Background
Nanomaterials form an important new class of technological materials that have numerous novel and useful properties. The expected growth in production and use of such materials makes it increasingly likely that human and environmental exposure will occur. The scientific discussion regarding the toxicological properties of nanomaterials raised the question whether existing test methods used in regulatory settings are sufficient for the evaluation of nanomaterials.
As part of its programme of work, the OECD Working Party on Manufactured Nanomaterials (WPMN) includes a project to review the test guidelines to assess whether or not they are suitable for manufactured nanomaterials. There might be the need to modify or supplement those standard tests for nanomaterial specific evaluations like special characterisation of the material, electron microscopy and assessing additional parameters.
Cefic is currently undertaking a significant research project as its contribution to support the work of the OECD WPMN, especially Steering Group 3 Safety Testing of a Representative Set of Manufactured Nanomaterials. This group will develop a programme towards the understanding of the kind of information on intrinsic properties that may be relevant for effects assessment of nanomaterials by testing representative nanomaterials for a specified set of human health endpoints. So far neither the OECD WPMN nor the current Cefic project assesses potential reproductive or developmental toxicity of nanomaterials.
Objectives
The overall objective of this proposal is to analyze the suitability of current OECD guidelines to assess the reproductive toxicity of nanomaterials. Using two materials, present on the OECD list of'representative manufactured nanomaterials for testing' (1) silicon dioxide and zinc oxide, the ability of current reproductive toxicity OECD guidelines to identify hazard associated with nanomaterials will be tested in this project. Performing the studies under GLP is strongly encouraged.
Scope
- The studies should be undertaken according to OECD reproductive / developmental toxicity guidelines (i.e. TG 414, 415, 416, extended one generation study, 421 and/or 422) to assess their suitability for nanomaterials. The use of in vitro studies does not meet the objectives of the proposal and are therefore discouraged.
- Develop a testing strategy for nanomaterials concerning reproductive toxicity needed for a comprehensive assessment of this endpoint. In case of zinc oxide inhalation exposure will be the route of administration, for silicon dioxide oral administration is required.
- Identify key endpoints, exposure routes and critical effects and evaluate whether existing OECD reproductive toxicity guidelines suitably address these.
- Develop guidance on how to prepare and administer dosing material for reproductive toxicity studies. The proposed testing strategy should contain a description of how the test materials will be prepared for experimental application (preferably in the form corresponding to anticipate human exposure) and how the particle characterisation, the concentration and homogeneity of the preparations are maintained throughout the studies. This part of the project needs to be closely coordinated with CEFIC N1 to avoid unnecessary duplication of the analysis between the two projects.
- Develop recommendations for possible needs to generate new or revised guidelines for reproductive toxicity.
- Coordinate / align the project plan with the CEFIC N1. Nano Health project team (Fraunhofer, study monitors)
At the end of the project the results should address the following questions:
o Do the existing OECD reproductive toxicity test guidelines adequately assess a potential hazard posed by nanomaterials?
o Can the existing guidelines benefit from some revisions to better understand health risks posed by nanomaterials?
o Are there endpoints used to assess the potential hazard of industrial chemicals which may be inappropriate for testing nanomaterials?
Monitoring
The Principal Investigator will be required to submit a progress report at six-monthly intervals during the course of the programme. At the end of the project, a detailed review of the research and its accomplishments will need to be provided by the Principal Investigator. It is expected that the results will be published in peer-reviewed journals and the investigators are encouraged to present their preliminary findings in appropriate scientific meetings.
