Showing papers in "Nanotoxicology in 2021"

Organ-specific toxicity of magnetic iron oxide-based nanoparticles.

Abstract: The unique properties of magnetic iron oxide nanoparticles determined their widespread use in medical applications, the food industry, textile industry, which in turn led to environmental pollution. These factors determine the long-term nature of the effect of iron oxide nanoparticles on the body. However, studies in the field of chronic nanotoxicology of magnetic iron particles are insufficient and scattered. Studies show that toxicity may be increased depending on oral and inhalation routes of administration rather than injection. The sensory nerve pathway can produce a number of specific effects not seen with other routes of administration. Organ systems showing potential toxic effects when injected with iron oxide nanoparticles include the nervous system, heart and lungs, the thyroid gland, and organs of the mononuclear phagocytic system (MPS). A special place is occupied by the reproductive system and the effect of nanoparticles on the health of the first and second generations of individuals exposed to the toxic effects of iron oxide nanoparticles. This knowledge should be taken into account for subsequent studies of the toxicity of iron oxide nanoparticles. Particular attention should be paid to tests conducted on animals with pathologies representing human chronic socially significant diseases. This part of preclinical studies is almost in its infancy but of great importance for further medical translation on nanomaterials to practice.

8-Hydroxy-2'-deoxyguanosine (8-OHdG) as a biomarker of oxidative DNA damage induced by occupational exposure to nanomaterials: a systematic review.

Abstract: In nuclear and mitochondrial DNA, 8-hydroxy-2'-deoxyguanosine (8-OHdG) is one of the predominant forms of reactive oxygen species (ROSs) lesions, which commonly used as a biomarker for oxidative stress. Studies showed that the different nanomaterials can induce toxicity by ROSs in human body. So, this study is going to review the studies about oxidative DNA damage caused by occupational exposure to nanomaterials, using 8-OHdG biomarker.Systematic review was managed based on Cochrane systematic review guideline. Literature search was conducted in scientific databases with the main terms of "biomarkers," "biological markers," combined with "occupational exposure" and "nanomaterials." All papers in the field of occupational exposure to nanomaterials until 2020 December were included. To evaluate the quality and bias of studies, GRADE method (Grading of Recommendations, Assessment, Development, and Evaluation) was used.Two hundred twenty-six studies were primarily achieved. By considering the inclusion criteria, overall 8 articles were selected. The majority of the studies were classified as the moderate quality studies (six studies). Also, the study-level bias was critical. This review shows that there is a significant relationship between job title and amount of produced nanomaterials and the existence of 8-OHdG. Also, the levels of 8-OHdG can be measured in urine, blood, and inhalation samples by instrumental procedures.Oxidative damages are an important threat for workers exposed to nanomaterial. Blood and EBC 8-OHdG level can be introduced as a biomarker for metal nanomaterials, but urinary 8-OHdG needs to be taken with caution. So, it is recommended that evaluation not be solely based on one biomarker.

Interaction of nanoparticles with biological macromolecules: a review of molecular docking studies.

Abstract: The high frequency of using engineered nanoparticles in various medical applications entails a deep understanding of their interaction with biological macromolecules. Molecular docking simulation is now widely used to study the binding of different types of nanoparticles with proteins and nucleic acids. This helps not only in understanding the mechanism of their biological action but also in predicting any potential toxicity. In this review, the computational techniques used in studying the nanoparticles interaction with biological macromolecules are covered. Then, a comprehensive overview of the docking studies performed on various types of nanoparticles will be offered. The implication of these predicted interactions in the biological activity and/or toxicity is also discussed for each type of nanoparticles.

In vivo impact assessment of orally administered polystyrene nanoplastics: biodistribution, toxicity, and inflammatory response in mice.

Abstract: To assess the in vivo impact of nanoplastics (NP) and coagulation-based purified NP (PurNP), this study analyzed for alterations in the biodistribution, toxicity and inflammatory response in ICR mice exposed to three different doses of NP (5, 25, and 50 mg/kg) and PurNP for 2 weeks. Except water consumption, which was dose-dependently and significantly increased in all NP-treated groups, most factors assessed for feeding behaviors and excretions remained constant, without any significant change. Orally administered NP was detected in the intestine, kidneys, and liver at all concentrations, although the accumulation was higher in the intestine than in the kidneys and liver. No significant alterations were detected in the levels of serum biochemical markers and histopathological structures. However, compared to the vehicle group, expressions of the inflammatory response proteins (iNOS and COX-2) and mRNA levels of the inflammatory cytokines were remarkably increased in the liver, kidneys, and intestine of NP-treated mice. A similar increase was detected in the oxidative stress responses, including ROS concentration, SOD activity, and Nrf2 expression. Furthermore, similar inflammatory responses were observed in the PurNP-treated group, as compared to the vehicle-treated group. The results presented in this study provide the first strong evidence that oral administration of NP for 2 weeks results in high accumulation in the liver, kidneys, and intestine of ICR mice, and induces severe inflammatory and oxidative stress responses. These results additionally confirm the efficacy of water purification using the tannic acid-mediated coagulation removal technique.

A methodology for developing key events to advance nanomaterial-relevant adverse outcome pathways to inform risk assessment.

Abstract: Significant advances have been made in the development of Adverse Outcome Pathways (AOPs) over the last decade, mainly focused on the toxicity mechanisms of chemicals. These AOPs, although relevant to manufactured nanomaterials (MNs), do not currently capture the reported roles of size-associated properties of MNs on toxicity. Moreover, some AOs of relevance to airborne exposures to MNs such as lung inflammation and fibrosis shown in animal studies may not be targeted in routine regulatory decision making. The primary objective of the present study was to establish an approach to advance the development of AOPs of relevance to MNs using existing, publicly available, nanotoxicology literature. A systematic methodology was created for curating, organizing and applying the available literature for identifying key events (KEs). Using a case study approach, the study applied the available literature to build the biological plausibility for 'tissue injury', a KE of regulatory relevance to MNs. The results of the analysis reveal the various endpoints, assays and specific biological markers used for assessing and reporting tissue injury. The study elaborates on the limitations and opportunities of the current nanotoxicology literature and provides recommendations for the future reporting of nanotoxicology results that will expedite not only the development of AOPs for MNs but also aid in application of existing data for decision making.

Polystyrene nanoplastics exposure caused defective neural tube morphogenesis through caveolae-mediated endocytosis and faulty apoptosis

Abstract: Growing evidence demonstrated that bioaccumulation of polystyrene nanoplastics (PS-NPs) in various organisms including human beings caused destructive effects on health. Nanoplastics may adversely affect fetal development potentially since they can pass through the placental barrier. However, very little has been known about the embryonic toxicity of polystyrene nanoplastics, especially in embryonic neurulation, the early developmental stage of the fetus, as well as the corresponding mechanisms. In this study, we first observed that 60- or 900-nm PS-NPs (especially 60-nm PS-NPs) could cross mouse placentas and affect developing mice fetuses. To avoid the indirect adverse effects derived from the restricted placenta, we employed early chick embryos as a developmental model to evaluate direct adverse effects of PS-NPs on embryo/fetal development, revealing suppressive effects on embryo development and an increased frequency of congenital abnormalities (especially in the nervous system), including neural tube defects. Thus, we focused on the potential negative effects of PS-NPs on neurulation, the earliest stage of nervous system development. Using caveolin-1 immunofluorescent staining of SH-SY5Y cells exposed to PS-NPs-GFP, we demonstrated that PS-NPs were internalized by SH-SY5Y cells via caveolae-mediated endocytosis. Transmission electron microscopy; LC3B immunofluorescent staining; and Atg7, Atg5, p62 and LC3B western blot results revealed that autophagy was activated in SH-SY5Y cells exposed to PS-NPs. However, PS-NPs were not degraded by the autophagic-lysosomal system given the lack of LAMP1 changes and minimal PS-NPs-GFP and LAMP1 colocalization. Furthermore, the cytoplasmic accumulation of PS-NPs caused faulty apoptotic cell death in SH-SY5Y cells and the developing neural tube as revealed by c-caspase3 immunofluorescent staining. Thus, defective neural tube morphogenesis, as demonstrated by neural tube defects, occurred during embryogenesis in the context of PS-NP exposure.

Rationale and decision rules behind the ECETOC NanoApp to support registration of sets of similar nanoforms within REACH

Abstract: New registration requirements for nanomaterials under REACH consider the possibility to form ‘sets of similar nanoforms’ for a joined human health and environmental hazard, exposure and risk assess...

Occupational exposure to graphene and silica nanoparticles. Part II: pilot study to identify a panel of sensitive biomarkers of genotoxic, oxidative and inflammatory effects on suitable biological matrices.

Abstract: The available biomonitoring studies on workers producing/handling nanomaterials (NMs) focused on potential effects on respiratory, immune and cardio-vascular system. Aim of this study was to identify a panel of sensitive biomarkers and suitable biological matrices to evaluate particularly genotoxic and oxidative effects induced on workers unintentionally exposed to graphene or silica nanoparticles during the production process. These nanomaterials have been chosen for 'NanoKey' project, integrating the workplace exposure assessment (reported in part I) with the biomonitoring of exposed workers reported in the present work. Simultaneously to workplace exposure characterization, we monitored the workers using: Buccal Micronucleus Cytome (BMCyt) assay, fpg-comet test (lymphocytes), oxidized DNA bases 8-oxoGua, 8-oxoGuo and 8-oxodGuo measurements (urine), analysis of oxidative stress biomarkers in exhaled breath condensate (EBC), FENO measurement and cytokines release detection (serum). Since buccal cells are among the main targets of NM occupational exposure, particular attention was posed to the BMCyt assay that represents a noninvasive assay. This pilot study, performed on 12 workers vs.11 controls, demonstrates that BMCyt and fpg-comet assays are the most sensitive biomarkers of early, still reparable, genotoxic and oxidative effects. The findings suggest that these biomarkers could represent useful tools for the biomonitoring of workers exposed to nanoparticles, but they need to be confirmed on a high number of subjects. However, such biomarkers don't discriminate the effects of NM from those due to other chemicals used in the NM production process. Therefore, they could be suitable for the biomonitoring of workers exposed to complex scenario, including nanoparticles exposure.

Neutrophil activation by nanomaterials in vitro: comparing strengths and limitations of primary human cells with those of an immortalized (HL-60) cell line.

Abstract: Assessment of nanomaterial (NM) induced inflammatory responses has largely relied on rodent testing via measurement of leukocyte accumulation in target organs. Despite observations that NMs activat...

Biomedical nanomaterials: applications, toxicological concerns, and regulatory needs.

Abstract: Advances in cutting-edge technologies such as nano- and biotechnology have created an opportunity for re-engineering existing materials and generating new nano-scale products that can function beyo...

Multi-walled carbon nanotubes trigger lysosome-dependent cell death (pyroptosis) in macrophages but not in neutrophils.

Abstract: Carbon nanotubes (CNTs) have been extensively investigated, and several studies have shown that multi-walled CNTs can trigger inflammation and fibrosis in animal models. However, while neutrophils ...

Inhaled multi-walled carbon nanotubes differently modulate global gene and protein expression in rat lungs

Abstract: Inhalation of multi-walled carbon nanotubes (MWCNTs) induces lung inflammation. Depending on industrial applications, CNTs with different physicochemical characteristics are produced and workers ca...

Metallic-nanoparticle release systems for biomedical implant surfaces: effectiveness and safety.

Abstract: The current focus of bioengineering for implant devices involves the development of functionalized surfaces, bioactive coatings, and metallic nanoparticles (mNPs) with a controlled release, togethe...

Pulmonary toxicity of synthetic amorphous silica - effects of porosity and copper oxide doping

Abstract: Materials can be modified for improved functionality. Our aim was to test whether pulmonary toxicity of silica nanomaterials is increased by the introduction of: a) porosity; and b) surface doping ...

Impact of copper oxide particle dissolution on lung epithelial cell toxicity: response characterization using global transcriptional analysis.

Abstract: The in vitro and in vivo toxicity of copper oxide nanoparticles (CuO NPs) is attributed to both particle and dissolved copper ion species. However, a clear understanding of (1) the specific cellula...

Time-course effect of ultrasmall superparamagnetic iron oxide nanoparticles on intracellular iron metabolism and ferroptosis activation.

Abstract: Ferroptosis is an iron-dependent cell death caused by excessive peroxidation of polyunsaturated fatty acids. It can be activated by iron-based nanoparticles as a potential cancer therapeutic target. However, the intracellular transformation of iron-based nanoparticles is still ambiguous and the subsequent ferroptosis mechanism is also obscure. Here, we identified the time-course metabolism of ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) in cells by using X-ray absorption near edge structure spectroscopy. Also, the integrated quantitative transcriptome and proteome data obtained from the cells exposed to USPIO exhibited hallmark features of ferroptosis. With the chemical species of iron oxide transforming to ferritin, the intracellular GPX4 down-regulated, and lipid peroxide began to accumulate. These results provide evidence that the intracellular metabolism of USPIO induced ferroptosis in a time-dependent manner, and iron over-loaded in cytoplasm along with lipid peroxidation of the membrane are involved in the detailed mechanism of ferroptosis signaling activation.

Antibacterial application and toxicity of metal-organic frameworks.

Abstract: Metal-organic frameworks (MOFs), which are also referred to as coordination polymers, have been widely used in adsorption separation and catalysis, especially in the field of physical chemistry in the past few years, because of their unique physical structure and potential chemical properties. In recent years, particularly with the continuous expansion of the research field, deepening of research levels, and sustained advancements in science and technology, powerful and diverse MOFs that have demonstrated great biomedical application potential have been successively developed. Consequently, this study summarizes the origin, development, and common synthesis methods of MOFs, with major emphasis on their antibacterial application and safety evaluation in biomedicine.

Ecotoxicological assessment of commercial boron nitride nanotubes toward Xenopus laevis tadpoles and host-associated gut microbiota.

Abstract: Despite the growing interest for boron nitride nanotubes (BNNT) due to their unique properties, data on the evaluation of the environmental risk potential of this emerging engineered nanomaterial are currently lacking. Therefore, the ecotoxicity of a commercial form of BNNT (containing tubes, hexagonal-boron nitride, and boron) was assessed in vivo toward larvae of the amphibian Xenopus laevis. Following the exposure, multiple endpoints were measured in the tadpoles as well as in bacterial communities associated to the host gut. Exposure to BNNT led to boron accumulation in host tissues and was not associated to genotoxic effects. However, the growth of the tadpoles increased due to BNNT exposure. This parameter was associated to remodeling of gut microbiome, benefiting to taxa from the phylum Bacteroidetes. Changes in relative abundance of this phylum were positively correlated to larval growth. The obtained results support the finding that BNNT are biocompatible as indicated by the absence of toxic effect from the tested nanomaterials. In addition, byproducts, especially free boron present in the tested product, were overall beneficial for the metabolism of the tadpoles.

Iron oxide nanoparticles aggravate hepatic steatosis and liver injury in nonalcoholic fatty liver disease through BMP-SMAD-mediated hepatic iron overload.

Abstract: Nonalcoholic fatty liver disease (NAFLD) is the leading hepatic manifestation of metabolic syndrome worldwide, and is clinically accompanied by iron overload. As the increasing application of iron oxide nanoparticles (IONPs) on the imaging and diagnosis in NAFLD, the potential hepatic effect and mechanism of IONPs on NAFLD should be well studied. Here, we demonstrate that carboxyl-modified (COOH-IONPs) and amino-coated IONPs (NH2-IONPs) exhibit no significant hepatic toxicity in normal mice at the clinical injection dose, but aggravate SREBP-1c-mediated de novo lipogenesis (DNL) in the livers of mice with NAFLD induced by high-fat diet (HFD) and in HepG2 cells incubated with oleic acid (OA), especially in those treated by the positive NH2-IONPs. In the present study, mice receiving IONPs for 7 day show mild iron overload in the liver and exhibit enhanced hepatic inflammation in NAFLD. The BMP-SMAD pathway is initiated by hepatic iron overload and is aggravated in NAFLD. In conclusion, BMP-SMAD-mediated hepatic iron overload aggravated lipid accumulation in the liver and hepatic inflammatory responses, implying that effective measures in addition to hepatic iron overload are needed for individuals at the risk of IONPs in NAFLD.

Reactive oxygen species production, genotoxicity and telomere length in FE1-Muta™Mouse lung epithelial cells exposed to carbon nanotubes.

Abstract: Carbon nanotubes (CNTs) are fiber-like nanomaterials, which are used in various applications with possible exposure to humans. The genotoxicity and carcinogenic potential of CNTs remain to be fully understood. This study assessed the genotoxicity of three different multi-walled carbon nanotubes (MWCNTs) (MWCNT-7, NM-401 and NM-403) and one single-walled carbon nanotube (SWCNT) (NM-411) in FE1-Muta™Mouse lung epithelial (MML) cells using the alkaline comet assay. With the 2',7'-dichlorodihydrofluorescein diacetate fluorescent probe, we assessed the effect of CNT-exposure on the intracellular production of reactive oxygen species (ROS). We measured the effect of a 10-week CNT exposure on telomere length using quantitative PCR. Two of the included MWCNTs (NM-401 and MWCNT-7) and the SWCNT (NM-411) caused a significant increase in the level of DNA damage at concentrations up to 40 µg/ml (all concentrations pooled, p < 0.05), but no concentration-response relationships were found. All of the CNTs caused an increase in intracellular ROS production compared to unexposed cells (ptrend < 0.05). Results from the long-term exposure showed longer telomere length in cells exposed to MWCNTs compared to unexposed cells (p < 0.01). In conclusion, our results indicated that the included CNTs cause ROS production and DNA strand breaks in FE1-MML cells. Moreover, the MWCNTs, but not the SWCNT, had an impact on telomere length in a long-term exposure scenario.

Toxicity assessment of industrial engineered and airborne process-generated nanoparticles in a 3D human airway epithelial in vitro model.

Abstract: The advanced ceramic technology has been pointed out as a potentially relevant case of occupational exposure to nanoparticles (NP). Not only when nanoscale powders are being used for production, but also in the high-temperature processing of ceramic materials there is also a high potential for NP release into the workplace environment. In vitro toxicity of engineered NP (ENP) [antimony tin oxide (Sb2O3•SnO2; ATO); zirconium oxide (ZrO2)], as well as process-generated NP (PGNP), and fine particles (PGFP), was assessed in MucilAir™ cultures at air-liquid interface (ALI). Cultures were exposed during three consecutive days to varying doses of the aerosolized NP. General cytotoxicity [lactate dehydrogenase (LDH) release, WST-1 metabolization], (oxidative) DNA damage, and the levels of pro-inflammatory mediators (IL-8 and MCP-1) were assessed. Data revealed that ENP (5.56 µg ATO/cm2 and 10.98 µg ZrO2/cm2) only caused mild cytotoxicity at early timepoints (24 h), whereas cells seemed to recover quickly since no significant changes in cytotoxicity were observed at late timepoints (72 h). No meaningful effects of the ENP were observed regarding DNA damage and cytokine levels. PGFP affected cell viability at dose levels as low as ∼9 µg/cm2, which was not seen for PGNP. However, exposure to PGNP (∼4.5 µg/cm2) caused an increase in oxidative DNA damage. These results indicated that PGFP and PGNP exhibit higher toxicity potential than ENP in mass per area unit. However, the presence of a mucociliary apparatus, as it occurs in vivo as a defense mechanism, seems to considerably attenuate the observed toxic effects. Our findings highlight the potential hazard associated with exposure to incidental NP in industrial settings.

In vivo percutaneous permeation of gold nanomaterials in consumer cosmetics: implication in dermal safety assessment of consumer nanoproducts.

Abstract: The increasing emergence of nano-cosmetics in the marketplace provokes safety concerns with respect to percutaneous permeation and toxicity of nanomaterials inside the human body. In this study, in vivo percutaneous permeation and dermal safety of cosmetic cream containing Au nanosheets and extracted Au nanosheets from cosmetic creams are investigated with guinea pigs. Quantitative percutaneous permeation data suggests that Au nanosheets in cosmetic creams permeate into the skin epidermis, dermis, and subcutaneous layer after 10 d cutaneous exposure, but cannot enter the systemic circulation. However, more Au nanosheets are accumulated in the skin and the permeation of Au nanosheets increased after embedded into the cream matrix. Synchrotron radiation X-ray fluorescence (SRXRF) imaging reveals that Au nanosheets in cosmetics penetrate mainly through hair follicles in a time-dependent manner. Cosmetic creams rather than extracted Au nanosheets decrease the cell viability of keratinocytes and slightly induce apoptosis/necrosis of keratinocytes and skin dermal fibroblasts. Intriguingly, the growth of hair is inhibited by the cosmetic cream and the extracted Au nanosheets revealed by HE staining and immunohistochemistry (IHC) assay. Altogether this study provides insights into the comprehensive understanding of percutaneous permeation and dermal safety of cosmetic creams containing Au nanosheets. This work provides reliable methods to study the skin permeation, biodistribution, and dermal safety of nano-cosmetics and reminds the community of the crucial need to combine the assays at molecular, cellular, and organ levels in nanotoxicology research.

MiR-939-5p suppresses PM2.5-induced endothelial injury via targeting HIF-1α in HAECs.

Abstract: Ambient air pollution is a leading cause of non-communicable disease in the world. PM2.5 has the potential to change the miRNAs profiles, which in turn causes cardiovascular effects. Hypoxia-inducible factor (HIF)-1 plays a critical role in the development of atherosclerosis. Yet, the possible role of miR-939-5p/HIF-1α in PM2.5-induced endothelial injury remains elusive. Therefore, the study aims to investigate the effects of miR-939-5p and HIF-1α on PM2.5-triggered endothelial injury. The results from immunofluorescence, qRT-PCR, LSCM, and western blot assays demonstrated that PM2.5 increased the levels of HIF-1α, inflammation and apoptosis in human aortic endothelial cells (HAECs). Yet, the inflammatory response and mitochondrial-mediated apoptosis pathway were effectively inhibited in HIF-1α knockdown HAECs lines. The expression of miR-939-5p was significantly down-regulated in HAECs after exposed to PM2.5. The luciferase reporter, qRT-PCR and western blot results demonstrated that miR-939-5p could directly targeted HIF-1α. And the miR-939-5p overexpression restricted PM2.5-triggered decreases in cell viability and increases in lactic dehydrogenase (LDH) activity, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and inflammation. In addition, miR-939-5p overexpression remarkably suppressed PM2.5-triggered BcL-2/Bax ratio reduction and Cytochrome C, Cleaved Caspase-9 and Cleaved Caspase-3 expression increase, revealed that miR-939-5p hampered PM2.5-induced endothelial apoptosis through mitochondrial-mediated apoptosis pathway. Our results demonstrated that PM2.5 increased the expression of HIF-1α followed by a pro-inflammatory and apoptotic response in HAECs. The protective effect of miR-939-5p on PM2.5-triggered endothelial cell injury by negatively regulating HIF-1α. miR-939-5p might present a new therapeutic target for PM2.5 induced endothelial injury.

Stabilization of Nrf2 leading to HO-1 activation protects against zinc oxide nanoparticles-induced endothelial cell death.

Abstract: With the abundant production and wide application of zinc oxide nanoparticles (ZnONPs), the potential health risks of ZnONPs have raised serious concerns. Oxidative stress is recognized as the most important outcome of the toxicity induced by ZnONPs. The Nrf2-Keap1 system and its downstream antioxidative genes are the fundamental protective mechanisms for redox hemeostasis. However, the detailed mechanisms of Nrf2 activation in ZnONPs-treated endothelial cells and murine blood vessels have yet to be elucidated. Herein, we show that Nrf2 was activated and played a negative role in cell death induced by ZnONPs. Moreover, we demonstrate that HO-1 was the most extensively upregulated antioxidative gene-activated by Nrf2. Forced overexpression of HO-1, pharmacological activation of HO-1 with the agonists RTA-408 (omaveloxolone, an FDA-approved drug) and RTA-402 repressed cell death, and treatment with HO-1 antagonist SnPP exacerbated the cell death. Importantly, loss of HO-1 diminished the cytoprotective role induced by Nrf2 in ZnONPs-treated HUVEC cells, indicating that the Nrf2-HO-1 axis was the crucial regulatory mechanism for the antioxidative response in the context of ZnONPs-induced endothelial damage. Mechanistically, we demonstrate that the p62-Keap1 axis was not involved in the activation of Nrf2. Intriguingly, the degradation half-life of Nrf2 in HUVEC cells was increased from less than 1 h under quiescent conditions to approximately 6 h under ZnONPs treatment condition; moreover, ZnONPs treatment induced activation of Nrf2/HO-1 and accumulation of ubiquitin in the aorta ventralis of mouse, suggesting that the ubiquitin-proteasome system had been perturbed, which subsequently led to the stabilization of Nrf2 and activation of HO-1. This study might contribute to a better understanding of ZnONPs-associated toxicity.

Interaction of nanoparticles with endotoxin Importance in nanosafety testing and exploitation for endotoxin binding.

Abstract: The interaction between engineered nanoparticles and the bacterial lipopolysaccharide, or endotoxin, is an event that warrants attention Endotoxin is one of the most potent stimulators of inflamma

Surface atomic arrangement of nanomaterials affects nanotoxicity.

Abstract: Understanding the roles of the properties of nanomaterials in biological interactions is a key issue in their safe applications, but the surface atomic arrangement, as an important property of engi...

Creating sets of similar nanoforms with the ECETOC NanoApp: real-life case studies.

Abstract: The ECETOC NanoApp was developed to support industry in the registration of sets of nanoforms, as well as regulators in the evaluation of these registration dossiers. The ECETOC NanoApp uses a systematic approach to create and justify sets of similar nanoforms, following the ECHA guidance in a transparent and evidence-based manner. The rational and decision rules behind the ECETOC NanoApp are described in detail in "Janer, G., R. Landsiedel, and W. Wohlleben. 2021. [Rationale and Decision Rules Behind the ECETOC NanoApp to Support Registration of Sets of Similar Nanoforms within REACH. Nanotoxicology 15 (2): 145-122. https://doi.org/10.1080/17435390.2020.1842933]". The decision criteria apply to human health and environmental hazards and risks. Here, we focus mostly on human health hazards; the decision rules are applied to a series of case studies, each consisting of real nanoforms: two barium sulfate nanoforms, four colloidal silica nanoforms, eight ceria nanoforms, and four copper phthalocyanine nanoforms. For each of them, we show step by step how the ECETOC NanoApp rules are applied. The cases include nanoforms that are justified as members of the same set of similar nanoforms based on sufficient similarity of their intrinsic properties (Tier 1). They also include other nanoforms with a relatively high (but insufficient) similarity of intrinsic properties; their similarity could be justified by functional properties (Tier 2). The case studies also include nanoforms that are concluded not to belong to the same set of similar nanoforms. These outcomes of the NanoApp were overall consistent (sometimes conservative) with available in vivo data. We also noted that datasets for various nanoforms were limited and use of the NanoApp may require the generation of data relevant to the decision criteria.

Machine learning predictions of concentration-specific aggregate hazard scores of inorganic nanomaterials in embryonic zebrafish.

Abstract: The possibility of employing computational approaches like nano-QSAR or nano-read-across to predict nanomaterial hazard is attractive from both a financial, and most importantly, where in vivo tests are required, ethical perspective. In the present work, we have employed advanced Machine Learning techniques, including stacked model ensembles, to create nano-QSAR tools for modeling the toxicity of metallic and metal oxide nanomaterials, both coated and uncoated and with a variety of different core compositions, tested at different dosage concentrations on embryonic zebrafish. Using both computed and experimental descriptors, we have identified a set of properties most relevant for the assessment of nanomaterial toxicity and successfully correlated these properties with the associated biological responses observed in zebrafish. Our findings suggest that for the group of metal and metal oxide nanomaterials, the core chemical composition, concentration and properties dependent upon nanomaterial surface and medium composition (such as zeta potential and agglomerate size) are significant factors influencing toxicity, albeit the ranking of different variables is sensitive to the exact analysis method and data modeled. Our generalized nano-QSAR ensemble models provide a promising framework for anticipating the toxicity potential of new nanomaterials and may contribute to the transition out of the animal testing paradigm. However, future experimental studies are required to generate comparable, similarly high quality data, using consistent protocols, for well characterized nanomaterials, as per the dataset modeled herein. This would enable the predictive power of our promising ensemble modeling approaches to be robustly assessed on large, diverse and truly external datasets.

Broiler welfare is preserved by long-term low-dose oral exposure to zinc oxide nanoparticles: preliminary study.

Abstract: The potential public health risk through utilizing of zinc oxide nanoparticles (ZnO NPs) in food constitutes the major obstacle to the expansion of nanoparticle (NP) in food industry Liver histolo

Multiple pathways of alveolar macrophage death contribute to pulmonary inflammation induced by silica nanoparticles.

Abstract: In our previous study, 20 nm-sized amorphous silica nanoparticles (20-SiNPs), but not 50 nm-sized amorphous silica nanoparticles (50-SiNPs), induced pulmonary inflammatory response in rats exposed repeatedly for 14 days (12.5, 25, and 50 μg/time, total six times). In this study, we tried to clarify the causes of different responses induced by both SiNPs using mice (12.5, 25, and 50 μg/lung) and mouse alveolar macrophage cells. When exposed to alveolar macrophage cells for 24 h, both SiNPs decreased cell viability and enhanced ROS generation compared to controls. The 20- and 50-SiNPs also formed giant and autophagosome-like vacuoles in the cytoplasm, respectively. Structural damage of organelles was more pronounced in 20-SiNPs-treated cells than in 50-SiNPs-treated cells, and an increased mitochondrial membrane potential and mitochondrial calcium accumulation were observed only in the 20-SiNPs-treated cells. Additionally, a single intratracheal instillation of both sizes of SiNPs to mice clearly elevated the relative proportion of neutrophils and inhibited differentiation of macrophages and expression of an adhesion molecule. Meanwhile, interestingly, the total number of pulmonary cells and the levels of pro-inflammatory mediators more notably increased in the lungs of mice exposed to 20-SiNPs compared to 50-SiNPs. Given that accumulation of giant vacuoles and dilation of the ER and mitochondria are key indicators of paraptosis, we suggest that 20-SiNPs-induced pulmonary inflammation may be associated with paraptosis of alveolar macrophages.