Risk Assessment Of Engineered Nanomaterials Research Articles

Computational Nanotoxicology Models for Environmental Risk Assessment of Engineered Nanomaterials.

Although engineered nanomaterials (ENMs) have tremendous potential to generate technological benefits in numerous sectors, uncertainty on the risks of ENMs for human health and the environment may impede the advancement of novel materials. Traditionally, the risks of ENMs can be evaluated by experimental methods such as environmental field monitoring and animal-based toxicity testing. However, it is time-consuming, expensive, and impractical to evaluate the risk of the increasingly large number of ENMs with the experimental methods. On the contrary, with the advancement of artificial intelligence and machine learning, in silico methods have recently received more attention in the risk assessment of ENMs. This review discusses the key progress of computational nanotoxicology models for assessing the risks of ENMs, including material flow analysis models, multimedia environmental models, physiologically based toxicokinetics models, quantitative nanostructure-activity relationships, and meta-analysis. Several challenges are identified and a perspective is provided regarding how the challenges can be addressed.

Aquatic Mesocosm Strategies for the Environmental Fate and Risk Assessment of Engineered Nanomaterials.

In the past decade, mesocosms have emerged as a useful tool for the environmental study of engineered nanomaterials (ENMs) as they can mimic the relevant exposure scenario of contamination. Herein, we analyzed the scientific outcomes of aquatic mesocosm experiments, with regard to their designs, the ENMs tested, and the end points investigated. Several mesocosm designs were consistently applied in the past decade to virtually mimic various contamination scenarios with regard to ecosystem setting as well as ENMs class, dose, and dosing. Statistical analyses were carried out with the literature data to identify the main parameters driving ENM distribution in the mesocosms and the potential risk posed to benthic and planktonic communities as well as global ecosystem responses. These analyses showed that at the end of the exposure, mesocosm size (water volume), experiment duration, and location indoor/outdoor had major roles in defining the ENMs/metal partitioning. Moreover, a higher exposure of the benthic communities is often observed but did not necessarily translate to a higher risk due to the lower hazard posed by transformed ENMs in the sediments (e.g., aggregated, sulfidized). However, planktonic organisms were generally exposed to lower concentrations of potentially more reactive and toxic ENM species. Hence, mesocosms can be complementary tools to existing standard operational procedures for regulatory purposes and environmental fate and risk assessment of ENMs. To date, the research was markedly unbalanced toward the investigation of metal-based ENMs compared to metalloid- and carbon-based ENMs but also nanoenabled products. Future studies are expected to fill this gap, with special regard to high production volume and potentially hazardous ENMs. Finally, to take full advantage of mesocosms, future studies must be carefully planned to incorporate interdisciplinary approaches and ensure that the large data sets produced are fully exploited.

Robustness of Indoor Aquatic Mesocosm Experimentations and Data Reusability to Assess the Environmental Risks of Nanomaterials

Indoor aquatic mesocosms are increasingly used in nanosafety to assess the behavior, fate, and impacts of engineered nanomaterials (ENMs) in aquatic environments using relevant exposure scenarios. The robustness of 60 L freshwater mesocosm experimentation was tested on the basis of the reusability of the data collected in a database named MESOCOSM regarding mesocosm experiments examining the environmental risks of CeO2 ENMs. We observed high reliability of the measured variables across replicates. The sensitivity of this mesocosm methodology was evidenced by the contrasted ecosystem responses revealed by a multivariate analysis. We also observed that adding variables to the data set up to 15% did not affect the outcome of the analysis of the results. This ability to buffer this variability demonstrates that the indoor aquatic mesocosms are robust tools contributing to the environmental risk assessment of ENMs, and stresses the benefit of reusing the data stored in databases such as MESOCOSM adhering to the findable, accessible, interoperable, reusable (FAIR) data principles.

An Exploratory Assessment of Applying Risk Management Practices to Engineered Nanomaterials.

The widespread industrial application of nanotechnology has increased the number of workers exposed to engineered nanomaterials (ENMs), but it is not clear to what extent prevention guidance is practiced. Our aim was to explore the extent that companies manufacturing and/or using ENMs apply risk assessment and management measures. Thirty-four companies were surveyed with an international 35-item questionnaire investigating company and workforce features, types of ENM handled, and risk evaluation and preventive measures adopted. Among participating companies, 62% had a maximum of 10 employees. Metal-based nanomaterials were most frequently identified (73%). Environmental monitoring was performed by 41% of the companies, while engineering exposure controls were approximately reported by 50%. Information and training programs were indicated by 85% of the sample, only 9% performed specific health surveillance for ENM workers. Personal protective equipment primarily included gloves (100%) and eye/face protection (94%). This small-scale assessment can contribute to the limited amount of published literature on the topic. Future investigations should include a greater number of companies to better represent ENM workplaces and a direct access to industrial settings to collect information on site. Finally, deeper attention should be paid to define standardized frameworks for ENM risk assessment that may guide nano-specific preventive actions.

Material-specific properties applied to an environmental risk assessment of engineered nanomaterials – implications on grouping and read-across concepts

Engineered nanomaterials (ENMs) are intentionally designed in different nano-forms of the same parent material in order to meet application requirements. Different grouping and read-across concepts are proposed to streamline risk assessments by pooling nano-forms in one category. Environmental grouping concepts still are in their infancy and mainly focus on grouping by hazard categories. Complete risk assessments require data on environmental release and exposure not only for ENMs but also for their nano-forms. The key requirement is to identify and to distinguish the production volumes of the ENMs regarding nano-form-specific applications. The aim of our work was to evaluate whether such a grouping is possible with the available data and which influence it has on the environmental risk assessment of ENMs. A functionality-driven approach was applied to match the material-specific property (i.e. crystal form/morphology) with the functions employed in the applications. We demonstrate that for nano-TiO2, carbon nanotubes (CNTs), and nano-Al2O3 the total production volume can be allocated to specific nano-forms based on their functionalities. The differentiated assessments result in a variation of the predicted environmental concentrations for anatase vs. rutile nano-TiO2, single-wall vs. multi-wall CNTs and α- vs. γ-nano-Al2O3 by a factor of 2 to 13. Additionally, the nano-form-specific predicted no-effect concentrations for these ENMs were derived. The risk quotients for all nano-forms indicated no immediate risk in freshwaters. Our results suggest that grouping and read-across concepts should include both a nano-form release potential for estimating the environmental exposure and separately consider the nano-forms in environmental risk assessments.

Sublethal Effects of Ionic and Nanogold on the Nematode Caenorhabditis elegans.

The nematode Caenorhabditis elegans is used as an ecotoxicological model species in both aqueous medium and solid substrates. It is easy and of low cost to maintain in the laboratory and it produces hundreds of offspring within a short period of time. It also has a small body size (1 mm), making it possible for in vivo assays to be conducted in 12-well plates. Engineered nanomaterials (ENMs) are a class of emerging pollutants. Nanogold (nAu) is used in many consumer products and in vivo drug delivery. These materials can be released into the aquatic environment during production or discarding of consumer products. As nAu is insoluble in water, the sediment would become the final depository for the materials. It has become increasingly important to use sediment dwelling organisms to screen for possible toxicity of these ENMs. In this study C. elegans was exposed to a range of concentrations of nAu and ionic gold in M9-media, acting as a substitute for pore water. After 96-hour growth, fertility and reproduction were determined. Internal structure damage and internalisation of particles in C. elegans were determined by using SEM and CytoViva® Darkfield Imaging. From these images the nanomaterials are distributed around the oocytes in the reproductive organs, as well as the pharynx. Results obtained indicate that nAu affects reproduction more than growth due to internal gonad damage, albeit at very high exposure concentrations, indicating no toxicity at environmentally relevant concentrations. Ionic Au is more toxic than nAu and effects fertility and reproduction due to ion release. These results give more information regarding the toxicity and in vivo uptake of nAu and form part of an environmental risk assessment of ENMs.

Bridge knowledge gaps in environmental health and safety for sustainable development of nano-industries

Abstract Sustainable development of nanotechnology relies on the design and production of engineered nanomaterials (ENMs) with substantial benefits and manageable risks to the environment and human beings, and requires a thorough understanding of environmental health and safety (EHS) impacts. In this review, we elaborate the importance of improved understanding of EHS of ENMs for the sustainable development of nano-industries. Based on our analysis of the current knowledge gaps and challenges in nano-EHS research, we propose that future research directions should mainly focus on: elucidating the impacts of environmental exposure, transport, transformation and fate of EMMs on their toxicity and health risks; identifying more appropriate assays and biomarkers for ENMs risk assessment framework; taking a systems innovation approach for scaling up from laboratory to industrial level.

Considering the forms of released engineered nanomaterials in probabilistic material flow analysis

Most existing models for assessing the releases of engineered nanomaterials (ENMs) into the environment are based on the assumption that ENMs remain in their pristine forms during their whole life cycle. It is known, however, that this is not always the case as ENMs are often embedded into solid matrices during manufacturing and can undergo physical or chemical transformations during their life cycle, e.g. upon release to wastewater. In this work, we present a method for systematically assessing the forms in which nano-Ag and nano-TiO2 flow through their life cycle (i.e. production, manufacturing, use and disposal) to their points of release to air, soil and surface water. Input data on the forms of released ENMs were probability distributions based on peer-reviewed literature. Release data were incorporated into a probabilistic material flow analysis model to quantify the proportions of ENMs in product-embedded, matrix-embedded, pristine, transformed and dissolved forms in all technical and environmental compartments into which they flow, at the European scale. Releases of nano-Ag to surface water and soil were modelled to occur primarily in transformed forms (Q25 and Q75 of 34–58% and 78–86%, respectively, with means of 53% and 82%), while releases to air were mostly in pristine and matrix-embedded forms (38–46% and 36–44%, respectively, with means of 42% and 40%). In contrast, nano-TiO2 releases to air, soil and water were estimated to be predominantly in pristine form (75–85%, 90–95%, 96–98%, respectively, with means of 80%, 91% and 97%). The distributions of ENM releases between forms developed here will improve the representativeness and appropriateness of input data for environmental fate modelling and risk assessment of ENMs.

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.

Scientific rationale for the development of an OECD test guideline on engineered nanomaterial stability

Standardized methods for assessing the behaviour of engineered nanomaterials (ENMs) under relevant environmental conditions are an important part of ENM risk assessment. Existing assays, often developed for traditional chemicals, are frequently not applicable to ENMs, which present special challenges due to their particulate nature and complex intrinsic and extrinsic properties. Here we present the development of the novel OECD test guideline (TG) No. 318 for studying the “dispersion stability of nanomaterials in simulated environmental media”. We discuss the rationalization of the test design and required simplifications to develop a test, which can be executed in standard laboratories on a routine basis at reasonable costs. The relevance of the test for capturing ENM stability in surface waters is ensured by a strategic selection of adequate test media and testing scheme. As an example, we present data of a full test performed according to the new OECD TG using NM 105 as a representative TiO2 ENM. Limitations of the test in terms of scarce kinetic information and a focus on homo- instead of heteroaggregation are discussed. The developed OECD Test No. 318 represents the first standardized assay for ENMs using an operationally defined testing scheme capable of systematically comparing different ENMs in terms of their dispersion stability under environmentally relevant conditions. It will provide crucial data to inform risk assessment and regulation and can be adapted to different types of test media if needed.

Species sensitivity weighted distribution for ecological risk assessment of engineered nanomaterials: the n-TiO2 case study.

Societal concerns about the environmental risks of engineered nanomaterials (ENMs) have recently increased, but nano-ecological risk assessments are constrained by significant gaps in basic information on long-term effects and exposures, for example. An approach to the ecological risk assessment of ENMs is proposed that can operate in the context of high uncertainty. This approach further develops species sensitivity weighted distribution (SSWD) by including 3 weighting criteria (species relevance, trophic level abundance, and nanotoxicity data quality) to address nano-specific needs (n-SSWD). The application of n-SSWD is illustrated for nanoscale titanium dioxide (n-TiO2 ), which is available in different crystal forms; it was selected because of its widespread use in consumer products (e.g., cosmetics) and the ample availability of data from ecotoxicological studies in the literature (including endpoints for algae, invertebrates, bacteria, and vertebrates in freshwater, saltwater, and terrestrial compartments). The n-SSWD application resulted in estimation of environmental quality criteria (hazard concentration affecting 5% and 50% of the species) and ecological risk (potentially affected fraction of species), which were then compared with similar results obtained by applying the traditional species sensitivity distribution (SSD) approach to the same dataset. The n-SSWDs were also built for specific trophic levels (e.g., primary producers) and taxonomic groups (e.g., algae), which helped to identify the most sensitive organisms. These results showd that n-SSWD is a valuable risk tool, although further testing is suggested.

Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells

Understanding toxicity pathways of engineered nanomaterials (ENM) has recently been brought forward as a key step in twenty-first century ENM risk assessment. Molecular mechanisms linked to phenotypic end points is a step towards the development of toxicity tests based on key events, which may allow for grouping of ENM according to their modes of action. This study identified molecular mechanisms underlying mitochondrial dysfunction in human bronchial epithelial BEAS 2B cells following exposure to one of the most studied multi-walled carbon nanotubes (Mitsui MWCNT-7). Asbestos was used as a positive control and a non-carcinogenic glass wool material was included as a negative fibre control. Decreased mitochondrial membrane potential (MMP↓) was observed for MWCNTs at a biologically relevant dose (0.25 μg/cm2) and for asbestos at 2 μg/cm2, but not for glass wool. Extensive temporal transcriptomic and microRNA expression analyses identified a 330-gene signature (including 26 genes with known mitochondrial function) related to MWCNT- and asbestos-induced MMP↓. Forty-nine of the MMP↓-associated genes showed highly similar expression patterns over time (six time points) and the majority was found to be regulated by two transcription factors strongly involved in mitochondrial homeostasis, APP and NRF1. In addition, four miRNAs were correlated with MMP↓ and one of them, miR-1275, was found to negatively correlate with a large part of the MMP↓-associated genes. Cellular processes such as gluconeogenesis, mitochondrial LC-fatty acid β-oxidation and spindle microtubule function were enriched among the MMP↓-associated genes and miRNAs. These results are expected to be useful in the identification of key events in ENM-related toxicity pathways for the development of molecular screening techniques.

Guidance for the prognostic risk assessment of nanomaterials in aquatic ecosystems

Our understanding of the environmental fate and effects of engineered nanomaterials (ENMs) is in a state of fast transition. Recent scientific developments open new and powerful perspectives to define a framework for the prognostic risk assessment of ENMs in aquatic ecosystems. This requires abandoning the reductionist's approach of mechanistic analysis on particle or cellular scales and calls for engineering solutions that deal with uncertainties by applying assessment factors and probabilistic approaches. An ecological risk assessment (ERA) framework for ENMs is similar to that for other classes of substances, in that it requires clear protection goals based on ecosystem services, evidence-based concepts that link exposure to effects, and a transparent tiered effect assessment. Here, we discuss approaches to assess exposure and effects of ENMs. This includes recent developments in ENP fate modeling that greatly expanded the potential of prognostic exposure assessments. For the effect assessment, we advise a cost-effective screening based on principles of read-across as a conservative first tier. The feasibility of using species sensitivity distributions as a higher tier option is discussed. Controlled model ecosystem field experiments are proposed as a highest experimental tier, and are required for the calibration of the lower tiers. An outlook to unify information from various tiers by experimental work, fate modeling, and effect modeling as cost-effective prognostic tools for the ERA of ENMs is provided.

Bioaccumulation Dynamics and Modeling in an Estuarine Invertebrate Following Aqueous Exposure to Nanosized and Dissolved Silver

Predicting the environmental impact of engineered nanomaterials (ENMs) is increasingly important owing to the prevalence of emerging nanotechnologies. We derived waterborne uptake and efflux rate constants for the estuarine snail, Peringia ulvae, exposed to dissolved Ag (AgNO(3)) and silver nanoparticles (Ag NPs), using biodynamic modeling. Uptake rates demonstrated that dissolved Ag is twice as bioavailable as Ag in nanoparticle form. Biphasic loss dynamics revealed the faster elimination of Ag from Ag NPs at the start of depuration, but similar slow efflux rate constants. The integration of biodynamic parameters into our model accurately predicted Ag tissue burdens during chronic exposure with 85% of predicted values within a factor of 2 of observed values. Zeta potentials for the Ag NPs were lower in estuarine waters than in waters of less salinity; and uptake rates in P. ulvae were slower than reported for the freshwater snail Lymnaea stagnalis in similar experiments. This suggests aggregation of Ag NPs occurs in estuarine waters and reduces, but does not eliminate, bioavailability of Ag from the Ag NPs. Biodynamic modeling provides an effective methodology to determine bioavailable metal concentrations (originating from metal and metal-oxide nanoparticles) in the environment and may aid future ENM risk assessment.

Eating Nanomaterials: Cruelty-free and Safe? The EFSA Guidance on Risk Assessment of Nanomaterials in Food and Feed

Nanomaterials are increasingly being added to food handling and packaging materials, or directly, to human food and animal feed. To ensure the safety of such engineered nanomaterials (ENMs), in May 2011, the European Food Safety Authority (EFSA) published a guidance document on Risk assessment of the application of nanoscience and nanotechnologies in the food and feed chain. It states that risk assessment should be performed by following a step-wise procedure. Whenever human or animal exposure to nanomaterials is expected, the general hazard characterisation scheme requests information from in vitro genotoxicity, toxicokinetic and repeated dose 90-day oral toxicity studies in rodents. Numerous prevailing uncertainties with regard to nanomaterial characterisation and their hazard and risk assessment are addressed in the guidance document. This article discusses the impact of these knowledge gaps on meeting the goal of ensuring human safety. The EFSA's guidance on the risk assessment of ENMs in food and animal feed is taken as an example for discussion, from the point of view of animal welfare, on what level of uncertainty should be considered acceptable for human safety assessment of products with non-medical applications, and whether animal testing should be considered ethically acceptable for such products.

Safety assessment for nanotechnology and nanomedicine: concepts of nanotoxicology

Nanotechnology, nanomedicine and nanotoxicology are complementary disciplines aimed at the betterment of human life. However, concerns have been expressed about risks posed by engineered nanomaterials (ENMs), their potential to cause undesirable effects, contaminate the environment and adversely affect susceptible parts of the population. Information about toxicity and biokinetics of nano-enabled products combined with the knowledge of unintentional human and environmental exposure or intentional delivery for medicinal purposes will be necessary to determine real or perceived risks of nanomaterials. Yet, results of toxicological studies using only extraordinarily high experimental doses have to be interpreted with caution. Key concepts of nanotoxicology are addressed, including significance of dose, dose rate, and biokinetics, which are exemplified by specific findings of ENM toxicity, and by discussing the importance of detailed physico-chemical characterization of nanoparticles, specifically surface properties. Thorough evaluation of desirable versus adverse effects is required for safe applications of ENMs, and major challenges lie ahead to answer key questions of nanotoxicology. Foremost are assessment of human and environmental exposure, and biokinetics or pharmacokinetics, identification of potential hazards, and biopersistence in cells and subcellular structures to perform meaningful risk assessments. A specific example of multiwalled carbon nanotubes (MWCNT) illustrates the difficulty of extrapolating toxicological results. MWCNT were found to cause asbestos-like effects of the mesothelium following intracavitary injection of high doses in rodents. The important question of whether inhaled MWCNT will translocate to sensitive mesothelial sites has not been answered yet. Even without being able to perform a quantitative risk assessment for ENMs, due to the lack of sufficient data on exposure, biokinetics and organ toxicity, until we know better it should be made mandatory to prevent exposure by appropriate precautionary measures/regulations and practicing best industrial hygiene to avoid future horror scenarios from environmental or occupational exposures. Similarly, safety assessment for medical applications as key contribution of nanotoxicology to nanomedicine relies heavily on nano-specific toxicological concepts and findings and on a multidisciplinary collaborative approach involving material scientists, physicians and toxicologists.