Website: http://www.nanosafetycluster.eu/working-groups/materials-wg.html Chair: Sergio Moya Co-Chair: Rune Karlsson
Table 1 Working Group Contributing projects List.
No. Project Acronym Role in Working Group Representative
1 NanoSolutions Safety classification Sergio Moya
2 NanoDefine Methods development Rune Karlsson
3 NanoDefine Nanomaterial definitions Rudolf Reuther
4 NanoMILE Nanomaterials libraries Douglas Gilliland
5 FutureNanoNeeds Nanomaterials libraries Wolfgang Parak
6 NanoDefine Batch Variability Hans Marvin
Contents
1 Scientific and technological challenges... 186
2 Objectives (short, medium & long term) ... 186
3 Progress and Outcomes to date ... 187
4 Final status report ... 188
5 Suggestions actions for new WGs ... 188
6 Copyright ... 188
1 Scientific and technological challenges
Existing test methods are not likely to enable safety assessments of the numerous novel nanomaterials (NMs) and products based or entailing NMs that are emerging at an ever increasing pace. The international dialogue and collaboration activities have helped to understand the complexity of EHS aspects, further highlighting the need for joint international efforts in developing protocols and test methods to assess the health and safety impact of NMs and to provide proper characterization methods and protocols that are relevant for the NMs description in view of the toxicological tests.
The necessity for an improved characterisation of NMs with a minimum of physico-chemical properties necessary to describe the NMs for toxicological testing has recently emerged as a crucial aspect for the reliable assessment of the risks associated with ENP-handling and potential emission of NMs from products and devices including nanomaterials in their formulations through their life cycle . However, to date there is no clear understanding about what minimum requirements are necessary to establish a reference material (RMs)and the best set of properties necessary for the NM description which can be used to validate and compare toxicology methods. Actual approaches to RMs for nanotoxicology are based on the certification of one parameter, either size or composition, and frequently ignore other important characteristics such as particle size distribution in real testing media, nanomaterial stability, degradation, aging, protein corona formation, etc. One- parametric RMs are probably insufficient for the realisation of reliable and comparable toxicological studies.
2 Objectives (short, medium & long term)
Short term: Worldwide, various groups e.g., governments, treaty-based organisations, standards development organisations, and research consortia, have more or less independently generated priority lists of NMs for the potential development of RMs, and created lists of characterisation requirements for the RMs to better understand the results of exposure and toxicity assessments. It is generally recognised that one of the principal obstacles to obtaining adequate characterization of NMs and their potential risk is the scarcity of reliable RMs (that is, RMs produced in a scientifically valid way) for the development and validation of exposure assessment tools (instruments, protocols, methods) and toxicological evaluations (materials, protocols). RMs can provide researchers with suitable materials (including positive and negative controls) to develop harmonised protocols for in vitro and in vivo toxicity testing and elucidate mechanisms of toxicity resulting from nanoscale properties. Also, materials to verify instrument or method performance and operator or laboratory proficiency can be made available.
Medium term: There have been multiple efforts to define NMs, including a focus on defining them for regulatory purposes which enables products containing NMs to be identified and regulated with limited success to date. Most of these definitions focus solely on size aspect at the nanoscale with some also including surface, area and shape. There have also been several suggestions for approaches to classify and prioritise NMs for safety assessments,
including the OECD Sponsorship Programme approach based on commercial importance and volume of production.
Long term: Some of the longer term required research priorities identified for material characteristics include: development of systematic sets of ENMs with physical-chemical properties varied in a stepwise manner allowing the assessment of the significance of each property for toxicity; descriptions of “reference” states and media compositions to enable the identification of significant biomarkers and facilitate a move towards a predictive toxicity assessment; development of reference analytical methods that enable the studying of the longer term fate of particles following their interaction with living systems, i.e. complex matrices and developing risk assessment procedures that include the changes of ENM during their life cycle in a targeted manner. The emphasis in the EU Commission’s definition on NMs is on external dimensions, which may result in the exclusion from the definition of materials with an internal structure (e.g. porous materials with a relatively large internal surface area) or materials with a surface structure at the nanoscale. Therefore, further information is necessary on the interpretation of information on NMs in products and the impact of porosity (internal surface area) on the hazard of NMs. Closely related to the problems associated with the definition of NMs is the choice of a proper metrics for NMs. Particularly complex is how to define the metrics to measure nanomaterial concentration for toxicological testing: particle number, surface area, element concentration, etc. The proper detection, quantification and characterization of NMs are critical prerequisite tests for the safety assessment of the materials under analysis.
1. Classification by dimensionality / shape / morphology:
Shape-based classification is related to defining NMs, and has been synopsised in the ISO terminology. The dimensionality relevance is high-lighted with the recent development of graphene, which can be considered a two dimensional material. Shape and morphology are associated concepts. Nanomaterial shape if round, elongated, and morphology, if the NMs entails peaks, defects or display a rough surfaces, can impact on the toxicological response.
2. Classification by composition / chemistry:
This approach groups NMs based on their chemical properties.
NMs are made upon organic molecules, polymers, metal/metal oxides and carbon in SP2/SP3 hybridisation or by a combination of some of these elements. NMs often offer a core shell structure.
NMs are often engineered with a coating to modify their surface properties. Changing the surface chemistry for the same core may results on very different toxicological end points.
3. Classification by complexity / functionality:
Currently, the NMs that are in routine use in products are likely to be displaced by NMs designed to have multiple functionalities or resulting from hierarchical fabrication, displaying supramolecular organization, etc. ; the so called 2nd-4th generation NMs.
4. Classification by biointerface:
There is also the hypothesis that NMs acquire a biological identity upon contact with biofluids and living entities, formed by proteins, lipids and sugars.
Multiple reports have identified sets of physical-chemical parameters that should be reported for NMs. However, not all properties are relevant for all NMs in regards to their toxicological evaluation, and many are not easily measured on a routine basis.
An additional challenge is the fact that many of the physical-chemical properties of NMs are dependent on the environment and, as such, will be subject to change, depending on the surroundings in which the ENM are presented. The distinction between the synthetic and biological identities of NMs is therefore suggested. The synthetic identity describes the chemical, structural and compositional nature of the nanoparticles, including any surface coatings, ligands or labelling molecules; the biological identity describes the bio molecules that absorb to the nanomaterials under specific conditions and the impact of these on their dispersion properties
-Long term: A full understanding of the key descriptors for characterising ENM along with validated methods to identify and quantify ENMs in complex matrices is vital in order to identify crucial parameters relevant for risk assessment. This is also important for the measurement of the relevant ENM properties that correlate exposure with biological impacts. This will require agreed reference states for NM characterization, libraries of reference materials, and a framework for understanding later generation NMs.
The required research priorities to achieve this are to:
1. Develop systematic sets of ENMs with properties varied in a stepwise manner that will allow assessment of the significance of each property for toxicity.
2. Describe “reference” states and agreed media compositions to enable identification of significant biomarkers and enable a move towards a predictive toxicity assessment.
3 Progress and Outcomes to date
NanoDefine hosted the 2nd NSC Synergy Workshop in Brussels on 2nd February 2016. The event was attended by experts from a number of EU projects in addition to NanoDefine, including NANoREG, NanoSolutions, SUN, GUIDEnano, NanoMILE, eNanoMapper, NanoMag, NanoDetector and NanoValid. The aim was to identify overlaps and synergies existing between different projects that could develop into cooperation opportunities.
Among the topics discussed were the exchange of test and reference materials, protocols and SOPs for characterisation method testing, validation and standardisation, and planning of joint ILC studies. The number one interest of NanoDefine is to get as much as possible reliable information related to sizing techniques, e.g. DLS and EM. The particular field of BET is also of importance due to evaluation of size from BET measurements in NanoDefine. Another point as critical as the sizing techniques themselves are sample preparation SOPs. Uniform protocols for at least some classes of materials are clearly needed.
In the framework of the NanoMILE-NanoSOLUTIONS meeting in Stockholm, Sweden, issues on material selection, characterization and SOPs for dispersion and characterization in both projects were discussed among the participants. The different criteria for material selection among the projects were analyzed.
Dr. S.E. Moya participated in the scientific committee of the 2nd Nanosafety Forum for Young Scientists in Li, Sweden 15-16 september 2016. Materials was one of the topics adressed by the presentation.
There has been a continuous discussion on materials issues related to nanotoxicology among the member of the working group in the different meetings of the involved projects and in the nanosafety cluster meetings.
4 Final status report
WG 1 Materials has aimed at contributing to a harmonised terminology regarding nanomaterials definition, metrics, etc., since at the moment this hinders accurate description of many nanomaterial properties. There has been a continuous discussion within the cluster and with different stakeholders to build consensus within the nanotechnology, and environmental, health and safety communities to prioritise reference methods needs and better define the required properties and physical-chemical characteristics of possible materials for the description of the NMs in a toxicological context.
The WG has also aimed to further, discuss and clarify that where RMs are not available if “representative test materials” that lack reference or certified values may be useful for toxicology testing towards establishing validated methods for the characterisation of nanomaterials as well as for their delivery in relevant media and administration to toxicological models.
5 Suggestions actions for new WGs
Activities from the WG materials that can be transferred to future WPs include:
- Continue with the compilation of materials list that are under consideration/development as RMs from various groups;
- Continue with the reviewing of literature to identify which physical chemistry properties are priorities for risk assessment of ENPs; search on new developments on material science that could be of interest for the nanosafety community.
- Continue discussion on the physic0 chemical characterization issues related to 2nd to 4th generation nanomaterials in a nanosafety context.
- Promote discussion among the participants in the WG and with other WGs within the cluster on issues related to the materials in the perspective of nanosafety evaluation in cluster meetings, project meetings and scientific/innovation venues.
- Foster discussion on materials issues in the nanotoxicological field within the broader scientific community.
6 Copyright
© 2017, Dr. Sergio Moya, CIC biomagune on behalf of the WG1 of the NanoSafety Cluster.
WG1 is a Working Group of the European Commission’s NanoSafety Cluster, which is the collection of all nanosafety-related projects funded under the European Commission's 7th Framework Programme.
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