Toxicological studies in recent years have shown that the prediction of pathogenic properties of nanomaterials is not per se possible and that significant knowledge on the nanomaterial itself and its behaviour in the environment is necessary. Quite a few of these studies also strongly indicate that particle surface area and the potential to form reactive oxidants are highly promising metrics to predict the toxic potency of manufactured nanomaterials (MNM).
In the project nanOxiMet a grouping of MNMs is envisaged by using a combined strategy which, on the one hand, comprises an in-depth analysis of the physical characteristics of selected MNM suspensions and, on the other hand, the thorough evaluation of their toxic response in human cells.
The study will focus on the most appropriate prediction metrics for nanomaterials, the surface area and the oxidant generation potency. It will be investigated which type of surface reactivity is most relevant and in how far the novel prediction metrics (oxidant generation capacity/reactivity and surface area, combined to reactivity per surface area) can be used, standardized and ultimately implemented to reduce toxicological screening of MNM and improve hazard and risk assessment. It is envisaged that this approach provides bridging of nanomaterial characterization and toxicity evaluation by simplifying a MNM classification e. g. for MNM producers.
The project nanOxiMet is divided into six Work Packages (WPs): Work Package 1 deals with the management of the project and its dissemination activities. All data collected in the project will be collated in WP6 and processed to be distributed to core stakeholders such as standardisation and regulating agencies, industrial related groups such as NIA and VCI, but also to researchers in e.g. national and international projects.
In Work Package 2 a broad variety of physical characterisation of the selected MNM in different liquid media (after being brought into suspension) will be performed. Beside the size or the morphology especially detection and estimating of the surface area of MNM in liquids will be done in the WP2.
Linked to WP2 as a physical-chemical characteristic Work Package 3 will focus on the intrinsic oxidative generation potency (also named here generation of reactive oxygen species – ROS) and prepare due to possible standardisation an inter-comparison between different detection methods. All data produced in WP2 and WP3 are basic information also for subsequent investigations to link in WP6 later on.
In Work Package 4, the MNM-suspension induced intracellular ROS and oxidative damages will be identified by using in-vitro experiments with several widespread toxicological endpoints in a dose and time treatment dependent manner.
In Work Package 5 biological responses due to ROS generation will be more finely determined by investigating modulation of gene expression linked to either antioxidant adaptive response or inflammation according to the level of oxidative stress.
All work conducted in WP2-5 will use OECD guidelines as far as possible to facilitate the implementation of e.g. guidance tools on how to interpret particle reactivity measurements and how to group nanomaterials.
Finally in Work Package 6 the entire data will be collated and evaluated. Beside other the evaluation will be focusing on ROS linked to surface area unified in a surface reactivity metric as one particle characteristic for MNM grouping in view of toxicological hazard. Also a part of this WP6 will be the writing of standard operation procedures for using the applied characterisation and detection methods to ensure the comparability transcended this project.