The Effects of Nanomaterials as Endocrine Disruptors

In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is a serious lack of information on the potential nanoparticle hazard to human health, particularly on their possible toxic effects on the endocrine system. This topic is of primary importance since the disruption of endocrine functions is associated with severe adverse effects on human health. Consequently, in order to gather information on the hazardous effects of nanoparticles on endocrine organs, we reviewed the data available in the literature regarding the endocrine effects of in vitro and in vivo exposure to different types of nanoparticles. Our aim was to understand the potential endocrine disrupting risks posed by nanoparticles, to assess their underlying mechanisms of action and identify areas in which further investigation is needed in order to obtain a deeper understanding of the role of nanoparticles as endocrine disruptors. Current data support the notion that different types of nanoparticles are capable of altering the normal and physiological activity of the endocrine system. However, a critical evaluation of these findings suggests the need to interpret these results with caution since information on potential endocrine interactions and the toxicity of nanoparticles is quite limited.     

Perinatal Exposure to Phthalates: From Endocrine to Neurodevelopment Effects

Phthalates, as other endocrine disrupting chemicals (EDCs), may alter the homeostasis and the action of hormones and signaling molecules, causing adverse health outcomes. This is true especially for infants, who are both more exposed and sensitive to their effects. Phthalates are particularly harmful when the exposure occurs during certain critical temporal windows of the development, such as the prenatal and the early postnatal phases. Phthalates may also interfere with the neuroendocrine systems (e.g., thyroid hormone signaling or metabolism), causing disruption of neuronal differentiation and maturation, increasing the risk of behavioral and cognitive disorders (ADHD and autistic behaviors, reduced mental, psychomotor, and IQ development, and emotional problems). Despite more studies being needed to better understand the role of these substances, plenty of evidence suggests the impact of phthalates on the neuroendocrine system development and function. This review aims to update the knowledge on the neuroendocrine consequences of neonatal and perinatal exposure to phthalates.     

Impact of Chemical Endocrine Disruptors and Hormone Modulators on the Endocrine System

There is growing concern regarding the health and safety issues of endocrine-disrupting chemicals (EDCs). Long-term exposure to EDCs has alarming adverse health effects through both hormone-direct and hormone-indirect pathways. Non-chemical agents, including physical agents such as artificial light, radiation, temperature, and stress exposure, are currently poorly investigated, even though they can seriously affect the endocrine system, by modulation of hormonal action. Several mechanisms have been suggested to explain the interference of EDCs with hormonal activity. However, difficulty in quantifying the exposure, low standardization of studies, and the presence of confounding factors do not allow the establishment of a causal relationship between endocrine disorders and exposure to specific toxic agents. In this review, we focus on recent findings on the effects of EDCs and hormone system modulators on the endocrine system, including the thyroid, parathyroid glands, adrenal steroidogenesis, beta-cell function, and male and female reproductive function.     

Ozone-Based Decomposition of Main Endocrine Disruption Chemicals in Sewage Effluent

In order to decompose endocrine disruption chemicals (EDCs) in sewage effluent, ozone based oxidation of nonylphenol (NP), bisphenol A (BPA) and 17β-estradiol (E2) was investigated. Experimental results showed that these EDCs were decomposed easily even in the presence of other organic substances of TOC 5 mg/L. The simulation using kinetic constants obtained from the experiments indicated that these EDCs in sewage effluent were removed to below the detection limit with an amount of ozone consumed less than 0.5 mg/L. Ozonation also reduced the estrogenic activity and the aquatic acute toxicity of these EDCs solution. From these results it was concluded that ozonation was very effective in decomposing these EDCs in sewage effluent.     

The potential risks of nanomaterials: a review carried out for ECETOC

During the last few years, research on toxicologically relevant properties of engineered nanoparticles has increased tremendously. A number of international research projects and additional activities are ongoing in the EU and the US, nourishing the expectation that more relevant technical and toxicological data will be published. Their widespread use allows for potential exposure to engineered nanoparticles during the whole lifecycle of a variety of products. When looking at possible exposure routes for manufactured Nanoparticles, inhalation, dermal and oral exposure are the most obvious, depending on the type of product in which Nanoparticles are used. This review shows that (1) Nanoparticles can deposit in the respiratory tract after inhalation. For a number of nanoparticles, oxidative stress-related inflammatory reactions have been observed. Tumour-related effects have only been observed in rats, and might be related to overload conditions. There are also a few reports that indicate uptake of nanoparticles in the brain via the olfactory epithelium. Nanoparticle translocation into the systemic circulation may occur after inhalation but conflicting evidence is present on the extent of translocation. These findings urge the need for additional studies to further elucidate these findings and to characterize the physiological impact. (2) There is currently little evidence from skin penetration studies that dermal applications of metal oxide nanoparticles used in sunscreens lead to systemic exposure. However, the question has been raised whether the usual testing with healthy, intact skin will be sufficient. (3) Uptake of nanoparticles in the gastrointestinal tract after oral uptake is a known phenomenon, of which use is intentionally made in the design of food and pharmacological components. Finally, this review indicates that only few specific nanoparticles have been investigated in a limited number of test systems and extrapolation of this data to other materials is not possible. Air pollution studies have generated indirect evidence for the role of combustion derived nanoparticles (CDNP) in driving adverse health effects in susceptible groups. Experimental studies with some bulk nanoparticles (carbon black, titanium dioxide, iron oxides) that have been used for decades suggest various adverse effects. However, engineered nanomaterials with new chemical and physical properties are being produced constantly and the toxicity of these is unknown. Therefore, despite the existing database on nanoparticles, no blanket statements about human toxicity can be given at this time. In addition, limited ecotoxicological data for nanomaterials precludes a systematic assessment of the impact of Nanoparticles on ecosystems.     

Endocrine-Disrupting Chemicals and Infectious Diseases: From Endocrine Disruption to Immunosuppression

Endocrine-disrupting chemicals (EDCs) are hormonally active compounds in the environment that interfere with the body’s endocrine system and consequently produce adverse health effects. Despite persistent public health concerns, EDCs remain important components of common consumer products, thus representing ubiquitous contaminants to humans. While scientific evidence confirmed their contribution to the severity of Influenza A virus (H1N1) in the animal model, their roles in susceptibility and clinical outcome of the coronavirus disease (COVID-19) cannot be underestimated. Since its emergence in late 2019, clinical reports on COVID-19 have confirmed that severe disease and death occur in persons aged ≥65 years and those with underlying comorbidities. Major comorbidities of COVID-19 include diabetes, obesity, cardiovascular disease, hypertension, cancer, and kidney and liver diseases. Meanwhile, long-term exposure to EDCs contributes significantly to the onset and progression of these comorbid diseases. Besides, EDCs play vital roles in the disruption of the body’s immune system. Here, we review the recent literature on the roles of EDCs in comorbidities contributing to COVID-19 mortality, impacts of EDCs on the immune system, and recent articles linking EDCs to COVID-19 risks. We also recommend methodologies that could be adopted to comprehensively study the role of EDCs in COVID-19 risk.     

Effects of multiwalled carbon nanotubes and triclocarban on several eukaryotic cell lines: elucidating cytotoxicity,endocrine disruption,and reactive oxygen species generation

To date, only a few reports about studies on toxic effects of carbon nanotubes (CNT) are available, and their results are often controversial. Three different cell lines (rainbow trout liver cells (RTL-W1), human adrenocortical carcinoma cells (T47Dluc), and human adrenocarcinoma cells (H295R)) were exposed to multiwalled carbon nanotubes, the antimicrobial agent triclocarban (TCC) as well as the mixture of both substances in a concentration range of 3.13 to 50 mg CNT/L, 31.25 to 500 μg TCC/L, and 3.13 to 50 mg CNT/L + 1% TCC (percentage relative to carbon nanotubes concentration), respectively. Triclocarban is a high-production volume chemical that is widely used as an antimicrobial compound and is known for its toxicity, hydrophobicity, endocrine disruption, bioaccumulation potential, and environmental persistence. Carbon nanotubes are known to interact with hydrophobic organic compounds. Therefore, triclocarban was selected as a model substance to examine mixture toxicity in this study. The influence of multiwalled carbon nanotubes and triclocarban on various toxicological endpoints was specified: neither cytotoxicity nor endocrine disruption could be observed after exposure of the three cell lines to carbon nanotubes, but the nanomaterial caused intracellular generation of reactive oxygen species in all cell types. For TCC on the other hand, cell vitality of 80% could be observed at a concentration of 2.1 mg/L for treated RTL-W1 cells. A decrease of luciferase activity in the ER Calux assay at a triclocarban concentration of 125 μg/L and higher was observed. This effect was less pronounced when multiwalled carbon nanotubes were present in the medium. Taken together, these results demonstrate that multiwalled carbon nanotubes induce the production of reactive oxygen species in RTL-W1, T47Dluc, and H295R cells, reveal no cytotoxicity, and reduce the bioavailability and toxicity of the biocide triclocarban.     

A Mixture of Endocrine Disrupting Chemicals Associated with Lower Birth Weight in Children Induces Adipogenesis and DNA Methylation Changes in Human Mesenchymal Stem Cells

Endocrine Disrupting Chemicals (EDCs) are man-made compounds that alter functions of the endocrine system. Environmental mixtures of EDCs might have adverse effects on human health, even though their individual concentrations are below regulatory levels of concerns. However, studies identifying and experimentally testing adverse effects of real-life mixtures are scarce. In this study, we aimed at evaluating an epidemiologically identified EDC mixture in an experimental setting to delineate its cellular and epigenetic effects. The mixture was established using data from the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) study where it was associated with lower birth weight, an early marker for prenatal metabolic programming. This mixture was then tested for its ability to change metabolic programming of human mesenchymal stem cells. In these cells, we assessed if the mixture induced adipogenesis and genome-wide DNA methylation changes. The mixture increased lipid droplet accumulation already at concentrations corresponding to levels measured in the pregnant women of the SELMA study. Furthermore, we identified differentially methylated regions in genes important for adipogenesis and thermogenesis. This study shows that a mixture reflecting human real-life exposure can induce molecular and cellular changes during development that could underlie adverse outcomes.     

Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity,Including the Immune System

Titanium dioxide (TiO₂) is used as a food additive (E171) and can be found in sauces, icings, and chewing gums, as well as in personal care products such as toothpaste and pharmaceutical tablets. Along with the ubiquitous presence of TiO₂ and recent insights into its potentially hazardous properties, there are concerns about its application in commercially available products. Especially the nano-sized particle fraction (<100 nm) of TiO₂ warrants a more detailed evaluation of potential adverse health effects after ingestion. A workshop organized by the Dutch Office for Risk Assessment and Research (BuRO) identified uncertainties and knowledge gaps regarding the gastrointestinal absorption of TiO₂, its distribution, the potential for accumulation, and induction of adverse health effects such as inflammation, DNA damage, and tumor promotion. This review aims to identify and evaluate recent toxicological studies on food-grade TiO₂ and nano-sized TiO₂ in ex-vivo, in-vitro, and in-vivo experiments along the gastrointestinal route, and to postulate an Adverse Outcome Pathway (AOP) following ingestion. Additionally, this review summarizes recommendations and outcomes of the expert meeting held by the BuRO in 2018, in order to contribute to the hazard identification and risk assessment process of ingested TiO₂.     

环境内分泌干扰物双酚A的降解研究进展

双酚A是一种典型的环境内分泌干扰物,其负面作用随着使用的扩大而日益受到人们的重视。介绍了双酚A的理化性质、应用情况、生物毒性及污染现状,概述了国内外学者对双酚A降解方法与技术（物理法、化学法、生物法等）的研究及影响因素的探讨,并提出了未来研究的主要方向。     

Recovery of the N,N-Dibutylimidazolium Chloride Ionic Liquid from Aqueous Solutions by Electrodialysis Method

Ionic liquids (ILs), named also as liquid salts, are compounds that have unique properties and molecular architecture. ILs are used in various industries; however, due to their toxicity, the ILs’ recovery from the postreaction solutions is also a very important issue. In this paper, the possibility of 1,3-dialkylimidazolium IL, especially the N,N-dibutylimidazolium chloride ([C₄C₄IM]Cl) recovery by using the electrodialysis (ED) method was investigated. The influence of [C₄C₄IM]Cl concentration in diluate solution on the ED efficiency was determined. Moreover, the influence of IL on the ion-exchange membranes’ morphology was examined. The recovery of [C₄C₄IM]Cl, the [C₄C₄IM]Cl flux across membranes, the [C₄C₄IM]Cl concentration degree, the energy consumption, and the current efficiency were determined. The results showed that the ED allows for the [C₄C₄IM]Cl recovery and concentration from dilute solutions. It was found that the [C₄C₄IM]Cl content in the concentrates after ED was above three times higher than in the initial diluate solutions. It was noted that the ED of solutions containing 5–20 g/L [C₄C₄IM]Cl allows for ILs recovery in the range of 73.77–92.45% with current efficiency from 68.66% to 92.99%. The [C₄C₄IM]Cl recovery depended upon the initial [C₄C₄IM]Cl concentration in the working solution. The highest [C₄C₄IM]Cl recovery (92.45%) and ED efficiency (92.99%) were obtained when the [C₄C₄IM]Cl content in the diluate solution was equal 20 g/L. Presented results proved that ED can be an interesting and effective method for the [C₄C₄IM]Cl recovery from the dilute aqueous solutions.     

Removal of 17β-oestradiol and 17α-ethinyl oestradiol from water by activated carbons and hypercrosslinked polymeric phases

There has been growing concern about man-made and naturally occurring chemicals in the environment in recent years. These chemicals interfere with the hormone (or endocrine) system, suggesting far-reaching effects on reproduction and development in current and future man and wildlife generations. Recent research has highlighted the existence of these substances in sewage and industrial effluents and their potential for recycling back into the environment, including drinking water, through point and non-point sources. 17β-Oestradiol (E2) and 17α-ethinyl oestradiol (EE2) are amongst the compounds of concern since they were found to cause adverse effects to fish even at low concentration levels.In this work, the adsorption of E2 and EE2 onto several granular activated carbons and Macronet polymers was investigated by batch experiments after a low level detection system was developed using Gas Chromatography Mass Spectrometry (GC/MS). Equilibrium experiments were carried out for all adsorbents to quantify the sorption capacity for E2 and EE2 and the data were correlated using conventional theoretical treatments. For better assessment of the sorbents, their physical properties including surface area, average pore diameter and micropore volume and chemical structure were characterised by N₂ adsorption experiments. Further characterisation was performed with scanning electron microscopy (SEM), FTIR spectroscopy, sodium capacity determination, pH titration, development of proton-binding curves and zeta potential measurements. Kinetic experiments were performed at different size ranges of adsorbents and the results were analysed by applying a particle diffusion model. This study demonstrates the potential of these adsorbents for the removal of endocrine-disrupting compounds from aqueous solution.     

农药对蜜蜂生物毒性及安全性评价研究回顾

农药对环境生物毒性及安全性评价是防止农药污染、保护生态健康的重要措施.从农药对蜜蜂急性生物毒性测试方法、毒性分级标准、目前世界上主要使用的农药品种对蜜蜂急性毒性及潜在风险以及农药对蜜蜂生物安全性评价体系等方面综合回顾了该领域的研究进展.针对我国在农药对蜜蜂生物安全性评价工作中的不足之处提出了几点建议:提高内吸性农药对蜜蜂生长、发育、繁殖等方面影响的测试技术,建立较为深入、全面的生物毒性实验方法;建立高层次毒性实验技术,完善农药对蜜蜂生物安全性评价技术;加强农药对蜜蜂毒性机理研究,提高农药环境生物安全性风险评价结果的可靠性和科学性.     

Green Propulsion: Catalysts for the European FP7 Project GRASP

The Green Advanced Space Propulsion (GRASP) project investigated the issue of green propulsion and the possibility of replacing presently used toxic hydrazine propellant by green propellants. This project was financed by the European Commission in the 7th Framework Program (FP7). A large data base of about 100 green propellants was compiled including physical and material properties, toxicity and performance data. A preliminary selection was conducted to identify the most promising green propellant candidates for experimental work. Catalytic ignition, a very simple and robust subsystem with restart possibility, was thoroughly investigated focusing on the catalyst–propellant couple. For the whole project, more than 50 catalyst variations have been prepared comprising ceramic pellets, ceramic monoliths, metallic foams or gauzes. Very promising green propellant candidates, e.g. ammonium dinitramide-based monopropellants, have been methodically investigated leading to the development and manufacturing of advanced pellet-based catalysts for ionic liquid decomposition. The decomposition of concentrated hydrogen peroxide (87.5 wt%) for bipropellant applications led to a thorough investigation of monolithic catalysts. Examination of monolith parameters (channel shape, channel density, material) and preparation parameters (washcoating procedure, active phase precursor) led to the development of very efficient catalysts showing high activity and stability: 17.9 kg of H₂O₂ could be decomposed for the first time by a single monolithic catalyst.     

Inroads to Predict in Vivo Toxicology-An Introduction to the eTOX Project

There is a widespread awareness that the wealth of preclinical toxicity data that the pharmaceutical industry has generated in recent decades is not exploited as efficiently as it could be. Enhanced data availability for compound comparison ("read-across"), or for data mining to build predictive tools, should lead to a more efficient drug development process and contribute to the reduction of animal use (3Rs principle). In order to achieve these goals, a consortium approach, grouping numbers of relevant partners, is required. The eTOX ("electronic toxicity") consortium represents such a project and is a public-private partnership within the framework of the European Innovative Medicines Initiative (IMI). The project aims at the development of in silico prediction systems for organ and in vivo toxicity. The backbone of the project will be a database consisting of preclinical toxicity data for drug compounds or candidates extracted from previously unpublished, legacy reports from thirteen European and European operation-based pharmaceutical companies. The database will be enhanced by incorporation of publically available, high quality toxicology data. Seven academic institutes and five small-to-medium size enterprises (SMEs) contribute with their expertise in data gathering, database curation, data mining, chemoinformatics and predictive systems development. The outcome of the project will be a predictive system contributing to early potential hazard identification and risk assessment during the drug development process. The concept and strategy of the eTOX project is described here, together with current achievements and future deliverables.     

Impact of physicochemical properties of cerium oxide nanoparticles on their toxicity effects

The advancing production and application of cerium oxide nanoparticles (CeO₂-NPs) in recent years have raised scientists concern about their toxicity. Numerous investigations have been performed to study the toxicity of CeO₂-NPs although their results are sometimes contradictory. In this review, we display the most important factors that are effective in CeO₂-NPs toxicity. The studies are classified based on the target that is selected for toxicity assessment (cytotoxicity, respiratory toxicity, hepatotoxicity, neurotoxicity, dermal toxicity, phytotoxicity, and environmental toxicity). Various representative examples are presented in each class. It seems to be difficult to achieve a comprehensive view and a deterministic conclusion since several parameters are involved in interpreting the results. In order to reach repeatable and comparable results, it is necessary to design a standard protocol to study the toxicity of CeO₂-NPs. Physicochemical properties of nanoparticles, experiment set up, and toxicity assessment methods are some parameters that should be considered in this standardization.