Background of the task Clause Samples
Background of the task. TEM analyses can play an important role in the implementation of the newly established regulatory framework of the European Commission (EC) regulating the use of nanomaterials in consumer products [2-8]. TEM is one of the few techniques that can identify nanoparticles according to the current definitions. If particles can be brought on an electron microscopy (EM) grid and if their distribution is homogeneous and representative for the sample, the combination of transmission electron microscopy (TEM) imaging with image analysis is one of the few methods that allow obtaining number-based distributions of the particle size and shape, describing the sample quantitatively [9-11]. EM further is a well suited technique because of its resolution covering the size range from 1 nm to 100 nm specified in various definitions of NM [12], and its ability to visualize colloidal nanomaterials as well as primary particles in aggregates in two dimensions. Disadvantages of EM analysis of nanomaterials include the bias from suboptimal sampling and sample preparation, the estimation of properties of 3D objects from 2D projections, the interpretation of the size of primary particles in aggregates or agglomerates, the relatively high number of particles required for measurement, and the need to develop algorithms for automated image analysis for each separate type of nanomaterial. In many cases, technical solutions that can overcome these disadvantages are available or under development, e.g. more advanced EM techniques such as electron tomography and cryo-EM can be used to obtain information about the 3rd dimension of the particles and to avoid artefacts [13-17]. A review discussing the different steps required for the physical characterization of nanomaterials in dispersion by transmission electron microscopy in a regulatory framework is given by ▇▇▇▇ et al. [18]. The implementation of the EC-definition of a nanomaterial [4] across various regulatory fields requires a detailed detection and characterization of manufactured nanomaterials by appropriate, validated testing methods [19, 20]. In this deliverable, SOPs for quantitative TEM analysis in the context of the EC definition are proposed and applied and validated on a series of nanomaterials, by intra-laboratory and inter-laboratory validation based on the estimation of the measurement uncertainties and by interpretation of the obtained results with alternative methods. These include ensemble techniques based on light scatt...
Background of the task. Task 3.2 is divided in two sub-tasks, dealing with two different aspects concerning the creation of a database management system, which i) ISA-TAB-NANO as backbone for a common database (T3.2.1) and ii) Minimum requirements in ontology and naming conventions (T3.
Background of the task. In the last years, there has been an emphasis on the experimental testing of nanomaterials using in vitro and in vivo approaches. However, several essential questions on nanomaterial toxicology cannot yet be clarified by such approaches. One of these questions is a putative carcinogenicity of nanomaterials. Due to reasons of feasibility it is not possible to test each single nanomaterial for carcinogenicity. Grouping approaches for safety testing can be chosen in case a common mode of action is known. A relevant group of nanomaterials are likely to share a common mode of carcinogenic action. These nanomaterials belong to a group of materials named poorly soluble, low toxicity particles (PSLT) (▇▇▇▇▇▇▇▇ et al. 2007), poorly soluble particles of low cytotoxicity (PSP) (Oberdorster 2002) or respirable granular biodurable particles without known significant specific toxicity (GBP) (Roller and Pott 2006). All terms describe the same type of materials. Industrial-relevant nanomaterials like carbon black or titanium dioxide belong to this group. There is a current scientific controversy, whether the lung tumours detected in chronic rat inhalation studies induced by PSLT only appear at high exposure concentrations (i.e. so-called dust ‘overloading’ of the lungs) associated with inflammation. According to the overload hypothesis, in lower (and real-life) exposure levels there is no dust overloading and no inflammation in the lung and consequentially no tumour risk in case an exposure threshold is not exceeded. Several authors (e.g. (▇▇▇▇▇▇ 1992) describe that dust overloading in the rat becomes evident in respirable dust concentrations higher than 1 mg/m³ in a chronic study. Further up to now unclarified aspects with respect to putative health hazards of nanomaterials will be studied. This comprises the systemic distribution of particles after chronic inhalation exposure and a putative accumulation in tissues like brain or the cardiovascular system and putative adverse effects associated with this chronic accumulation. Long-term exposure to biopersistent, poorly soluble nanomaterials and possible carcinogenicity induced thereof, has been identified as one of the major data gaps for regulatory decision process in the field of nanomaterials (▇▇▇▇▇▇ et al. 2011). While an increasing number of short-term data becomes available, long- term inhalation studies according to GLP and OECD TG guidelines in rodents are technically demanding and the resources needed require a h...
Background of the task. In a 2 year inhalation study, conducted according to OECD TG 453, CeO2 nanoparticles (NM-212, Ø 28 nm) were used as a representative of poorly soluble, respirable granular biodurable particles without known significant specific toxicity (GBP). The objective was to investigate potential low dose effects caused by chronic inhalation and also to compare the particle distribution in lung tissue by the use of imaging techniques. In order to correlate particle distribution with potential effects of CeO2 nanoparticles, slices for ToF-▇▇▇▇ and IBM studies are being taken adjacent to those for histopathological investigations.
Background of the task. ECHA (The European Chemicals Agency) is currently developing guidance documents and appendixes to facilitate registration and risk assessment of manufactured nanomaterials (MNM) under REACH and CLP. This report consequently adhere to the recommended regulatory definition of a nanomaterial proposed by the EC (2011/696/EU) (▇▇▇▇▇▇▇▇ 2011) and adopted by ECHA for implementation in REACH. In line with the purpose of the REACH regulation, ECHA considers only manufactured nanomaterials and not incidental and natural nanomaterials, which are also covered by the EC recommendation for definition of nanomaterial. To structure the registration of material and chemical substances, REACH provides a number of guidance documents, annexes, appendixes to guide the registrants on required end-points to be reported and recommended methods for data generation. The Guidance consists of two major parts: Concise guidance (Part A to F) and supporting reference guidance (Chapters R.2 to R.20) and are linked as illustrated below in Figure 1.
Figure 1. Structure and interlinkage between concise guidance documents and reference guidance documents provided by ECHA to so support generation of REACH information requirements and chemical safety assessments (from: ▇▇▇▇▇://▇▇▇▇.▇▇▇▇▇▇.▇▇/guidance- documents/guidance-on-information-requirements-and-chemical-safety-assessment).
Background of the task. As mentioned in the DoW, task 1.5 was entrusted with the development of the NANoREG data platform. The platform, as expansion of point a) in the DoW of T1.5 (see section 1 above) had to allow for:
i) The adequate management of all documents produced by the various NANoREG entities – Project Office, Coordinator, Management Committee, Advisory Bodies, Work Packages, etc. –, support the flow of that information and implement the correct access permissions to the information by individuals; (see CIRCABC, paragraph 2.4.1)
ii) Manage as efficiently as possible the flow of NM sample orders placed by ▇▇▇▇▇▇▇ partners to the NM distributors of the project; (see paragraph 2.4.2)
iii) Link, where possible the Safe-by-design database developed by WP6; (see paragraph 2.4.3)
iv) Guide the output of information and data in the platform towards the future NANoREG Toolbox (see paragraph 2.4.4). Points b), c) and d) revolved around the choice of a data management strategy within NANoREG, which could lead to optimal exploitation of the data generated in the project and link it to other initiatives, such as other EU- funded projects. The works also entailed the development of tools to record and export the experimental data. This implied the creation of other components of the platform: the NANoREG database and, eventually, the NANoREG-eNanoMapper database. The execution of those activities by T1.5 and an external contractor are described in paragraph 2.4.5.
Background of the task. Task 1.6 Working Groups (addressing Value Chain Case Studies and other R&D related activities) aims to provide case-specific information on how a specific nanomaterial is used along a given value chain. Furthermore, by employing expertise from within the NANoREG project, data will be produced that show the fate and behaviour of the specific nanomaterial at given stages of the appropriate value chain. The fate and behaviour data are especially important for assessment of whether release of a nanomaterial can occur, and if so, for whom the release is important (i.e. if occupational exposure or exposure to consumers or to the environment can take place). Based on the specific results, the task will identify if there are critical knowledge gaps regarding safety assessments that need to be covered, and by which means in such a case. Knowledge generated in work with Task 1.6 can feed into especially Tasks 1.3, 1.4, and 1.7.
Background of the task. The VSSA concept was introduced to characterize the size of a monodispersed distribution of spherical, non-porous particles. Such an ideal model simply uses the ratio surface/volume of the particle, which is easily understandable when all the particles are spherical and have the same size. However, in reality, the nanoparticles have a high tendency to aggregate or agglomerate, and the hence the VSSA should consider the reality of the nanomaterials. In practice, it is important to assess how the VSSA concept can be applied to polydisperse distributions of non-spherical particles. A theoretical approach was developed to determine the role of particle shape and polydispersity on the VSSA concept and a model to calculate VSSA for polydisperse non-spherical particles was proposed. To avoid confusion, the VSSA obtained by this model is called total VSSA. These calculated values will then be compared to the measured ones. The most feasible approach to determine the VSSA is by combining the BET surface area and the skeletal density of the powder. The BET surface area analysis normally, include both the external and internal surface (porosity) of the particles while the VSSA concept for identification of an MN may be linked to the external dimensions of the particles. If the particles have an internal porosity (i.e., the porosity from micropores, micro channels, cracks in particles,.., etc.), the BET surface area will be larger than the external surface area and will result in an identification of false positive nano-materials. It means that numerous powders can potentially be falsely identified to consist of MN. A methodology to complete characterisation of powders by in-depth analysis of nitrogen adsorption isotherms was demonstrated to enable the discriminate between the external and internal surface areas in powders. The method is readily applicable to the dry powders without any treatment. For the solid suspended in liquid like colloids, the suspension could potentially be gently dried to collect the solid part. The objective of this study is to determine the applicability and reliability of the VSSA approach to distinguish between nano- and non-nano-materials without necessarily using the number particle size distribution. The work was carried out in the following stages: As a first step, a theoretical study of the effect of particle shape and particle size distribution on the VSSA values and thresholds has been carried out and a model to calculate the VSSA...
Background of the task. The process for the definition of common call topics was inspired by the EC project office based on experiences made within the SIINN project (Safe Implementation of Innovative Nanoscience and Nanotechnology, GA 265799). The following instruments developed during the execution of ▇▇▇▇▇ were used by this ProSafe task: - Liaison with the funding agencies to finance projects addressing the safe implementation of nanomaterials and nano technologies. - Process to elaborate common topics for calls based on recommendations of an internal working group, consolidated with the ProSafe Consortium as well as potential funding partners.
Background of the task. Task 1.3 implements the link between the scientific WPs 2-6 and WP1. It helps to identify the crucial aspects of the regulation of nanomaterials that NANoREG needs to address (better) and fuels the dialogue between WP1 and the other WPs, helping to oversee how NANoREG actually works on (partially) answering the questions of regulatory relevance (D1.1). Information generated in T1.6 during the implementation of the safety in the value chain case studies (SVCCSs) shall be taken into account. The output of T1.3 feeds directly into the development of the NANoREG framework for the safety assessment of nanomaterials (D1.10 of T1.4) and the related NANoREG Toolbox (D1.12 of T1.7).