Towards a New Paradigm in Nano-Genotoxicology

Changes in paradigm contribute to advances in research. The current paradigms for the evaluation of toxicity of chemicals refer to linear or curvilinear dose-response curves with or without threshold and to surface-dependent induction of oxidative damage for particles. The unique physicochemical properties and biological/genotoxic activity of engineered nanomaterials (NMs) require the development of a new paradigm. Because of their unusual dosimetry and their multiple interactions at NM level (agglomeration/aggregation) and at different cellular and extracellular levels, NMs are likely to have complex modes of action (multiple hits at multiple targets) leading to complex thresholded-non-thresholded dose-response curves. Understanding their cellular targets and their modes of action will contribute to the production of safe-by-design NMs. An integrative, cell-by-cell approach for genotoxic effects should be applied to tackle this emerging paradigm in nano-genotoxicology.