Nanotoxicology and Exposure in the Occupational Setting

Nanotechnology refers to the ability to control the composition of molecules and atoms within the range of 1.00 - 100 nm. At this scale, many materials exhibit novel properties when compared with their micro or macro-sized equivalents, including, for example, chemical reactivity, strength, mobility and solubility. Nanoparticles are prime candidates for toxicity because they possess a much greater surface to volume ratio (i.e. the surface area compared to the volume) than larger particles of that same material;they can have biopersistance and higher oxidant capacity, penetrate epithelium and reach interstitial pulmonary region. In an industrial setting, workers may present the main exposure risk potential among humans, and they may be involved in the entire product life cycle. There are needs to protect public and environmental health and safety. Currently, no standards or regulations exist that apply or refer specifically to nanomaterials impacts.

Biochemical and cellular evidence of the benefit of a combination of cerium oxide nanoparticles and selenium to diabetic rats

AIM: To study the combinative effects of nanocerium and selenium in a murine model of diabetes. METHODS: Cerium oxide (CeO2) nanoparticles (60 mg/kg per day) and sodium selenite (5 μmol/kg per day) aloneor in combination, or the metal form of CeO2 (60 mg/kg) were administered for 2 wk by intraperitoneal injection to streptozotocin-induced diabetic rats. At the end of treatment blood was collected, liver tissue dissected and then oxidative stress markers, extent of energy depletion and lipid prof ile were evaluated.RESULTS: Antioxidant enzymes and high density lipoprotein decreased whereas oxidative stress, adenosine diphosphate/adenosine triphospahte levels, cholesterol, triglyceride and low density lipoprotein increased on induction of diabetes. All were improved by a combination of nanocerium and sodium selenite. There was a relative amelioration by CeO2 nanoparticles or sodium selenite alone, but the metal form of CeO2 showed no signif icant improvement. CONCLUSION: The combination of nanocerium and sodium selenite is more effective than either alone in improving diabetes-induced oxidative stress.

Nanoparticle Technology as a Double-Edged Sword: Cytotoxic, Genotoxic and Epigenetic Effects on Living Cells

Nanoparticles are considered as powerful tools in nanotechnological applications. Due to their unique physicochemical properties, their interactions with different biological systems have been shown. Nanomaterials have been successfully used as coating materials or treatment and diagnosis tools. Nevertheless, toxic effects of nanoparticles in vitro and in vivo have also been reported. Here, we summarize the current state of knowledge on exposure routes, cellular uptake and toxicological activities of the commonly used nanoparticles. In this context, we discuss the mechanisms of toxicity of nanoparticles involving perturbation of redox milieu homeostasis and cellular signaling pathways.

Nanomaterials and Cell Interactions: A Review

Nanotoxicology, a branch of bionanoscience focuses on the study of the hazardous interactions between nanomaterials and the ecosystem and ascertaining its consequent implications. Nanomaterial-cell interactions are dependent on numerous factors such as size, shape, type and surface coatings/charge of nanomaterials. These factors in association with cell membrane factors such as charge and formation of the protein corona influence the uptake and internalization of these particles leading to their potential toxicity. Understanding the different routes of exposure, their transport, behaviour and eventual fate is also of importance. Toxicities that occur to the living systems are consequences of various causes/dysfunctions such as ROS production, loss of membrane integrity, releases of toxic metal ions that bind with specific cell receptors and undergo certain conformations that inhibit normal cell function resulting in cytotoxicity, genotoxicity and possible cell necrosis. This paper attempts to review the available research pertaining to nanomaterial-cell interactions and their potential toxicity.

Analytical Model for Nanotoxic Assessment of a Human Respiratory System

A computational model for nanotoxicology was developed based on the model proposed by International Commission on Radiological Protection.Herein,the fate and transport of inhaled nanoparticles in human respiratory tract were investigated by employing the compartmental model.The uncertainty analysis using Latin hypercube technique was performed to address the uncertainty level of the required parameters in modeling.This methodology could be employed in assessing the heath risks associated with general public or occupational exposure.

Continuous-Flow Removal of Arsenic in Drinking Water by Filtering down through Fe3O4@SiO2 Magnetic Composite

Natural contamination of world groundwater supplies with arsenic of volcanic origin has become a complicated and growing problem given current shortage of water. Maintenance cost of treatments that are based on ion exchange and reverse osmosis is considered high, in addition to the high production of sludge with such methods. On the other hand, efficiency of treatments employing coagulation/filtration is usually relative, depending on the method of application. Currently, emerging treatments that use nanotechnology are gaining relevance, due to their high efficiency and low cost. These methods are highly selective, with minimum generation of toxic wastes, as long as particle release into the environment is kept under control to avoid health risks. The present study developed filters with magnetic nanoparticles of Fe3O4 (magnetite) supported on porous silica (Fe3O4@SiO2) at a mass ratio of 2:1. The nanoparticles were synthetized by co-precipitation of Fe(II) and Fe(III) using NH4OH(ac) under inert atmosphere. Average sizes of 15 nm were obtained, measured by means of Transmission Electronic Microscopy (TEM) and characterized by X-ray Powder Diffraction (XRD);the magnetic power was qualitatively determined. The efficiency of the composite material (Fe3O4@SiO2) was determined in a prototype laboratory with a height of 60 cm and a diameter of 5 cm, assembled with five filters of the composite material, with 1 g each filter. The filters were wrapped in resistant water-porous fabric to favor continuous flow at a ratio of 0.015 L/min. The test was performed with arsenic solutions at (43.7 ± 2.1 μg/L), similar to the amount present in water supplies currently treated in Costa Rica. The removal was completed in 7 minutes with 0 N.T.U and less than 10 μg/L arsenic concentration (maximum limit allowed in Costa Rica), quantified by Atomic Absorption Spectrometry with Hydride Generation. After the reaction filters, the prototype was assembled with cleaning filters at a ratio of 1:8. The final way out was through a magnetized tube to ensure that no nanoparticles were released outside with the water, thus contributing to nanotoxicology safety for people and the environment.

Unveiling the nanotoxicological aspects of Se nanomaterials differing in size and morphology

Although the general concept of nanotechnology relies on exploitation of size-dependent properties of nanoscaled materials,the relation between the size/morphology of nanoparticles with their biological activity remains not well understood.Therefore,we aimed at investigating the biological activity of Se nanoparticles,one of the most promising candidates of nanomaterials for biomedicine,possessing the same crystal structure,but differing in morphology(nanorods vs.spherical particles)and aspect ratios(AR,11.5 vs.22.3 vs.1.0)in human cells and BALB/c mice.Herein,we report that in case of nanorod-shaped Se nanomaterials,AR is a critical factor describing their cytotoxicity and biocompatibility.However,spherical nanoparticles(AR 1.0)do not fit this statement and exhibit markedly higher cytotoxicity than lower-AR Se nanorods.Beside of cytotoxicity,we also show that morphology and size substantially affect the uptake and intracellular fate of Se nanomaterials.In line with in vitro data,in vivo i.v.administration of Se nanomaterials revealed the highest toxicity for higher-AR nanorods followed by spherical nanoparticles and lower-AR nanorods.Moreover,we revealed that Se nanomaterials are able to alter intracellular redox homeostasis,and affect the acidic intracellular vesicles and cytoskeletal architecture in a size-and morphology-dependent manner.Although the tested nanoparticles were produced from the similar sources,their behavior differs markedly,since each type is promising for several various application scenarios,and the presented testing protocol could serve as a concept standardizing the biological relevance of the size and morphology of the various types of nanomaterials and nanoparticles.

Toxic effects of metal oxide nanoparticles and their underlying mechanisms

Nanomaterials have attracted considerable interest owing to their unique physicochemical properties.The wide application of nanomaterials has raised many concerns about their potential risks to human health and the environment.Metal oxide nanopartides（MONPs）,one of the main members of nanomaterials,have been applied in various fields,such as food,medicine,cosmetics,and sensors.This review highlights the bio-toxic effects of widely applied MONPs and their underlying mechanisms.Two main underlying toxicity mechanisms,reactive oxygen species（ROS）-and non-ROS-mediated toxidties,of MONPs have been widely accepted.ROS activates oxidative stress,which leads to lipid peroxidation and cell membrane damage.In addition,ROS can trigger the apoptotic pathway by activating caspase-9 and-3.Non-ROS-mediated toxicity mechanism includes the effect of released ions,excessive accumulation of NPs on the cell surface,and combination of NPs with specific death receptors.Furthermore,the combined toxicity evaluation of some MONPs is also discussed.Toxicity may dramatically change when nanomaterials are used in a combined system because the characteristics of NPs that play a key role in their toxicity such as size,surface properties,and chemical nature in the complex system are different from the pristine NPs.

The impact of multi-walled carbon nanotubes(MWCNTs)on macrophages:contribution of MWCNT characteristics

Multi-walled carbon nanotubes(MWCNTs) have wide application prospects but also exhibit notable biotoxicity that is tightly associated with macrophages. Macrophages simultaneously act as initiators and defenders in MWCNT-induced organ lesions,and targeting macrophages with MWCNTs may be a potential immunotherapy and oncotherapy approach. This review focuses on the impacts of MWCNTs on macrophages and further discusses the influence of MWCNT characteristics on their bioactivity.Based on existing studies, MWCNTs stimulate macrophage migration, induce secretion of various cytokines and activate inflammatory pathways in macrophages, especially NLRP3-mediated IL-1β production. This inflammatory state, together with the oxidative stress and cell membrane lesions induced by MWCNTs, contributes to decreased phagocytic ability and cell viability, which finally results in cell apoptosis and necrosis. A series of intracellular and systemic components, such as toll-like receptor, high-mobility group box 1, Rho-associated kinases, scavenger receptor and complement components, may be involved in the above-mentioned cell-MWCNT interactions. The characteristics of MWCNTs can influence their bioactivity in macrophages both mechanically and chemically. The size(length and/or diameter), functionalization, purification and even the experimental method can affect the influence of MWCNTs on macrophages, and a better understanding of these MWCNT characteristics may benefit utilization of this nanomaterial in associated nanomedical applications.

Biomedical Effects and Nanomaterials： Nanosafety of Engineered Recent Progress

With the development of nanotechnology, there are growing concerns about biological effects and biosafety of engineered nanomaterials. On the other hand, nanoparticles are widely used in medical fields based on their novel interactions with biological entities. However, there are still a lot of challenges to establish systematic knowledge about nanotoxicology and develop biologically safer biomedical materials due to the variety of factors determining their biomedical effects and nanotoxicity. Understanding the interactions of engineered nanomaterials with the bio- logical entities becomes crucial to the further development of nanoscience and nanotechnology. In the past decade, colleagues in our laboratory intensively studied the toxic properties of various kinds of nanomaterials and their chemical mechanisms. In this paper we review the recent advance in the research on the biological effects of engi- neered nanomaterials and nanosafety issue, by focusing on the studies about representative nanomaterials in our la- boratory.

In Vivo Toxicity Assessment of Gold Nanoparticles in Drosophila melanogaster

The growing use of nanomaterials in commercial goods and novel technologies is generating increasing questions about possible risks for human health and environment, due to the lack of an in-depth assessment of their potential toxicity. In this context, we investigated the effects of citrate-capped gold nanoparticles （AuNPs） on the model system Drosophila melanogaster upon ingestion. We observed a significant in vivo toxicity of AuNPs, which elicited clear adverse effects in treated organisms, such as a strong reduction of their life span and fertility, presence of DNA fragmentation, as well as a significant overexpression of the stress proteins. Transmission electron microscopy demonstrated the localization of the nanoparticles in tissues of Drosophila. The experimental evidence of high in vivo toxicity of a nanoscale material, which is widely considered to be safe and biocompatible in its bulk form, opens up important questions in many fields, including nanomedicine, material science, health, drug delivery and risk assessment.

Coating independent cytotoxicity of citrate-and PEG-coated silver nanoparticles on a human hepatoma cell line

The antibacterial potential of silver nanoparticles（AgNPs） resulted in their increasing incorporation into consumer,industrial and biomedical products.Therefore,human and environmental exposure to AgNPs（either as an engineered product or a contaminant）supports the emergent research on the features conferring them different toxicity profiles.In this study,30 ran AgNPs coated with citrate or poly（ethylene glycol）（PEG） were used to assess the influence of coating on the effects produced on a human hepatoma cell line（HepG2）,namely in terms of viability,apoptosis,apoptotic related genes,cell cycle and cyclins gene expression.Both types of coated AgNPs decreased cell proliferation and viability with a similar toxicity profile.At the concentrations used（11 and 5 μg/mL corresponding to IC50 and-IC10 levels,respectively） the amount of cells undergoing apoptosis was not significant and the apoptotic related genes BCL2（anti-apoptotic gene）and BAX（pro-apoptotic gene） were both downregulated.Moreover,both AgNPs affected HepG2 cell cycle progression at the higher concentration（11 μg/mL） by increasing the percentage of cells in S（synthesis phase） and G2（Gap 2 phase） phases.Considering the cell-cycle related genes,the expression of cyclin B1 and cyclin E1 genes were decreased.Thus,this work has shown that citrate- and PEG-coated AgNPs impact on HepG2 apoptotic gene expression,cell cycle dynamics and cyclin regulation in a similar way.More research is needed to determine the properties that confer AgNPs at lower toxicity,since their use has proved helpful in several industrial and biomedical contexts.

(Q)SAR modelling of nanomaterial toxicity:A critical review

There is increasing recognition that some nanomaterials may pose a risk to human health and the environment. Moreover, the industrial use of the novel engineered nanomaterials （ENMs） increases at a higher rate than data generation for hazard assessment; consequently, many of them remain untested. The large number of nanomaterials and their variants （e.g., different sizes and coatings） requiring testing and the ethical pressure towards nonanimal testing means that in a first instance, expensive animal bioassays are precluded, and the use of（quantitative） structure-activity relationships （（Q）SARs） models as an alter- native source of （screening） hazard information should be explored. （Q）SAR modelling can be applied to contribute towards filling important knowledge gaps by making best use of existing data, prioritizing the physicochemical parameters driving toxicity, and providing practical solutions for the risk assessment problems caused by the diversity of ENMs. This paper covers the core components required for successful application of （Q）SAR methods to ENM toxicity prediction, summarizes the published nano-（Q）SAR studies, and outlines the challenges ahead for nano-（Q）SAR modelling. It provides a critical review of （1） the present availability of ENM characterization/toxicity data, （2） the characterization of nanostructures that meet the requirements for （Q）SAR analysis, （3） published nano-（Q）SAR studies and their limitations, （4） in silico tools for （Q）SAR screening of nanotoxicity, and （5） prospective directions for the development of nano-（Q）SAR models.

A method for assessing nanomaterial dispersion quality based on principal component analysis of particle size distribution data

Seemingly contradictory findings between studies are a major issue in nanoecotoxicological research and have been explained as a result of the lack of comparability between assay methods, with dispersion of nanomaterials being identified as a key factor. Here we show the use of a multivariate method, principal component analysis （PCA）, as a tool in protocol development and categorization of dispersion quality. Results show the significance of particle concentration within a protocol, and its effect on repeatability. Our results suggest that future studies should involve the use of PCA as a powerful data exploration tool to facilitate method development, comparability and integration of data across different laboratories.

Chronic effect of waterborne colloidal silver nanoparticles on plasma biochemistry and hematology of rainbow trout(Oncorhynchus mykiss)

Objective:To investigate the possible effects of silver nanoparticles(AgNPs)on some blood and plasma indices of rainbow trout(Oncorhynchus mykiss).Methods:Hence,fish were exposed for 21 days to sub-lethal concentrations of colloidal AgNPs and blood parameters including erythrocyte size and hematocrit,plasma parameters including cholinesterase,cortisol,sodium,chloride,and potassium,and also silver concentration in plasma were measured following the 11th and 21st days of exposure.Results:According to the results of present study,higher concentrations of AgNPs had more significant effects on plasma biochemistry and hematology of trout.The greatest impacts were decline of chloride ions and increase of cortisol and cholinesterase.Also fish exposed to AgNPs significantly increased silver concentration in the plasma.Conclusions:Further studies are needed to identify appropriate blood biomarkers following fish exposed to nanomaterials,especially AgNPs.