Abstracts: Possible health effects of manufactured nanomaterials
European Research Policy Towards Safe Nanotechnology
Georgios KATALAGARIANAKIS
Nanoscience and Nanotechnology are research domains which show extreme dynamism worldwide. Europe occupies a strong position due to the support that this domain receives from research funds of the European Union and of the Member States. Transfer and implementation of this new knowledge from the laboratory to a wide spectrum of industrial sectors is expected to be equally dynamic. Potential risks on health and environment associated with nanotechnology-based materials and products need to be addressed at the earliest possible stage. The European Union 7th Framework programme allocates significant amount of resources to research in this field. Integration of efforts between EU and national projects, integration of research infrastructure, building of knowledge networks for communication and synergy will allow addressing the problems at the interfaces between research and innovation including supporting actions like standardisation and training. The Nanosafety cluster is a step in this direction. Together with other stakeholders' networks it will help to define strategic research priorities, and to establish international cooperation in this field. Success on this level will yield significant benefits both for the research process and the technology life-cycle.
Overview on findings and
SCENIHR risk analysis approach
Mats-Olof MATTSSON
The Scientific Committee on Emerging and Newly Identified Health Risks, SCENIHR, is one of three independent non-food scientific committees sorting under DG SANCO. Its´ first mandate period spanned 2004-2008, with a new mandate period 2009-2011. According to its general mandate, SCENIHR provides opinions on questions concerning emerging or newly identified risks and on broad, complex or multidisciplinary issues requiring a comprehensive assessment of risks to consumer safety or public health and related issues not covered by other Community risk assessment bodies.
Examples of potential areas of activity include potential risks associated with interaction of risk factors, synergic effects, cumulative effects, antimicrobial resistance, new technologies such as nanotechnologies, medical devices including those incorporating substances of animal and/or human origin, tissue engineering, blood products, fertility reduction, cancer of endocrine organs, physical hazards such as noise and electromagnetic fields, and methodologies for assessing new risks.
The general process leading to a SCENIHR opinion is according to the following steps:
i) Identification of relevant publications.
ii) Preliminary examination of the data and selection of those publications that are considered important in order to address the questions posed to SCENIHR.
iii) Detailed examination of each of the individual publications selected in step ii) to assess the validity of the findings and to identify those that will be discussed in the opinion.
iv) Synthesis of the information from each such identified publication to answer particular parts of the questions posed. This implies integrating the results from all relevant individual studies.
v) Integration of the findings into a draft opinion that identifies the risks and the consistency of the data, the important data gaps and areas of uncertainty.
SCENIHR has so far produced four opinions on Nanotechnologies. These opinions deal with the appropriateness of existing methodologies for risk assessment of nanotechnology products (two opinions, 2006 and 2007), scientific aspects of definitions relating to products of nanoscience and nanotechnologies (2007), and risk assessment of products of nanotechnologies (2009). The presentation will provide specific details regarding the SCENIHR risk analysis methodology and the findings in the SCENIHR opinions on nanotechnology.
Overview of the methods and
techniques of measurement of nanoparticles
Hermann
STAMM
Manufactured nanomaterials are used in many novel applications because of their physico-chemical properties such as size, shape, large specific surface area, surface reactivity, etc. However, due to their unique properties, nanomaterials may possibly cause adverse effects in biological systems. The identification of hazards for assessing possible risks of nanomaterials requires appropriate toxicity testing and a sound understanding which characteristics may entail new hazards for human health.
Nanomaterials may overcome natural defences of humans (or other species) and reach different organs and/or penetrate into cells. The physico-chemical properties of nanomaterials determine their uptake at portals of entry (lungs, skin, gut), their translocation behaviour in the body and the mechanisms of interaction with living cells. For this reason the physico-chemical characterization of nanomaterials is an essential step for toxicity testing in order to produce comparable toxicological datasets. It is particularly important in identifying the right the dose metrics (mass, surface, number,…) for the determination of reliable dose-effect relationships.
The presentation will give an overview of current characterization methods and concentrate on those properties that are considered important for the toxicity assessment of manufactured nanomaterials as recommended by the OECD Working Party for Manufactured Nanomaterials (OECD WPMN) and the ISO Technical Committee on Nanotechnologies (ISO TC 229). Problems related to the consistency of different measurement methods for a given property and how to incorporate them into nanomaterials test strategies will be discussed.
NanoCare - Nanotoxicology and in vitro
studies
Katja NAU
Nanotechnology is increasingly considered to be the future technology. Besides the manifold technical applications the biological effects of nanomaterials have to be analyzed by in vitro and in vivo studies to assess a possible risk of the new nanomaterials. Both types of studies are important to analyze the nanoparticle toxicology. In vitro experiments have the advantage that they are much cheaper than animal studies and they hold no ethical pressure. In vitro studies are generally used to investigate mechanisms and they offer a better understanding of the molecular events underlying cellular responses. Thus, an increasing amount of studies were published using in vitro approaches but such studies require careful interpretation. The NanoCare consortium, a project funded by the German Federal Ministry of Education and Research 2006-2009, attached importance to accomplish in vitro and in vivo studies under standardized conditions. Nanoparticles were synthesized on a large laboratory scale and provided to all partners. This enables the comparison of all results of the project partners. These particles were analyzed and characterized first and then provided for biological testing. Two well known and already characterized materials (TiO2 and Carbon Black) were used in every experiment as reference. The toxicity of 11 synthetic nanomaterials was investigated in various cell-based in vitro systems. These experiments were carried out with cell cultures of different types and origins, with different methods of analysis to enable a broad evaluation of the adequate test system.
The biological studies focused mainly on in vitro testing but animal studies (instillation and inhalation) were carried out additionally to evaluate the in vitro results. As all groups within the consortium have used identical materials within their experiments, we now are able to compare directly the results of all studies, from the in vitro as well as from the in vivo experiments. The aim of this direct in vitro/in vivo comparison is to find a reliable method enabling us to predict biological effects of nanomaterials at least in part from in vitro studies.
In vivo findings:
Toxicokinetics of incorporated nanoparticles
Wolfgang
KREYLING
Nanoparticles (NP) are increasingly used in a wide range of applications in science, technology and medicine. Since they are produced for specific purposes which cannot be met by larger particles and bulk material they are likely to be highly reactive, in particular, with biological systems. Recently there is evidence that nanoparticles can cross body membranes and reach and accumulate in secondary target organs.
To quantitatively determine accumulated NP fractions in such organs the ultimate aim is to balance the NP fractions in all interesting organs and tissues including the remaining body and total excretion. Since these gross determinations of NP contents in organs and tissues do not provide microscopic information on the anatomical and cellular location of nanoparticles such studies are to be complemented by electron microscopy analysis as demonstrated for inhaled titanium dioxide nanoparticles.
Based on quantitative biokinetics in a rat model we found small NP fractions (iridium, carbon, gold, titanium dioxide) in all secondary organs studied including brain, heart and even in foetuses. Fractions per secondary organ were usually below 0.1 % of the administered dose but depended strongly on particle size and surface modifications as well as on the route of intake.
The current knowledge on systemic translocation of nanoparticles and their accumulation in secondary target organs and tissues of man and animal models does not suggest to cause acute effects but chronic exposure may lead to elevated NP accumulations resulting eventually in adverse health effects – a field barely studied yet.