Member states who are developing their skills on this topic were also included, with special attention to their needs through the implementation of audits, and if necessary, of training activities. The framework of the JA thus includes, if needed, depending on the capacities of the laboratories involved to correctly perform the experiments according to the protocols defined, the audit of laboratories and/or staff training to ensure that the different laboratories involved run studies in their own lab with the correct SOPs.

The technical role of each partner organization is clearly defined in the work package descriptions. The partners involved are key organizations in the field within each country; this and the close links with ministries in the JA will ensure that the JA results will be communicated to participating countries. Other countries will be informed of the JA through an active dissemination strategy with a number of proposed tools, and through possibilities for further possible involvement as collaborating partners (this is already the case with the UK and Ireland). In addition, various JA partners have had the opportunity to work together in the past in research projects (co-funded by the EC or other sources) as well as in programmes such as the OECD WPMN.

puce-ronde To build a robust reliable methodology with alternative tests for risk assessment of MNs, the following list of prerequisites will ensure that the testing results are comparable:

puce Standard operating procedures (SOPs) are used and disseminated to all participants by the WP leaders including handling, dosimetry and dispersion of MNs in culture medium etc. If a SOP is lacking, this will be the first priority milestone.

puce As far as possible, all experimental studies will use the same origin/source of particles (i.e. same production method and physicochemical characteristics). The aim is to use the same specifically designated batch for each WP. For each study, a control of the culture media used by the different laboratories will be done to check for possible variations.

puce OECD guidelines will be preferably used and, if needed, adapted to take into account MN specificities.

puce Each WP, for the same type of work, will harmonise practices to minimise potential variations due to different batches and methods of sample preparation

puce-ronde The JA has 4 scientific WPs:

1) To interpret and compare genotoxicity tests results, the MNs need to be fully characterized (WP 4) including detailed physicochemical properties and SOPs for producing suitable suspension of the MN types in mediums used for genotoxicity testing. MNs are delivered by industry with technical specifications and dispersed following standardized procedures to be agreed. Sufficient quantities from defined and characterized batches are supplied to partners at comparable qualities for each WP.

2) For in vitro genotoxicity testing (WP5), OECD GD 34 needs consideration in planning of the standardized round robin tests. All routes of exposure will be covered by different cell lines: pulmonary cell lines and one intestinal for all MNs, one reconstructed human full skin model only for TiO2 due to its specific use in cosmetics. Comet and micronucleus assays will be performed as well as MLA and lymphocytes micronucleus assay following the available international guidance documents.

3) For in vivo genotoxicity (WP6), as far as it remains feasible, in light of technical constraints and limitations (feasibility with regards to dispersion, characterization protocols, the reproducibility of the protocols etc.), pulmonary and oral exposure routes will be tested on selected MNs, using instillation to mimic inhalation and gavage for oral exposure. Skin models will not be used because rats are not sensitive to the dermal route and the use of other animals e.g. mini-pigs raise ethical problems.

4) For toxicokinetics (WP7), oral route and IV routes will be considered for TiO2 and SiO2 and only IV for CNT in order to know which doses to administer to rats and identify target organs for accumulation. Selection of the MN dose-range to be tested is crucial for in vitro and animal exposure: realistic doses (epidemiologically meaningful doses) will be used.

Each scientific work package, in order to achieve the third general objective of promoting the Establishment of a robust methodology must carry out, upstream, the first 2 general objectives mentioned through studying the state-of-the-art and existing data in order to choose what is relevant for MNs and justify their choice of protocols. Furthermore, each laboratory involved in the JA must run these protocols and it is important that each step is fully defined and justified as all scientific WPs are interlinked and dependant on the actions and results of the other scientific WPs. Hence, knowledge sharing is central to the JA.

Last Updated on Wednesday, 22 September 2010 10:20