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Journal: Nanotoxicology


Abstract Aggregation of metal oxide nanoparticles in aqueous media complicates interpretation of in vitro studies of nanoparticle-cell interactions. We used dynamic light scattering to investigate the aggregation dynamics of iron oxide and zinc oxide nanoparticles. Our results show that iron oxide particles aggregate more readily than zinc oxide particles. Pretreatment with serum stabilises iron oxide and zinc oxide nanoparticles against aggregation. Serum-treated iron oxide is stable only in pure water, while zinc oxide is stable in water or cell culture media. These findings, combined with zeta potential measurements and quantification of proteins adsorbed on particle surface, suggest that serum stabilisation of iron oxide particles occurs primarily through protein adsorption and resulting net surface charge. Zinc oxide stabilisation, however, also involves steric hindrance of particle aggregation. Fluid shear at levels used in flow experiments breaks up iron oxide particle aggregates. These results enhance our understanding of nanoparticle aggregation and its consequences for research on the biological effects of nanomaterials.

Concepts: Oxygen, Ultraviolet, Cell culture, Colloid, Oxides, Titanium dioxide, Zinc oxide, Colloidal chemistry


Abstract Substantial limitations and uncertainties hinder the exposure assessment of engineered nanomaterials (ENMs). The present deficit of reliable measurements and models will inevitably lead in the near term to qualitative and uncertain exposure estimations, which may fail to support adequate risk assessment and management. Therefore it is necessary to complement the current toolset with user-friendly methods for near-term nanosafety evaluation. This paper proposes an approach for relative exposure screening of ENMs. For the first time, an exposure model explicitly implements quantitative weight of evidence (WoE) methods and utilizes expert judgment for filling data gaps in the available evidence-base. Application of the framework is illustrated for screening of exposure scenarios for nanoscale titanium dioxide, carbon nanotubes and fullerenes, but it is applicable to other nanomaterials as well. The results show that the WoE-based model overestimates exposure for scenarios where expert judgment was substantially used to fill data gaps, which suggests its conservative nature. In order to test how variations in input data influence the obtained results, probabilistic Monte Carlo sensitivity analysis was applied to demonstrate that the model performs in stable manner.

Concepts: Risk, Carbon, Nanotechnology, Qualitative research, Graphite, Monte Carlo, Uncertainty, Risk assessment


Abstract Therapeutic nanoparticles (NPs) are used in nanomedicine as drug carriers or imaging agents, providing increased selectivity/specificity for diseased tissues. The first NPs in nanomedicine were developed to increase the efficacy of known drugs displaying dose-limiting toxicity and poor bioavailability, and to enhance disease detection. Nanotechnologies have gained much interest owing to their huge potential for applications in industry and medicine. It is necessary to ensure and control the biocompatibility of the components of therapeutic NPs to guarantee that intrinsic toxicity does not overtake the benefits. As well as monitoring their toxicity in vitro, in vivo and in silico, it is also necessary to understand their distribution in the human body, their biodegradation and excretion routes, and dispersion in the environment. Therefore, a deep understanding of their interactions with living tissues and of their possible effects in the human (and animal) body is required for the safe use of nanoparticulate formulations. Obtaining this information was the main aim of the NanoTEST project, and the goals of the reports collected together in this special issue are to summarize the observations and results obtained by the participating research teams, and to provide methodological tools for evaluating the biological impact of NPs.

Concepts: Medicine, Nanoparticle, In vivo, Nanotechnology, Nanomaterials, In vitro, Human body


Abstract In this study, the effect of ZnO nanoparticles and ZnCl2 on growth, reproduction and accumulation of zinc in Daphnia magna was determined in a 21 day chronic toxicity test. A variety of techniques were used to distinguish the free zinc ion, dissolved, nanoparticle and aggregated zinc fraction in the daphnia test medium. The results showed similar chronic effects on growth, reproduction and accumulation for the ZnO nanoparticles (EC10, 20, 50 reproduction: 0.030, 0.049, 0.112 mg Zn/l) and the ZnCl2 (EC10, 20, 50 reproduction: 0.014, 0.027, 0.082 mg Zn/l). A large fraction of the nanoparticles rapidly dissolved after introduction in the exposure medium. Aggregation of nanoparticles was also observed but within 48 hours of exposure most of these ZnO aggregates were dissolved. Based on the combined dissolution kinetics and toxicity results it can be concluded that the toxicological effects of ZnO nanoparticles at the chronic level can be largely attributed to the dissolved fraction rather than the nanoparticles or initially formed aggregates.

Concepts: Ultraviolet, Aggregate, Toxicology, Zinc, Zinc oxide, Brass, Dr. Dre, Zinc chloride


Abstract The release of nanoparticles (NPs) to the environment poses an increasing potential threat to biological systems. This study investigated the phytotoxicity and accumulation of copper oxide (CuO) NPs to Elsholtzia splendens (a Cu-tolerant plant) under hydroponic conditions. The 50 % effective concentration (EC(50)) of CuO NPs to E. splendens was about 480 mg/L, implying the tolerance of E. splendens to CuO NPs. The Cu content in the shoots treated with 1000 mg/L CuO NPs was much higher than those exposed to the comparable 0.5 mg/L soluble Cu and CuO bulk particles (BPs). CuO NPs-like deposits were found in the root cells and leaf cells. Cu K-edge X-ray absorption near-edge structure (XANES) analysis further revealed that the accumulated Cu species dominated as CuO NPs in the plant tissues. All these results suggested that CuO NPs can be absorbed by the roots and translocated to the shoots in E. splendens.

Concepts: Organism, Species, Natural environment, Copper, Root, Plant morphology, Copper(II) oxide, Copper(I) oxide


This study explored the potential for engineered nanoparticles (ENPs) to contaminate the UK drinking water supplies and established the significance of the drinking water exposure route compared to other routes of human exposure. A review of the occurrence and quantities of ENPs in different product types on the UK market as well as release scenarios, their possible fate and behaviour in raw water and during drinking water treatment was performed. Based on the available data, all the ENPs which are likely to reach water sources were identified and categorized. Worst case concentrations of ENPs in raw water and treated drinking water, using a simple exposure model, were estimated and then qualitatively compared to available estimates for human exposure through other routes. A range of metal, metal oxide and organic-based ENPs were identified that have the potential to contaminate drinking waters. Worst case predicted concentrations in drinking waters were in the low- to sub-µg/l range and more realistic estimates were tens of ng/l or less. For the majority of product types, human exposure via drinking water was predicted to be less important than exposure via other routes. The exceptions were some clothing materials, paints and coatings and cleaning products containing Ag, Al, TiO2, Fe2O3 ENPs and carbon-based materials.

Concepts: Oxygen, Water, Oxide, Oxides, Titanium dioxide, Water resources, Drinking water, Water treatment


Abstract Silver nanoparticles (NPs) are used in more consumer products than any other nanomaterial and their release into the environment is unavoidable. Of primary concern is the wastewater stream in which most silver NPs are transformed to silver sulfide NPs (Ag2S-NPs) before being applied to agricultural soils within biosolids. While Ag2S-NPs are assumed to be biologically inert, nothing is known of their effects on terrestrial plants. The phytotoxicity of Ag and its accumulation was examined in short-term (24 h) and longer-term (2-week) solution culture experiments with cowpea (Vigna unguiculata L. Walp.) and wheat (Triticum aestivum L.) exposed to Ag2S-NPs (0-20 mg Ag L(-1)), metallic Ag-NPs (0-1.6 mg Ag L(-1)), or ionic Ag (AgNO3; 0-0.086 mg Ag L(-1)). Although not inducing any effects during 24-h exposure, Ag2S-NPs reduced growth by up to 52% over a 2-week period. This toxicity did not result from their dissolution and release of toxic Ag(+) in the rooting medium, with soluble Ag concentrations remaining below 0.001 mg Ag L(-1). Rather, Ag accumulated as Ag2S in the root and shoot tissues when plants were exposed to Ag2S-NPs, consistent with their direct uptake. Importantly, this differed from the form of Ag present in tissues of plants exposed to AgNO3. For the first time, our findings have shown that Ag2S-NPs exert toxic effects through their direct accumulation in terrestrial plant tissues. These findings need to be considered to ensure high yield of food crops, and to avoid increasing Ag in the food chain.

Concepts: Wheat, Nanotechnology, Toxicity, Silver, Cowpea, Vigna, Silver sulfide, Argentite


Abstract The production of titanium dioxide nanoparticles (TiO2 NPs) for commercial applications has greatly increased over the last years and consequently the potential risk for human health. There is a growing awareness of the need to understand the behavior and influence these nanoparticles exert on the environment. Bioaccumulation serves as a good integrator to assess chemical exposure in aquatic systems and is dependent on factors, such as the exposure routes, diet and the aqueous medium. We analyzed the experimental bioaccumulation capability of ionic titanium and TiO2 NPs by zebrafish (Danio rerio) eleutheroembryos through bioconcentration factors (BCFs), after 48 or 72 h of exposure. The stability of both chemical forms in an aquatic medium was fully characterized for further bioaccumulation studies. Several stabilizing agents (humic acids, soluble starch, polyethylene glycol, Na4P2O7 and Na2HPO4) for anatase and rutile, the two allotrophs of TiO2 NPs, were evaluated to check the evolution of the aggregation process. Around 60% of TiO2 NPs remained disaggregated under simulated environmental conditions with the addition of 50 mg L(-1) of humic acids. However, the presence of eleutheroembryos in the exposure medium increased TiO2 NPs aggregation in the experimental tests. The BCFs values obtained in all cases were <100, which classifies ionic titanium and TiO2 NPs as non-bioaccumulative substances, under the REACH regulations.

Concepts: Oxide, Titanium dioxide, Titanium, Rutile, Danio kyathit, Anatase, Titanium tetrachloride, Ilmenite


Several tools to facilitate the Risk Assessment and Management of manufactured nanomaterials (MN) have been developed. Most of them require input data on physicochemical properties, toxicity and scenario-specific exposure information. However, such data are yet not readily available, and tools that can handle data gaps in a structured way to ensure transparent risk analysis for industrial and regulatory decision making are needed. This paper proposes such a quantitative risk prioritisation tool, based on a Multi-criteria Decision Analysis algorithm, which combines advanced exposure and dose-response modelling to calculate Margins of Exposure for a number of MN in order to rank their occupational risks. We demonstrated the tool in a number of workplace exposure scenarios involving the production and handling of nanoscale Titanium Dioxide, Zinc Oxide, Silver, and multi-walled carbon nanotubes. The results of this application demonstrated that bag/bin filling, manual un/loading, and dumping of large amounts of dry powders led to high emissions, which resulted in high risk associated with these exposure scenarios. The Zinc Oxide MN revealed considerable hazard potential in vivo, which significantly influenced the risk prioritization results. In order to study how variations in the input data affect our results we performed probabilistic Monte Carlo sensitivity/uncertainty analysis, which demonstrated that the performance of the proposed model is stable against changes in the exposure and hazard input variables.

Concepts: Decision making, Risk, Decision theory, Decision making software, Risk management, Monte Carlo, Titanium dioxide, Risk assessment


The unique behavior of engineered nanomaterials (ENM) in aqueous media and dynamic changes in particle settling, agglomeration and dissolution rates is a challenge to the consistency, reliability and interpretation of standard aquatic hazard bioassay results. While the toxicological endpoints (e.g., survival, growth, reproduction, etc.) in ecotoxicity bioassays are largely applicable to ENMs, the standard methods as written for dissolved substances are confounded by the dynamic settling, agglomeration and dissolution of particulate ENMs during the bioassay. A testing framework was designed to serve as a starting point to identify approaches for the consistent conduct of aquatic hazard tests that account for the behavior of ENMs in test media and suitable data collection to support representative exposure metrology. The framework was demonstrated by conducting three case studies testing ENMs with functionally distinct characteristics and behaviors. Pretests with a temporal sampling of particle concentration, agglomeration and dissolution were conducted on each ENM in test media. Results indicated that a silver nanoparticle (AgNP) powder was not dispersible, a nano-TiO2 powder was dispersible but unstable, and a polyvinylpyrrolidinone-coated AgNP was relatively stable in test media. Based on these functional results, Ceriodaphnia dubia bioassays were conducted to compare different exposure summary methods (nominal, arithmetic average, geometric average, time-weighted average) for calculating and expressing toxicity endpoints. Results indicated that while arithmetic means were effective for expressing the toxicity of more stable materials, time-weighted averaged concentrations were appropriate for the unstable nano-TiO2.

Concepts: Concentration, Water pollution, Arithmetic mean, Mean, Ecotoxicology, Average, Geometric mean, Conducting