of basal-cell carcinoma by sunscreen use or by betacarotene but the incidence of squamous-cell carcinoma was significantly lower in the sunscreen group than in the no daily sunscreen group (1115 vs 1832 per 100,000; 0.61 [0.46-0.81]). There was no harmful effect of daily use of sunscreen in this medium-term study. Cutaneous squamous-cell carcinoma, but not basal-cell carcinoma seems to be amenable to prevention through the routine use of sunscreen by adults for 4.5 years. There was no beneficial or harmful effect on the rates of either type of skin cancer, as a result of betacarotene supplementation.
Article
The incidence and mortality rates of melanoma have risen for many decades in the United States. Increased exposure to ultraviolet (UV) radiation is generally considered to be responsible. Sunburns, a measure of excess sun exposure, have been identified as a risk factor for the development of melanoma. Because sunburns are primarily due to UVB (280-320 nm) radiation, UVB has been implicated as a potential contributing factor to the pathogenesis of melanoma. The adverse role of UVA (320-400 nm) in this regard is less well studied, and currently there is a great deal of controversy regarding the relationship between UVA exposure and the development of melanoma. This article reviews evidence in the English-language literature that surrounds the controversy concerning a possible role for UVA in the origin of melanoma. Our search found that UVA causes DNA damage via photosensitized reactions that result in the production of oxygen radical species. UVA can induce mutations in various cultured cell lines. Furthermore, in two animal models, the hybrid Xiphophorus fish and the opossum (Mondelphis domestica), melanomas and melanoma precursors can be induced with UVA. UVA radiation has been reported to produce immunosuppression in laboratory animals and in humans. Some epidemiologic studies have reported an increase in melanomas in users of sunbeds and sunscreens and in patients exposed to psoralen and UVA (PUVA) therapy. There is basic scientific evidence of the harmful effects of UVA on DNA, cells and animals. Collectively, these data suggest a potential role for UVA in the pathogenesis of melanoma. To date evidence from epidemiologic studies and clinical observations are inconclusive but seem to be consistent with this hypothesis. Additional research on the possible role of UVA in the pathogenesis of melanoma is required.
Article
2-Hydroxy-4-methoxybenzophenone (HMB) occurs naturally in flower pigments and is synthesized for use in sunscreens, as a UV stabilizer in various cosmetic products, and in plastic surface coatings and polymers. Toxicity studies of HMB were performed in F344/N rats and B6C3F1 mice, by administering HMB in feed and by topical application, in studies of 2 weeks' (5 animals/sex, dose and species) and 13 weeks' (10 animals/sex, dose and species) duration. Assessments included hematology, clinical chemistry, urinalysis, reproductive toxicity, and histopathologic evaluations. In both 2- and 13-week dosed feed studies, rats received diets containing 0, 3125, 6250, 12500, 25000, or 50000 ppm HMB. One high-dose female rat died during the 2-week study. Body weight gains of high-dose male and female rats were reduced in the 13-week study. Liver and kidney weights were increased in dosed rats in both studies. In the 2-week studies, enlarged livers were associated with a marked hepatocyte cytoplasmic vacuolization in rats receiving diets containing concentrations of 6250 ppm HMB or higher; renal lesions, consisting of dilated tubules and regeneration of tubular epithelial cells, were found primarily in high-dose rats. In the 13-week studies, kidney lesions progressed to include papillary degeneration, or necrosis, and inflammation, while the liver lesion appeared to regress; liver enzymes in serum remained elevated. Rats receiving a diet with 50000 ppm HMB showed markedly lower epididymal sperm density and an increase in the length of the estrous cycle at the end of the 13-week studies. In 2-week dermal studies, rats received topical applications of 1.25 to 20 mg of HMB in an acetone or lotion vehicle. The only effects noted were small and variable increases in liver and kidney weights, reaching statistical significance primarily in the higher dose groups. In 13-week studies, rats received topical doses from 12.5 to 200 mg/kg HMB in acetone. Kidney weights were elevated in dosed groups of female rats. No other findings were attributed to HMB treatment. In 2- and 13-week dosed feed studies, mice received feed containing 0, 3125, 6250, 12500, 25000, or 50000 ppm HMB. A dose- related increase in liver weight associated with hepatocyte cytoplasmic vacuolization was the only finding in mice in the 2- week studies. Decreased body weight gains were dose-related in mice in the 13-week studies; mild increases in liver weights were seen in dosed mice of both sexes. Kidney weights were increased variably in dosed females. Microscopic lesions were noted only in the kidneys of males receiving 50000 ppm HMB; these included eosinophilic protein casts in dilated renal tubules and a mild inflammation associated with the dilated tubules. Mice in the highest dose group exhibited a decrease in epididymal sperm density and an increase in length of the estrous cycle. In 2-week dermal studies, mice received topical applications from 0.5 to 8 mg HMB in an acetone or lotion vehicle. The only effects noted were minimal, variable increases in liver and kidney weights, primarily in the higher dose groups. In 13-week studies, mice received topical doses of 22.75 to 364 mg/kg in acetone. Kidney weights were increased variably in dosed male mice. Epididymal sperm density was decreased at all 3 dose levels evaluated (22.75, 91, and 200 mg/kg). The genetic toxicity of HMB also was evaluated in mutagenicity studies with Salmonella typhimurium, in cytogenetic studies with Chinese hamster ovary (CHO) cells, and by evaluation of micronucleated erythrocytes in peripheral blood smears from mice in the 13-week studies. HMB was weakly mutagenic in Salmonella with metabolic activation, and induced sister-chromatid exchanges and chromosomal aberrations in CHO cells in the presence of a metabolic activation system. There was no increase in the frequency of micronucleated erythrocytes in the blood of mice receiving HMB. In summary, HMB produced generally similar effects following topical and oral administration to rats and mice. Consistent findings included decreases in epididymal sperm density, lengthened estrous cycle, and increased liver and kidney weights. Mice in the dosed feed studies exhibited microscopic changes in the kidneys, comprising tubular dilatation with eosinophilic protein casts. Dilatation, tubular regeneration, papillary degeneration, and inflammation were noted in the kidneys of rats; and liver lesions consisting of an apparently reversible hepatocyte cytoplasmic vacuolization occurred in both rats and mice. A no-observed-adverse-effect level (NOAEL) for microscopic lesions was 6250 ppm HMB in the diet for rats and mice. A NOAEL was not reached for decreased epididymal sperm density in the 13- week dermal study in mice (<23 mg/kg/day). Synonyms: Oxybenzone; 4-Methoxy-2-hydroxy-benzophenone; Cyasorb UV; Uvinul M 40; (2-hydroxy-4-methoxyphenyl)phenyl-methanone; NSC-7778; Spectra-sorb UV; Syntase 62; UF 3; USAF CY-9; NCI-C60957.
Article
Benzophenone-3 (BZ-3) is a commonly used, chemical UV-absorber. It has been used for many years to protect against UV-radiation. Previous studies have shown that BZ-3 penetrates the skin, and it can be found in urine, faeces, and blood. In this study we examined the percutaneous absorption of BZ-3. The amount of BZ-3 absorbed was measured in urine, as experimental studies in the rat have shown that urine is the major route of excretion. Eleven volunteers applied the recommended amount of a commercially available sunscreen and urine samples were collected during a 48-h period after application. The average total amount excreted was 11 mg, median 9.8 mg, which is approximately 0.4% of the applied amount of BZ-3. Some of the volunteers still excreted BZ-3 48 h after application. It is evident that BZ-3 undergoes conjugation in the body to make it water soluble. However, we do not know at what age the ability to conjugate is fully developed, and therefore for children physical filters such as titanium dioxide and/or zinc oxide might still be considered a more appropriate sunscreen component.
Article
Chemical UV-filters are used in sun protection products and various kinds of cosmetics. The lipophilic chemical UV-filter 3-benzylidene camphor was investigated for its capability to cause vitellogenin induction, possibly via oestrogen receptor binding, in a well-established in vivo fish assay (juvenile rainbow trout, Oncorhynchus mykiss, vitellogenin ELISA). A clear relationship was demonstrated between the dose of injected 3-benzylidene camphor and the concentration of plasma vitellogenin with a 105-times induction from 68 mg 3-benzylidene camphor /kg/injection and above compared to the control vitellogenin level. The relationship between the injected dose of 3-benzylidene camphor and the percent of responding fish (vitellogenin) was evaluated by logistic regression analysis and effective dose-values (ED-values) were determined. ED10, ED50 and ED90 of 3-benzylid