Nanomaterial-Biological Interactions Knowledgebase
Novel toxicological methods need to look at realistic exposure levels during first-pass hazard identification studies to minimise the time and materials required for testing and rapidly identify materials of high concern. The EZ Metric assay utilises developing zebrafish embryos (Danio rerio) as an integrated sensing and amplification system that is easy to evaluate non-invasively, providing the power of whole-animal investigations with the convenience of cell culture. Exposures are conducted in 96-well plates using intact organisms that have functional homeostatic feedback mechanisms and intercellular signalling. Twenty-one endpoints (morphological, physiological and behavioural) and mortality are evaluated for each exposure across a wide concentration range. The embryonic zebrafish assay (EZ Metric assay) requires minimal equipment to assess and involve no experimental treatments such as dyes or other indicators that could alter the impacts of the nanomaterials. All endpoints are observed under low-power magnification using dissecting scopes, methods that lend themselves to potential automated visual analyses. In order to consider multiple endpoints measured in the zebrafish as an integrated measure of toxicity valuable for developing predictive models, we assessed individual endpoints and weighted those responses relative to their theoretical biological impacts. The weighted responses were used to calculate an EZ Metric score representative of the integrated biological response at each exposure concentration. Data are available through the Nanomaterial- Biological Interactions (NBI) knowledgebase (nbi.oregonstate.edu). The NBI thus serves as a repository for annotated data on nanomaterial characterisation (e.g. purity, electronic and photonic properties, size, shape, charge, composition, functionalisation, agglomeration state, etc.), synthesis methods, and nanomaterial-biological interactions (EZ Metric) defined at multiple levels of biological organisation (e.g. molecular, cellular, or organismal).
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