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Carbon nanotubes (CNTs) have gained significant attention due to their unique mechanical, electrical, and thermal properties. These exciting properties of CNTs make them productive in various applications, from electronics to optics to therapeutics. However, concerns about the potential toxicity of carbon nanotubes have also been raised, prompting extensive research to understand their effects on human health and the environment. Several studies have investigated the toxicity of carbon nanotubes, and the results vary depending on factors such as size, shape, surface chemistry, and the route of exposure. This review highlights the toxicological aspects of CNTs with a special focus on the major consequences of CNT toxicity. The study unfolds the prospects on how the toxicity of CNTs causes adverse effects on the central nervous system, kidney, spleen, eye, cardiac, etc., and thus can influence numerous applications covering from clinical to environmental. Moreover, the report offers an imperative deliberation over the curing or remedies of CNT toxicity, which can provide collective insights for the researchers. Thus, this review report provides the developments, implications, and different approaches to CNT toxicity so that the readers can clearly understand the wide-ranging forecasts of CNT toxicity.

Background: New fourth generation electronic nicotine delivery system (ENDS) devices contain high levels of nicotine salt (up to 60 mg/mL), whose cellular and molecular effects on immune cells are currently unknown. Here, we used a physiologically-relevant in vitro air-liquid interface (ALI) exposure model to assess the toxicity of distinct ENDS, a 3rd-generation electronic-cigarette (e-cig) and two 4th-generation ENDS devices (JUUL and Posh Plus). Methods: Murine macrophages (RAW 264.7) were exposed at the ALI to either air, Menthol or Crème Brûlée-flavored ENDS aerosols generated from those devices for 1-hour per day for 1 or 3 consecutive days. Cellular and molecular toxicity was evaluated 24 h post-exposure. Results: 1-day of Menthol-flavored JUUL aerosol exposure significantly decreased cell viability and significantly increased lactate dehydrogenase (LDH) levels compared to air controls. Further, JUUL Menthol elicited significantly increased reactive oxygen species (ROS) and nitric oxide (NO) production compared to air controls. Posh Crème Brûlée-flavored aerosols displayed significant cytotoxicity – decreased cell viability and increased LDH levels –after 1- and 3-day exposures, while the Crème Brûlée-flavored aerosol produced by the 3rd-generation e-cig device only displayed significant cytotoxicity after 3 days compared to air controls. Further, both Posh and third-generation e-cig Crème Brûlée flavored-aerosols elicited significantly increased ROS plus high levels of 8-isoprostane after 1 and 3 days compared to air controls, indicating increased oxidative stress. Posh and third-generation e-cig Crème Brûlée flavored-aerosols elicited reduction in NO levels after one day, but elicited increase in NO after 3 days. Genes in common dysregulated by both devices after 1 day included α7nAChR, Cyp1a1, Ahr, Mmp12, and iNos. Conclusion: Our results suggest that ENDS Menthol and Crème Brûlée-flavored aerosol exposures from both 3rd- and 4th-generation ENDS devices are cytotoxic to macrophages and cause oxidative stress. This can translate into macrophage dysfunction. Although 4th-generation disposable ENDS devices have no adjustable operational settings and are considered low-powered ENDS devices, their aerosols can induce cellular toxicity compared to air-exposed control cells. This study provides scientific evidence for regulation of nicotine salt-based disposable ENDS products.

Non-viral gene delivery is a new therapeutic in the treating genetic disorders. The most important challenge in nonviral gene transformation is the immunogenicity of carriers. Nowadays, The immunogenicity of nanocarriers as a deliverer of nucleic acid molecules has received significant attention. In this research, hematite green nanocarriers were prepared in one step with rosemary extract. Synthetic nanocarriers were investigated by using XRD (X-ray diffraction analysis), FESEM-EDX (field emission scanning electron microscopy with energy dispersive X-Ray spectroscopy), HR-TEM (high-resolution transmission electron microscopy), VSM (value stream mapping), TGA- DTG (thermal gravimetric analysis-differential thermal analysis), FT-IR (fourier-transform infrared spectroscopy), BET (brunauer–emmett–teller) and BJH (barrett-joyner-halenda) analyses. The cytotoxicity of synthetic nanocarriers was evaluated on HEK-293Tcell lines at concentration of 1–500 μg/ml using MTT method. Finally, targeted transfection of GFP plasmid using green porous particles was performed using an external magnetic field. Biogenic hematite nanoparticles with hexagonal crystal structures have a 3D pile flower-like morphology. The existence of rosemary phytochemicals in the construction of nanoparticles has caused minimal toxicity and high biocompatibility of nanocarriers. Also, TGA studies confirmed the stability of bionic nanoparticles. Superparamagnetic green nanocarriers at concentrations above 500 μg/ml is not toxic to HEK293T cells. The delivery efficiency of the plasmid was optimal at an N/P ratio of 3. Therefore, the porous α-Fe2O3 green nanocarriers are non-viral and safe carriers with potential applications in gene therapy.

Cotton bollworm (Helicoverpa armigera) is a highly polyphagous, widely prevalent, and persistent Old World insect pest that affects numerous important crops that are directly consumed by people, including tomato, cotton, pigeon pea, chickpea, rice, sorghum, and cowpea. Insects do not synthesize steroids but obtain them from their diet. Inhibition of dietary uptake of steroids by insects is a potentially effective insecticidal mechanism that should not be toxic to humans and other mammals, who synthesize their steroids. Ten curcumin derivatives were tested against H. armigera sterol carrier protein-2 (HaSCP-2) for their potential as insecticidal agents. Curcumin derivatives were initially docked at the binding site of HaSCP-2 to determine their binding affinities and plausible binding modes. The binding modes predominantly show hydrophobic interactions of derivatives with Phe53, Phe110, and Phe89 as core interacting residues in the active site. Validation of in silico results was carried out by performing a fluorescence binding and displacement assay to determine the binding affinities of curcumin derivatives. Among a collection of curcumin derivatives tested, Cur10 showed the lowest IC50 value of 9.64 μM, while Cur07 was 19.86 μM, and Cur06 was 20.79 μM. There was a significant negative correlation between the ability of the curcumin derivatives tested to displace the fluorescent probe from the sterol binding site of HaSCP-2 and to inhibit Sf9 insect cell growth in culture, which is consistent with the curcumin derivatives acting by the novel mechanism of blocking sterol uptake. Then molecular dynamics simulation studies validated the predicted binding modes and the interactions of curcumin derivatives with HaSCP-2 protein. In conclusion, these studies support the potential use of curcumin derivatives as insecticidal agents.

Background: Today, many research groups in the world are struggling to fully understand the mechanisms leading to the carcinogenesis of hazardous mineral fibres, like asbestos, in view of devising effective cancer prevention strategies and therapies. Along this research line, our work attempts the completion of a model aimed at evaluating how, and to what extent, physical-crystal-chemical and morphological parameters of mineral fibres prompt adverse effects in vivo leading to carcinogenesis. Methods: In vitro toxicology tests that deliver information on the 10 key characteristics of carcinogens adopted by the International Association for Research on Cancer (IARC) have been systematically collected for a commercial chrysotile, standard UICC crocidolite and wollastonite. The analysis of the in vitro data allowed us to assess the major fibre parameters responsible for alterations in the key characteristics of carcinogens for each investigated fibre and the intensity of their effect. Results: Crystal habit and density of the fibres affect exposure but are not major parameters contributing to the KCs. For chrysotile, besides length, we found that fibre parameters that greatly contribute to the KCs are the surface area and the dissolution rate with the related velocity of release of metals (namely iron). For crocidolite, they are the fibre length, iron content and related parameters like the ferrous iron content, iron nuclearity, transition metals content and zeta potential. Conclusions: The results of our study can be a starting point for developing personalized cancer screening and prevention strategies as long as the nature of the fibre of the exposed patient is known. We can speculate on a future personalized prevention therapy targeting the fibres with surface-engineered nanocarriers with active complexes that are selective for the surface charge of the fibres. For chrysotile, a complex with deferasirox that can chelate Fe2+ and deferoxamine that preferentially chelates Fe3+ is proposed with the anchorage to the silica chrysotile surface driven by aspartic acid. For crocidolite, deferiprone chelating both Fe3+ and Fe2+ combined with lysine to attract the silica crocidolite surface is proposed.

Amphotericin B (AmB) is an amphiphilic drug commonly formulated in liposomes and administered intravenously to treat systemic fungal infections. Recent studies on the liposomal drug product have shed light on the AmB aggregation status in the bilayer, which heat treatment (curing) modifies. Although toxicity was found related to aggregation status - loose aggregates significantly more toxic than tight aggregates - the precise mechanism linking aggregation and toxicity was not well understood. This study directly measured drug release rate from various AmB liposomal preparations made with modified curing protocols to evaluate correlations among drug aggregation state, drug release, and in vitro toxicity. UV–Vis spectroscopy of these products detected unique curing-induced changes in the UV spectral features: a ∼25 nm blue-shift of the main absorption peak (λmax) in aqueous buffer and a decrease in the OD346/OD322 ratio upon thermal curing, reflecting tighter aggregation. In vitro release testing (IVRT) data showed, by applying and fitting first-order release kinetic models for one or two pools, that curing impacts two significant changes: a 3–5-fold drop in the overall drug release rate and a ten-fold decrease in the ratio between the loosely aggregated and the tightly aggregated, more thermodynamically stable drug pool. The kinetic data thus corroborated the trend independently deduced from the UV–Vis spectral data. The in vitro toxicity assay indicated a decreased toxicity with curing, as shown by the significantly increased concentration, causing half-maximal potassium release (TC50). The data suggest that the release of AmB requires dissociation of the tight complexes within the bilayer and that the reduced toxicity relates to this slower rate of dissociation. This study demonstrates the relationship between AmB aggregation status within the lipid bilayer and drug release (directly measured rate constants), providing a mechanistic link between aggregation status and in vitro toxicity in the liposomal formulations.

Airborne fibres and particularly asbestos represent hazards of great concern for human health because exposure to these peculiar particulates may cause malignancies such as lung cancer and mesothelioma. Currently, many researchers worldwide are focussed on fully understanding the patho-biological mechanisms leading to carcinogenesis prompted by pathogenic fibres. Along this line, the present work introduces a novel approach to correlate how and to what extent the physical/crystal-chemical and morphological parameters (including length, chemistry, biodurability, and surface properties) of mineral fibres cause major adverse effects with an emphasis on asbestos. The model described below conceptually attempts to bridge the gap between toxicity and carcinogenicity of mineral fibres and has several implications: 1) it provides a tool to measure the toxicity and pathogenic potential of asbestos minerals, allowing a quantitative rank of the different types (e.g. chrysotile vs. crocidolite); 2) it can predict the toxicity and pathogenicity of “unregulated” or unclassified fibres; 3) it reveals the parameters of a mineral fibre that are active in stimulating key characteristics of cancer, thus offering a strategy for developing specific cancer prevention strategies and therapies.Chrysotile, crocidolite and fibrous glaucophane are described here as mineral fibres of interest.

The uncertainty of potential risks associated with micro- and nanoplastics (MNPs) are of growing public concern. However, the diversity of MNPs in the environment makes a systematic analysis of potential health effects challenging. New tools and approaches are necessary to investigate biological effects of MNPs. With this quick scoping review, we aim to analyse the suitability of in vitro models for assessing the interaction of MNPs with intestinal cells. Our analysis revealed that currently the majority of in vitro tests are based on the three cell lines Caco-2, HT-29, and HCT-116. They have particularly been used to assess endpoints related to basal cytotoxicity, the internalisation of MNPs and effects on the intestinal barrier. When co-cultured with various cell lines, they also allow to investigate additional effects such as inflammation, metabolic actions and the relevance of the intestinal mucus. However, methodological gaps remain regarding the assessment of a potential accumulation of MNPs, leaching of additives/impurities and in resulting long-term effects as well as cell-type specific toxicities. In addition, only few in vitro studies investigated effects of MNPs on the microbiome. Stem cell-based assays using, for example, the emerging organoid technology are promising for analysing MNP effects on tissue-like structures, while avoiding the particular characteristics of the currently used cancer derived cell lines. The various cell lines and culture techniques can be combined in testing strategies, to better elucidate potential biological interaction of MNPs with biological systems. We suggest to implement a tiered testing strategy, in which monocultures can serve as a tool for high-throughput testing of MNPs. In the next steps co-cultures can be used to assess the potential of a systemic uptake of MNPs and organ-on-a-chip models will provide more reliable insights into relevant doses triggering biological effects. Finally, organoids can help to discover new and more complex reactions initiated by MNPs.

Manganese oxide (MnO 2 ) is one of the most abundant metal oxides, and it is renowned for its ability to degrade various phenolic micropollutants. However, under MnO 2 -mediated transformation, BP-3 transforms into 12 different radical-coupled transformation products (TPs) out of 15 identified TPs. These radical-coupled TPs are reported with adverse environmental impacts. This study explored the effects of MnO 2 on organic UV filter mixtures and different water constituents (i.e., bicarbonate ion (HCO 3 - ), humic acid (HA) and halide ions) in terms of degradation efficiency and transformation chemistry. When a mixture of benzophenone-3 (BP-3) and avobenzone (AVO) underwent transformation by MnO 2 , hybrid radical-coupled TPs derived from both organic UV filters were generated. These hybrid radical-coupled TPs were evaluated by an in silico prediction tool and Vibrio fischeri bioluminescence inhibition assay (VFBIA). Results showed that these TPs were potentially toxic to aquatic organisms, even more so than their parent compounds. The higher the concentration of HCO 3 - , HA, chloride ion (Cl - ) and bromide ion (Br - ), the greater the reduction in the efficiencies of degrading BP-3 and AVO. Contrastingly, in the presence of iodide ion (I - ), degradation efficiencies of BP-3 and AVO were enhanced; however, iodinated TPs and iodinated radical-coupled TPs were formed, with questionable toxicity. This study has revealed the environmental risks of hybrid radical-coupled TPs, iodinated TPs and iodinated radical-coupled TPs when the organic UV filters BP-3 and AVO are transformed by MnO 2 ., Competing Interests: Declaration of competing interest The authors report no declarations of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Electronic cigarettes (E-cigarette) are an alternative for traditional cigarette smokers to quit smoking. Based on the current understanding, electronic cigarettes have rapidly become popular among existing smokers and former non-smokers. However, increasing research at different levels reveals that e-cigarettes are unsafe. This review provides an overview of the toxicology of e-cigarettes based on existing in vivo and in vitro studies and compares their toxicity with that of traditional cigarettes. Moreover, we describe the associated toxicity components in e-cigarettes, as well as the potential mechanism by which e-cigarettes exert toxic effects. As is known to all, the nicotine in traditional cigarettes and e-cigarettes has certain toxicity. Besides, a few studies have shown that propylene glycol and vegetable glycerin mixture and flavoring agents in e-cigarettes also are the key components causing adverse effects in animals or cells. There is insufficient scientific evidence on the toxicity of e-cigarettes due to the lack of standardized research methods, prompting the need to conduct a comprehensive toxicity assessment of e-cigarette toxicity to elucidate the safety issues of e-cigarettes. Eventually, a basis for decision-making on whether people use e-cigarettes will be obtained., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The health hazard represented by the exposure to asbestos may also concern other minerals with asbestos-like crystal habit. One of these potentially hazardous minerals is fibrous glaucophane. Fibrous glaucophane is a major component of blueschist rocks of California (USA) currently mined for construction purposes. Dust generated by the excavation activities might potentially expose workers and the general public. The aim of this study was to determine whether fibrous glaucophane induces in vitro toxicity effects on lung cells by assessing the biological responses of cultured human pleural mesothelial cells (Met-5A) and THP-1 derived macrophages exposed for 24 h and 48 h to glaucophane fibres. Crocidolite asbestos was tested for comparison. The experimental configuration of the in vitro tests included a cell culture without fibres (i.e., control), cell cultures treated with 50 μg/mL (i.e., 15.6 μg/cm 2 ) of crocidolite fibres and 25-50-100 μg/mL (i.e., 7.8-15.6-31.2 μg/cm 2 ) of glaucophane fibres. Results showed that fibrous glaucophane may induce a decrease in cell viability and an increase in extra-cellular lactate dehydrogenase release in the tested cell cultures in a concentration dependent mode. Moreover, it was found that fibrous glaucophane has a potency to cause oxidative stress. The biological reactivity of fibrous glaucophane confirms that it is a toxic agent and, although it apparently induces lower toxic effects compared to crocidolite, exposure to this fibre may be responsible for the development of lung diseases in exposed unprotected workers and population., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The increasing application of nanomaterials in various fields such as drug delivery, cosmetics, disease detection, cancer treatment, food preservation etc. has resulted in high levels of engineered nanoparticles in the environment, thus leading to higher possibility of direct or indirect interactions between these particles and biological systems. In this study, the toxic effects of three commercially available nanomaterials; copper oxide nanoparticles, copper-iron oxide nanopowders and carbon nanopowders were determined in the human hepatoma HepG2 cells using various toxicological assays which are indicative of cytotoxicity (MTT and neutral red assays), mutagenicity (cytokinesis-block micronucleus assay), oxidative stress (total reactive oxygen species and superoxide anion production) and mitochondrial impairment (cellular oxygen consumption). There was increased cytotoxicity, mutagenicity, and mitochondrial impairment in the cells treated with higher concentrations of the nanomaterials, especially the copper oxide nanoparticles. The fold production of reactive oxygen species was similar at the concentrations tested in this study but longer exposure duration resulted in production of more superoxide anions. The results of this study showed that copper oxide nanoparticles are highly toxic to the human HepG2 cells, thus implying that the liver is a target organ in human for copper oxide nanoparticles toxicity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

During extrusion of some polymers, fused filament fabrication (FFF) 3-D printers emit billions of particles per minute and numerous organic compounds. The scope of this study was to evaluate FFF 3-D printer emission-induced toxicity in human small airway epithelial cells (SAEC). Emissions were generated from a commercially available 3-D printer inside a chamber, while operating for 1.5 h with acrylonitrile butadiene styrene (ABS) or polycarbonate (PC) filaments, and collected in cell culture medium. Characterization of the culture medium revealed that repeat print runs with an identical filament yield various amounts of particles and organic compounds. Mean particle sizes in cell culture medium were 201 ± 18 nm and 202 ± 8 nm for PC and ABS, respectively. At 24 h post-exposure, both PC and ABS emissions induced a dose dependent significant cytotoxicity, oxidative stress, apoptosis, necrosis, and production of pro-inflammatory cytokines and chemokines in SAEC. Though the emissions may not completely represent all possible exposure scenarios, this study indicate that the FFF could induce toxicological effects. Further studies are needed to quantify the detected chemicals in the emissions and their corresponding toxicological effects., (Copyright © 2019 Elsevier B.V. All rights reserved.)

ZnO nanoparticles (NPs) possess a wide range of biological functions in pharmaceutical and cosmetic applications due to their excellent antimicrobial, optical and UV protective properties. This study first reports the toxicological assessment of ZnO NPs green synthesized from Jatropha curcas shells for multifunctional biomedical applications. The hot water extract of J.curcas shells is utilized as a chelating agent for the reduction of zinc acetate and then, the prepared ZnO NPs are broadly characterized using X-ray spectroscopic and electron microscopic observations. The prepared ZnO NPs acquire high purity (100%) wurtzite crystal with hexagonal structure with the average particle size of 53 nm. In vitro and in vivo toxicity evaluation against human tumor cell lines and zebrafish embryos have ascertained the purpose of ZnO NPs in clinical research. Toxic effects of ZnO NPs were observed by a dose-dependent reduction of bacterial growth at ≥1   μg ml -1 , by teratogenicity and genotoxicity in zebrafish embryos (from 3 to 90 μg ml -1 ) and by a significant nanoparticle uptake (0.5 ng μl -1 ) by a fish serum. In contrast, ZnO NPs fail to reduce the proliferation of human bladder tumor cells (UC6) and cell viability of A549 cells in vitro up to 500 μg ml -1 . All these observations limit the unobstructed application of ZnO NPs at higher concentrations. Thus, abundantly used metal oxide nanoparticles like ZnO NPs examined in our present study in different animal models under in vitro and in vivo conditions will be the significant screening strategy to determine the nanotoxicity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Epidemiological studies have established the correlations between PM 2.5 and a wide variety of pulmonary diseases. However, their underlying pathogeneses have not been clearly elucidated yet. In the present study, the epithelial-mesenchymal transition (EMT) phenotype with enhanced proliferation and migration activity of human pulmonary epithelial cell line BEAS-2B was observed after exposure to low dose PM 2.5 exposure (50 μg/ml) for 30 passages. Then, epithelial cells derived-exosomal micro-RNA (miRNA) and intracellular total RNA were extracted, and the differentially expressed exosomal miRNAs (DE-Exo-MiRs) as well as differentially expressed protein coding genes (DEGs) were identified by RNA sequencing (RNA-seq) and transcriptome analysis. We found that chronic PM 2.5 exposure stimulated the release of pulmonary epithelium derived exosomes. 45 DE-Exo-MiRs including 32 novelly predicted miRNAs and 843 DEGs between PM 2.5 exposed group and the normal control were detected. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DEGs were significantly enriched in extracellular matrix organization, focal adhesion and cancer related terms. Besides, the enrichment analyses on 7774 mRNA targets of 27 DE-Exo-MiRs predicted by MiRanda software also revealed the potential regulatory role of exosomal miRNAs in pathways in cancer, Wingless/Integrated (Wnt) signaling pathway, focal adhesion related genes and other multiple pathogenic pathways. Moreover, the interactive exosomal miRNA-mRNA pair networks were constructed using Cytoscape software. Our results provided a novel basis for a better understanding of the mechanisms of chronic PM 2.5 exposure induced pulmonary disorders including pulmonary fibrosis and cancer, in which exosomal miRNAs (Exo-MiRs) potentially functions by dynamically regulating gene expressions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Diesel exhaust particles (DEP) are responsible for both respiratory and cardiovascular effects. However many questions are still unravelled and the mechanisms behind the health effects induced by the exposure to ultrafine particles (UFP) need further investigations. Furthermore, different emission sources can lead to diverse biological responses. In this perspective, here we have compared the effects of three DEPs, two standard reference materials (SRM 1650b and 2975) and one DEP directly sampled from a EuroIV vehicle without Diesel Particulate Filter (DPF). For the biological investigations, different in vitro lung models involving both epithelial and vascular endothelial cells, were used. Cell viability, oxidative stress, inflammation, DNA damage and endothelial activation markers were investigated at sub-cytotoxic DEP doses. The data obtained have shown that only DEP EuroIV, which had the major content of polycyclic aromatic hydrocarbons (PAHs) and metals, was able to induce oxidative stress, inflammation and consequent endothelial activation, as demonstrated by the expression of adhesion molecules (ICAM-1 and VCAM-1) and the release of inflammatory markers (IL-8) from endothelial cells. Standard reference materials were not effective under our experimental conditions. These data suggest that oxidative stress, endothelial activation and systemic inflammatory cytokines release are crucial events after DEP exposure and that the source of DEP emission, responsible of the particle chemical fingerprint, may have a key role in the resulting adverse biological outcomes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Epidemiological and toxicological studies have reported that ambient fine particulate matter (PM 2.5 ) exposure are linked to adverse effects of cardiopulmonary system. An in vitro suitable model that assesses the interaction among various cell types should be developed to explain the toxic mechanisms occurred in cardiopulmonary system. The Transwell culture method was used to establish bi-culture consisting of A549 alveolar epithelial cells monoculture in apical chamber and EA.hy926 endothelial cells in the basolateral chamber, while tri-culture systems consisting of co-culture (A549 cells and THP-1 differentiated macrophages) in the apical chamber and also EA.hy926 endothelial cells in the basolateral chamber. Ambient PM 2.5 collecting from Shanghai city in China was used for experiments. Our results showed that apical exposure of co-cultured cells to PM 2.5 (20, 60, 180 μg/ml) for 24 h elicited stronger inflammatory responses than apical exposure of monocultured A549. Endothelial function was assessed via detecting gene expression in EA.hy926 cells, exposure of co-cultured cells induced more vigorous ICAM-1 and caveolin-1 mRNA expression in the tri-culture model than monocultured cells at the same dose of PM 2.5 in the bi-culture model. Particles uptake were observed in both epithelial cells and endothelial cells according to TEM images. In conclusion, PM 2.5 were able to pass through epithelial barrier and deposited in endothelium to further induce direct effect on endothelium function. The tri-culture system was more realistic and sensitive model to evaluate the impact of particles on the cardiopulmonary system than the bi-culture system. Therefore, the tri-culture system will contribute to explaining of the relationships between PM 2.5 and cardiopulmonary diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We evaluated the influence of nanoencapsulation of the flavonoid Dihydromyricetin (DMY) in reducing the genotoxicity and cytotoxicity induced by cationic nanocapsules. Assays were conducted in order to evaluate the potential of protein corona formation, cytotoxicity, genotoxicity and the antioxidant capacity. Nanocapsules containing DMY (NC-DMY) and free DMY (DMY-F) did not demonstrate cytotoxicity and genotoxicity. However, Eudragit RS100 ® nanocapsules (NC-E) increased cytotoxicity and DNA damage formation. NC-DMY and NC-E presented high interaction with the DNA in vitro, suggesting DNA sequestration. These results indicate that nanoencapsulated DMY does not induce cytotoxicity or genotoxicity, and demonstrates high antioxidant capacity. This antioxidant capacity is probably associated with DMY, and occurs due to its ability to avoid the formation of free radicals, thus preventing the toxicity caused by the nanostructure with the cationic polymer Eudragit RS100 ® . Therefore, NC-DMY can be considered an important formulation with significant antioxidant potential to be exploited by nanomedicine., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Silver nanoparticles (Ag-NPs) are increasingly being applied in many consumer products due to their unique properties. Widespread use of Ag-NPs leads to an increasing human exposure to Ag-NPs in many different pathways. This review summarized the toxicity mechanisms of Ag-NPs based on various environmentally relevant test species, such as bacteria, cells, plants, aquatic animals and mammals, in both in vitro and in vivo experiments. Nanoparticles were usually exposed to combination chemicals but to single chemicals in the environment and thereby exert combined toxicities to the organisms. Therefore, the joint effects of nanomaterials and their co-existing characteristics were also discussed. The current knowledge gaps and safe product designs of Ag-NPs have been discussed in detail. The limited and existing data implied that understanding the toxicity mechanisms is crucial to the future research development of nanomaterials., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Bushfires produce many toxic pollutants and the smoke has been shown to have negative effects on human health, especially to the respiratory system. Bushfires are predicted to increase in size and frequency, leading to a greater incidence of smoke and impacts. While there are many epidemiological studies of the potential impact on populations, there are few studies using in vitro methods to investigate the biological effects of bushfire emissions to better understand its toxicity and significance. This review focused on the literature pertaining to in vitro toxicity testing to determine the state of knowledge on current methods and findings on the impacts of bushfire smoke. There was a considerable variation in the experimental conditions, outcomes and test concentrations used by researchers using in vitro methods. Of the studies reviewed, most reported adverse impacts of particulate matter (PM) on cytotoxic and genotoxic responses. Studies on whole smoke were rare. Finer primary particulates from bushfire smoke were generally found to be more toxic than the coarse particulates and the toxicological endpoints of bushfire PM different to ambient PM. However the variation in study designs and experimental conditions made comparisons difficult. This review highlights the need for standard protocols to enable appropriate comparisons between studies to be undertaken including the assessment of physiologically relevant outcomes. Further work is essential to establish the effect of burning different vegetation types and combustion conditions on the toxicity of bushfire emissions to better inform both health and response agencies on the significance of smoke from bushfires., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Within this work we evaluated the cytotoxicity towards the Channel Catfish Ovary (CCO) cell line of some imidazolium-based ionic liquids containing different functionalized and unsaturated side chains. The toxic effects were measured by the reduction of the WST-1 dye after 72 h exposure resulting in dose- and structure-dependent toxicities. The obtained data on cytotoxic effects of 14 different imidazolium ionic liquids in CCO cells, expressed as EC50 values, were used in a preliminary quantitative structure-toxicity relationship (QSTR) study employing regression- and classification-based approaches. The toxicity of ILs towards CCO was chiefly related to the shape and hydrophobicity parameters of cations. A significant influence of the quantum topological molecular similarity descriptor ellipticity (ε) of the imine bond was also observed., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Deep eutectic solvents (DESs) have been dramatically expanding in popularity as a new generation of environmentally friendly solvents with possible applications in various industrial fields, but their ecological footprint has not yet been thoroughly investigated. In the present study, three choline chloride-based DESs with glucose, glycerol and oxalic acid as hydrogen bond donors were evaluated for in vitro toxicity using fish and human cell line, phytotoxicity using wheat and biodegradability using wastewater microorganisms through closed bottle test. Obtained in vitro toxicity data on cell lines indicate that choline chloride: glucose and choline chloride:glycerol possess low cytotoxicity (EC50>10 mM for both cell lines) while choline chloride:oxalic acid possess moderate cytotoxicity (EC50 value 1.64 mM and 4.19 mM for fish and human cell line, respectively). Results on phytotoxicity imply that tested DESs are non-toxic with seed germination EC50 values higher than 5000 mg L(-1). All tested DESs were classified as'readily biodegradable' based on their high levels of mineralization (68-96%). These findings indicate that DESs have a green profile and a good prospect for a wider use in the field of green technologies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In this study we quantified the concentrations of nine haloacetamides (HAcAms) and nine halomethanes (HMs) in the final waters of five drinking water treatment plants (DWTPs) that use either chlorination or chloramination for disinfection and evaluated the toxicity of dichloroacetamide (DCAcAm) and dichloromethane (DCM) in normal rat kidney (NRK) cells using four in vitro toxicity assays. All the DWTPs final waters contained primarily di-HAcAms, followed by tri- and mono-HAcAms, and DCAcAm was the most abundant species of the 9 HAcAms, regardless of chlorination or chloramination being applied. In the final waters of DWTPs using chlorination, tri-HMs (trihalomethanes, THMs) accounted for the majority of HMs, whereas chloramination resulted in more di-HMs (especially DCM) than THMs. All four in vitro toxicity assays indicated that the NRK cell chronic cytotoxicity and acute genotoxicity of DCAcAm were substantially higher than that of DCM. In view of observed occurrence concentrations and quantified toxicity levels, the findings of this study suggest that DCAcAm represents a higher toxicity risk than DCM in chloraminated drinking waters., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A novel Zn mononuclear complex with 3-carboxy-pyrazole ligand has been prepared using conventional routes and characterized by X-ray diffraction. The structure consists of discrete neutral [Zn(C6H3N2O2)2(H2O)2] molecules held together by hydrogen interactions. This compound exhibits a potential in vivo antidiabetic activity and the in vitro toxicity can be considered negligible., (© 2013.)

Diaryltriazines (DATAs) constitute a class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) that are being investigated for use as anti-HIV microbicides. The aim of the present study was (1) to assess the biopharmaceutical properties of the DATA series, (2) to select the lead candidate as vaginal microbicide and (3) to develop and evaluate gel formulations of the lead candidate. First, the vaginal tissue permeation potential of the different DATAs was screened by performing permeability and solubility measurements. To obtain a suitable formulation of the lead microbicide candidate, several hydroxyethylcellulose-based gels were assessed for their cellular toxicity, stability and ability to enable UAMC01398 epithelial permeation. Also, attention was given to appropriate preservative selection. Because of its favourable in vitro activity, safety and biopharmaceutical profile, UAMC01398 was chosen as the lead microbicide candidate among the DATA series. Formulating UAMC01398 as a vaginal gel did not affect its anti-HIV activity. Safe and chemically stable gel formulations of UAMC01398 (0.02%) included a non-solubilizing gel and a gel containing sulfobutyl ether-β-cyclodextrin (SBE-βCD, 5%) as solubilizing excipient. Inclusion of SBE-βCD in the gel formulation resulted in enhanced microbicide flux across HEC-1A epithelial cell layers, to an extent that could not be achieved by simply increasing the dose of UAMC01398. The applied rational (pre)formulation approach resulted in the development of aqueous-based gel formulations that are appropriate for further in vivo investigation of the anti-HIV microbicide potential of the novel NNRTI UAMC01398., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Exposure of the respiratory tract to airborne particles (including metal-dusts and nano-particles) is considered as a serious health hazard. For a wide range of substances basic knowledge about the toxic properties and the underlying pathomechanisms is lacking or even completely missing. Legislation demands the toxicological characterization of all chemicals placed on the market until 2018 (REACH). As toxicological in vivo data are rare with regard to acute lung toxicity or exhibit distinct limitations (e.g. inter-species differences) and legislation claims the reduction of animal experiments in general ("3R" principle), profound in vitro models have to be established and characterized to meet these requirements. In this paper we characterize a recently introduced advanced in vitro exposure system (Cultex® RFS) showing a great similarity to the physiological in vivo exposure situation for the assessment of acute pulmonary toxicity of airborne materials. Using the Cultex® RFS, human lung epithelial cells (A549 cells) were exposed to different concentrations of airborne metal dusts (nano- and microscale particles) at the air-liquid-interface (ALI). Cell viability (WST-1 assay) as a parameter of toxicity was assessed 24h after exposure with special focus on the intra- and inter-laboratory (three independent laboratories) reproducibility. Our results show the general applicability of the Cultex® RFS with regard to the requirements of the ECVAM (European Centre for the Validation of Alternative Methods) principles on test validity underlining its robustness and stability. Intra- and inter-laboratory reproducibility can be considered as sufficient if predefined quality criteria are respected. Special attention must be paid to the pure air controls that turned out to be a critical parameter for a rational interpretation of the results. Our results are encouraging and future work is planned to improve the inter-laboratory reproducibility, to consolidate the results so far and to develop a valid prediction model., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)