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Can Oxybenzone Cause Hirschsprung’s Disease?
Abstract
Oxybenzone is a ultraviolet (UV) absorber used in 70% of sunscreen products, is a recognized endocrine disrupting chemical (EDC) and is small enough to pass through skin and placenta barriers. Numerous studies have identified this chemical in the urine/blood of pregnant women as well as in fetal and umbilical cord blood. A recent study demonstrated that women with medium to high levels of oxybenzone in their urine was associated with giving birth to neonates with Hirschsprung's Disease (HSCR). Testing in human cell lines confirmed that low levels of oxybenzone has the potential to disrupt cell migration and function in a manner similar to what is associated with HSCR. Analysis of human exposure levels to oxybenzone from sunscreen use, under normal conditions, demonstrates that enough chemical can cross into the mother's blood making it available to the fetus at high enough levels that can indeed inhibit migration of neural crest cells during critical embryonic development.
... Of them, Benzophenone-3 (also known as Oxybenzone 3, BP-3) is one of the most widely used UV filters, showing weak estrogen and strong anti-androgenic effects [15]. Also, it is small enough to pass through skin and placenta barriers, and it has been detected in the urine/blood of pregnant women as well as in fetal and umbilical cord blood [48]. Besides, BP-3 has good permeability through the BBB [18]. ...
... Maternal exposure to BP-3 was also epidemiologically associated to a higher Hirschsprung disease incidence in children, as higher urine concentrations correlated with higher HSCR [15]. Aside from that, under normal conditions BP-3 can travel to maternal blood reaching the fetus at high enough levels to inhibit migration of neural crest cells during critical embryonic development [15,48]. ...
... While there are unknowns about the impact of nanoparticles have on the body, the small size of these substances suggest that it allows for deeper skin penetration [100]. In addition, oxybenzones like BP-3, usually present in sunblockers, have been already associated to congenital enteropathies like Hirschsrpung disease [15,48]. Given these factors together, it is important that the neurotoxic effects of sunscreen products should be considered more closely in the future. ...
The inclusion of various chemical substances in personal care products (PCPs) and cosmetic formulations can be associated with disruption and damage to the nervous system. Microplastics, benzophenones, parabens, phthalates and metals are among the most common chemical substances found in cosmetics that have been shown to induce neurotoxic mechanisms. Although cosmetic neurotoxin exposure is believed to be minimal, different exposure scenarios of cosmetics suggest that these neurotoxins remain a threat. Special attention should be paid to early exposure in the first gestation weeks, when critical processes, like the migration and proliferation of the neural crest derived cells start to form the ENS. Importantly, cosmetic’s neurotoxins can cross the placenta barrier and so affect the future embryo, but are also secreted in the breast milk, so that babies remain exposed for longer periods, even after birth. In this review we explore how neurotoxins contained in cosmetic and PCPs may have a role in the pathogenesis of various neurodevelopment disorders and neurodegenerative diseases, and therefore also in congenital enteric aganglionosis as well as in postnatal motility disorders. Understanding the mechanisms of these chemicals used in cosmetic formulations and their role in neurotoxicity is crucial to determining the safety of use for cosmetic products during pregnancy.
... Since oxybenzone and octinoxate exhibit endocrine disrupting properties, any soluble organic UV filter like avobenzone and octocrylene is a potential EDC, like the way the structural analogues dichlorodiphenyltrichloroethane (DDT), Bisphenyl A (BPA), phthalates, and others have similar actions on humans and lower species. • We present only a few of the numerous contemporary reviews or reports that detail this toxic assault on humans and wildlife [27][28][29][30][31]. Many earlier studies suggest that generally, reproductive organs and the central nervous system represent sensitive targets for developmental effects of endocrine active xenobiotics [25,26]. ...
... Many earlier studies suggest that generally, reproductive organs and the central nervous system represent sensitive targets for developmental effects of endocrine active xenobiotics [25,26]. Contemporary reviews describe widespread effects in human and wildlife from soluble UV filters and their structural analogues like DDT, BPA, and other EDCs [27][28][29][30][31]. A review of 85 scientific papers in humans and lower species concluded that aromatic hydrocarbon UV filters are generally involved in the disruption of the hypothalamic-pituitary-gonadal system [27]. ...
... More recent studies confirm that soluble UV hydrocarbon filters, and other phenols including the preservative parabens, affect levels of virtually every sex hormone, pituitary hormones, thyroid hormones and certain growth factors in both pregnant and non-pregnant women [27,28]. Contemporary reports show the wide spectrum of potential adverse effects in pregnancymiscarriage, fetal growth retardation, preeclampsia, newborn congenital defects like spina bifida and Hirschsprung's' disease [31,32,33]. Particularly worrisome are the subtle effects on neurohormonal programing and the abnormalities in all endocrine and metabolic systems showing up in later life. ...
Review and analysis of the science related to the toxicity of Soluble Organic UV Filters (SOUVF) and the data from global skin cancer statistics and published papers that provide evidence that they do not prevent skin cancer in the general population.
They are all bioavailable to human cells - even those in the fetus and brain. Their potential and proven toxicity are replete in the published literature. We work to advance the imperative that they are contraindicated for use in anyone, particularly in expectant or nursing mothers, young or adolescent children, and couples trying to conceive. We advocate that their continued use is arguably a violation of Medicine's First Rule ( Primum Non Nocere or First Do No Harm) and The Precautionary Principle. For no Benefit- they have polluted humans and the entire global environment
... It is remarkable that UVFs have been found in breast milk [38,47], placental tissues [48], and urine [49,50]. During pregnancy an increased incidence of neonatal dysfunction (Hirschprung's disease) due to exposure to BP-3 has been observed [51,52]. In several studies, possible correlations with uterine leiomyoma formation and increased mobility of breast and lung cancer cells have been found [53][54][55][56]. ...
... UVFs (especially BP-3, avobenzone, OC, amiloxate, and PABA) seem to cause various forms of irritant dermatitis as well as allergic contact and/or photo-allergens [52,[57][58][59]. ...
... studies, possible correlations with uterine leiomyoma formation and increased mobility of breast and lung cancer cells have been found [53][54][55][56]. UVFs (especially BP-3, avobenzone, OC, amiloxate, and PABA) seem to cause various forms of irritant dermatitis as well as allergic contact and/or photo-allergens [52,[57][58][59]. ...
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.
... Those who live in a sunny location and use sunscreen with oxybenzone daily all year round may have a higher risk factor than someone who uses it less frequently (e.g., on vacation). Also, it was reported that babies that are exposed to an endocrine disruptor like oxybenzone can face problems including poor sleep, adult attention-deficit/hyperactivity disorder (ADHD), and an increase in certain illnesses like bronchitis and sinusitis [59]. ...
... Also, another suggestion from studies is to recommend eating a diet high in fruits and vegetables (aim for nine to twelve cups daily). After discussing with the doctor, also consider taking a B complex supplement and extra folate which may help decrease the flow of toxins to the fetus [59]. ...
This review aimed to identify the risks of cosmetics during the sensitive period of pregnancy. Pregnancy causes many hormonal changes and skin issues, such as red stretch marks, cellulite, and more. These aesthetic concerns can impact both the appearance and health of the pregnant woman. Cosmetics and aesthetic treatments can help improve these problems and positively affect the mental well-being of these women. However, the lack of clinical trials regarding the safety of such treatments during pregnancy has led to the recommendation of only the mildest aesthetic applications. Additionally, professional aestheticians and dermatologists who provide cosmetics and other aesthetic treatments (e.g., laser, radiofrequency (RF), ultrasound) during pregnancy face challenging and sometimes adverse working conditions. They should be treated with respect for their situation, with careful consideration of all the peculiarities associated with pregnancy. Further research and additional recorded data are crucial for better understanding the use of cosmetics and aesthetic treatments during pregnancy.
... Of them, Benzophenone-3 (BP-3, also known as Oxybenzone 3) is one of the most widely used UV filters, showing weak estrogen and strong anti-androgenic effects [19]. Also, it is small enough to pass through skin and placental barriers, and it has been detected in the urine/blood of pregnant women as well as in fetal and umbilical cord blood [52]. In addition, BP-3 has good permeability through the BBB [22]. ...
... Maternal exposure to BP-3 was also epidemiologically associated to a higher HSCR incidence in children, as higher urine concentrations correlated with higher HSCR [19]. Aside from that, under normal conditions BP-3 can travel to the maternal blood reaching the fetus at high enough levels to inhibit migration of neural crest cells during critical embryonic development [19,52]. ...
Pregnancy is a particularly vulnerable period for the growing fetus, when exposure to toxic agents, especially in the early phases, can decisively harm embryo development and compromise the future health of the newborn. The inclusion of various chemical substances in personal care products (PCPs) and cosmetic formulations can be associated with disruption and damage to the nervous system. Microplastics, benzophenones, parabens, phthalates and metals are among the most common chemical substances found in cosmetics that have been shown to induce neurotoxic mechanisms. Although cosmetic neurotoxin exposure is believed to be minimal, different exposure scenarios of cosmetics suggest that these neurotoxins remain a threat. Special attention should be paid to early exposure in the first weeks of gestation, when critical processes, like the migration and proliferation of the neural crest derived cells, start to form the ENS. Importantly, cosmetic neurotoxins can cross the placental barrier and affect the future embryo, but they are also secreted in breast milk, so babies remain exposed for longer periods, even after birth. In this review, we explore how neurotoxins contained in cosmetics and PCPs may have a role in the pathogenesis of various neurodevelopmental disorders and neurodegenerative diseases and, therefore, also in congenital enteric aganglionosis as well as in postnatal motility disorders. Understanding the mechanisms of these chemicals used in cosmetic formulations and their role in neurotoxicity is crucial to determining the safety of use for cosmetic products during pregnancy.
... [11][12][13] In humans, it has been associated with photo contact allergy reactions, considered as a potential endocrine disruptor, and has been linked to Hirschsprung's disease. [14,15] Nevertheless, many health organizations, such as the FDA and the American Academy of Dermatology, continue to deem oxybenzone safe for use. The protective benefits of oxybenzone against skin cancer generally outweigh the concerns about its potential toxicity. ...
A one‐pot methodology for the tandem acylation and oxidative aromatization of vinylogous thioesters to 2‐acyl‐5‐(alkyl/arylthio) phenols is presented. Initially, cyclohexane‐1,3‐diones were converted to vinylogous thioesters through FeCl3‐mediated thioenolization. This was followed by LiTMP‐mediated acylation and DDQ‐mediated aromatization, which resulted in the synthesis of sulphur derived oxybenzone analogs. Notably, replacing the methoxy group of oxybenzone with alkylthioxy or arylthioxy groups significantly enhanced UV absorption properties. The newly synthesized oxybenzone analogs exhibited superior UV absorption, effectively covering the entire UVA and UVB regions spanning from 240 to 440 nm. Furthermore, toxicity studies conducted on HEK293T cells demonstrated that many of the thio‐analogs exhibit lower toxicity compared to parent oxybenzone, suggests potential for safer and more effective UV protection formulas.
... At present, there is a lot of interest among consumers in sunscreens' safety during pregnancy and nursing [74], and there are no strict recommendations for females at these stages in life to use specific UV filters [75]. There is, however, some evidence (based mainly on in vitro studies or animal data) that certain sunscreens (including BP-3, OCR, BMDM, EHMC, MBC, OS and HMS) should be avoided by pregnant and breast-feeding women [76][77][78], and new facts contraindicating the use of these substances during pregnancy are being discovered-for example, there are some early reports that BP-3 may be associated with Hirschsprung's disease [76,79,80]. It seems that there are several suscreens in the studied group that are, potentially, very good placenta penetrators and, at the same time, likely ligands for GST and/or NAT2 enzymes, which confirms the notion that, during pregnancy, organic sunscreens should be used with caution, and new evidence against their excessive use is likely to appear. ...
One of the functions of placenta is to protect the fetus against harmful xenobiotics. Protective mechanisms of placenta are based on enzymes, e.g., antioxidant enzymes from the glutathione S-transferases group (GST) or human N-acetyltransferase 2 (NAT2). Many organic sunscreens are known to cross biological barriers—they are detected in mother’s milk, semen, umbilical cord blood or placental tissues. Some organic sunscreens are able to cross the placenta and to interfere with fetal development; they are known or suspected endocrine disruptors or neurotoxins. In this study, 16 organic sunscreens were investigated in the context of their placenta permeability and interactions with gluthatione S-transferase and human N-acetyltransferase 2 enzymes present in the human placenta. Binary permeability models based on discriminant analysis and artificial neural networks proved that the majority of studied compounds are likely to cross the placenta by passive diffusion. Molecular docking analysis suggested that some sunscreens show stronger affinity for glutathione S-transferase and human N-acetyltransferase 2 that native ligands (glutathione and Coenzyme A for GST and NAT2, respectively)—it is therefore possible that they are able to reduce the enzyme’s protective activity. It was established that sunscreens bind to the studied enzymes mainly by alkyl, hydrogen bonds, van der Waals, π-π, π-alkyl and π-sulfur interactions. To conclude, sunscreens may become stressors affecting humans by different mechanisms and at different stages of development.
... 9 A direct association has recently been found between OXB and Hirschsprung's disease (a neonatal intestinal abnormality derived from the failed migration of enteric neural crest cells) in infants under normal use conditions of sunscreen products by expecting mothers. 11 Although OXB permeation is not known to present any acute danger to adults, chronic effects and pediatric toxicities are still not fully understood. Furthermore, although OXB has recently been Fig. 1 Chemical structure of (a) oxybenzone; (b) C-methylresorcin [4] arene. ...
Oxybenzone (OXB), a very widely used sunscreen ingredient has the potential to block both UVA and UVB but can penetrate through skin. Studies have revealed its presence in the blood and urine of most humans, which may lead to long-term health effects. As the confined cavities of macrocycles can alter the physical and chemical properties of encapsulated guests, in this study, we investigated the formation of host–guest complexes between C-methylresorcin[4]arene and OXB. Combined experimental (NMR spectroscopy, UV/vis absorption, and fluorescence spectroscopy) and theoretical investigation confirmed the formation of a weak host–guest complex that had a 1 : 1 stoichiometry. Furthermore, skin permeation testing revealed that complexation by C-methylresorcin[4]arene significantly reduced the skin permeation of OXB which can potentially limit the harmful effects of this organic sunscreen.
... Oxybenzone induces toxicity through a variety of distinct mechanisms, ranging from endocrine disruption and genotoxicity to pathological changes in homeostasis and development (Watanabe et al., 2015;DiNardo and Downs, 2019;Santovito et al., 2019;Majhi et al., 2020;Li et al., 2023a;Zhang et al., 2023). Several studies have demonstrated that oxybenzone is an acute photo-toxicant, and that UV light exacerbates its toxicity in a broad range of species, including bacteria, a broad range of algae and plants, cnidarians and arthropods, as well as human skin (Kim et al., 2018;Lozano et al., 2020;Vuckovic et al., 2022;Yang et al., 2023). ...
Oxybenzone, an environmental pollutant affecting both agriculture and aquatic ecological integrity, has been demonstrated to act as a physiological and metabolic inhibitor on plants, animals, and microorganisms. Research on oxybenzone in higher plants has focused on the above-ground anatomy (leaves), while research on the under-ground parts (roots) has been neglected. In this study, the changes in plant root protein expression and metabolic pathways under oxybenzone treatment were explored through a combined proteomics and metabolomics analysis. A total of 506 differential proteins and 96 differential metabolites were identified, which were mainly distributed in critical pathways such as those for carbon (C) and nitrogen (N) metabolism, lipid metabolism, and antioxidation. Bioinformatics analysis shows that oxybenzone toxicity is predominantly reflected in alterations to root respiratory homeostasis and the manifestation of damaging reactive oxygen species (ROS) and membrane lipid peroxidation, changes to disease resistance-associated proteins, changes to normal C-flow distribution, and the inhibition of cell absorption and utilization of N sources. Plants respond to oxybenzone stress mainly by reconfiguring the mitochondrial electron-transport-chain to bypass oxidative-damage components; improving the efficiency of the antioxidant system to remove excessively accumulated ROS; promoting the detoxification of harmful membrane lipid peroxides; increasing osmotic adjustment substance (such as proline and raffinose) accumulation; adjusting C flow distribution to produce more nicotinamide adenine dinucleotide phosphate (NADPH) for the glutathione cycle; and accumulating free amino acids to increase plant stress tolerant. Our results are the first to map the changes in the physiological and metabolic regulatory network of higher plant roots under oxybenzone stress.
... Fertilization/spawning events may not be the only critical facet of an organism's life cycle. In corals, fish and mammals, environmentally relevant oxybenzone-exposure in utero or during embryonic development may result in disease, ranging from morbid deformities and bleaching in coral planulae to Hirschsprung Disease from exposure during the first trimester in mammals and abnormal development of the nervous system in fish (Downs et al., 2016;Huo et al., 2016;DiNardo and Downs, 2019;Wang et al., 2021;Han et al., 2022). ...
In 2019, sands in nearby runoff streams from public beach showers were sampled on three islands in the State of Hawaii and tested for over 18 different petrochemical UV filters. Beach sands that are directly in the plume discharge of beach showers on three of the islands of Hawaii (Maui, Oahu, Hawai’i) were found to be contaminated with a wide array of petrochemical-based UV-filters that are found in sunscreens. Sands from beach showers across all three islands had a mean concentration of 5,619 ng/g of oxybenzone with the highest concentration of 34,518 ng/g of oxybenzone at a beach shower in the Waikiki area of Honolulu. Octocrylene was detected at a majority of the beach shower locations, with a mean concentration of 296.3 ng/g across 13 sampling sites with the highest concentration of 1,075 ng/g at the beach shower in Waikiki. Avobenzone, octinoxate, 4-methylbenzylidene camphor and benzophenone-2 were detected, as well as breakdown products of oxybenzone, including benzophenone-1, 2,2'-dihydroxy-4-methoxybenzophenone, and 4-hydroxybenzophenone. Dioxybenzone (DHMB) presented the highest concentration in water (75.4 ng/mL), whereas octocrylene was detected in all water samples. Some of these same target analytes were detected in water samples on coral reefs that are adjacent to the beach showers. Risk assessments for both sand and water samples at a majority of the sampling sites had a Risk Quotient >1, indicating that these chemicals could pose a serious threat to beach zones and coral reef habitats. There are almost a dozen mitigation options that could be employed to quickly reduce contaminant loads associated with discharges from these beach showers, like those currently being employed (post-study sampling and analysis) in the State of Hawaii, including banning the use of sunscreens using petrochemical-based UV filters or educating tourists before they arrive on the beach.
... Work by Wnuk and co-workers has elucidated the neuropathological pathways of oxybenzone exposure, generating several distinct pathways of neuronal cell death, as well as inducing epigenetic changes in affected neurons (Pomierny et al., 2019;Wnuk et al., 2018aWnuk et al., , 2018bWnuk et al., , 2019Wnuk and Kajta, 2021). Oxybenzone is argued to play a role in Hirschsprung's Disease, exhibiting a neuropathological role similarly described by Wnuk et al. that induces cell death and prevents neuro-stem cell migration during development via modification of cellular signal pathways (DiNardo and Downs, 2019;Huo et al., 2016;Viola and Grant-Kels, 2021;Wang et al., 2021). Recently, oxybenzone was demonstrated to induce alterations in mammary gland morphology and may even promote mammary tumorigenesis at environmentally relevant concentrations (Altamirano et al., 2020;Kariagina et al., 2020;LaPlante et al., 2018;Majhi et al., 2020). ...
A preponderance of recent evidence indicates that oxybenzone and other personal-care product chemicals threaten the biota inhabiting various ecological niches. What is understudied is the ecotoxicological impact of oxybenzone, a UV filter in sunscreens and anti-aging products, to terrestrial/soil organisms that are keystone species in these habitats. In the present study, acute exposure (14-day) to oxybenzone resulted in earthworm mortality (LC 50 of 364 mg/kg) and growth rate inhibition. Environmentally relevant concentration of oxy-benzone (3.64, 7.28 and 36.4 mg/kg) at exposures of 7-day, 14-day, 28-day induced oxidative stress and neurotoxicity followed by perturbations in reproduction processes and changes in vital organs. Decreased levels of superoxide dismutase (SOD) and catalase (CAT) activity were statistically lower than controls (p < 0.05) on day 14 for all three concentrations, while glutathione-s-transferase (GST) activity was significantly elevated from controls on days 7 and 14. On day 28, SOD and CAT activities were either not significantly different from the control or were higher, demonstrating a temporal multiphasic response of anti-oxidant enzymes. GST activity on day 28 was significantly reduced compared to controls. Acetylcholinesterase levels across the three-time points exhibited a complicated behaviour, with every exposure concentration being significantly different from the control. Chronic exposure negatively influences earthworm health status with elevated biomarker values analysed using IBRv2 index. This, in turn, impacted higher levels of hierarchical organization, significantly impairing reproduction and organismal homeostasis at the histological level and manifesting as decreasing cocoon formation and successful hatching events. Thus, the overall findings demonstrate that oxybenzone is toxic to Eisenia fetida at low-level, long-term exposure. Based on the concentration verification analysis and application of the EPA PestDF tool, oxybenzone undergoes single first-order kinetics degradation in OECD soil with DT50 and DT90 as 8.7-28.9 days, respectively.
... Contemporary reviews show the disruption of endocrine, reproductive, and metabolic systems, leading to a variety of human disorders and cancers [84][85][86]. Some effects from fetal exposure are seen in newborns -spina bifida [91] and Hirschsprung's dis-ease [92,93], others in adolescents -delayed puberty [94,95], and others delayed until adult lifeendometriosis [96,97] and infertility [98], usually serious and often irreversible. ...
Sunscreen application to UV-exposed skin is promoted to prevent skin cancer and sun damage, within a comprehensive photoprotection strategy that also includes sun avoidance and wearing UV protective clothing. The benefits of sunscreen are verified in preventing sunburn but appear to be largely presumptive in skin cancer prevention. Contemporary science establishes UVA as a primary driver of melanoma and photoaging. Consequentially, the traditional UVB-skewed protection of sunscreens provides an intellectual and logical explanation for rising skin cancer rates and, in particular, their failure to protect against melanoma. Better protection could be achieved with more balanced UVB/UVA sunscreens, toward spectral homeostasis protection. Greater balanced protection has another advantage of attenuating fewer UVB rays, which aid synthesis of vitamin D and nitric oxide. Percutaneous absorption of Soluble Organic UV Filters leads to systemic exposure, which becomes the relevant safety consideration. It is minimized by selecting Insoluble UV Filters with low absorption potential from a molecular weight above 500 Da. The filters must also be very hydrophilic, very lipophilic, or consist of particles. The risk-benefit ratio is a medical imperative, more so for cosmetics or sunscreens, since in principle there should be no risk from their use. The production of ideal sunscreens that mimic the effective, balanced UVB/UVA attenuation of textiles and shade is now possible, while maintaining an acceptable therapeutic margin of safety in humans and a favorable ecologic profile. Sunscreens with a favorable risk-benefit ratio and good esthetic properties or other consumer-friendly attributes will improve compliance and may achieve substantial clinical benefits.
... Corals exposed to BP3 are more susceptible to bleaching (Danovaro et al., 2008). Recently, Hawaii and the Pacific island nation Palau have enacted laws to protect marine ecosystems banning the use of BP3 as sunscreen ingredients (DiNardo and Downs, 2019;Republic of Palau, 2018). ...
Benzophenone UV filters (BPs) are a group of contaminants of emerging concern due to their widespread occurrence and adverse effects on aquatic ecosystems. In this study, the transformation of BPs by nitrite sensitized photodegradation was comprehensively investigated. radical dotOH and NO2radical dot generated by nitrite photolysis reacted with BPs, forming hydroxylated and nitrated products, respectively. Kinetic modeling revealed that the steady-state concentrations of NO2radical dot were approximately six orders of magnitude higher than those of radical dotOH in the UV/nitrite process, although the second-order rate constants of NO2radical dot reactions with BPs were six orders of magnitude lower. With the increase in nitrite concentration, BPs degradation was accelerated, and the contribution of NO2radical dot increased as well. At initial nitrite concentration of 10 μM, the contributions of radical dotOH and NO2radical dot to the degradation of 2,4-dihydroxybenzophenone (BP1) were 66.1% and 21.5%, respectively. However, NO2radical dot only contributed a tiny fraction to the degradation of 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (BP4), due to the presence of an electron-withdrawing sulfonate group in the molecule. Natural organic matter (NOM) inhibited the nitrite sensitized degradation of BPs, due to light screening and radical scavenging effects. This study suggests that BPs can be effectively transformed in sunlit waters in the presence of nitrite, leading to nitrated products.
... Moreover, the fish gastrointestinal tract has been suggested to be one of the internal targets of TiO 2 NPs, showing toxic effects related to oxidative stress responses [59,60]. Although there is no information about BP-3 effects in fish intestine, studies in neonates correlated the presence of intestinal abnormalities with the levels of BP-3 in the urine of pregnant women [61,62]. ...
UV filters are potentially harmful to marine organisms. Given their worldwide dissemination and the scarcity of studies on marine fish, we evaluated the toxicity of an organic (oxybenzone) and an inorganic (titanium dioxide nanoparticles) UV filter, individually and in a binary mixture, in the turbot (Scophthalmus maximus). Fish were intraperitoneally injected and a multi-level assessment was carried out 3 and 7 days later. Oxybenzone and titanium dioxide nanoparticles induced mild effects on turbot, both isolated and in mixture. Neither oxidative stress (intestine, liver and kidney) nor neurotoxicity (brain) was found. However, liver metabolic function was altered after 7 days, suggesting the impairment of the aerobic metabolism. An increased motility rate in oxybenzone treatment was the only behavioural alteration (day 7). The intestine and liver were preferentially targeted, while kidney and brain were unaffected. Both infra- and supra-additive interactions were perceived, with a toxicodynamic nature, resulting either in favourable or unfavourable toxicological outcomes, which were markedly dependent on the organ, parameter and post-injection time. The combined exposure to the UV filters did not show a consistent increment in toxicity in comparison with the isolated exposures, which is an ecologically relevant finding providing key information towards the formulation of environmentally safe sunscreen products.
Topical sunscreens and the UV filters in them have achieved mainstream significance in today’s age. Many advances have occurred in sunscreen science, making this space vibrant and exciting. Inorganic filters include titanium dioxide and zinc oxide, with a potential new entrant into the space, cerium salts, in the future. Among chemical sunscreens, bemotrizinol awaits US FDA approval as the first chemical filter to undergo the Maximum Usage Trial (MUsT) process. Newer proprietary filters such as Methoxypropylamino Cyclohexenylidene Ethoxyethylcyanoacetate (MCE) and Phenylene Bis-Diphenyltriazine (Triazorb) and the anticipated HAA-299 filter are all expected to enhance sun protection from the new age sunscreens, by providing more coverage in the UVA region to achieve spectral homeostasis. Further addition of antioxidants and tints, which can further reach into the visible light and the infrared region, may be of great clinical significance to preventing pigmentary conditions in SOC. This chapter gives a comprehensive but simple overview of the UV filters from inorganic filters to chemical filters to just discovered agents with protective properties in the solar spectrum.
Organic UV filters like oxybenzone (BP3) in sunscreens are seawater pollutants suspected to transfer to the atmosphere via sea spray aerosol (SSA). This study examines the photoinitiated degradation of BP3 in artificial and real seawater compared to SSA mimics containing NaCl and 4-benzoylbenzoic acid (4-BBA). We investigated pure, binary, and ternary mixtures of BP3, NaCl, and 4-BBA using solar-simulated light to isolate the effects of salt and photosensitization on BP3 degradation. Results showed significantly faster degradation in the aerosol phase (Jeff,env ≈ 10–3–10–2 s–1 or t1/2 < 10 min) compared to bulk solutions (Jeff,env ≈ 10–6 s–1 or t1/2 > 1 day). The photosensitizer enhanced BP3 photodegradation in both phases more than when mixed with salt or all three components in solutions. BP3 photodegradation was most enhanced by salt in the aerosol phase. High-resolution molecular analysis via Orbitrap LC-MS/MS revealed more acutely toxic compounds (benzophenone, benzoic acid, and benzaldehyde) in irradiated aerosols than in solution, supported by electronic structure and toxicity modeling. These findings highlight that seawater may serve as a reservoir for BP3 and other organic UV filters and that upon transfer into SSA, BP3 rapidly transforms, increasing aerosol toxicity.
This paper provides insights into the occurrence of sunscreen products in the aquatic environment due to their excessive use and their potential damage to aquatic ecosystems. Sunscreens applied on human skin to eliminate the negative effects of ultraviolet (UV) light are mixtures containing not only UV filters, organic and inorganic compounds, but also emulsifiers, gelling agents, sensation enhancers, preservatives, antimicrobial agents, and antioxidants. The growing use of sunscreens, along with the boost of tourism, has led to the detection of these compounds in the environment. Ingredients of sunscreens often pose a threat to water quality, marine environment, aquatic life, even in agriculture, and therefore constitute an emerging risk to environmental and public health. The UV filters presented in water affect marine organisms and aquatic receptors, and can even end up in humans’ bodies via the food chain. Through a literature review, the occurrence of sunscreen ingredients in the aquatic environment was investigated, as well as the possible solutions for mitigation of sunscreen pollution. Mitigation of sunscreen pollution can be achieved through environmental education, the development of environmentally friendly products as well as with effective removal processes in wastewater treatment plants. Well-rounded campaigns can provide information and raise awareness, to motivate consumers to make proper use of products taking environmental concerns into account. The findings of this paper underline the extent and the severity of sunscreen pollution as well as the significance of education as a valuable tool for the mitigation of water pollution. In general, this review offers a comprehensive overview of the subject.
Background/Purpose
Nowadays, there are emerging trends in customized and personalized photoprotection, focusing on the innovative approaches to enhance sun protection efficacy tailored to individual needs.
Methods
We conducted an electronic search of the following databases: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Skin Group Specialised Skin Register, and TESEO. Specific search terms related to personalized photoprotection and the variables of age, genetic predisposition, skin phototype, photodermatosis, and physiological conditions such as pregnancy, as well as lifestyle habits were used.
Results/Conclusion
The article highlights the challenges and opportunities in adopting personalized photoprotection strategies, aiming to promote skin health and prevent the harmful effects of UV radiation in the era of precision medicine.
The use of sunscreens is a fundamental strategy of an effective photoprotection scheme. Currently, several ultraviolet (UV) filters have been questioned for their side effects, mainly those that harm the environment. Therefore, there is a demand to find compounds with photoprotective properties. In this regard, natural products have traditionally been a promising source of compounds with diverse biological activities, including those related to photoprotection. Recently, natural microbial products have shown very promising opportunities supported by biotechnological advances, including those possibilities opened by computer-aided tools. Under this scenario, several studies have recognized the great potential of the phylum Actinomycetota as a source of compounds with photoprotective properties. This review examines how solar radiation induces skin photodamage, explores existing photoprotection strategies, and highlights the immense potential that lies in the specialized metabolism of actinomycetes. These microorganisms offer a rich and untapped source for the development of innovative products that could transform the sun protection industry.
Sunscreen pollution can be a symptom of unsustainable tourism and coastal development, impacting marine and aquatic resources. When introduced into marine and freshwater ecosystems, sunscreen pollution can cause a cascade of insults to the ecological structure, from impacting primary production to reducing wildlife reproductive viability and fecundity.
Without intervention, tourism and its associated development in these coastal areas may become self‐destructive, ultimately degrading or destroying the natural resources that are the principal attractions. The environmental sciences that focus on pollution, such as ecotoxicology, environmental contaminant surveys and monitoring, and ecological risk assessments are critical for both describing the pollution phenomenon and identifying pollution sources, as well as providing the basis for mitigation.
As a case study, the Republic of Palau has taken the step of implementing a precautionary governance policy to tourism that conserves and protects its marine and aquatic resources from chemical factors that are known to contribute to sunscreen and cosmetic pollution.
Governance policies can inspire the cosmetic and fashion industries to innovate product formulations that are shown to be ecologically safer – a critical and viable option for pollution mitigation and an essential component for sustained conservation. Safer products and a precautionary approach to governance, when combined with ecologically and culturally cognizant branding and education, may contribute to an authentic experience that effectively promotes environmentally sustainable tourism.
Hanauma Bay is a 101-acre bay created by the partial collapse of a volcanic cone and once supported a vibrant coral reef system. It is the most popular swimming area in the Hawaiian Islands and has been reported to have averaged between 2.8 and 3.5 million visitors a year between the 1980s and the 2010s, with visitors averaging between 3000–4000 a day and peaking around 10,000–13,000 per day. Concentrations of oxybenzone and other common UV filters were measured in subsurface water samples and in sands from the beach-shower areas in Hanauma Bay. Results demonstrate that beach showers also can be a source of sunscreen environmental contamination. Hydrodynamic modeling indicates that oxybenzone contamination within Hanauma Bay's waters could be retained between 14 and 50 h from a single release event period. Focusing on only oxybenzone, two different Hazard and Risk Assessment analyses were conducted to determine the danger of oxybenzone to Hanauma Bay's coral reef system. Results indicate that oxybenzone contamination poses a significant threat to the wildlife of Hanauma Bay. To recover Hanauma Bay's natural resources to a healthy condition and to satisfactorily conserve its coral reef and sea grass habitats, effective tourism management policies need to be implemented that mitigate the threat of sunscreen pollution.
The distribution of organic ultraviolet absorbers (OUVAs) in outdoor dust remains poorly understood, especially in megacities. We measured the concentrations of 11 OUVAs in street dust from Tianjin, China, by a gas chromatography-mass spectrometry, and found total concentrations in the range of 10.3-129 ng/g. These OUVAs were prevalent in the study street dust, but their concentrations were much lower than those in indoor dust reported in other areas previously. Benzophenone and octocrylene were the dominant OUVAs, representing medians of 15.5% and 13.1% of total OUVA concentrations, respectively. Total concentrations of dust OUVAs in the industrial area were higher than the residential, cultural and new urban areas. Source assessment indicated that the OUVAs likely originated mainly from the manufacture and consumption of cosmetics and personal care products, and some may have been from the production and use of OUVA-containing consumer products. The calculated non-carcinogenic risks of OUVAs in street dust were low. Our results further confirmed that the OUVAs were prevalent in the environment, provide useful information for understanding potential risks of these chemicals and developing risk management strategies. Further studies are needed to investigate the occurrence, environmental behaviors and potential risks of these emerging contaminants in outdoor environment.
Background
Sunscreens are topical preparations containing one or more compounds that filter, block, reflect, scatter, or absorb ultraviolet (UV) light. Part 2 of this review focuses on the environmental, ecological effects and human toxicities that have been attributed to UV filters.
Methods
Literature review using NIH databases (eg, PubMed and Medline), FDA and EPA databases, Google Scholar, the Federal Register, and the Code of Federal Regulations (CFR).
Conclusions
In vivo and in vitro studies on the environmental and biological effects of UV filters show a wide array of unanticipated adverse effects on the environment and exposed organisms. Coral bleaching receives considerable attention from the lay press, but the scientific literature identifies potential toxicities of endocrine, neurologic, neoplastic and developmental pathways. These effects harm a vast array of aquatic and marine biota, while almost no data supports human toxicity at currently used quantities (with the exception of contact allergy). Much of these data are from experimental studies or field observations; more controlled environmental studies and long-term human use data are limited. Several jurisdictions have prohibited specific UV filters, but this does not adequately address the dichotomy of the benefits of photoprotection vs lack of eco-friendly, safe, and FDA-approved alternatives.
Sonnenschein bereitet gute Laune, ruft aber durch UV(Ultraviolett)-A- und UV-B-Strahlung Zellschäden in der Epidermis und Dermis hervor. Dies kann sich durch akute Beschwerden äußern, etwa eine Dermatitis solaris, oder mit Verzögerung zur Hautalterung und Entwicklung von Hautkrebs führen. Deshalb wird konsequenter Lichtschutz empfohlen, der vor allem ein umsichtiges Verhalten hinsichtlich starker Sonnenexposition beinhaltet. Des Weiteren sollen textiler Lichtschutz und Lichtschutzmittel korrekt angewendet werden.
Benzophenone-3 (BP-3) is the most widely used compound among UV filters for the prevention of photodegradation. Population studies have demonstrated that it penetrates through the skin and crosses the blood-brain barrier. However, little is known about the impact of BP-3 on the nervous system and its possible adverse effects on the developing brain. We demonstrated that the neurotoxic effects of BP-3 were accompanied by the induction of apoptosis, as evidenced by apoptosis-related caspase-3 activation and apoptotic body formation as well as the inhibition of autophagy, as determined by the downregulation of autophagy-related genes, decreased autophagosome formation, and reduced LC3B-to-LC3A ratio. In this study, we showed for the first time that the BP-3-induced apoptosis of neuronal cells is mediated via the stimulation of RXRα signaling and the attenuation of RXRβ/RXRγ signaling, as demonstrated using selective antagonist and specific siRNAs as well as by measuring the mRNA and protein expression levels of the receptors. This study also demonstrated that environmentally relevant concentrations of BP-3 were able to inhibit autophagy and disrupt the epigenetic status of neuronal cells, as evidenced by the inhibition of global DNA methylation as well as the reduction of histone deacetylases and histone acetyl transferases activity, which may increase the risks of neurodevelopmental abnormalities and/or neural degenerations.
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.
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.
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.
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.
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.
Current evidence indicates that benzophenone-3 (BP-3) can pass through the placental and blood-brain barriers and thus can likely affect infant neurodevelopment. Despite widespread exposure, data showing the effects of BP-3 on the developing nervous system are scarce. This study revealed for the first time that prenatal exposure to BP-3 led to apoptosis and neurotoxicity, altered the levels of estrogen receptors (ERs) and changed the epigenetic status of mouse neurons. In the present study, multiple subcutaneous injections of pregnant mice with BP-3 at 50 mg/kg, which is an environmentally relevant dose, evoked activation of caspase-3 and lactate dehydrogenase (LDH) release as well as substantial loss of mitochondrial membrane potential in neocortical cells of their embryonic offspring. Apoptosis-focused microarray analysis of neocortical cells revealed up-regulation of 22 genes involved in apoptotic cell death. This effect was supported by increased BAX and CASP3 mRNA and protein levels, as evidenced by qPCR, ELISAs and western blots. BP-3-induced apoptosis and neurotoxicity were accompanied by decreases in the mRNA and protein expression levels of ESR1 and ESR2 (also known as ERα and ERβ), with a simultaneous increase in GPER1 (also known as GPR30) expression. In addition to the demonstration that treatment of pregnant mice with BP-3 induced apoptosis, caused neurotoxicity and altered ERs expression levels in neocortical cells of their embryonic offspring, we showed that prenatal administration of BP-3 inhibited global DNA methylation as well as reduced DNMTs activity. BP-3 also caused specific hypomethylation of the genes Gper1 and Bax, an effect that was accompanied by increased mRNA and protein expression levels. In addition, BP-3 caused hypermethylation of the genes Esr1, Esr2 and Bcl2, which could explain the reduced mRNA and protein levels of the receptors. This study demonstrated for the first time that prenatal exposure to BP-3 caused severe neuronal apoptosis that was accompanied by impaired ESR1/ESR2 expression, enhanced GPER1 expression, global DNA hypomethylation and altered methylation statuses of apoptosis-related and ERs genes. We suggest that the effects of BP-3 in embryonic neurons may be the fetal basis of the adult onset of nervous system disease.
Environmental phenols are used commonly in personal care products and exposure is widespread in pregnant women. In this study, we sought to assess the association between maternal urinary phenol concentrations in pregnancy and fetal growth. The study population included 476 mothers who participated in the prospective LIFECODES birth cohort between 2006 and 2008 at Brigham and Women's Hospital in Boston, Massachusetts, USA. Dichlorophenols (DCPs), benzophenone-3, parabens, triclosan, triclocarban, and bisphenol-S were measured in urine from three time points during pregnancy and averaged. Outcome measures were all standardized to create gestational-age specific z-scores and included: 1) birth weight; 2) ultrasound parameters measured at up to two time points in pregnancy (head and abdominal circumference and femur length); and 3) ultrasound estimates of fetal weight from two time points in combination with birth weight. Models were stratified to investigate sex differences. Inverse associations were observed between average 2,4- and 2,5-DCP concentrations and birth weight z-scores in males. For example, an interquartile range difference in 2,4-DCP was associated with a 0.18 standard deviation decrease in birth weight z-score (95% confidence interval [CI]=-0.33, -0.02). These associations were observed in models that included repeated ultrasound estimates of fetal weight during gestation as well. Also in males, we noted inverse associations between average triclosan exposure over pregnancy and estimated fetal weight combined with birth weight in repeated measures models. For females, associations were generally null. However, mothers with a detectable concentration of bisphenol-S at any of the study visits had lower weight females. In conclusion, we observed inverse associations between indicators of maternal phenol exposure during pregnancy and fetal growth, with several differences observed by sex.
UV filters (UV-Fs) are a group of hormonally active chemical compounds used to protect against the deleterious effects of UVA and UVB solar radiation, which are currently present in most consumer goods (personal care products, plastics, fabrics, paints, etc). Last years the concern about these emerging contaminants has been on the rise, and increasing efforts are being taken in order to properly asses the hazard that the exposure to these compounds in the early stages of life may pose. In this study, a new method for the analysis of 11 UV-Fs residues in human breast milk samples has been developed. The method is based on turbulent flow chromatography coupled to liquid chromatography-tandem mass spectrometry (TFC-HPLC-MS/MS). The validated method was successfully applied to 79 human breast milk samples from mothers in Barcelona (Spain). Twenty-four per cent of the samples contained UV-Fs, with major contributors being oxybenzone (benzophenone 3, BP3), its metabolite 4,4'-dihydroxybenzophenone (4DHB), and UV320 showing maximum concentrations of 779.9, 73.3, and 523.6ngg-1 milk, respectively. Additionally, the plastic containers of the milks were also analysed, revealing high concentrations of BP3 and 4DHB, up to 10.6µgg-1 plastic. The calculated mean ΣUV-Fs were useful to estimate the daily intake (EDI) by babies, which were 69.1µg d-1kg-1 body weight.
Background:
Previous studies have demonstrated widespread exposure of humans to certain benzophenones commonly used as UV filters or UV absorbers; some of which have been demonstrated to have endocrine disrupting abilities.
Objectives:
To examine whether benzophenones present in pregnant women pass through the placental barrier to amniotic fluid and further to the fetal blood circulation.
Methods:
A prospective study of 200 pregnant women with simultaneously collected paired samples of amniotic fluid and maternal serum and urine. In addition, unique samples of human fetal blood (n=4) obtained during cordocentesis: and cord blood (n=23) obtained at delivery, both with paired maternal samples of serum and urine collected simultaneously, were used. All biological samples were analyzed by TurboFlow-liquid chromatography - tandem mass spectrometry for seven different benzophenones.
Results:
Benzophenone-1 (BP-1), benzophenone-3 (BP-3), 4-methyl-benzophenone (4-MBP), and 4-hydroxy-benzophenone (4-HBP) were all detectable in amniotic fluid and cord blood samples and except 4-HBP also in fetal blood; albeit at a low frequency. BP-1 and BP-3 were measured at ~10-times lower concentrations in fetal and cord blood compared to maternal serum and 1000-times lower concentration compared to maternal urine levels. Therefore BP-1 and BP-3 were only detectable in the fetal circulation in cases of high maternal exposure indicating some protection by the placental barrier. 4-MBP seems to pass into fetal and cord blood more freely with a median 1:3 ratio between cord blood and maternal serum levels. Only for BP-3, which the women seemed to be most exposed to, did the measured concentrations in maternal urine and serum correlate to concentrations measured in amniotic fluid. Thus, for BP-3, but not for the other tested benzophenones, maternal urinary levels seem to be a valid proxy for fetal exposure.
Conclusions:
Detectable levels of several of the investigated benzophenones in human amniotic fluid as well as in fetal and cord blood calls for further investigations of the toxicokinetic and potential endocrine disrupting properties of these compounds in order for better assessment of the risk to the developing fetus.
Hirschsprung's disease (HSCR) is neonatal intestinal abnormality which derived from the faliure of enteric neural crest cells migration to hindgut during embryogenesis from 5 to 12 weeks. Currenly, the knowledge of environmental factors contributing to HSCR is still scarce. Benzophenone-3 (BP-3) is one of the most widely used UV filters, and has weak estrogen and strong anti-androgenic effects. In order to examine the effect of maternal BP-3 exposure on development of offspring and explore the potential mechanism, we conducted case and control study and in vitro study. In this work, BP-3 concertrations in maternal urine was detected by ultra-high performance liquid chromatography. Besides, we investigated the cytotoxicity and receptor tyrosine kinase (RET) expression in cells exposed to BP-3. The results showed that maternal BP-3 exposure was associated with offspring's HSCR in the population as well as inhibited migration of 293T and SH-SY5Y cells. What's more, we discovered dose-response relationship between RET expression and BP-3 exposure dose, and miR-218 and some other genes involved in SLIT2/ROBO1-miR-218-RET/PLAG1 pathway were also related to BP-3 exposure. Therefore, we deduced that BP-3 influenced cell migration via SLIT2/ROBO1-miR-218-RET/PLAG1 pathway. Our study firstly revealed the relationship between maternal BP-3 exposure and HSCR as well as its potential mechanism.
Many phenols are known to mimic or antagonize hormonal activities and may adversely affect fetal growth. A study of 567 pregnant women was conducted to investigate the relationship between prenatal phenol exposure and birth outcomes, including birth weight, length, and gestational age. We measured the concentrations of bisphenol A, benzophenone-3, 4-n-octylphenol and 4-n-nonylphenol in maternal urine and examine their association with birth outcomes. Categories of urinary benzophenone-3 concentration were associated with decreased gestational age in all infants (p for trend = 0.03). Between middle and low exposure groups, we also found bisphenol A was negatively associated with gestational duration (βadjusted = -0.48 week; 95% confidence interval: -0.91, -0.05). After stratification by gender, we found the consistent results in infant boys with those in all infants, but we did not observe significant association for girls. In conclusion, we found prenatal phenol exposure was sex-specifically related to birth outcomes.
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.
Human skin has unique properties of which functioning as a physicochemical barrier is one of the most apparent. The human integument is able to resist the penetration of many molecules. However, especially smaller molecules can surpass transcutaneously. They are able to go by the corneal layer, which is thought to form the main deterrent. We argue that the molecular weight (MW) of a compound must be under 500 Dalton to allow skin absorption. Larger molecules cannot pass the corneal layer. Arguments for this "500 Dalton rule" are; 1) virtually all common contact allergens are under 500 Dalton, larger molecules are not known as contact sensitizers. They cannot penetrate and thus cannot act as allergens in man; 2) the most commonly used pharmacological agents applied in topical dermatotherapy are all under 500 Dalton; 3) all known topical drugs used in transdermal drug-delivery systems are under 500 Dalton. In addition, clinical experience with topical agents such as cyclosporine, tacrolimus and ascomycins gives further arguments for the reality of the 500 Dalton rule. For pharmaceutical development purposes, it seems logical to restrict the development of new innovative compounds to a MW of under 500 Dalton, when topical dermatological therapy or percutaneous systemic therapy or vaccination is the objective.
Recent in vitro and animal studies have reported estrogen-like activity of chemicals used in sunscreen preparations. We investigated whether the three sunscreens benzophenone-3 (BP-3), octyl-methoxycinnamate (OMC), and 3-(4-methylbenzylidene) camphor (4-MBC) were absorbed and influenced endogenous reproductive hormone levels in humans after topical application. In this 2-wk single-blinded study 32 healthy volunteers, 15 young males and 17 postmenopausal females, were assigned to daily whole-body topical application of 2 mg per cm(2) of basic cream formulation without (week 1) and with (week 2) the three sunscreens at 10% (wt/wt) of each. Maximum plasma concentrations were 200 ng per mL BP-3, 20 ng per mL 4-MBC, and 10 ng per mL OMC for females and 300 ng per mL BP-3, 20 ng per mL 4-MBC, and 20 ng per mL OMC for men. All three sunscreens were detectable in urine. The reproductive hormones FSH, LH were unchanged but minor differences in testosterone levels were observed between the 2 wk. A minor difference in serum estradiol and inhibin B levels were observed in men only. These differences in hormone levels were not related to sunscreen exposure.
Benzophenone-3 (BZ-3; 2-hydroxy-4-methoxybenzophenone, oxybenzone) is commonly used to absorb ultraviolet (UV) radiation. BZ-3 penetrates the skin and can be found in the urine. The amount varies between 0.4% and 2%. This seems to be the main metabolic pathway in rats.
To investigate the total amount of BZ-3 excreted in the urine after repeated topical whole-body applications of a sunscreen and to see if UV radiation has any effect on the amount excreted.
Twenty-five volunteers applied a commercially available sunscreen containing 4% BZ-3 morning and night for 5 days. Their urine was measured during those 5 days and during a further 5 days after the last application. They were divided into groups A (unirradiated) and B. Group B received UV radiation according to skin type: UVA between 400 and 707 J cm(-2), and UVB between 0.46 and 2.0 J cm(-2). BZ-3 in urine was analysed with a high-performance liquid chromatography method.
The volunteers excreted 1.2-8.7% (mean 3.7%) of the total amount of BZ-3 applied. There was no significant difference between the two groups (P < 0.99, t-test).
We show that a large amount of BZ-3 is absorbed. BZ-3 is accumulated in the body as the volunteers excreted BZ-3 5 days after the last application.
To provide a teratology update for prescription and non-prescription drugs and infections during pregnancy.
Limited to teratology principles and possible common exposures during pregnancy.
A search of Medline and textbooks was conducted for information published to June 2006 on teratology exposure risks. This document represents an abstraction of the information.
This consensus provides practitioners with a summary of information regarding teratology risks for drug, chemical, and infection exposures during pregnancy.
- M S Wolff
- S M Engel
- G S Berkowitz
- X Ye
- M J Silva
- C Zhu
- J Wetmur
- A M Calafat
M.S. Wolff, S.M. Engel, G.S. Berkowitz, X. Ye, M.J. Silva, C. Zhu, J. Wetmur,
A.M. Calafat, Prenatal phenol and phthalate exposures and birth outcomes, Environ.
Health Perspect. 116 (2008) 1092-1097.