Properties Of Engineered Nanomaterials Research Articles

ADOPTION OF THE PRECAUTIONARY PRINCIPLE ON THE SAFETY AND HEALTH RISKS OF NANOFOOD IN MALAYSIA

Food derived from nanotechnology or contains engineered nanomaterials (ENMs) is widely available for consumers in the marketplace. Oral exposure to ENMs has been linked to various potential adverse effects on human safety and health. In Malaysia, nanofood is regulated with a regulatory framework designed for conventional food without considering the unique and novel properties of ENMs. The adequacy of the existing framework for regulating the safety and health risks of nanofood is ambiguous. This study examined the necessity for Malaysia of having such regulatory framework to govern the safety and health risks of nanofood using the precautionary principle. By adopting the doctrinal analysis, the finding suggests that the existing food safety framework must be amended to incorporate specific provisions on nanotechnology, and that the amendment must be based on the precautionary principle. The new regulatory framework enables the food safety authority to implement the earliest precautionary measure, protecting consumers from serious future harm caused by nanofood. The proposed regulatory framework will strengthen the domestic food safety framework and national food safety policy in meeting the challenge posed by nanofood.

Analytical chemistry of engineered nanomaterials: Part 1. Scope, regulation, legislation, and metrology (IUPAC Technical Report)

Abstract Analytical chemistry is crucial for understanding the complex behavior observed for engineered nanomaterials (ENMs). A variety of analytical chemistry techniques and methodological approaches are used for isolation/purification and determination of the composition of pristine nanomaterials and for the detection, identification, and quantification of nanomaterials in nano-enabled consumer products and the complex matrices found in cosmetics, food, and environmental and biological samples. Adequate characterization of ENMs also requires physicochemical characterization of number of other properties, including size, shape, and structure. The requirement for assessment of a number of ENM properties frequently requires interdisciplinary approaches and multi-modal analysis methods. This technical report starts with an overview of ENMs definitions and classification, their properties, and analytical scenarios encountered with the analysis of both pristine nanomaterials and complex matrices containing different nanomaterials. An evaluation of the current status regarding nanomaterial identification and characterization for regulatory purposes and legislation, including emerging regulations and related scientific opinions, is provided. The technical report also presents a large and critical overview of the metrology of nanomaterials, including available reference materials and the development and validation of standardized methods that are currently available to address characterization and analysis challenges. The report focuses mainly on chemical analysis techniques and thus it is complementary to previous IUPAC technical reports focused on characterizing the physical parameters of ENMs and on nanotoxicology.

Diverse Pathways of Engineered Nanoparticle-Induced NLRP3 Inflammasome Activation.

With the rapid development of engineered nanomaterials (ENMs) in biomedical applications, their biocompatibility and cytotoxicity need to be evaluated properly. Recently, it has been demonstrated that inflammasome activation may be a vital contributing factor for the development of biological responses induced by ENMs. Among the inflammasome family, NLRP3 inflammasome has received the most attention because it directly interacts with ENMs to cause the inflammatory effects. However, the pathways that link ENMs to NLRP3 inflammasome have not been thoroughly summarized. Thus, we reviewed recent findings on the role of major ENMs properties in modulating NLRP3 inflammasome activation, both in vitro and in vivo, to provide a better understanding of the underlying mechanisms. In addition, the interactions between ENMs and NLRP3 inflammasome activation are summarized, which may advance our understanding of safer designs of nanomaterials and ENM-induced adverse health effects.

Nanowaste: Another Future Waste, Its Sources, Release Mechanism, and Removal Strategies in the Environment

Nanowaste is defined as waste derived from materials with at least one dimension in the 1–100 nm range. The nanomaterials containing products are considered as “nanoproducts” and they can lead to the development of nanomaterial-containing waste, also termed as “nanowaste”. The increased production and consumption of these engineered nanomaterials (ENMs) and nanoproducts that generate enormous amounts of nanowaste have raised serious concerns about their fate, behavior, and ultimate disposal in the environment. It is of the utmost importance that nanowaste is disposed of in an appropriate manner to avoid an adverse impact on human health and the environment. The unique properties of ENMs, combined with an inadequate understanding of appropriate treatment techniques for many forms of nanowaste, makes nanowaste disposal a complex task. Presently, there is a lack of available information on the optimized standards for identifying, monitoring, and managing nanowaste. Therefore, this review highlights concerns about nanowaste as future waste that need to be addressed. The review focuses on ENMs waste (in the form of NP, nanotubes, nanowires, and quantum dots) generated from the manufacture of a wide variety of nanoproducts that end up as nanowaste and adversely affect the environment. Furthermore, the review considers different types of ENMs in waste streams and environmental compartments (i.e., soil, water, and air). Detailed studies are still required to identify data gaps and implement strategies to remove and control this future waste.

An EPA database on the effects of engineered nanomaterials-NaKnowBase

The US EPA Office of Research and Development (ORD) has conducted a research program assessing potential risks of emerging materials and technologies, including engineered nanomaterials (ENM). As a component of that program, a nanomaterial knowledge base, termed “NaKnowBase”, was developed containing the results of published ORD research relevant to the potential environmental and biological actions of ENM. The experimental data address issues such as ENM release into the environment; fate, transport and transformations in environmental media; exposure to ecological species or humans; and the potential for effects on those species. The database captures information on the physicochemical properties of ENM tested, assays performed and their parameters, and the results obtained. NaKnowBase (NKB) is a relational SQL database, and may be queried either with SQL code or through a user-friendly web interface. Filtered results may be output in spreadsheet format for subsequent user-defined analyses. Potential uses of the data might include input to quantitative structure-activity relationships (QSAR), meta-analyses, or other investigative approaches.

Engineered Nanomaterials in Soil: Their Impact on Soil Microbiome and Plant Health.

A staggering number of nanomaterials-based products are being engineered and produced commercially. Many of these engineered nanomaterials (ENMs) are finally disposed into the soil through various routes in enormous quantities. Nanomaterials are also being specially tailored for their use in agriculture as nano-fertilizers, nano-pesticides, and nano-based biosensors, which is leading to their accumulation in the soil. The presence of ENMs considerably affects the soil microbiome, including the abundance and diversity of microbes. In addition, they also influence crucial microbial processes, such as nitrogen fixation, mineralization, and plant growth promoting activities. ENMs conduct in soil is typically dependent on various properties of ENMs and soil. Among nanoparticles, silver and zinc oxide have been extensively prepared and studied owing to their excellent industrial properties and well-known antimicrobial activities. Therefore, at this stage, it is imperative to understand how these ENMs influence the soil microbiome and related processes. These investigations will provide necessary information to regulate the applications of ENMs for sustainable agriculture and may help in increasing agrarian production. Therefore, this review discusses several such issues.

Commentary: Revisiting nanoparticle-assay interference: There's plenty of room at the bottom for misinterpretation.

Engineered nanomaterials (ENMs) are a diverse class of materials whose distinct properties make them desirable in a multitude of applications. The proliferation of nanotoxicology research has improved our understanding of ENM toxicity, but an under appreciation for their potential to interfere with biochemical assays has hampered progress in the field. The physicochemical properties of ENMs can promote their interaction with membranes or biomacromolecules (e.g. proteins, genomic material). This can influence the activity of enzymes used as biomarkers or as reagents in biochemical assay protocols, bind indicator dyes in cytotoxicity tests, and/or interfere with the cellular mechanisms controlling the uptake of such dyes. The spectral characteristics of some ENMs can cause interference with common assay chromophores, fluorophores, and radioisotope scintillation cocktails. Finally, the inherent chemical reactivity of some ENMs can short circuit assay mechanisms by directly oxidizing or reducing indicator dyes. These processes affect data quality and may lead to significant misinterpretations regarding ENM safety. We provide an overview of some ENM properties that facilitate assay interference, examples of interference and the erroneous conclusions that may result from it, and a number of general and specific recommendations for validating cellular and biochemical assay protocols in nanotoxicology studies.

High-Throughput Screening Platform for Nanoparticle-Mediated Alterations of DNA Repair Capacity.

The potential genotoxic effects of engineered nanomaterials (ENMs) may occur through the induction of DNA damage or the disruption of DNA repair processes. Inefficient DNA repair may lead to the accumulation of DNA lesions and has been linked to various diseases, including cancer. Most studies so far have focused on understanding the nanogenotoxicity of ENM-induced damages to DNA, whereas the effects on DNA repair have been widely overlooked. The recently developed fluorescence multiplex-host-cell reactivation (FM-HCR) assay allows for the direct quantification of multiple DNA repair pathways in living cells and offers a great opportunity to address this methodological gap. Herein an FM-HCR-based method is developed to screen the impact of ENMs on six major DNA repair pathways using suspended or adherent cells. The sensitivity and efficiency of this DNA repair screening method were demonstrated in case studies using primary human small airway epithelial cells and TK6 cells exposed to various model ENMs (CuO, ZnO, and Ga2O3) at subcytotoxic doses. It was shown that ENMs may inhibit nucleotide-excision repair, base-excision repair, and the repair of oxidative damage by DNA glycosylases in TK6 cells, even in the absence of significant genomic DNA damage. It is of note that the DNA repair capacity was increased by some ENMs, whereas it was suppressed by others. Overall, this method can be part of a multitier, in vitro hazard assessment of ENMs as a functional, high-throughput platform that provides insights into the interplay of the properties of ENMs, the DNA repair efficiency, and the genomic stability.

Characterisation of Engineered Nanomaterials in Nano-Enabled Products Exhibiting Priority Environmental Exposure.

Analytical limitations have constrained the determination of nanopollution character from real-world sources such as nano-enabled products (NEPs), thus hindering the development of environmental safety guidelines for engineered nanomaterials (ENMs). This study examined the properties of ENMs in 18 commercial products: sunscreens, personal care products, clothing, and paints—products exhibiting medium to a high potential for environmental nanopollution. It was found that 17 of the products contained ENMs; 9, 3, 3, and 2 were incorporated with nTiO2, nAg, binaries of nZnO + nTiO2, and nTiO2 + nAg, respectively. Commonly, the nTiO2 were elongated or angular, whereas nAg and nZnO were near-spherical and angular in morphology, respectively. The size ranges (width × length) were 7–48 × 14–200, 34–35 × 37–38, and 18–28 nm for nTiO2, nZnO, and nAg respectively. All ENMs were negatively charged. The total concentration of Ti, Zn, and Ag in the NEPs were 2.3 × 10−4–4.3%, 3.4–4.3%, and 1.0 × 10−4–11.3 × 10−3%, respectively. The study determined some key ENM characteristics required for environmental risk assessment; however, challenges persist regarding the accurate determination of the concentration in NEPs. Overall, the study confirmed NEPs as actual sources of nanopollution; hence, scenario-specific efforts are recommended to quantify their loads into water resources.

Apellis: An online tool for read-across model development

In this study, we present Apellis, a web application developed for training grouping/read-across models for the prediction of engineered nanomaterials (ENMs) toxicity-related endpoints. The application applies a generic and novel computational workflow for estimating the endpoint of interest, which can be either categorical or numerical. During the training procedure, the application selects the most important ENM properties of concern that affect their toxic behaviour. In the process of grouping ENMs for performing read-across predictions, the multi-perspective characterization of ENMs can be taken into account, by defining more than one similarity criteria. The workflow converges to the grouping hypothesis that leads to the most accurate read-across estimations. Visualisation tools are included in the application, which offer better and more clear understanding of grouping and similarities among ENMs. The trained models can be saved in an electronic format, so that they can be easily retrieved, for calculating new predictions. In addition, this allows model developers to disseminate and share the produced models with the community. Apellis is free to use and accessible at apellis.jaqpot.org.

Advanced In Vitro Testing Strategies and Models of the Intestine for Nanosafety Research.

There is growing concern about the potential adverse effects of oral exposure to engineered nanomaterials (ENM). Recent years have witnessed major developments in and advancement of intestinal in vitro models for nanosafety evaluation. The present paper reviews the key factors that should be considered for inclusion in nonanimal alternative testing approaches to reliably reflect the in vivo dynamics of the physicochemical properties of ENM as well the intestinal physiology and morphology. Currently available models range from simple cell line-based monocultures to advanced 3D systems and organoids. In addition, in vitro approaches exist to replicate the mucous barrier, digestive processes, luminal flow, peristalsis, and interactions of ENM with the intestinal microbiota. However, while the inclusion of a multitude of individual factors/components of particle (pre)treatment, exposure approach, and cell model approximates in vivo-like conditions, such increasing complexity inevitably affects the system's robustness and reproducibility. The selection of the individual modules to build the in vitro testing strategy should be driven and justified by the specific purpose of the study and, not least, the intended or actual application of the investigated ENM. Studies that address health hazards of ingested ENM likely require different approaches than research efforts to unravel the fundamental interactions or toxicity mechanisms of ENM in the intestine. Advanced reliable and robust in vitro models of the intestine, especially when combined in an integrated testing approach, offer great potential to further improve the field of nanosafety research.

Au nanorod-induced NLRP3 inflammasome activation is mediated by ER stress

Abstract The widespread and increasing use of engineered nanomaterials (ENM) increases the risk of human exposure, generating concern that ENM may provoke adverse health effects. In this respect, their physicochemical characteristics are critical. The immune system may respond to specific ENM properties by inflammatory reactions. Inflammasome activation has drawn significant attention since inflammasomes, especially NLRP3 respond to a wide range of stimuli including nanoparticles, and their activation is associated with various inflammatory diseases, including lung fibrosis, obesity and type-2 diabetes. Endoplasmic reticulum (ER) stress has been reported as one of the mechanisms underlying NLRP3 inflammasome activation. In this study, PEGylated Au ENM of ≈60 nm, having different shapes (stars, spheres and rods) were extensively characterized, and tested for possible LPS contamination. PMA-activated THP-1 cells were exposed to these ENM, and cell viability and IL-1β production were measured to assess NLRP3 activation. In addition, the exposed cells were subjected to gene expression analysis using microarray analysis to investigate related signalling pathway regulation. PEGylated Au nanorods (NR), but not nanostars or nanospheres, showed NLRP3 inflammasome activation. Cells deficient in the NLRP3 scaffold or ASC adaptor did not show this effect. Only NR-exposed cells showed down-regulation of ER-associated cholesterol metabolism. This finding may suggest that ER stress mediates NLRP3 inflammasome activation by Au NR. Supported by the EU funded project FutureNanoNeeds (Grant agreement N° 604602).

Engineered Nanomaterials and Type I Allergic Hypersensitivity Reactions.

Type I allergic hypersensitivity disorders (atopy) including asthma, atopic dermatitis, allergic rhinitis, and food allergy are on the rise in developed and developing countries. Engineered nanomaterials (ENMs) span a large spectrum of material compositions including carbonic, metals, polymers, lipid-based, proteins, and peptides and are being utilized in a wide range of industries including healthcare and pharmaceuticals, electronics, construction, and food industry, and yet, regulations for the use of ENMs in consumer products are largely lacking. Prior evidence has demonstrated the potential of ENMs to induce and/or aggravate type I allergic hypersensitivity responses. Furthermore, previous studies have shown that ENMs could directly interact with and activate key T-helper 2 (Th2) effector cell types (such as mast cells) and the complement system, which could result in pseudoallergic (non-IgE-mediated) hypersensitivity reactions. Nevertheless, the underlying molecular mechanisms of ENM-mediated induction and/or exacerbation of type I immune responses are poorly understood. In this review, we first highlight key examples of studies that have demonstrated inherent immunomodulatory properties of ENMs in the context of type I allergic hypersensitivity reactions, and most importantly, we attempt to put together the potential molecular mechanisms that could drive ENM-mediated stimulation and/or aggravation of type I allergic hypersensitivity responses.

Physical Properties of Carbon Nanomaterials and Nanoceria Affect Pathways Important to the Nodulation Competitiveness of the Symbiotic N2 -Fixing Bacterium Bradyrhizobium diazoefficiens.

The pathogenicity and antimicrobial properties of engineered nanomaterials (ENMs) are relatively well studied. However, less is known regarding the interactions of ENMs and agriculturally beneficial microorganisms that affect food security. Nanoceria (CeO2 nanoparticles (NPs)), multiwall carbon nanotubes (MWCNTs), graphene nanoplatelets (GNPs), and carbon black (CB) have been previously shown to inhibit symbiotic N2 fixation in soybeans, but direct rhizobial susceptibility is uncertain. Here, Bradyrhizobium diazoefficiens associated with symbiotic N2 fixation in soybeans is assessed, evaluating the role of soybean root exudates (RE) on ENM-bacterial interactions and the effects of CeO2 NPs, MWCNTs, GNPs, and CB on bacterial growth and gene expression. Although bacterial growth is inhibited by 50 mg L-1 CeO2 NPs, MWCNTs, and CB, all ENMs at 0.1 and 10 mg L-1 cause a global transcriptomic response that is mitigated by RE. ENMs may interfere with plant-bacterial signaling, as evidenced by suppressed upregulation of genes induced by RE, and downregulation of genes encoding transport RNA, which facilitates nodulation signaling. MWCNTs and CeO2 NPs inhibit the expression of genes conferring B. diazoefficiens nodulation competitiveness. Surprisingly, the transcriptomic effects on B. diazoefficiens are similar for these two ENMs, indicating that physical, not chemical, ENM properties explain the observed effects.

Prediction of protein corona on nanomaterials by machine learning using novel descriptors

Effective in silico methods to predict protein corona compositions on engineered nanomaterials (ENMs) could help elucidate the biological outcomes of ENMs in biosystems without the need for conducting lengthy experiments for corona characterization. However, the physicochemical properties of ENMs, used as the descriptors in current modeling methods, are insufficient to represent the complex interactions between ENMs and proteins. Herein, we utilized the fluorescence change (FC) from fluorescamine labeling on a protein, with or without the presence of the ENM, as a novel descriptor of the ENM to build machine learning models for corona formation. FCs were significantly correlated with the abundance of the corresponding proteins in the corona on diverse classes of ENMs, including metal and metal oxides, nanocellulose, and 2D ENMs. Prediction models established by the random forest algorithm using FCs as the ENM descriptors showed better performance than the conventional descriptors, such as ENM size and surface charge, in the prediction of corona formation. Moreover, they were able to predict protein corona formation on ENMs with very heterogeneous properties. We believe this novel descriptor can improve in silico studies of corona formation, leading to a better understanding on the protein adsorption behaviors of diverse ENMs in different biological matrices. Such information is essential for gaining a comprehensive view of how ENMs interact with biological systems in ENM safety and sustainability assessments.

The neurotoxicity induced by engineered nanomaterials.

Engineered nanomaterials (ENMs) have been widely used in various fields due to their novel physicochemical properties. However, the use of ENMs has led to an increased exposure in humans, and the safety of ENMs has attracted much attention. It is universally acknowledged that ENMs could enter the human body via different routes, eg, inhalation, skin contact, and intravenous injection. Studies have proven that ENMs can cross or bypass the blood–brain barrier and then access the central nervous system and cause neurotoxicity. Until now, diverse in vivo and in vitro models have been developed to evaluate the neurotoxicity of ENMs, and oxidative stress, inflammation, DNA damage, and cell death have been identified as being involved. However, due to various physicochemical properties of ENMs and diverse study models in existing studies, it remains challenging to establish the structure-activity relationship of nanomaterials in neurotoxicity. In this paper, we aimed to review current studies on ENM-induced neurotoxicity, with an emphasis on the molecular and cellular mechanisms involved. We hope to provide a rational material design strategy for ENMs when they are applied in biomedical or other engineering applications.

Creative use of analytical techniques and high-throughput technology to facilitate safety assessment of engineered nanomaterials.

With the rapid development and numerous applications of engineered nanomaterials (ENMs) in science and technology, their impact on environmental health and safety should be considered carefully. This requires an effective platform to investigate the potential adverse effects and hazardous biological outcomes of numerous nanomaterials and their formulations. We consider predictive toxicology a rational approach for this effort, which utilizes mechanism-based in vitro high-throughput screening (HTS) to make predictions on ENMs' adverse outcomes in vivo. Moreover, this approach is able to link the physicochemical properties of ENMs to toxicity that allows the development of structure-activity relationships (SARs). To build this predictive platform, extensive analytical and bioanalytical techniques and tools are required. In this review, we described the predictive toxicology approach and the accompanying analytical and bioanalytical techniques. In addition, we elaborated several successful examples as a result of using the predictive approach.

Advanced tools for the safety assessment of nanomaterials.

Engineered nanomaterials (ENMs) have tremendous potential to produce beneficial technological impact in numerous sectors in society. Safety assessment is, of course, of paramount importance. However, the myriad variations of ENM properties makes the identification of specific features driving toxicity challenging. At the same time, reducing animal tests by introducing alternative and/or predictive in vitro and in silico methods has become a priority. It is important to embrace these new advances in the safety assessment of ENMs. Indeed, remarkable progress has been made in recent years with respect to mechanism-based hazard assessment of ENMs, including systems biology approaches as well as high-throughput screening platforms, and new tools are also emerging in risk assessment and risk management for humans and the environment across the whole life-cycle of nano-enabled products. Here, we highlight some of the key advances in the hazard and risk assessment of ENMs.

The impact of nanomaterial characteristics on inhalation toxicity.

During the last few decades, nanotechnology has evolved into a success story, apparent from a steadily increasing number of scientific publications as well as a large number of applications based on engineered nanomaterials (ENMs). Its widespread uses suggest a high relevance for consumers, workers and the environment, hence justifying intensive investigations into ENM-related adverse effects as a prerequisite for nano-specific regulations. In particular, the inhalation of airborne ENMs, being assumed to represent the most hazardous type of human exposure to these kinds of particles, needs to be scrutinized. Due to an increased awareness of possible health effects, which have already been seen in the case of ultrafine particles (UFPs), research and regulatory measures have set in to identify and address toxic implications following their almost ubiquitous occurrence. Although ENM properties differ from those of the respective bulk materials, the available assessment protocols are often designed for the latter. Despite the large benefit ensuing from the application of nanotechnology, many issues related to ENM behavior and adverse effects are not fully understood or should be examined anew. The traditional hypothesis that ENMs exhibit different or additional hazards due to their "nano" size has been challenged in recent years and ENM categorization according to their properties and toxicity mechanisms has been proposed instead. This review summarizes the toxicological effects of inhaled ENMs identified to date, elucidating the modes of action which provoke different mechanisms in the respiratory tract and their resulting effects. By linking particular mechanisms and adverse effects to ENM properties, grouping of ENMs based on toxicity-related properties is supposed to facilitate toxicological risk assessment. As intensive studies are still required to identify these "ENM classes", the need for alternatives to animal studies is evident and advances in cell-based test systems for pulmonary research are presented here. We hope to encourage the ongoing discussion about ENM risks and to advocate the further development and practice of suitable testing and grouping methods.

Bio-nano interface and environment: A critical review.

The bio-nano interface is the boundary where engineered nanomaterials (ENMs) meet the biological system, exerting the biological function for which they have been designed or inducing adverse effects on other cells or organisms when they reach nontarget scenarios (i.e., the natural environment). Research has been performed to determine the fate, transport, and toxic properties of ENMs, but much of it is focused on pristine or so-called as-manufactured ENMs, or else modifications of the materials were not assessed. We review the most recent progress regarding the bio-nano interface and the transformations that ENMs undergo in the environment, paying special attention to the adsorption of environmental biomolecules on the surface of ENMs. Whereas the protein corona has received considerable attention in the fields of biomedics and human toxicology, its environmental analogue (the eco-corona) has been much less studied. A section dedicated to the analytical methods for studying and characterizing the eco-corona is also presented. We conclude by presenting and discussing the key problems and knowledge gaps that need to be resolved in the near future regarding the bio-nano interface and the eco-corona. Environ Toxicol Chem 2017;36:3181-3193. © 2017 SETAC.