Lessons learnt from using alternative models to assess nanomaterial safety

Assessing the safety of engineered nanomaterials (NMs) is paramount to the responsible and sustainable development of nanotechnology, which provides huge societal benefits. Currently, there is no evidence that engineered NMs cause detrimental health effects in humans. However, a rigorous assessment of their toxicity is required to ensure their safe use. There is a need to reduce reliance on rodent testing in nanotoxicology for ethical, financial and legislative reasons. Furthermore, there is evidence that rodent models do not always predict the human response and that there are problems with their reproducibility. We advocate that in vitro models and zebrafish embryos should have greater prominence in screening NM safety, to better align nanotoxicology with the 3Rs principles (which promote the refinement, reduction and replacement of animal testing in scientific research). There is growing acceptance of the use of zebrafish in biomedical research, however few existing studies have exploited this model to assess the impacts of NMs on human health. Our preliminary data suggests that zebrafish could be a powerful tool to assess NM toxicity, however there have been some challenges associated with their use which will be discussed during the seminar. Whilst in vitro models are commonly used to screen NM toxicity, their use is often criticised due to their lack of relevancy to the in vivo situation. However, they have the potential to make toxicology testing more time efficient and less costly. We have compared the response of primary human neutrophils to NMs with a cell line, and have demonstrated that similar responses are observed. Whilst the use of primary cells is often promoted, we suggest that the use of cell lines is prioritised when screening NM toxicity. The evidence for this will be discussed during the seminar. I will outline how we are developing a tiered testing strategy for NM hazard assessment that promotes the more widespread adoption of non-rodent, alternative models to make nanotoxicology testing more ethical, relevant, and cost and time efficient. Both the advantages and limitations of using alternative models will be explored, in order to provide recommendations for their employment in the future. Opportunities to collaborate will also be identified in order to address current knowledge gaps.