ECETOC and EEMS (European Environmental Mutagen Society) repeated their successful collaboration this year to organise a symposium and forum on the first day of the 10th International Conference on Environmental Mutagens (ICEM) which took place this 21-25 August in Florence, Italy. The aim of the symposium and forum discussion on the genotoxicity of engineered nanomaterials (ENM) was to review the biological significance of the available information on ENM and discuss approaches to identify and evaluate possible genotoxic effects. Knowledge of the mechanism of genotoxicity should support the rationale of genotoxicity testing of NM.
Speakers at the symposium explained that the major target organs of NM exposure are the lung, the central nervous system, and the cardiovascular system. An important point is the physico-chemical characterisation of the test material according to the endpoint studied (e.g. inflammatory response, DNA damages). Furthermore, it is essential to clarify whether NM induce primary genotoxicity (as a result of direct interaction with the DNA and/or spindle apparatus or indirectly as a consequence of oxidative stress and interaction with a non-DNA target), or cause secondary effects (as a result of inflammation). For example, DNA damage, as determined by the Comet assay, and micronucleus production are indicators for genotoxicity but as endpoints incapable of differentiating between a primary or secondary mechanism. In vitro studies need to be conducted using p53 proficient cell lines [Note: p53 is a transcription factor which regulates the cell cycle and thus functions as a tumour suppressor]. In all studies, the human relevance of effective doses seen in experimental studies needs to be evaluated. Particularly with aerosols, agglomeration and aggregation of NM makes it difficult to define the actual concentration at the target.
The forum expanded on the problems associated with genotoxicity testing of nanomaterials, and elucidated possible genotoxic mechanisms to support improved test strategies. In the ensuing discussion the audience addressed four questions, whether: (i) current OECD tests are appropriate and sufficient, (ii) NM found systemically are biologically relevant, (iii) there is a minimal set of parameters to be reported in a study, and (iv) which NM material can be used as a reference?
A set of articles will be published as a Special Issue of Nanotoxicology (Prof. V. Stone, Napier University, Editor-in-chief). Guest Editors overseeing the peer review process will be Prof. Stone and Dr. M. Donner (DuPont Haskell Laboratory).