Implementation of a novel in vitro methodology to assess pulmonary toxicological response mechanisms to high aspect ratio and complex materials

The main goal of this work is to assess the use of a novel in vitro methodology for lung toxicity testing of high aspect ratio nanomaterials (HARN).

The candidate has substantial experience in exposure science and risk assessment, but her expertise regarding particle toxicity is currently relatively limited.

The purpose of this application is to build a strong background in particle pulmonary toxicity, which will complement her expertise and consolidate her as a multidisciplinary researcher increasing her future career opportunities.

Currently, to assess health risk due to exposure to different materials, the European regulation mainly relays on in vivo animal data. However, testing the multitude of new materials in vivo is challenging due to high costs, and ethical issues. In vitro tests are available, but still show limitations when compared to in vivo.

HARN are particularly serious for human health, and one has been classified as carcinogenic. This is due to their size (small diameters that makes them respirable), needle-like shape, and biopersistency.

In particular, this type of materials show specific issues for in vitro testing such as difficulty on preparing homogeneous and temporal stable dispersions, or the agglomeration of fibres in the suspension preventing single fibre exposures as opposed to what may occur in the lung.

Therefore, new in vitro methods are needed in order to reduce in vivo testing and to overcome some of the mentioned limitations.

The proposed work aims to fill this gap by testing a novel in vitro methodology that allows very high control of the particles morphology and dose administrated to lung cells at a thin liquid layer by aeroslosation and deposition into µ-dishes prior cell exposure.

The results from this research will contribute to the current state of the art on fibre lung toxicity mechanisms, help on the implementation of a novel in vitro methodology for lung toxicity, and work towards the reduction of in vivo testing.