Showing papers in "Nanotoxicology in 2017"
TL;DR: This is the first review paper evaluating the current state of knowledge regarding the joint effects of NPs and co-contaminationants and future research needs are discussed so as to better understand risk associated with NPs-contaminant co-exposure.
Abstract: With their growing production and application, engineered nanoparticles (NPs) are increasingly discharged into the environment. The released NPs can potentially interact with pre-existing contaminants, leading to biological effects (bioaccumulation and/or toxicity) that are poorly understood. Most studies on NPs focus on single analyte exposure; the existing literature on joint toxicity of NPs and co-existing contaminants is rather limited but beginning to develop rapidly. This is the first review paper evaluating the current state of knowledge regarding the joint effects of NPs and co-contaminants. Here, we review: (1) methods for investigating and evaluating joint effects of NPs and co-contaminants; (2) simultaneous toxicities from NPs co-exposed with organic contaminants, metal/metalloid ions, dissolved organic matter (DOM), inorganic ligands and additional NPs; and (3) the influence of NPs co-exposure on the bioaccumulation of organic contaminants and heavy metal ions, as well as the influence...
217 citations
TL;DR: Application of a dual layered silver–HA nanocoating to titanium alloy implants creates a surface with antibiofilm properties without compromising the HA biocompatibility required for successful osseointegration and accelerated bone healing.
Abstract: One of the most common causes of implant failure is peri-implantitis, which is caused by bacterial biofilm formation on the surfaces of dental implants. Modification of the surface nanotopography has been suggested to affect bacterial adherence to implants. Silver nanoparticles are also known for their antibacterial properties. In this study, titanium alloy implants were surface modified following silver plating, anodisation and sintering techniques to create a combination of silver, titanium dioxide and hydroxyapatite (HA) nanocoatings. Their antibacterial performance was quantitatively assessed by measuring the growth of Streptococcus sanguinis, proportion of live/dead cells and lactate production by the microbes over 24 h. Application of a dual layered silver-HA nanocoating to the surface of implants successfully inhibited bacterial growth in the surrounding media (100% mortality), whereas the formation of bacterial biofilm on the implant surfaces was reduced by 97.5%. Uncoated controls and titanium dioxide nanocoatings showed no antibacterial effect. Both silver and HA nanocoatings were found to be very stable in biological fluids with material loss, as a result of dissolution, to be less than 0.07% for the silver nanocoatings after 24 h in a modified Krebs-Ringer bicarbonate buffer. No dissolution was detected for the HA nanocoatings. Thus, application of a dual layered silver-HA nanocoating to titanium alloy implants creates a surface with antibiofilm properties without compromising the HA biocompatibility required for successful osseointegration and accelerated bone healing.
141 citations
TL;DR: Copper(II) oxide nanoparticles (NPCuO) generate significantly more ROS and DNA damage in the presence of ascorbate than can be explained simply from dissolved copper, and the NPCuO surface must play a large role.
Abstract: Copper(II) oxide nanoparticles (NPCuO) have many industrial applications, but are highly cytotoxic because they generate reactive oxygen species (ROS). It is unknown whether the damaging ROS are generated primarily from copper leached from the nanoparticles, or whether the nanoparticle surface plays a significant role. To address this question, we separated nanoparticles from the supernatant containing dissolved copper, and measured their ability to damage plasmid DNA with addition of hydrogen peroxide, ascorbate, or both. While DNA damage from the supernatant (measured using an electrophoresis assay) can be explained solely by dissolved copper ions, damage by the nanoparticles in the presence of ascorbate is an order of magnitude higher than can be explained by dissolved copper and must, therefore, depend primarily upon the nanoparticle surface. DNA damage is time-dependent, with shorter incubation times resulting in higher EC50 values. Hydroxyl radical (•OH) is the main ROS generated by NPCuO/hydrogen peroxide as determined by EPR measurements; NPCuO/hydrogen peroxide/ascorbate conditions generate ascorbyl, hydroxyl, and superoxide radicals. Thus, NPCuO generate ROS through several mechanisms, likely including Fenton-like and Haber-Weiss reactions from the surface or dissolved copper ions. The same radical species were observed when NPCuO suspensions were replaced with the supernatant containing leached copper, washed NPCuO, or dissolved copper solutions. Overall, NPCuO generate significantly more ROS and DNA damage in the presence of ascorbate than can be explained simply from dissolved copper, and the NPCuO surface must play a large role.
129 citations
TL;DR: Since chronic, oral uptake of TiO2 particles by consumers has continuously increased in the past decades, the possibility of chronic accumulation of such biopersistent nanoparticles in secondary organs and the skeleton raises questions about the responsiveness of their defense capacities, and whether these could be leading to adverse health effects in the population at large.
Abstract: The biokinetics of a size-selected fraction (70 nm median size) of commercially available and 48V-radiolabeled [48V]TiO2 nanoparticles has been investigated in female Wistar-Kyoto rats at retention timepoints 1 h, 4 h, 24 h and 7 days after oral application of a single dose of an aqueous [48V]TiO2-nanoparticle suspension by intra-esophageal instillation. A completely balanced quantitative body clearance and biokinetics in all organs and tissues was obtained by applying typical [48V]TiO2-nanoparticle doses in the range of 30–80 μg•kg−1 bodyweight, making use of the high sensitivity of the radiotracer technique. The [48V]TiO2-nanoparticle content was corrected for nanoparticles in the residual blood retained in organs and tissue after exsanguination and for 48V-ions not bound to TiO2-nanoparticles. Beyond predominant fecal excretion about 0.6% of the administered dose passed the gastro-intestinal-barrier after one hour and about 0.05% were still distributed in the body after 7 days, with quantifiabl...
116 citations
TL;DR: The results support the hypothesis that intra-cellular AgNP dissociate into high toxic Ag+.
Abstract: The rapid growth in silver nanoparticles (AgNPs) commercialization has increased environmental exposure, including aquatic ecosystem. It has been reported that the AgNPs have damaging effects on photosynthesis and induce oxidative stress, but the toxic mechanism of AgNPs is still a matter of debate. In the present study on the model aquatic higher plant Spirodela polyrhiza, we found that AgNPs affect photosynthesis and significantly inhibit Photosystem II (PSII) maximum quantum yield (Fv/Fm) and effective quantum yield (ΦPSII). The changes of non-photochemical fluorescence quenching (NPQ), light-induced non-photochemical fluorescence quenching [Y(NPQ)] and non-light-induced non-photochemical fluorescence quenching [Y(NO)] showed that AgNPs inhibit the photo-protective capacity of PSII. AgNPs induce reactive oxygen species (ROS) that are mainly produced in the chloroplast. The activity of ribulose-1, 5-bisphosphate carboxylase–oxygenase (Rubisco) was also very sensitive to AgNPs. The internalized Ag, regardless of whether the exposure was Ag+ or AgNPs had the same capacity to generate ROS. Our results support the hypothesis that intra-cellular AgNP dissociate into high toxic Ag+. Rubisco inhibition leads to slowing down of CO2 assimilation. Consequently, the solar energy consumption decreases and then the excess excitation energy promotes ROS generation in chloroplast.
102 citations
TL;DR: Human hepatic uptake of 40 and 80 nm AuNP with branched polyethylenimine (BPEI), lipoic acid (LA) and polyethylene glycol (PEG) coatings as well as human plasma protein (HP) and human serum albumin (HSA) coronas was investigated to better understanding of the dramatic effect of protein coronas (PC) on AuNP cellular uptake, cytotoxicity and their underlying molecular mechanisms of action.
Abstract: Protein corona formation over gold nanoparticles (AuNP) can modulate cellular responses by altering AuNP physicochemical properties. The liver plays an essential role in metabolism, detoxification and elimination of xenobiotics and drugs as well as circulating NP clearance. We investigated human hepatic uptake of 40 and 80 nm AuNP with branched polyethylenimine (BPEI), lipoic acid (LA) and polyethylene glycol (PEG) coatings as well as human plasma protein (HP) and human serum albumin (HSA) coronas. AuNP-mediated cytotoxicity, reactive oxygen/reactive nitrogen species (ROS/RNS), and CYP activity in human hepatocytes as well as molecular mechanisms with 40 nm bare and HP BPEI–AuNP were investigated. Time-dependent increase in uptake occurred for all bare AuNP but HP and HSA decreased uptake except for 40 nm HP PEG–AuNP. BPEI–AuNP showed time-and concentration-dependent increase in ROS/RNS which correlated with cytotoxicity at 24 h. HP corona substantially reduced ROS/RNS. The 40 and 80 nm bare, HP o...
100 citations
TL;DR: Data show that E171 induces only moderate toxicity in epithelial intestinal cells, via oxidation, which is less intense after acute exposure compared to repeated exposure, which correlated with higher Ti accumulation.
Abstract: The whitening and opacifying properties of titanium dioxide (TiO2) are commonly exploited when it is used as a food additive (E171). However, the safety of this additive can be questioned as TiO2 nanoparticles (TiO2-NPs) have been classed at potentially toxic. This study aimed to shed some light on the mechanisms behind the potential toxicity of E171 on epithelial intestinal cells, using two in vitro models: (i) a monoculture of differentiated Caco-2 cells and (ii) a coculture of Caco-2 with HT29-MTX mucus-secreting cells. Cells were exposed to E171 and two different types of TiO2-NPs, either acutely (6–48 h) or repeatedly (three times a week for 3 weeks). Our results confirm that E171 damaged these cells, and that the main mechanism of toxicity was oxidation effects. Responses of the two models to E171 were similar, with a moderate, but significant, accumulation of reactive oxygen species, and concomitant downregulation of the expression of the antioxidant enzymes catalase, superoxide dismutase a...
99 citations
TL;DR: It is proved that NPs are able to reach and cross the mouse placenta and suggest that precaution should be taken with respect to acute exposure to nanoparticles during pregnancy.
Abstract: Recently, interest for the potential impact of consumer-relevant engineered nanoparticles on pregnancy has dramatically increased. This study investigates whether inhaled silver nanoparticles (AgNPs) reach and cross mouse placental barrier and induce adverse effects. Apart from their relevance for the growing use in consumer products and biomedical applications, AgNPs are selected since they can be unequivocally identified in tissues. Pregnant mouse females are exposed during the first 15 days of gestation by nose-only inhalation to a freshly produced aerosol of 18-20 nm AgNPs for either 1 or 4 h, at a particle number concentration of 3.80 × 107 part./cm-3 and at a mass concentration of 640 μg/m³. AgNPs are identified and quantitated in maternal tissues, placentas and foetuses by transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy and single-particle inductively coupled plasma mass spectrometry. Inhalation of AgNPs results in increased number of resorbed foetuses associated with reduced oestrogen plasma levels, in the 4 h/day exposed mothers. Increased expression of pregnancy-relevant inflammatory cytokines is also detected in the placentas of both groups. These results prove that NPs are able to reach and cross the mouse placenta and suggest that precaution should be taken with respect to acute exposure to nanoparticles during pregnancy.
98 citations
TL;DR: NP surface chemistry is shown to play the dominant role over size in determining the biocorona composition, which in turn modulates cell uptake, and biological responses, consequently defining the potential safety and efficacy of nanoformulations.
Abstract: This study investigated the role of nanoparticle size and surface chemistry on biocorona composition and its effect on uptake, toxicity and cellular responses in human umbilical vein endothelial cells (HUVEC), employing 40 and 80 nm gold nanoparticles (AuNP) with branched polyethyleneimine (BPEI), lipoic acid (LA) and polyethylene glycol (PEG) coatings. Proteomic analysis identified 59 hard corona proteins among the various AuNP, revealing largely surface chemistry-dependent signature adsorbomes exhibiting human serum albumin (HSA) abundance. Size distribution analysis revealed the relative instability and aggregation inducing potential of bare and corona-bound BPEI-AuNP, over LA- and PEG-AuNP. Circular dichroism analysis showed surface chemistry-dependent conformational changes of proteins binding to AuNP. Time-dependent uptake of bare, plasma corona (PC) and HSA corona-bound AuNP (HSA-AuNP) showed significant reduction in uptake with PC formation. Cell viability studies demonstrated dose-depende...
97 citations
TL;DR: The observations point to the possibility that fruits, seeds and other edible parts may become contaminated by translocation processes in plants exposed to AgNPs, and an important contribution to improve the risk assessment of NPs under environmental exposure scenarios.
Abstract: The widespread use of silver nanoparticles (AgNPs) raises concerns both about their accumulation in crops and human exposure via crop consumption. Plants take up AgNPs through their leaves and roots, but foliar uptake has been largely ignored. To better understand AgNPs–plant interactions, we compared the uptake, phytotoxicity and size distribution of AgNPs in soybean and rice following root versus foliar exposure. At similar AgNP application levels, foliar exposure led to 17–200 times more Ag bioaccumulation than root exposure. Root but not foliar exposure significantly reduced plant biomass, while root exposure increased the malondialdehyde and H2O2 contents of leaves to a larger extent than did foliar exposure. Following either root or foliar exposure, Ag-containing NPs larger (36.0–48.9 nm) than the originally dosed NPs (17–18 nm) were detected within leaves. These particles were detected using a newly developed macerozyme R-10 tissue extraction method followed by single-particle inductively c...
97 citations
TL;DR: It is highlighted that PS-NH2 are able to disrupt sea urchin embryos development by modulating protein and gene profile providing new understandings into the signalling pathways involved.
Abstract: Polystyrene nanoparticles have been shown to pose serious risk to marine organisms including sea urchin embryos based on their surface properties and consequently behaviour in natural sea water. The aim of this study is to investigate the toxicity pathways of amino polystyrene nanoparticles (PS-NH2, 50 nm) in Paracentrotus lividus embryos in terms of development and signalling at both protein and gene levels. Two sub-lethal concentrations of 3 and 4 μg/mL of PS-NH2 were used to expose sea urchin embryos in natural sea water (PS-NH2 as aggregates of 143 ± 5 nm). At 24 and 48 h post-fertilisation (hpf) embryonic development was monitored and variations in the levels of key proteins involved in stress response and development (Hsp70, Hsp60, MnSOD, Phospho-p38 Mapk) as well as the modulation of target genes (Pl-Hsp70, Pl-Hsp60, Pl-Cytochrome b, Pl-p38 Mapk, Pl-Caspase 8, Pl-Univin) were measured. At 48 hpf various striking teratogenic effects were observed such as the occurrence of cells/masses random...
TL;DR: The theoretical results obtained are strongly consistent with the experimental evidence found in the literature, suggesting that the present QSTR-perturbation model can be viewed as a promising and reliable computational tool for probing the toxicity of NPs.
Abstract: Nanoparticles (NPs) are part of our daily life, having a wide range of applications in engineering, physics, chemistry, and biomedicine. However, there are serious concerns regarding the harmful ef...
TL;DR: The unintentional adsorption of LPS onto the NP surface can affect the biocorona formation and the inflammatory properties of NPs.
Abstract: Nanoparticles (NPs) are easily contaminated by bacterial endotoxin (lipopolysaccharide [LPS]). The presence of LPS can be responsible for many immune/inflammatory effects attributed to NPs. In this study, we examined the effects of LPS adsorption on the NP surface on the formation of a biocorona in biological fluids and on the subsequent inflammation-inducing activity of NPs. Different gold (Au) NPs with sizes ranging from 10 to 80 nm and with different surface functionalization (sodium citrate, lipoic acid, and branched polyethyleneimine (BPEI), or polyethylene glycol (PEG)) were exposed to E. coli LPS under different conditions. The binding capacity of LPS to the surface of AuNPs was dose- and time-dependent. LPS attached to sodium citrate and lipoic acid coatings, but did not adhere to BPEI- or PEG-coated NPs. By computational simulation, the binding of LPS to AuNPs seems to follow the Langmuir absorption isotherm. The presence of LPS on AuNP surface interfered and caused a decrease in the formation of the expected biomolecular corona upon incubation in human plasma. LPS-coated AuNPs, but not the LPS-free NPs, induced significant inflammatory responses in vitro. Notably, while free LPS did also induce an anti-inflammatory response, LPS bound to NPs appeared unable to do so. In conclusion, the unintentional adsorption of LPS onto the NP surface can affect the biocorona formation and the inflammatory properties of NPs. Thus, for an accurate interpretation of NP interactions with cells, it is extremely important to be able to distinguish the intrinsic NP biological effects from those caused by biologically active contaminants such as endotoxin.
TL;DR: The biokinetics patterns after IT-instillation and GAV were similar but both were distinctly different from the pattern after intravenous injection disproving the latter to be a suitable surrogate of the former applications.
Abstract: The biokinetics of a size-selected fraction (70 nm median size) of commercially available and 48V-radiolabeled [48V]TiO2 nanoparticles has been investigated in healthy adult female Wistar-Kyoto rats at retention time-points of 1 h, 4 h, 24 h, 7 d and 28 d after intratracheal instillation of a single dose of an aqueous [48V]TiO2-nanoparticle suspension. A completely balanced quantitative biodistribution in all organs and tissues was obtained by applying typical [48V]TiO2-nanoparticle doses in the range of 40–240 μg·kg−1 bodyweight and making use of the high sensitivity of the radiotracer technique. The [48V]TiO2-nanoparticle content was corrected for residual blood retained in organs and tissues after exsanguination and for 48V-ions not bound to TiO2-nanoparticles. About 4% of the initial peripheral lung dose passed through the air-blood-barrier after 1 h and were retained mainly in the carcass (4%); 0.3% after 28 d. Highest organ fractions of [48V]TiO2-nanoparticles present in liver and kidneys re...
TL;DR: It is demonstrated that CuO NPs may undergo transformation processes in soil upon weathering that subsequently impact NPs availability in terrestrial food chains.
Abstract: This study evaluates the bioaccumulation of unweathered (U) and weathered (W) CuO in NP, bulk and ionic form (0–400 mg/kg) by lettuce exposed for 70 d in soil co-contaminated with field incurred chlordane. To evaluate CuO trophic transfer, leaves were fed to crickets (Acheta domestica) for 15 d, followed by insect feeding to lizards (Anolis carolinensis). Upon weathering, the root Cu content of the NP treatment increased 214% (327 ± 59.1 mg/kg) over unaged treatment. Cu root content decreased in bulk and ionic treatments from 70–130 mg/kg to 13–26 mg/kg upon aging in soil. Micro X-ray fluorescence (μ-XRF) analysis of W-NP-exposed roots showed a homogenous distribution of Cu (and Ca) in the tissues. Additionally, micro X-ray absorption near-edge (μ-XANES) analysis of W-NP-exposed roots showed near complete transformation of CuO to Cu (I)-sulfur and oxide complexes in the tissues, whereas in unweathered treatment, most root Cu remained as CuO. The expression level of nine genes involved in Cu transp...
TL;DR: The results demonstrate the crucial protection role of antimicrobial proteins for animals in response to environmental ENMs’ exposure and elucidated different signaling cascades mediated by antimacterial proteins provide important molecular targets for future toxicity assessment and chemical modification of GO.
Abstract: Upon exposure to environmental engineered nanomaterials (ENMs), animals will activate certain response signals to protect themselves from the toxic effects. However, the underlying molecular mechanisms for this response are still largely unclear. Using in vivo assay system of Caenorhabditis elegans, we here found that antimicrobial proteins of LYS-1, LYS-8, SPP-1, DOD-6, and F55G11.4 were activated by graphene oxide (GO) exposure. These antimicrobial proteins functioned as molecular targets of transcriptional factor DAF-16 in insulin signaling pathway, and acted in intestine to regulate the response to GO. Among these antimicrobial proteins, DOD-6, F55G11.4, and SPP-1 participated in the formation of signaling cascade of DAF-16-DOD-6-SOD-3-F55G11.4/SPP-1 in response to GO exposure by activating the antioxidation system. Different from this, LYS-1 and LYS-8, two lysozymes, mediated TUB-2 signaling and DAF-8-DAF-5 signaling cascade, respectively, to regulate the response to GO exposure. During the r...
TL;DR: The common hypothesis that IV-injection is a suitable predictor for the biokinetics fate of nanoparticles administered by different routes is disproved by this series of studies.
Abstract: Submicrometer TiO2 particles, including nanoparticulate fractions, are used in an increasing variety of consumer products, as food additives and also drug delivery applications are envisaged. Beyond exposure of occupational groups, this entails an exposure risk to the public. However, nanoparticle translocation from the organ of intake and potential accumulation in secondary organs are poorly understood and in many investigations excessive doses are applied. The present study investigates the biokinetics and clearance of a low single dose (typically 40–400 μg/kg BW) of 48V-radiolabeled, pure TiO2 anatase nanoparticles ([48V]TiO2NP) with a median aggregate/agglomerate size of 70 nm in aqueous suspension after intravenous (IV) injection into female Wistar rats. Biokinetics and clearance were followed from one-hour to 4-weeks. The use of radiolabeled nanoparticles allowed a quantitative [48V]TiO2NP balancing of all organs, tissues, carcass and excretions of each rat without having to account for chem...
TL;DR: There is evidence that metal-based NPs lead to an overall difference in biological responses from that of their dissolved counterparts, and the IBR could thus be considered as an efficient tool to transfer research results to stakeholders with possible implementation for regulatory purposes.
Abstract: Nanotechnology is a much promising field of science and technology with applications in a wide range of areas such as electronics, biomedical applications, energy and cosmetics. Metal-based engineered nanoparticles (ENPs) are common in many technological applications; some of the most common nanoparticles available commercially are silver, gold, copper oxide (CuO), zinc oxide (ZnO) and cadmium sulphide (CdS). The toxicity of metal-based NPs may be either due to their specific physical characteristics as NPs or to the specific toxicity of metals released from NPs under environmental conditions. In this study we evaluated the toxicity effects of a range of ENPs (Ag, Au, CuO, CdS, ZnO) along with a control containing equivalent quantities of dissolved metal on two endobenthic species: the ragworm Hediste diversicolor and the bivalve Scrobicularia plana. A suite of complementary biomarkers was used to reveal toxicity effects. A common challenge in multibiomarkers studies is to go beyond an independent interpretation of each one, and to assess a global response of individuals. The Integrated Biomarker Response (IBR) was calculated for both species exposed to the different metal-based ENPs studied or to their dissolved metal counterpart to provide efficient and easy tools for environmental managers. We evidence that metal-based NPs lead to an overall difference in biological responses from that of their dissolved counterparts. The IBR could thus be considered as an efficient tool to transfer research results to stakeholders with possible implementation for regulatory purposes.
TL;DR: It is demonstrated that the BN may be used by different stakeholders at several stages in the risk assessment to predict certain properties of a nanomaterials of which little information is available or to prioritize nanommaterials for further screening.
Abstract: In this study, a Bayesian Network (BN) was developed for the prediction of the hazard potential and biological effects with the focus on metal- and metal-oxide nanomaterials to support human health risk assessment. The developed BN captures the (inter) relationships between the exposure route, the nanomaterials physicochemical properties and the ultimate biological effects in a holistic manner and was based on international expert consultation and the scientific literature (e.g., in vitro/in vivo data). The BN was validated with independent data extracted from published studies and the accuracy of the prediction of the nanomaterials hazard potential was 72% and for the biological effect 71%, respectively. The application of the BN is shown with scenario studies for TiO2, SiO2, Ag, CeO2, ZnO nanomaterials. It is demonstrated that the BN may be used by different stakeholders at several stages in the risk assessment to predict certain properties of a nanomaterials of which little information is available or to prioritize nanomaterials for further screening.
TL;DR: Embedded nanomaterials of diverse chemical compositions can be grouped according to their inflammatory potential, and it is shown that PPAR-γ played an important role in the activation of inflammatory responses in cells exposed to TiO2 and SiO2 NMs.
Abstract: Engineered nanomaterials (ENMs) are being produced for an increasing number of applications. Therefore, it is important to assess and categorize ENMs on the basis of their hazard potential. The immune system is the foremost defence against foreign bodies. Here we performed cytokine profiling of a panel of nineteen representative ENMs procured from the Joint Research Centre (JRC) and commercial sources. Physicochemical characterization was performed using dynamic light scattering. The ENMs were all shown to be endotoxin content free. The human macrophage-differentiated THP.1 cell line was employed for cytotoxicity screening and based on the calculated IC50 values, the multi-walled carbon nanotubes (MWCNTs), ZnO, Ag and SiO2 NMs were found to be the most cytotoxic while single-walled carbon nanotubes (SWCNTs), TiO2, BaSO4 and CeO2 NMs, as well as the nanocellulose materials, were non-cytotoxic (at doses up to 100 µg/mL). Multiplex profiling of cytokine and chemokine secretion indicated that the TiO2...
TL;DR: Ex vivo exposure of embryos to PSNP demonstrated a similar accumulation of PSNP in or on lipophilic cells, illustrating the likelihood of brood pouch-mediated PSNP uptake by embryos.
Abstract: Nanoplastic debris is currently expected to be ubiquitously distributed in aquatic environments and an emerging environmental issue affecting organisms across trophic levels. While ingestion of particles receives most attention, other routes of uptake and cellular accumulation remain unexplored. Here, the planktonic filter feeder Daphnia magna was used to track routes of uptake and target tissues of polystyrene nanoparticles (PSNPs). A sublethal concentration of 5 mg L−1 fluorescent PSNPs (25 nm) was used to monitor accumulation in adult animals as well as their embryos in the open brood pouch. A time series throughout embryonic development within the brood pouch revealed accumulation of PSNP in or on lipophilic cells in the early stages of embryonic development while the embryo is still surrounded by a chorion and before the beginning of organogenesis. In contrast, PSNP particles were neither detected in the gut epithelium nor in lipid droplets in adults. An ex vivo exposure of embryos to PSNP de...
TL;DR: It is found that exposure to MNMs measured at selected workplaces may exceed even the highest proposed OEL, indicating that the application and use of OELs may be useful for exposure reduction.
Abstract: Background: The toxicological properties of manufactured nanomaterials (MNMs) can be different from their bulk-material and uncertainty remains about the adverse health effects they may have on humans. Proposals for OELs have been put forward which can be useful for risk management and workers’ protection. We performed a systematic review of proposals for OELs for MNMs to better understand the extent of such proposals, as well as their derivation methods.Methods: We searched PubMed and Embase with an extensive search string and also assessed the references in the included studies. Two authors extracted the data independently.Results: We identified 20 studies that proposed in total 56 OEL values. Of these, two proposed a generic level for all MNMs, 14 proposed a generic OEL for a category of MNMs and 40 proposed an OEL for a specific nanomaterial. For specific fibers, four studies proposed a similar value but for carbon nanotubes (CNTs) the values differed with a factor ranging from 30 to 50 and fo...
TL;DR: The presence of humic acid like substances of EPS on the surface of nano-Seb plays a major role in lowering the bioavailability (uptake) and toxicity of nano -Seb by decreasing the interactions between nanoparticles and embryos.
Abstract: Microbial reduction of selenium (Se) oxyanions to elemental Se is a promising technology for bioremediation and treatment of Se wastewaters. But a fraction of biogenic nano-Selenium (nano-Seb) form...
TL;DR: It is demonstrated that the localisation of NPs in whole living organisms can be visualised in real-time, using LSM, and supports that the route of exposure is essential for the uptake and subsequentLocalisation of nanoparticles in zebrafish.
Abstract: A major challenge in nanoecotoxicology is finding suitable methods to determine the uptake and localisation of nanoparticles on a whole-organism level. Some uptake methods have been associated with artefacts induced by sample preparation, including staining for electron microscopy. This study used light sheet microscopy (LSM) to define the uptake and localisation of fluorescently labelled nanoparticles in living organisms with minimal sample preparation. Zebrafish (Danio rerio) were exposed to fluorescent gold nanoparticles (Au NPs) and fluorescent polystyrene NPs via aqueous or dietary exposure. The in vivo uptake and localisation of NPs were investigated using LSM at different time points (1, 3 and 7 days). A time-dependent increase in fluorescence was observed in the gut after dietary exposure to both Au NPs and polystyrene NPs. No fluorescence was observed within gut epithelia regardless of the NP exposure route indicating no or limited uptake via intestinal villi. Fish exposed to polystyrene ...
TL;DR: Signs of early effects of occupational exposure to MWCNTs on lung health and the immune system are observed.
Abstract: Background: Multi-wall carbon nanotubes (MWCNTs) are manufactured nanomaterials to which workers and the general population will be increasingly exposed in coming years. Little is known about potential human health effects of exposure to MWCNTs, but effects on the lung and the immune system have been reported in animal and mechanistic studies. Objectives: We conducted a cross-sectional study to assess the association between occupational exposure to MWCNTs and effects on lung health and the immune system. Methods: We assessed 51 immune markers and three pneumoproteins in serum, complete blood cell counts (CBC), fractional exhaled nitric oxide (FENO), and lung function among 22 workers of a MWCNT producing facility and 39 age- and gender-matched, unexposed controls. Measurements were repeated four months later among 16 workers also included in the first phase of the study. Regression analyses were adjusted for potentially confounding parameters age, body mass index, smoking, and sex, and we explored potential confounding by other factors in sensitivity analyses. Results: We observed significant upward trends for immune markers C-C motif ligand 20 (p =.005), basic fibroblast growth factor (p =.05), and soluble IL-1 receptor II (p =.0004) with increasing exposure to MWCNT. These effects were replicated in the second phase of the study and were robust to sensitivity analyses. We also observed differences in FENO and several CBC parameters between exposed and non-exposed, but no difference in lung function or the pneumoproteins. Conclusions: We observed indications of early effects of occupational exposure to MWCNTs on lung health and the immune system. © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
TL;DR: In vivo assay system of Caenorhabditis elegans demonstrated that the neuronal ERK signaling-mediated signaling pathway and the intestinal p38 MAPK- mediated signaling pathway functioned synergistically in the regulation of response to GO exposure.
Abstract: ERK signaling is one of the important mitogen-activated protein kinases (MAPKs). However, the role of ERK signaling in the regulation of response to engineered nanomaterial exposure is still largely unclear. In this study, using in vivo assay system of Caenorhabditis elegans, we investigated the function of ERK signaling in response to graphene oxide (GO) exposure and the underlying molecular mechanism. GO exposure increased the expression of MEK-2/MEK and MPK-1/ERK in the ERK signaling pathway. Mutation of mek-2 or mpk-1 resulted in a susceptibility to GO toxicity. Both the MEK-2 and the MPK-1 acted in neurons to regulate the response to GO exposure, and the neuronal expression of MEK-2 or MPK-1 caused a resistance to GO toxicity. In the neurons, SKN-1b/Nrf acted downstream of the MPK-1, and AEX-3, a guanine exchange factor for GTPase, further acted downstream of the SKN-1b to regulate the response to GO exposure. Therefore, a signaling cascade of MEK-2-MPK-1-SKN-1b/-AEX-3 was identified in the n...
TL;DR: This study provides evidence that tNGs are locally well tolerated and underlines their potential for cutaneous drug delivery.
Abstract: Novel nanogels that possess the capacity to change their physico-chemical properties in response to external stimuli are promising drug-delivery candidates for the treatment of severe skin diseases. As thermoresponsive nanogels (tNGs) are capable of enhancing penetration through biological barriers such as the stratum corneum and are taken up by keratinocytes of human skin, potential adverse consequences of their exposure must be elucidated. In this study, tNGs were synthesized from dendritic polyglycerol (dPG) and two thermoresponsive polymers. tNG_dPG_tPG are the combination of dPG with poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)) and tNG_dPG_pNIPAM the one with poly(N-isopropylacrylamide) (pNIPAM). Both thermoresponsive nanogels are able to incorporate high amounts of dexamethasone and tacrolimus, drugs used in the treatment of severe skin diseases. Cellular uptake, intracellular localization and the toxicological properties of the tNGs were comprehensively characterized in primary normal human keratinocytes (NHK) and in spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (HaCaT). Laser scanning confocal microscopy revealed fluorescently labeled tNGs entered into the cells and localized predominantly within lysosomal compartments. MTT assay, comet assay and carboxy-H2DCFDA assay, demonstrated neither cytotoxic or genotoxic effects, nor any induction of reactive oxygen species of the tNGs in keratinocytes. In addition, both tNGs were devoid of eye irritation potential as shown by bovine corneal opacity and permeability (BCOP) test and red blood cell (RBC) hemolysis assay. Therefore, our study provides evidence that tNGs are locally well tolerated and underlines their potential for cutaneous drug delivery.
TL;DR: This study shows how long term AgNPs exposure may promote ultrastructural damage to kidney causing inflammation and expression of cell survival factors and changes in the long term could lead to inhibition of the beneficial apoptotic pathway and promotion of necrotic cell death in kidneys.
Abstract: Silver nanoparticles (AgNPs) are one of the most widely used nanomaterials. Following oral exposure, AgNPs can accumulate in various organs including kidneys where they show gender specific accumulation. There is limited information on their effect on renal system following long-term animal exposure especially at the ultramicroscopic and molecular level. In this study, we have assessed the effect of 60 days oral AgNPs treatment on kidneys of female Wistar rats at doses of 50 ppm and 200 ppm that are below previously reported lowest observed adverse effect level (LOAEL). AgNPs treatment led to decrease in kidney weight and some loss of renal function as seen by increased levels of serum creatinine and early toxicity markers such as KIM-1, clusterin and osteopontin. We also observed significant mitochondrial damage, loss of brush border membranes, pronounced swelling of podocytes and degeneration of their foot processes using transmission electron microscopy (TEM). These symptoms are similar to thos...
TL;DR: The results highlight the distinct biological and molecular mechanisms of GO and rGO exposure and the role of Wnt-MAPK pathway crosstalk in regulating GO-induced reproductive failure in in vivo systems, and they will contribute to the development of efficient and innocuous graphene applications as well to improvements in mechanism-based risk assessment.
Abstract: The potential hazards of graphene nanomaterials were investigated by exposing the nematode Caenorhabditis elegans to graphene oxide (GO) and reduced graphene oxide (rGO). The underlying mechanisms of the nano–bio interaction were addressed with an integrated systems toxicology approach using global transcriptomics, network-based pathway analysis, and experimental validation of the in-silico-derived hypotheses. Graphene oxide was found to reduce the worms’ reproductive health to a greater degree than rGO, but it did not affect survival (24 h endpoint). Comparative analysis of GO vs. rGO effects found that the wingless-type MMTV integration site family (Wnt) pathway and the mitogen-activated protein kinase (MAPK) pathway were evoked in GO- but not in rGO-exposed worms. We therefore hypothesized that crosstalk between the Wnt and MAPK pathways is responsible for C. elegans’ reproductive sensitivity to GO exposure. By targeting the individual components of the Wnt-MAPK crosstalk pathway (with qPCR gen...
TL;DR: The need to include very low concentrations of NPs in soil toxicological studies is pointed out, and the lack of relevance of classical dose–response tests and ecotoxicological dose metrics for TiO2-NPs impact on soil microorganisms is highlighted.
Abstract: Titanium-dioxide nanoparticles (TiO2-NPs) are increasingly released in agricultural soils through, e.g. biosolids, irrigation or nanoagrochemicals. Soils are submitted to a wide range of concentrations of TiO2-NPs depending on the type of exposure. However, most studies have assessed the effects of unrealistically high concentrations, and the dose–response relationships are not well characterized for soil microbial communities. Here, using soil microcosms, we assessed the impact of TiO2-NPs at concentrations ranging from 0.05 to 500 mg kg−1 dry-soil, on the activity and abundance of ammonia-oxidizing archaea (AOA) and bacteria (AOB), and nitrite-oxidizing bacteria (Nitrobacter and Nitrospira). In addition, aggregation and oxidative potential of TiO2-NPs were measured in the spiking suspensions, as they can be important drivers of TiO2-NPs toxicity. After 90 days of exposure, non-classical dose–response relationships were observed for nitrifier abundance or activity, making threshold concentrations...