Showing papers in "Nanotoxicology in 2014"
TL;DR: The need for appropriate methodologies to be used for investigation of genotoxic effects of NPs, in vitro and in vivo is suggested and advantages and potential problems with different methods are described.
Abstract: Engineered nanoparticles (NPs) are widely used in different technologies but their unique properties might also cause adverse health effects. In reviewing recent in vitro and in vivo genotoxicity studies we discuss potential mechanisms of genotoxicity induced by NPs. Various factors that may influence genotoxic response, including physico-chemical properties and experimental conditions, are highlighted. From 4346 articles on NP toxicity, 112 describe genotoxicity studies (94 in vitro, 22 in vivo). The most used assays are the comet assay (58 in vitro, 9 in vivo), the micronucleus assay (31 in vitro, 14 in vivo), the chromosome aberrations test (10 in vitro, 1 in vivo) and the bacterial reverse mutation assay (13 studies). We describe advantages and potential problems with different methods and suggest the need for appropriate methodologies to be used for investigation of genotoxic effects of NPs, in vitro and in vivo.
526 citations
TL;DR: Metal-containing nanomaterials have the potential to be used in dentistry for infection control, but little is known about their antibacterial properties, and Ag NPs were the best disinfectant and performed better than chlorhexidine.
Abstract: Metal-containing nanomaterials have the potential to be used in dentistry for infection control, but little is known about their antibacterial properties This study investigated the toxicity of silver (Ag), titanium dioxide and silica nanoparticles (NPs) against the oral pathogenic species of Streptococcus mutans, compared to the routine disinfectant, chlorhexidine The bacteria were assessed using the minimum inhibitory concentration assay for growth, fluorescent staining for live/dead cells, and measurements of lactate All the assays showed that Ag NPs had the strongest antibacterial activity of the NPs tested, with bacterial growth also being 25-fold lower than that in chlorhexidine The survival rate of bacteria under the effect of 100 mg l(-1) Ag NPs in the media was 2% compared to 60% with chlorhexidine, while the lactate concentration was 06 and 40 mM, respectively Silica and titanium dioxide NPs had limited effects Dialysis experiments showed negligible silver dissolution Overall, Ag NPs were the best disinfectant and performed better than chlorhexidine Improvements to the MIC assay are suggested
398 citations
TL;DR: This review provides a comprehensive and critical literature overview on Ag, ZnO and CuO NPs’ toxicity mechanisms on the basis of various environmentally relevant test species and mammalian cells in vitro and three major phenomena driving the toxicity of these nanoparticles are revealed.
Abstract: Silver, ZnO and CuO nanoparticles (NPs) are increasingly used as biocides. There is however increasing evidence of their threat to “non-target” organisms. In such a context, the understanding of the toxicity mechanisms is crucial for both the design of more efficient nano-antimicrobials, i.e. for “toxic by design” and at the same time for the design of nanomaterials that are biologically and/or environmentally benign throughout their life-cycle (safe by design). This review provides a comprehensive and critical literature overview on Ag, ZnO and CuO NPs’ toxicity mechanisms on the basis of various environmentally relevant test species and mammalian cells in vitro. In addition, factors modifying the toxic effect of nanoparticles, e.g. impact of the test media, are discussed. Literature analysis revealed three major phenomena driving the toxicity of these nanoparticles: (i) dissolution of nanoparticles, (ii) organism-dependent cellular uptake of NPs and (iii) induction of oxidative stress and conseq...
309 citations
TL;DR: The current mechanistic understanding of the toxicity of inorganic metal and metal oxide engineered nanomaterials towards bacterial and aquatic microalgal model organisms based on the paradigm of oxidative stress is presented along with a detailed compilation of available literature on the major toxicity factors and research methods.
Abstract: Nanotechnology has revolutionised many areas of modern life, technology and research, which is reflected in the steadily increasing global demand for and consumption of engineered nanomaterials and the inevitable increase of their release into the environment by human activity. The overall long-term impact of engineered nanomaterials on ecosystems is still unknown. Various inorganic nanoparticles have been found to exhibit bactericidal properties and cause growth inhibition in model aquatic microalgae, but the mechanisms of toxicity are not yet fully understood. The causal link between particle properties and biological effects or reactive oxygen species generation is not well established and represents the most eminent quest of nanoecotoxicological investigation. In this review, the current mechanistic understanding of the toxicity of inorganic metal and metal oxide engineered nanomaterials towards bacterial and aquatic microalgal model organisms based on the paradigm of oxidative stress is presented along with a detailed compilation of available literature on the major toxicity factors and research methods.
266 citations
TL;DR: In the spleen of treated animals TiO2 aggregates and increased white pulp were detected, even though Ti tissue levels remained low reflecting the low doses and the short exposure time, and prompted to comprehensively assess endocrine and reproductive effects in the safety evaluation of nanomaterials.
Abstract: The study explored possible reproductive and endocrine effects of short-term (5 days) oral exposure to anatase TiO2 nanoparticles (0, 1, 2 mg/kg body weight per day) in rat. Nanoparticles were characterised by scanning electron microscopy (SEM) and transmission electron microscopy, and their presence in spleen, a target organ for bioaccumulation, was investigated by single-particle inductively coupled plasma mass spectrometry and SEM/energy-dispersive X-ray. Analyses included serum hormone levels (testosterone, 17-β-estradiol and triiodothyronine) and histopathology of thyroid, adrenals, ovary, uterus, testis and spleen. Increased total Ti tissue levels were found in spleen and ovaries. Sex-related histological alterations were observed at both dose levels in thyroid, adrenal medulla, adrenal cortex (females) and ovarian granulosa, without general toxicity. Altered thyroid function was indicated by reduced T3 (males). Testosterone levels increased in high-dose males and decreased in females. In the spleen of treated animals TiO2 aggregates and increased white pulp (high-dose females) were detected, even though Ti tissue levels remained low reflecting the low doses and the short exposure time. Our findings prompt to comprehensively assess endocrine and reproductive effects in the safety evaluation of nanomaterials.
160 citations
TL;DR: Results suggested that CuO NPs can be absorbed by the roots and translocated to the shoots in E. splendens, a Cu-tolerant plant under hydroponic conditions.
Abstract: The release of nanoparticles (NPs) to the environment poses an increasing potential threat to biological systems. This study investigated the phytotoxicity and accumulation of copper oxide (CuO) NPs to Elsholtzia splendens (a Cu-tolerant plant) under hydroponic conditions. The 50% effective concentration (EC50) of CuO NPs to E. splendens was about 480 mg/L, implying the tolerance of E. splendens to CuO NPs. The Cu content in the shoots treated with 1000 mg/L CuO NPs was much higher than those exposed to the comparable 0.5 mg/L soluble Cu and CuO bulk particles. CuO NPs-like deposits were found in the root cells and leaf cells. Cu K-edge X-ray absorption near-edge structure analysis further revealed that the accumulated Cu species existed predominantly as CuO NPs in the plant tissues. All these results suggested that CuO NPs can be absorbed by the roots and translocated to the shoots in E. splendens.
133 citations
Heriot-Watt University1, Fraunhofer Society2, National Research Council3, Dublin Institute of Technology4, University of Vienna5, Helmholtz Centre for Environmental Research - UFZ6, Ca' Foscari University of Venice7, University of Pisa8, Aarhus University9, Swiss Federal Laboratories for Materials Science and Technology10
TL;DR: A vision for concern-driven integrated approaches for the (eco-)toxicological testing and assessment (IATA) of NM is presented, which allow accelerating the risk assessment process and reducing testing costs and animal use.
Abstract: Bringing together topic-related European Union (EU)-funded projects, the so-called “NanoSafety Cluster” aims at identifying key areas for further research on risk assessment procedures for nanomaterials (NM). The outcome of NanoSafety Cluster Working Group 10, this commentary presents a vision for concern-driven integrated approaches for the (eco-)toxicological testing and assessment (IATA) of NM. Such approaches should start out by determining concerns, i.e., specific information needs for a given NM based on realistic exposure scenarios. Recognised concerns can be addressed in a set of tiers using standardised protocols for NM preparation and testing. Tier 1 includes determining physico-chemical properties, non-testing (e.g., structure–activity relationships) and evaluating existing data. In tier 2, a limited set of in vitro and in vivo tests are performed that can either indicate that the risk of the specific concern is sufficiently known or indicate the need for further testing, including deta...
127 citations
TL;DR: The bioaccumulation of CuO NPs in plant was shown, indicating the need to evaluate organisms of higher trophic level, and the role of particle solubility in NPs toxicity was determined.
Abstract: Copper oxide nanoparticles (CuO NPs) are used as a biocide in paints, textiles and plastics. Their application may lead to the contamination of aquatic ecosystems, where potential environmental effects remain to be determined. Toxic effects may be related to interactions of NPs with cellular systems or to particles' solubilisation releasing metal ions. In this report, we evaluated CuO NPs and soluble copper effects on photosynthesis of the aquatic macrophyte Lemna gibba L to determine the role of particle solubility in NPs toxicity. When L. gibba plants were exposed 48 h to CuO NPs or soluble copper, inhibition of photosynthetic activity was found, indicated by the inactivation of Photosystem II reaction centers, a decrease in electron transport and an increase of thermal energy dissipation. Toxicity of CuO NPs was mainly driven by copper ions released from particles. However, the bioaccumulation of CuO NPs in plant was shown, indicating the need to evaluate organisms of higher trophic level.
126 citations
TL;DR: It is suggested that for this ecologically relevant organism photocatalytic ageing of nTiO2 does not significantly alter toxicity, and that bulk TiO2 may be less ecotoxicologically inert than previously assumed.
Abstract: Marine bivalves (Mytilus galloprovincialis) were exposed to titanium dioxide (10 mg L(-1)) either as engineered nanoparticles (nTiO2; fresh, or aged under simulated sunlight for 7 days) or the bulk equivalent. Inductively coupled plasma-optical emission spectrometry analyses of mussel tissues showed higher Ti accumulation (>10-fold) in the digestive gland compared to gills. Nano-sized TiO2 showed greater accumulation than bulk, irrespective of ageing, particularly in digestive gland (>sixfold higher). Despite this, transcriptional expression of metallothionein genes, histology and histochemical analysis suggested that the bulk material was more toxic. Haemocytes showed significantly enhanced DNA damage, determined by the modified comet assay, for all treatments compared to the control, but no significant differences between the treatments. Our integrated study suggests that for this ecologically relevant organism photocatalytic ageing of nTiO2 does not significantly alter toxicity, and that bulk TiO2 may be less ecotoxicologically inert than previously assumed.
122 citations
TL;DR: Overall, it is shown that NDs effectively entered the cells but NDs do not induce any significant cytotoxic or genotoxic effects on the six cell lines up to an exposure dose of 250 µg/mL.
Abstract: Although nanodiamonds (NDs) appear as one of the most promising nanocarbon materials available so far for biomedical applications, their risk for human health remains unknown. Our work was aimed at defining the cytotoxicity and genotoxicity of two sets of commercial carboxylated NDs with diameters below 20 and 100 nm, on six human cell lines chosen as representative of potential target organs: HepG2 and Hep3B (liver), Caki-1 and Hek-293 (kidney), HT29 (intestine) and A549 (lung). Cytotoxicity of NDs was assessed by measuring cell impedance (xCELLigence® system) and cell survival/death by flow cytometry while genotoxicity was assessed by γ-H2Ax foci detection, which is considered the most sensitive technique for studying DNA double-strand breaks. To validate and check the sensitivity of the techniques, aminated polystyrene nanobeads were used as positive control in all assays. Cell incorporation of NDs was also studied by flow cytometry and luminescent N–V center photoluminescence (confirmed by Ram...
114 citations
TL;DR: Zn toxicity, especially for reproduction, was influenced by pH for all Zn forms, and the importance of considering the relationship between uptake and toxicity in nanotoxicology studies is suggested.
Abstract: To determine how soil properties influence nanoparticle (NP) fate, bioavailability and toxicity, this study compared the toxicity of nano zinc oxide (ZnO NPs), non-nano ZnO and ionic ZnCl2 to the earthworm Eisenia fetida in a natural soil at three pH levels. NP characterisation indicated that reaction with the soil media greatly controls ZnO properties. Three main conclusions were drawn. First that Zn toxicity, especially for reproduction, was influenced by pH for all Zn forms. This can be linked to the influence of pH on Zn dissolution. Secondly, that ZnO fate, toxicity and bioaccumulation were similar (including relationships with pH) for both ZnO forms, indicating the absence of NP-specific effects. Finally, earthworm Zn concentrations were higher in worms exposed to ZnO compared to ZnCl2, despite the greater toxicity of the ionic form. This observation suggests the importance of considering the relationship between uptake and toxicity in nanotoxicology studies.
TL;DR: The findings suggest that silver nanoparticles may indeed overcome the gastrointestinal juices in their particulate form without forming large quantities of aggregates, and presume that the particles can reach the intestinal epithelial cells after ingestion with only a slight reduction in their cytotoxic potential.
Abstract: Orally ingested nanoparticles may overcome the gastrointestinal barrier, reach the circulatory system, be distributed in the organism and cause adverse health effects. However, ingested nanoparticles have to pass through different physicochemical environments, which may alter their properties before they reach the intestinal cells. In this study, silver nanoparticles are characterised physicochemically during the course of artificial digestion to simulate the biochemical processes occurring during digestion. Their cytotoxicity on intestinal cells was investigated using the Caco-2 cell model. Using field-flow fractionation combined with dynamic light scattering and small-angle X-ray scattering, the authors found that particles only partially aggregate as a result of the digestive process. Cell viabilities were determined by means of CellTiter-Blue® assay, 4',6-diamidino-2-phenylindole-staining and real-time impedance. These measurements reveal small differences between digested and undigested particles (1-100 µg/ml or 1-69 particles/cell). The findings suggest that silver nanoparticles may indeed overcome the gastrointestinal juices in their particulate form without forming large quantities of aggregates. Consequently, the authors presume that the particles can reach the intestinal epithelial cells after ingestion with only a slight reduction in their cytotoxic potential. The study indicates that it is important to determine the impact of body fluids on the nanoparticles of interest to provide a reliable interpretation of their nano-specific cytotoxicity testing in vivo and in vitro.
TL;DR: It is demonstrated that ZnONPs cause cardiopulmonary impairments and the findings highlight the occupational health effects for ZnonP-exposed workers.
Abstract: Exposure to zinc oxide (ZnO) metal fumes is linked to adverse human health effects; however, the hazards of ZnO nanoparticles (ZnONPs) remain unclear. To determine pulmonary exposure to occupationally relevant ZnONPs cause cardiopulmonary injury, Sprague-Dawley rats were exposed toZnONPs via intratracheal (IT) instillation and inhalation. The relationship between intrapulmonary zinc levels and pulmonary oxidative-inflammatory responses 72 h after ZnONP instillation was determined in bronchoalveolar lavage fluid (BALF). Instilled ZnONPs altered zinc balance and increased the levels of total cells, neutrophils, lactate dehydrogenase (LDH) and total protein in BALF and 8-hydroxy-2¢deoxyguanosine (8-OHdG) in blood after 72 h. The ZnONPs accumulated predominantly in the lungs over 24 h, and trivial amounts of zinc were determined in the heart, liver, kidneys and blood. Furthermore, the inflammatory-oxidative responses induced by occupationally relevant levels of 1.1 and 4.9 mg/m 3 of ZnONP inhalation for 2 weeks were determined in BALF and blood at 1, 7 and 30 days post-exposure. Histopathological examinations of the rat lungs and hearts were performed. Inhalation of ZnONP caused an inflammatory cytological profile. The total cell, neutrophil, LDH and total protein levels were acutely increased in the BALF, and there was an inflammatory pathology in the lungs. There were subchronic levels of white blood cells, granulocytes and 8-OHdG in the blood. Cardiac inflammation and the development of fibrosis were detected 7 days after exposure. Degeneration and necrosis of the myocardium were detected 30 days after exposure. The results demonstrate that ZnONPs cause cardiopulmonary impairments. These findings highlight the occupational health effects for ZnONP-exposed workers.
TL;DR: The differential silver nanoparticle–silver nitrate response indicates that the toxic effect of labile Ag(I) in the system depends upon the mechanism of delivery to the target cell.
Abstract: We report the whole-transcriptome response of Escherichia coli bacteria to acute treatment with silver nanoparticles (AgNPs) or silver ions [Ag(I)] as silver nitrate using gene expression microarrays. In total, 188 genes were regulated by both silver treatments, 161 were up-regulated and 27 were down-regulated. Significant regulation was observed for heat shock response genes in line with protein denaturation associated with protein structure vulnerability indicating Ag(I)-labile -SH bonds. Disruption to iron-sulphur clusters led to the positive regulation of iron-sulphur assembly systems and the expression of genes for iron and sulphate homeostasis. Further, Ag ions induced a redox stress response associated with large (>600-fold) up-regulation of the E. coli soxS transcriptional regulator gene. Ag(I) is isoelectronic with Cu(I), and genes associated with copper homeostasis were positively regulated indicating Ag(I)-activation of copper signalling. Differential gene expression was observed for the silver nitrate and AgNP silver delivery. Nanoparticle delivery of Ag(I) induced the differential regulation of 379 genes; 309 genes were uniquely regulated by silver nanoparticles and 70 genes were uniquely regulated by silver nitrate. The differential silver nanoparticle-silver nitrate response indicates that the toxic effect of labile Ag(I) in the system depends upon the mechanism of delivery to the target cell.
TL;DR: It is revealed that the morphologies, ion release rate of NPs as well as the species-specific vulnerabilities of cells should all be considered when explaining and extrapolating toxicity test results among particles and among species.
Abstract: The four copper nanoparticles (CuNPs) with the size of 25, 50, 78 and 100 nm and one type of micron-sized particles (MPs) (~500 nm) were exposed to two mammalian (H4IIE and HepG2) and two piscine (PLHC-1 and RTH-149) cell lines to test the species-specific toxicities of CuNPs. The results showed that the morphologies, ion release and size of the particles all played an important role when investigating the toxicity. Furthermore, the authors found that the particle forms of CuNPs in suspensions highly contribute to the toxicity in all exposed cell lines whereas copper ions (Cu(2+)) only caused significant responses in mammalian cell lines, indicating the species-specific toxicity of CuNPs. This study revealed that the morphologies, ion release rate of NPs as well as the species-specific vulnerabilities of cells should all be considered when explaining and extrapolating toxicity test results among particles and among species.
TL;DR: The results suggest that in vivo pathogenicity of the BMWCNT and FMWCNT correlates with activation of the NLRP3 inflammasome in the lung.
Abstract: The current study tests the hypothesis that multi-walled carbon nanotubes (MWCNT) with different surface chemistries exhibit different bioactivity profiles in vivo. In addition, the study examined the potential contribution of the NLRP3 inflammasome in MWCNT-induced lung pathology. Unmodified (BMWCNT) and MWCNT that were surface functionalised with -COOH (FMWCNT), were instilled into C57BL/6 mice. The mice were then examined for biomarkers of inflammation and injury, as well as examined histologically for development of pulmonary disease as a function of dose and time. Biomarkers for pulmonary inflammation included cytokines, mediators and the presence of inflammatory cells (IL-1β, IL-18, IL-33, cathepsin B and neutrophils) and markers of injury (albumin and lactate dehydrogenase). The results show that surface modification by the addition of the -COOH group to the MWCNT, significantly reduced the bioactivity and pathogenicity. The results of this study also suggest that in vivo pathogenicity of t...
TL;DR: In this article, the bioavailability, toxicity, and transfer of silver nanoparticles (AgNPs) in comparison with AgNO3 in two model food chain organisms: the alga Chlamydomonas reinhardtii and the grazing crustacean Daphnia magna were evaluated.
Abstract: This study assessed the bioavailability, toxicity, and transfer of silver nanoparticles (AgNPs) in comparison with AgNO3 in two model food chain organisms: the alga Chlamydomonas reinhardtii and the grazing crustacean Daphnia magna. The effects of phosphate, a potential Ag(+)-binding ligand and a determinant of phytoplankton productivity, were evaluated. Nano Ag derived from coated AgNPs and AgNO3 was accumulated at similar concentrations into microalgae during high phosphate treatment, but AgNO3 accumulation was increased by low phosphate availability. After feeding on Ag-containing algae, D. magna equally accumulated AgNO3 and nano-derived Ag. There were significant reductions in feeding when D. magna were fed Ag-contaminated algae, with the AgNO3, low phosphate-exposed cells being ingested the least. Nutritional quality characteristics including fatty acid and trace nutrient content were similar in all algal samples, indicating that feeding reduction is specifically due to the presence of Ag, with AgNO3 being more toxic than nano Ag.
TL;DR: An integrated toxicology evaluation showed that the proposed nanotheranostics strategy does not exhibit significant toxicity, which is extremely relevant when translating into in vivo systems.
Abstract: Antisense therapy is a powerful tool for post-transcriptional gene silencing suitable for down-regulating target genes associated to disease. Gold nanoparticles have been described as effective intracellular delivery vehicles for antisense oligonucleotides providing increased protection against nucleases and targeting capability via simple surface modification. We constructed an antisense gold-nanobeacon consisting of a stem-looped oligonucleotide double-labelled with 3′-Cy3 and 5′-Thiol-C6 and tested for the effective blocking of gene expression in colorectal cancer cells. Due to the beacon conformation, gene silencing was directly detected as fluorescence increases with hybridisation to target, which can be used to assess the level of silencing. Moreover, this system was extensively evaluated for the genotoxic, cytotoxic and proteomic effects of gold-nanobeacon exposure to cancer cells. The exposure was evaluated by two-dimensional protein electrophoresis followed by mass spectrometry to perform...
TL;DR: Dosimetry modelling and experimental measurements reveal that on a delivered surface area basis, large and small agglomerates of carboxylated IONPs have similar inherent potency for the generation of ROS, induction of stress-related genes and eventual cytotoxicity, and reactive moieties on the Agglomerate surface are more efficient in catalysing cellular ROS production than molecules buried within the agglomersate core.
Abstract: Spontaneous agglomeration of engineered nanoparticles (ENPs) is a common problem in cell culture media which can confound interpretation of in vitro nanotoxicity studies. The authors created stable agglomerates of iron oxide nanoparticles (IONPs) in conventional culture medium, which varied in hydrodynamic size (276 nm-1.5 μm) but were composed of identical primary particles with similar surface potentials and protein coatings. Studies using C10 lung epithelial cells show that the dose rate effects of agglomeration can be substantial, varying by over an order of magnitude difference in cellular dose in some cases. Quantification by magnetic particle detection showed that small agglomerates of carboxylated IONPs induced greater cytotoxicity and redox-regulated gene expression when compared with large agglomerates on an equivalent total cellular IONP mass dose basis, whereas agglomerates of amine-modified IONPs failed to induce cytotoxicity or redox-regulated gene expression despite delivery of similar cellular doses. Dosimetry modelling and experimental measurements reveal that on a delivered surface area basis, large and small agglomerates of carboxylated IONPs have similar inherent potency for the generation of ROS, induction of stress-related genes and eventual cytotoxicity. The results suggest that reactive moieties on the agglomerate surface are more efficient in catalysing cellular ROS production than molecules buried within the agglomerate core. Because of the dynamic, size and density-dependent nature of ENP delivery to cells in vitro, the biological consequences of agglomeration are not discernible from static measures of exposure concentration (μg/ml) alone, highlighting the central importance of integrated physical characterisation and quantitative dosimetry for in vitro studies. The combined experimental and computational approach provides a quantitative framework for evaluating relationships between the biocompatibility of nanoparticles and their physical and chemical characteristics.
TL;DR: It is demonstrated that the AgNPs can reach mouse bone marrow and liver, and generate cytotoxicity to the reticulocytes and oxidative DNA damage to the liver.
Abstract: Silver nanoparticles (AgNPs) are among the most commercially used nanomaterials and their toxicity and genotoxicity are controversial. Although many in vitro studies have been conducted to evaluate...
TL;DR: Antioxidant enzymes and cardiovascular markers, inflammation and oxidative stress markers, antioxidant enzymes and genotoxicity markers, and lung function tests are possible markers that could be useful for surveillance of nanomaterial-handling workers.
Abstract: The aim of this study was to identify the health hazards and possible exposure surveillance markers of workers exposed to nanoparticles during manufacturing and application in comparison to a group of unexposed workers. For this longitudinal study, we recruited 158 nanomaterial-handling workers and 104 non-exposed workers from 14 manufacturing plants in Taiwan (baseline). Among them, 124 nanomaterial-handling workers and 77 unexposed workers were monitored 6 months later. We investigated pulmonary and cardiovascular disease markers, inflammation and oxidative stress markers, antioxidant enzymes and genotoxicity markers. Antioxidant enzymes (superoxide dismutase, glutathione peroxidase) and cardiovascular markers (vascular cell adhesion molecule, paraoxonase) were significantly associated with nanomaterial-handling during the 6-month follow-up period. In addition, the small airway damage marker (Clara cell protein 16) and lung function test parameters were also significantly associated with handling nanomaterials. The study markers and lung function tests are possible markers that could be useful for surveillance of nanomaterial-handling workers.
TL;DR: Results indicate nano-TiO2 enhances BDE-209 bioavailability and metabolism, leading to thyroid endocrine disruption and developmental neurotoxicity in zebrafish.
Abstract: Interactions between organic toxicants and nanoparticles (NPs) in the aquatic environment may modify toxicant bioavailability and consequently the toxicant's environmental fate and toxicity. Therefore, we investigated the influence of titanium dioxide NPs (nano-TiO2) on deca-BDE (BDE-209; a polybrominated diphenyl ether congener) bioconcentration, metabolism and its effects on the thyroid endocrine system in zebrafish (Danio rerio) larvae. Zebrafish embryos were exposed to various concentrations of BDE-209 alone or in combination with nano-TiO2 (0.1 mg/L) until 7-day post-fertilization. Nano-TiO2 can adsorb BDE-209 and nano-TiO2 is taken up into developing zebrafish larvae. Chemical measurements showed that BDE-209 was bioconcentrated and metabolized in zebrafish larvae, and BDE-209 uptake was enhanced by nano-TiO2. Furthermore, increased BDE-209 metabolites were detected in larvae co-exposed with nano-TiO2. BDE-209 exposure significantly increased whole-body thyroid hormone contents (T-3 and T-4); T-4 content significantly increased in the larvae co-exposed with nano-TiO2. Nano-TiO2 exposure alone did not induce generation of reactive oxygen species, lipid peroxidative oxidation, gene transcription or thyroid hormone levels. Upregulation of several gene transcriptions (tsh beta, tg, diO(2)) in the hypothalamic-pituitary-thyroid axis was also observed. Furthermore, co-exposure of nano-TiO2 and BDE-209 caused a decrease in locomotion activity and downregulation of specific genes and proteins involved in the central nervous system of developing zebrafish larvae (e.g. myelin basic protein and alpha 1-tubulin). These results indicate nano-TiO2 enhances BDE-209 bioavailability and metabolism, leading to thyroid endocrine disruption and developmental neurotoxicity in zebrafish.
TL;DR: It is proved that particle functionalization influences the stability of the particle corona which, if intact, prevents hemolytic activity and membrane disrupture.
Abstract: Nano materials are commonly functionalized to boost their physicochemical properties. However, there is little known about the impact of these modifications on cellular systems. Herein, we synthesized eight types of polymeric nanoparticles (NPs) bearing different functional groups, and investigated their effects on interactions with cellular membranes. As models for particle membrane interactions, hemolysis assays using human red blood cells and culture with A549 cells were utilized. Under protein-free conditions, the NPs showed a wide distribution of zeta potentials (ζPs) which showed a good correlation with their hemolytic potential. However, in the presence of serum or lung lining fluid, the ζPs of all NPs coalesced towards a single common negative value and showed neither hemolytic activity nor cytotoxicity to A549 cells. Lipase and protease treatment of the coronated particles did not restore their reactivity. These result simply proves that particle functionalization influences the stability of the particle corona which, if intact, prevents hemolytic activity and membrane disrupture.
TL;DR: It was determined that the main mechanism of hatch inhibition by NPs is likely through the interaction of NPs with the zebrafish hatching enzyme and that the observed effects arose from the NPs themselves and not their dissolved metal components.
Abstract: Aquatic organisms are susceptible to waterborne nanoparticles (NP) and there is only limited understanding of the mechanisms by which these emerging contaminants may affect biological processes. This study used silicon (nSi), cadmium selenide (nCdSe), silver (nAg) and zinc NPs (nZnO) as well as single-walled carbon nanotubes (SWCNT) to assess NP effects on zebrafish (Danio rerio) hatch. Exposure of 10 mg/L nAg and nCdSe delayed zebrafish hatch and 100 mg/L of nCdSe as well as 10 and 100 mg/L of uncoated nZnO completely inhibited hatch and the embryos died within the chorion. Both the morphology and the movement of the embryos were not affected, and it was determined that the main mechanism of hatch inhibition by NPs is likely through the interaction of NPs with the zebrafish hatching enzyme. Furthermore, it was concluded that the observed effects arose from the NPs themselves and not their dissolved metal components.
TL;DR: Copper oxide nanoparticles with different shapes were used to examine the effect of shape on the various physicochemical properties and the behaviour by which CuO nanoparticles exhibit their biological response towards alveolar type-I cells.
Abstract: Copper oxide nanoparticles with different shapes were used to examine the effect of shape on the various physicochemical properties (reactivity, aggregation, suspension stability) and to examine the behaviour by which CuO nanoparticles exhibit their biological response towards alveolar type-I cells. The different shapes examined in this study include spherical-, rod- and spindle-shaped platelet particles. In vitro dissolution studies (7 days) in 1 mM NaNO3 matrix showed a marked difference in dissolved Cu release between the nanoparticles. However, in serum-free cell-culture media (exposure media to cells), the particles' dissolution was found to be significantly enhanced with close to complete dissolution reported for all particle types. Biological studies showed both shape and size of the CuO nanoparticles tested to have a significant effect on TT-1 cell viability and release of pro-inflammatory cytokines IL-6 and IL-8. This study shows a complex interplay between particulate and dissolved species triggering the biological response. Upon immediate exposure of CuO nanoparticles of different shapes, the particulate form contributes towards the toxicity. However, for any biological response observed over and beyond a period of 24 h, the dissolved fraction becomes significant.
TL;DR: The acute toxicity of Ag-NPs <20 nm alone and upon co-administration with food matrix component phenolic compounds (PCs) on the cell-based models of the gastrointestinal tract was investigated and it was demonstrated that the protective effect could be beneficial and decrease the potential toxicity of ingested Ag- NPs.
Abstract: The increasing commercial use of silver nanoparticles (Ag-NPs) will inevitably lead to elevated silver exposure and thus to potential human health complications. In this study the acute toxicity of Ag-NPs <20 nm alone and upon co-administration with food matrix component phenolic compounds (PCs) on the cell-based models of the gastrointestinal tract was investigated. An improved co-culture model of Caco-2 and RajiB cells was applied for more precise in vitro simulation of the gastrointestinal tract. The involvement of two major factors contributing to the toxicity of Ag-NPs, i.e. the release of Ag(+) and the induction of oxidative stress, was investigated. Ag-NPs were cytotoxic for Caco-2 cells with an EC50 of ca. 40 µg/ml. Ag-NPs led to oxidative stress starting from ca. 45 µg/ml. The epithelial barrier integrity disruption by Ag-NPs on Caco-2 cell mono- and co-cultures was established by decreased transepithelial electrical resistances and increased passages of Lucifer Yellow, a paracellular marker. Immunofluorescence staining demonstrated that Ag-NPs affect occludin and zonula occludens 1 distributions, suggesting the opening of tight junctions. Ag(+), corresponding to the release from Ag-NPs, demonstrated a partial contribution in the toxic parameters, induced by Ag-NPs. Two PCs, quercetin and kaempferol, partially protected the Caco-2 cells from Ag-NP-induced toxicity and maintained the epithelial barrier integrity, disrupted by NPs. No protective effect was observed for resveratrol. The protective effect could be beneficial and decrease the potential toxicity of ingested Ag-NPs. However, the precise mechanisms of barrier-integrity-destabilising action of Ag-NPs/Ag(+) and protective effect of PCs still require further elucidation.
TL;DR: It is concluded that, following short-term inhalation of solid QD nanoparticles, there is rapid olfactory uptake and axonal transport to the brain/olfactory bulb with observed activation of microglial cells, indicating a pro-inflammatory response.
Abstract: Nanoparticles are of wide interest due to their potential use for diverse commercial applications. Quantum dots (QDs) are semiconductor nanocrystals possessing unique optical and electrical properties. Although QDs are commonly made of cadmium, a metal known to have neurological effects, potential transport of QDs directly to the brain has not been assessed. This study evaluated whether QDs (CdSe/ZnS nanocrystals) could be transported from the olfactory tract to the brain via inhalation. Adult C57BL/6 mice were exposed to an aerosol of QDs for 1 h via nasal inhalation, and nanoparticles were detected 3 h post-exposure within the olfactory tract and olfactory bulb by a wide range of techniques, including visualisation via fluorescent and transmission electron microscopy. We conclude that, following short-term inhalation of solid QD nanoparticles, there is rapid olfactory uptake and axonal transport to the brain/olfactory bulb with observed activation of microglial cells, indicating a pro-inflammatory response. To our knowledge, this is the first study to clearly demonstrate that QDs can be rapidly transported from the nose to the brain by olfactory uptake via axonal transport following inhalation.
TL;DR: Long-term exposure of the cells to occupationally relevant concentrations of CNT in culture caused a neoplastic-like transformation phenotype as demonstrated by increased cell proliferation, anchorage-independent growth, invasion and angiogenesis.
Abstract: Accumulating evidence indicates that carbon nanotubes (CNTs) are biopersistent and can cause lung damage. With similar fibrous morphology and mode of exposure to asbestos, a known human carcinogen, growing concern has arisen for elevated risk of CNT-induced lung carcinogenesis; however, relatively little is known about the long-term carcinogenic effect of CNT. Neoplastic transformation is a key early event leading to carcinogenesis. We studied the ability of single- and multi-walled CNTs to induce neoplastic transformation of human lung epithelial cells compared to asbestos. Long-term (6-month) exposure of the cells to occupationally relevant concentrations of CNT in culture caused a neoplastic-like transformation phenotype as demonstrated by increased cell proliferation, anchorage-independent growth, invasion and angiogenesis. Whole-genome expression signature and protein expression analyses showed that single- and multi-walled CNTs shared similar signaling signatures which were distinct from asb...
TL;DR: Toxicity endpoints of reproduction/developmental screening test including mating, fertility, implantation, delivery and foetus were measured and there was no evidence of toxicity.
Abstract: Combined repeated-dose toxicity study of citrate-capped silver nanoparticles (7.9 ± 0.95 nm) with reproduction/developmental toxicity was investigated in rats orally treated with 62.5, 125 and 250 mg/kg, once a day for 42 days for males and up to 52 days for females. The test was performed based on the Organization for Economic Cooperation and Development test guideline 422 and Good Laboratory Practice principles. No death was observed in any of the groups. Alopecia, salivation and yellow discolouration of the lung were observed in a few rats but the symptoms were not dose-dependent. Haematology, serum biochemical investigation and histopathological analysis revealed no statistically significant differences between control group and the treated groups. Toxicity endpoints of reproduction/developmental screening test including mating, fertility, implantation, delivery and foetus were measured. There was no evidence of toxicity.
TL;DR: It is found that FG significantly enhances the cytotoxicity and the inflammatory response induced by SiO2, carbon and TiO2 NMs on alveolar macrophages, which underline the critical role played by FG in the toxic response to NMs.
Abstract: Many studies have shown that the composition of the protein corona dramatically affects the response of cells to nanomaterials (NMs). However, the role of each single protein is still largely unknown. Fibrinogen (FG), one of the most abundant plasma proteins, is believed to mediate foreign-body reactions. Since this protein is absent in cell media used in in vitro toxicological tests the possible FG-mediated effects have not yet been assessed. Here, the effect of FG on the toxicity of three different kinds of inorganic NMs (carbon, SiO2 and TiO2) on alveolar macrophages has been investigated. A set of integrated techniques (UV–vis spectroscopy, dynamic light scattering and sodium dodecyl sulphate-polyacrylamide gel electrophoresis) have been used to study the strength and the kinetics of interaction of FG with the NMs. The inflammatory response of alveolar macrophages (MH-S) exposed to the three NMs associated with FG has also been investigated. We found that FG significantly enhances the cytotoxi...