Research roadmap for nanosafety - Part III: Closer to the market (CTTM)

Nano-products and nano-enabled applications need a clear and easy-to-follow human and environmental safety framework for the development along the innovation chain from initial idea to market and beyond that facilitates navigation through the complex regulatory and approval processes under which different product categories fall. The missing framework results in a lack of (i) solid data regarding roadblocks to market penetration of nano-enabled products as well as the absence of (ii) transparency in terms of which products (e.g. containing nanomaterials (NMs); nano-enabled products) are on the market (e.g. registries) and voluntary schemes and labelling requirements for cosmetics and food, which processes are used for manufacturing nano-enabled products, and (iii) meager inclusiveness in the dialogue (between all stakeholders) most likely exist as a result of the missing framework. The Closer-to-the-Market-Roadmap (abbrev. CTTM) aims at speeding up the progress towards market implementation of nanotechnologies by outlining the steps needed to develop such a framework. In its current form it is addressed towards policy makers, but the ultimate framework will be designed for use by SME and enterprise organisations

Challenges in Characterizing the Environmental Fate and Effects of Carbon Nanotubes and Inorganic Nanomaterials in Aquatic Systems

The current lack of commonly used protocols for dispersion, characterization, and aquatic toxicity testing of nanomaterials (NMs) has resulted in inconsistent results, which make meaningful comparisons difficult. The need for standardized sample preparation procedures that allow the reproducible generation of relevant test conditions remains a key challenge for studies of the environmental fate and aquatic toxicity of NMs. Together with the further development of optimized and cost-effective analytical techniques for physicochemical characterization that depend on reproducible sample preparation, such methods have the potential to overcome the current uncertainties with regard to NM dispersion properties, effective dose, and particle dissolution. In this review, recent data available on the challenges are summarized, especially those associated with preparing and quantifying NM dispersions, determining NM uptake and accumulation in aquatic organisms, and the transformation of organic and inorganic NM in aquatic species. Additional limitations and challenges that are specific to certain types of NMs are highlighted. The release of highly persistent carbon nanotubes (CNTs) from nanocomposites is determined to be a potential source of environmental contamination. Furthermore, the role of NM dissolution and the contribution of ions versus particles to NM toxicity are discussed. A phenomenon of particular relevance for the environment is photoactivation of NMs. This is elucidated with regard to its consequences in complex aquatic ecosystems. Widespread implementation of standardized protocols alongside the consideration of phenomena associated with different life cycle stages of industrial products is crucial to the future establishment of NM environmental risk assessment.publishedVersio

Workshop on Regulatory Preparedness for Innovation in Nanotechnology

This report summarises the presentations and discussions at the first NanoReg2 Workshop on Regulatory Preparedness for Innovation in Nanotechnology held in Ispra, Italy 5 to 6 October 2017 and attended by approximately 60 regulators, industry representatives and other stakeholders. NanoReg2 is a European Union (EU) Horizon 2020 project. At the workshop, Regulatory Preparedness was defined as the regulators' timely awareness of innovations and the regulator's actions to check whether present legislation covers all safety aspects of each innovation, including initiating revision of the legislation as appropriate. Regulatory Preparedness, and Safe-by-Design (SbD) jointly constitute the NanoReg2 Safe Innovation Approach (SIA) for developing innovative products based on nanotechnology. The workshop aimed to gather views and identify current practices in regulatory work on safety of innovative products, tools already in use or needed, and potential difficulties in implementing Regulatory Preparedness in the EU. Presentations addressed the current state of the safety of nanotechnology innovation. The viewpoints included the regulatory framework, the principles behind it and the agencies and authorities enforcing it; nanosafety research projects and their support system (e.g. the current EU Horizon 2020 Framework Programme); national nanosafety initiatives; and the development of tools, such as foresight tools and harmonised test guidelines by the OECD for data generation. The workshop served to generate ideas for achieving Regulatory Preparedness. The participants recognised that while regulators deal with the safety of innovations, only few systematic approaches to this work exist. Some innovative products may reach the market before their safety has been appropriately assessed, as illustrated by RAPEX, the Rapid Exchange of Information System. A continuous and proactive combination of interconnected activities was considered to be required for ensuring Regulatory Preparedness. Thus, anticipation, e.g. horizon scanning, was seen as important, as was communication between regulators, innovators (industry) and other stakeholders. Regulators need to become aware of innovative products under development to ensure that the legislation and methods for safety assessment are available and adequate. Innovators must be aware of regulatory requirements and their likely development. This mutual awareness helps to develop safe products and to avoid delays or other problems in obtaining market approval. Awareness can be achieved through communication, which requires trust, e.g. promoted via "trusted environments" for confidential inquiries and information sharing. Furthermore, regulators need early access to the existing information and data relevant to safety assessment of innovative products to provide timely guidance and advice to Industry as well as to develop strategies for dealing with uncertainty, e.g. by applying the precautionary principle. Regulatory Preparedness was discussed as part of the SIA, and a "road map" of actions was suggested and outlined. The workshop has thus contributed towards acceptance of implementing Regulatory Preparedness for innovation in nanotechnology through the participation of a variety of stakeholders. This paves the way for a better dialogue among stakeholders in a fast economic development cycle, where it is even more important to quickly identify emerging needs for new approaches to regulatory issues for innovationJRC.F.2-Consumer Products Safet

Perspective on how regulators can keep pace with innovation: Outcomes of a European Regulatory Preparedness Workshop on nanomaterials and nano-enabled products

The rapid pace of nanotechnology innovation has created a gap between the pace of innovation and the pace of developing nano-specific risk governance. In order to identify how to minimize this gap, a Workshop on Regulatory Preparedness for Innovation in Nanotechnology was hosted by the European Commission's Joint Research Centre in 2017 under the European Union (EU) project NanoReg2. It was attended by regulators from the EU and the United States of America (USA), industry representatives and non-governmental organizations. The Regulatory Preparedness concept under development aspires to improve the anticipation capabilities of regulators and risk assessors and to facilitate the development of adaptable (safety) legislation that can keep up with the pace of nanomaterial and nano-enabled product innovation. Based on the outcome of the workshop, a multifaceted framework was proposed to support the development of such adaptable safety legislation. The findings discussed in this perspective are a first step towards an agile system of Regulatory Preparedness that is proactive, vigilant, anticipatory, adaptive, and resilient.JRC.F.2-Consumer Products Safet

Particle size-dependent organ distribution of gold nanoparticles after intravenous administration

A kinetic study was performed to determine the influence of particle size on the in vivo tissue distribution of spherical-shaped gold nanoparticles in the rat. Gold nanoparticles were chosen as model substances as they are used in several medical applications. In addition, the detection of the presence of gold is feasible with no background levels in the body in the normal situation. Rats were intravenously injected in the tail vein with gold nanoparticles with a diameter of 10, 50, 100 and 250 nm, respectively. After 24 h, the rats were sacrificed and blood and various organs were collected for gold determination. The presence of gold was measured quantitatively with inductively coupled plasma mass spectrometry (ICP-MS). For all gold nanoparticle sizes the majority of the gold was demonstrated to be present in liver and spleen. A clear difference was observed between the distribution of the 10 nm particles and the larger particles. The 10 nm particles were present in various organ systems including blood, liver, spleen, kidney, testis, thymus, heart, lung and brain, whereas the larger particles were only detected in blood, liver and spleen. The results demonstrate that tissue distribution of gold nanoparticles is size-dependent with the smallest 10 nm nanoparticles showing the most widespread organ distribution

Comparison of five in vitro digestion models to in vivo experimental results : lead bioaccessibility in the human gastrointestinal tract

This paper presents a multi-laboratory comparison study of in vitro models assessing bioaccessibility of soil-bound lead in the human gastrointestinal tract under simulated fasted and fed conditions. Oral bioavailability data from a previous human in vivo study on the same soil served as a reference point. In general, the bioaccessible lead fraction was significantly (P < 0.05) different between the in vitro methods and ranged for the fasted models from 2% to 33% and for the fed models from 7% to 29%. The in vivo bioavailability data from literature were 26.2 ± 8.1% for fasted conditions, compared to 2.5 ± 1.7% for fed conditions. Under fed conditions, all models returned higher bioaccessibility values than the in vivo bioavailability; whereas three models returned a lower bioaccessibility than bioavailability under fasted conditions. These differences are often due to the method's digestion parameters that need further optimization. An important outcome of this study was the determination that the method for separating the bioaccessible lead from the non-bioaccessible fraction (centrifugation, filtration, ultrafiltration) is crucial for the interpretation of the results. Bioaccessibility values from models that use more stringent separation methods better approximate in vivo bioavailability results, yet at the expense of the level of conservancy. We conclude from this study that more optimization of in vitro digestion models is needed for use in risk assessment. Moreover, attention should be paid to the laboratory separation method since it largely influences what fraction of the contaminant is considered bioaccessible

Considerations for Safe Innovation: The Case of Graphene.

The terms "Safe innovation" and "Safe(r)-by-design" are currently popular in the field of nanotechnology. These terms are used to describe approaches that advocate the consideration of safety aspects already at an early stage of the innovation process of (nano)materials and nanoenabled products. Here, we investigate the possibilities of considering safety aspects during various stages of the innovation process of graphene, outlining what information is already available for assessing potential hazard, exposure, and risks. In addition, we recommend further steps to be taken by various stakeholders to promote the safe production and safe use of graphene

Challenges in characterizing the environmental fate and effects of carbon nanotubes and inorganic nanomaterials in aquatic systems

Characterization of carbon nanotube dispersions requires measurement of both, concentration and surface area