Blood clearance and tissue distribution of PEGylated and non-PEGylated gold nanorods after intravenous administration in rats\ud

Aims: To develop and determine the safety of gold nanorods, whose aspect ratios can be tuned to obtain plasmon peaks between 650 and 850 nm, as contrast enhancing agents for diagnostic and therapeutic applications. Materials & methods: In this study we compared the blood clearance and tissue distribution of cetyl trimethyl ammonium bromide (CTAB)-capped and polyethylene glycol (PEG)-coated gold nanorods after intravenous injection in the tail vein of rats. The gold content in blood and various organs was measured quantitatively with inductively coupled plasma mass spectrometry. Results & discussion: The CTAB-capped gold nanorods were almost immediately (<15 min) cleared from the blood circulation whereas the PEGylation of gold nanorods resulted in a prolonged blood circulation with a half-life time of 19 h and more wide spread tissue distribution. While for the CTAB-capped gold nanorods the tissue distribution was limited to liver, spleen and lung, the PEGylated gold nanorods also distributed to kidney, heart, thymus, brain and testes. PEGylation of the gold nanorods resulted in the spleen being the organ with the highest exposure, whereas for the non-PEGylated CTAB-capped gold nanorods the liver was the organ with the highest exposure, per gram of organ. Conclusion: The PEGylation of gold nanorods resulted in a prolongation of the blood clearance and the highest organ exposure in the spleen. In view of the time frame (up to 48 h) of the observed presence in blood circulation, PEGylated gold nanorods can be considered to be promising candidates for therapeutic and diagnostic imaging purpose

Structure and the Physico-Mechanical Properties of the Ceramic Coatings Obtained by the Cumulative -Detonation Device

Dense, with good adhesion to the substrate, hard, wear-resistant coatings from the powder of Al2O3 were obtained on the surface of the steel (STE255) by using the cumulative-detonation device. The results of investigations of the structure and physico-mechanical properties of the coatings by using scanning, optical microscopy, X-ray phase analysis, microhardness and tribological tests are presented. It was found that optimization of plasma spraying to helps reduce the porosity of coatings of Al2O3 less than 1 % and to increase the hardness of them to 1250 HV0.3. The tribological investigations have shown that the coatings of Al2O3 significantly increase the wear resistance of the sample STE255 and provide a low ability to wear out the coating. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/3546

Concern-Driven Integrated Toxicity Testing Strategies for Nanomaterials - Report of the NanoSafety Cluster Working Group 10

Bringing together topic-related European Union-(EU)-funded projects, the so-called “NanoSafety Cluster” aims at identifying key areas for further research on risk assessment procedures for nanomaterials (NM). The outcome of NanoSafety Cluster Working Group 10, this commentary presents a vision for concern-driven integrated approaches for the (eco-)toxicological testing and assessment (IATA) of NM. Such approaches should start out by determining concerns, i.e. specific information needs for a given NM based on realistic exposure scenarios. Recognized concerns can be addressed in a set of tiers using standardized protocols for NM preparation and testing. Tier 1 includes determining physico-chemical properties, non-testing (e.g. structure activity relationships) and evaluating existing data. In tier 2, a limited set of in vitro and in vivo tests are performed that can either indicate that the risk of the specific concern is sufficiently known or indicate the need for further testing, including details for such testing. Ecotoxicological testing begins with representative test organisms followed by complex test systems. After each tier, it is evaluated whether the information gained permits assessing the safety of the NM so that further testing can be waived. By effectively exploiting all available information, IATA allow accelerating the risk assessment process and reducing testing costs and animal use (in line with the 3Rs principle implemented in EU Directive 2010/63/EU). Combining material properties, exposure, biokinetics, and hazard data, information gained with IATA can be used to recognize groups of NM based upon similar modes-of-action. Grouping of substances in return should form integral part of the IATA themselves

Similarity of multicomponent nanomaterials in a safer-by-design context : the case of core–shell quantum dots

Concepts of similarity, such as grouping, categorization, and read-across, enable a fast comparative screening of hazard, reducing animal testing. These concepts are established primarily for molecular substances. We demonstrate the development of multi-dimensional similarity assessment methods that can be applied to multicomponent nanomaterials (MCNMs) for the case of core–shell quantum dots (QDs). The term ‘multicomponent’ refers to their structural composition, which consists of up to four different heavy metals (cadmium, zinc, copper, indium) in different mass percentages, with different morphologies and surface chemistries. The development of concepts of similarity is also motivated by the increased need for comparison of innovative against conventional materials in the safe and sustainable by design (SSbD) context. This case study thus considers the industrial need for an informed balance of functionality and safety: we propose two different approaches to compare and rank the case study materials amongst themselves and against well-known benchmark materials, here ZnO NM110, BaSO4 NM220, TiO2 NM105, and CuO. Relative differences in the sample set are calibrated against the biologically relevant range. The choice of properties that are subjected to similarity assessment is guided by the integrated approaches to testing and assessment (IATA) for the inhalation hazard of simple nanomaterials, which recommends characterizing QDs by (i) dynamic dissolution in lung simulant fluids and (ii) the surface reactivity in the abiotic ferric reducing ability of serum (FRAS) assay. In addition, the similarity of fluorescence spectra was assessed as a measure of the QD performance for the intended functionality as a color converter. We applied two approaches to evaluate the data matrix: in the first approach, specific descriptors for each assay (i.e., leachable mass (%) and mass based biological oxidative damage (mBOD)) were selected based on expert knowledge and used as input data for generation of similarity matrices. The second approach introduces the possibility of evaluating multidimensional raw data by a meaningful similarity analysis, without the need for predefined descriptors. We discuss the strengths and weaknesses of each of the two approaches. We anticipate that the similarity assessment approach is transferable to the assessment of further advanced materials (AdMa) that are composed of multiple components

A framework for grouping and read-across of nanomaterials- supporting innovation and risk assessment

According to some legislation grouping can streamline data gap filling for the hazard assessment of substances. The GRACIOUS Framework aims to facilitate the application of grouping of nanomaterials or nanoforms (NFs), in a regulatory context and to support innovation. This includes using grouping to enable read-across from (a) source(s), for which data and information exist, to a similar target NF where information is lacking. The Framework provides an initial set of hypotheses for the grouping of NFs which take into account the identity and use(s) of the NFs, as well as the purpose of grouping. Initial collection of basic information allows selection of an appropriate pre-defined grouping hypothesis and a tailored Integrated Approach to Testing and Assessment (IATA), designed to generate new evidence to support acceptance or rejection of the hypothesis. Users needing to develop their own user-defined hypothesis (and IATA) are also supported by the Framework. In addition, the IATA guides acquisition of the information needed to support read-across. This approach gathers information to render risk assessment more efficient, affordable, as well as reducing the use of test animals

Grouping nanomaterials to predict their potential to induce pulmonary inflammation

The rapidly expanding manufacturing, production and use of nanomaterials have raised concerns for both worker and consumer safety. Various studies have been published in which induction of pulmonary inflammation after inhalation exposure to nanomaterials has been described. Nanomaterials can vary in aspects such as size, shape, charge, crystallinity, chemical composition, and dissolution rate. Currently, efforts are made to increase the knowledge on the characteristics of nanomaterials that can be used to categorise them into hazard groups according to these characteristics. Grouping helps to gather information on nanomaterials in an efficient way with the aim to aid risk assessment. Here, we discuss different ways of grouping nanomaterials for their risk assessment after inhalation. Since the relation between single intrinsic particle characteristics and the severity of pulmonary inflammation is unknown, grouping of nanomaterials by their intrinsic characteristics alone is not sufficient to predict their risk after inhalation. The biokinetics of nanomaterials should be taken into account as that affects the dose present at a target site over time. The parameters determining the kinetic behaviour are not the same as the hazard-determining parameters. Furthermore, characteristics of nanomaterials change in the life-cycle, resulting in human exposure to different forms and doses of these nanomaterials. As information on the biokinetics and in situ characteristics of nanomaterials is essential but often lacking, efforts should be made to include these in testing strategies. Grouping nanomaterials will probably be of the most value to risk assessors when information on intrinsic characteristics, life-cycle, biokinetics and effects are all combined

Grouping nanomaterials to predict their potential to induce pulmonary inflammation

The rapidly expanding manufacturing, production and use of nanomaterials have raised concerns for both worker and consumer safety. Various studies have been published in which induction of pulmonary inflammation after inhalation exposure to nanomaterials has been described. Nanomaterials can vary in aspects such as size, shape, charge, crystallinity, chemical composition, and dissolution rate. Currently, efforts are made to increase the knowledge on the characteristics of nanomaterials that can be used to categorise them into hazard groups according to these characteristics. Grouping helps to gather information on nanomaterials in an efficient way with the aim to aid risk assessment. Here, we discuss different ways of grouping nanomaterials for their risk assessment after inhalation. Since the relation between single intrinsic particle characteristics and the severity of pulmonary inflammation is unknown, grouping of nanomaterials by their intrinsic characteristics alone is not sufficient to predict their risk after inhalation. The biokinetics of nanomaterials should be taken into account as that affects the dose present at a target site over time. The parameters determining the kinetic behaviour are not the same as the hazard-determining parameters. Furthermore, characteristics of nanomaterials change in the life-cycle, resulting in human exposure to different forms and doses of these nanomaterials. As information on the biokinetics and in situ characteristics of nanomaterials is essential but often lacking, efforts should be made to include these in testing strategies. Grouping nanomaterials will probably be of the most value to risk assessors when information on intrinsic characteristics, life-cycle, biokinetics and effects are all combined

Overview of potential adverse health effects of oral exposure to nanocellulose.

Nanocellulose is an emerging material for which several food-related applications are foreseen, for example, novel food, functional food, food additive or in food contact materials. Nanocellulose materials can display a range of possible shapes (fibers, crystals), sizes and surface modifications. For food-related applications in the EU, information on the safety of substances must be assessed. The present review summarizes the current knowledge on (possible) adverse health effects of nanocellulose upon oral exposure, keeping EU regulatory aspects in mind. The overview indicates that toxicity data, especially from in vivo studies, are limited and outcomes are not unambiguous. The hazard assessment is further complicated by: the diversity in morphologies and surface modifications, lack of standard reference materials, limited knowledge about intestinal fate and absorption, analytical difficulties in biological matrices, dispersion issues, the possible presence of impurities and interferences within biological assays. Two subchronic in vivo toxicity studies show no indications of toxicity for two specific nanocellulose materials, even at high doses. However, these studies may have missed certain early or nano-specific toxic effects, such as inflammation potential, for which other, subacute studies provide some indications. Most in vitro studies show no cytotoxicity; however, several indicate that effects on oxidative stress and inflammatory responses depend on differences in size or surface treatments. Further, too few studies assessed genotoxicity of nanocelluloses. Therefore, immunotoxicity, oxidative stress and genotoxicity require further attention, as do absorption and effects on nutrient uptake. Recommendations for future research facilitating the safety assessment and safe-by-design of nanocellulose in food-related applications are provided

Possible effects of titanium dioxide particles on human liver, intestinal tissue, spleen and kidney after oral exposure.

Recent studies reported adverse liver effects and intestinal tumor formation after oral exposure to titanium dioxide (TiO2). Other oral toxicological studies, however, observed no effects on liver and intestine, despite prolonged exposure and/or high doses. In the present assessment, we aimed to better understand whether TiO2 can induce such effects at conditions relevant for humans. Therefore, we focused not only on the clinical and histopathological observations, but also used Adverse Outcome Pathways (AOPs) to consider earlier steps (Key Events). In addition, aiming for a more accurate risk assessment, the available information on organ concentrations of Ti (resulting from exposure to TiO2) from oral animal studies was compared to recently reported concentrations found in human postmortem organs. The overview obtained with the AOP approach indicates that TiO2 can trigger a number of key events in liver and intestine: Reactive Oxygen Species (ROS) generation, induction of oxidative stress and inflammation. TiO2 seems to be able to exert these early effects in animal studies at Ti liver concentrations that are only a factor of 30 and 6 times higher than the median and highest liver concentration found in humans, respectively. This confirms earlier conclusions that adverse effects on the liver in humans as a result of (oral) TiO2 exposure cannot be excluded. Data for comparison with Ti levels in human intestinal tissue, spleen and kidney with effect concentrations were too limited to draw firm conclusions. The Ti levels, though, are similar or higher than those found in liver, suggesting these tissues may be relevant too