Opportunities to enhance the use of alternative models when investigating nanomaterial inflammogenicity

The small size of nanomaterials (NMs) imparts novel properties not apparent in larger forms of the same material, which has led to an increase in the incorporation of NMs into a diverse array of products. Despite the increased production and use of NMs across various sectors (e.g. pharmaceuticals, cosmetics, textiles, food, electronics), there are concerns regarding their potential impact on human health and the environment. Although animal (rodent) testing is often the preferred testing system for NM hazard (toxicity) assessment by regulators, animal testing is not sustainable in the long term due to ethical, financial, time and legislative considerations. Accordingly, an increased reliance should be placed on alternatives to animal testing when assessing NM safety to enhance the implementation of the 3Rs principles (replacement, reduction, and refinement of animal testing).
Investigation of the capacity of NMs to stimulate inflammatory responses is commonly assessed in hazard studies. Neutrophils are immune cells which are part of the first line of defence of the immune system. The neutrophil response is a key early step in the inflammatory process that influences the characteristics of inflammation such as intensity and duration. Failure of neutrophillic inflammation to resolve can cause tissue damage due to the release of toxic mediators. Neutrophil accumulation is recognised globally as a key process to study when investigating NM toxicity; with high levels of neutrophil accumulation and lack of inflammation resolution representing high toxicity This seminar will explore the opportunities to enhance the use of in vitro (neutrophil) and transgenic zebrafish embryo models when assessing the inflammogenicity of NMs. This research has recently been funded by the NC3Rs (UK National Centre for the Reduction, Refinement and Replacement of animal testing).