Cefic-lri Programme | European Chemical Industry Council

N1: Tiered approach to testing and assessment of nanomaterial safety to human health – Deadline: July 27, 2008

Background

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. It is assumed that the battery of standardised OECD tests commonly used to perform hazard assessment of existing substances is also sufficient for nanomaterials and can be used in their hazard and, further on, in their risk assessment. However, there might be a need to modify or supplement those standard tests for nanomaterials with specific evaluations like special characterisation of the material, electron microscopy and assessing additional parameters.
Focusing on the most relevant exposure routes, inhalation and dermal contact, basic and extended data set testing will help to establish to which extent current testing guidelines are sufficient and where refinement is needed. In comparison with the results obtained for the corresponding non-nanoscale materials, sensitive toxicological endpoints or parameters will have to be identified which can be affected specifically due to the nano-size of a material. In the future, special screening tests could be developed to assess these endpoints and parameters.
Cefic is participating in OECD's Working Party on Manufactured Nanomaterials (WPMN). Steering Group 3 Safety Testing of a Representative Set of Manufactured Nanomaterials is developing a programme for a better understanding of the kind of information on intrinsic properties that may be relevant for hazard assessment of nanomaterials. This will be done by testing representative nanomaterials for a specified set of toxicological endpoints. The research to be sponsored under this RfP is intended as industry's contribution to the OECD programme. The results will be communicated to OECD through BIAC, the industry representation to OECD.

Objectives

The objective of the research project is to:

  • Test the suitability of OECD testing guidelines for nano zinc oxide and nano amorphous silicon dioxide particles (NB: these materials have been chosen because they are part of the OECD Representative Set of Manufactured Nanomaterials)
  • Define a tiered testing strategy for these nanoparticles

Remark: It is important first to develop a solid database with the most important standard methods before deciding on the most sensitive parameters and a testing strategy. The testing strategy for hazard assessment (if there is a need for a separate testing strategy compared to the commonly used procedures) should be developed based on the experience gained with the classical methods. A'stand alone' testing strategy for hazard assessment should be separated from a testing strategy for screening purposes and from a testing strategy to specifically bridge data, e.g. from bulk material to a nano-sized modified compound.

In particular, the project should:

  • Carry out the necessary studies to conduct a hazard assessment. The studies should be undertaken according to OECD testing guidelines to assess their suitability for nanoparticles. The studies should be performed under GLP (Good Laboratory Practice) protocol.
  • Develop a testing strategy for nanoparticles with regards to inhalation and dermal exposure, comprised of short- and long-term studies, needed for a comprehensive human health hazard assessment. The proposed testing strategy should also contain a description of how the test materials will be prepared for experimental application (preferably in the form corresponding to the anticipated human exposure) and the particle characterisation (e.g. particle size distribution, structure, surface chemistry, etc.). The concentration and homogeneity of the preparations as well as particle characteristics are to be maintained throughout the studies. The research should focus on key toxicological effects including, where possible, in vitro correlates. In particular, the research should evaluate the key endpoints highlighted by OECD including:
    • Site of contact; for example pulmonary and cardiovascular effects in mammals - with other possible considerations including bioaccumulation, ADME issues, transport across membranes of individual cells, or the formation of agglomerates.
    • Are the currently accepted'key toxicological endpoints' including sensitisation, reproductive toxicity, genotoxicity, etc. necessary for testing nanoparticles or are other endpoints more appropriate?
    • Can in vitro tests be used to examine potential toxicological modes of action, e.g. membrane toxicity or oxidative stress, and to supplement in vivo studies by focusing on transport across biological barriers (e.g. skin or gut).

Cefic is committed to refine, reduce and replace animal testing (3R principles). The testing strategy should also include in vitro testing, where appropriate, which needs to be correlated with human health effects.

Scope

The project has two key deliverables:

  1. Data generated by the studies carried out, in the form of reports and peer-reviewed publications
  2. Proposal for a testing strategy

At the end of the project the results should address the following questions:

  1. Do the existing OECD test guidelines adequately assess the potential hazards posed by nanoparticles - both acute and chronic?
  2. Should the existing guidelines be revised to better understand health risks posed by nanoparticles?
  3. Are there some key endpoints used to assess the potential hazard of industrial chemicals which may be inappropriate for testing nanoparticles?

Short interim reports on progress are required at 6-monthly intervals. It is expected that the findings will be developed into a peer reviewed publication, following presentation at a suitable scientific conference.

Timing: Project start October 2008, project duration up to 2 years

Cost: The budget is in the order of 1.5 Mill Euro. It is expected to sponsor one project for both materials or two projects for one material each.

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