NANOSOLUTIONS final report.

Engineered nanomaterials (ENM) have attracted a remarkable interest in recent years, due to their technologically unique properties. These properties and their applications have built up immense technological and economic expectations for industries using ENM. However, some of these properties have given rise to concern that they may be harmful to humans. The NANOSOLUTIONS project has developed an approach for predicting the safety of ENM. This is based on an understanding of their interactions with living organisms at molecular, cellular and organism levels. The main objective of the NANOSOLUTIONS project has been to identify and elaborate on the characteristics of ENM that determine their biological hazard potential at various levels of biological organisation in a range of cells and organisms. The approach in NANOSOLUTIONS explores how interactions with cellular structures and molecular processes may lead to the impairment of key cellular or organismal functions. Using a panel of 31 distinct ENM with different core chemistries and surface modifications, the project has provided evidence that these adverse effects may be associated in complex and diverse ways with multiple properties of ENM. A key goal of the project has been to develop a set of biomarkers of ENM toxicity to assess and predict the safety and toxicity of ENM across species. ENM interactions with living organisms are complex and may depend both on the chemical composition of the material, and other physicochemical and surface properties, and on the acquired ‘corona’ of adsorbed biomolecules. The objective of this research has been to build a means to develop an “ENM Safety Classifier”, based on the material characteristics of ENM, using the understanding of their interactions at different levels within living organisms. To this end, a wide range of in vitro and in vivo models relevant to human health and the environment were utilized. A considerable focus was devoted to omics-based approaches in order to capture the mechanisms of action of ENM. The project has identified a limited number of chemical and biological features which predict – with a high accuracy – whether a given ENM belongs into one of three hazard classes (low or no hazard, intermediate hazard, or high hazard). The nanosafety classifier is a computational tool and it is continuously developed as more data are entered. The main innovation of the NANOSOLUTIONS project has thus been the development of the ENM Safety Classifier. This novel hazard profiling principle will help in understanding and defining the toxic potential of different types of ENM. It can be used by the ENM industry as well as the regulatory community to manage, reduce ENM-associated uncertainties, and bring clarity to the current debate, since it enables classifying ENM into different hazard categories. During the course of the project, high-throughput screening (HTS) platforms for rapid screening of ENMs, based on robust and validated in vitro assays, have also been developed and optimized for ENMs. These platforms can be used to implement new assays based on the biomarkers identified by the Safety Classifier. The data gathered in the project has also contributed to the life cycle impact evaluation of ENM-based products, and will ultimately clarify their global environmental impact. Testing and validation of the tool is in progress and has the potential to be used within a few years. NANOSOLUTIONS has utilized a huge array of technologies from materials science to system biology, and has had access to eminent, relevant expertise. Validation of the ENM Safety Classifier tool has been carried out with industrially relevant materials. NANOSOLUTIONS will strive to make all data available to other qualified parties. This open access to high-quality data on the material characteristics of various classes of ENM and on the relevant biological outcomes across several species, including healthy and susceptible individuals, will serve as a valuable resource for future ENM safety prediction and classification.