National initiative towards developing a common approach to the regulatory testing of manufactured nanomaterials (NorNANoREG)

The project NorNANoREG was oriented towards responsible technology development and is complementary with the European FP7 flagship project NANoREG (http://www.nanoreg.eu/), were the aim was to create an internationally shared framework for performing regulatory testing of manufactured nanomaterials (NMs) in order to ensure their safety for human health and ecosystems. NorNANoREG continued with development tools that can be implemented into innovative testing strategies for NMs. NMs are regulated within REACH in similar way as chemicals. However, there are still many challenges in the hazard assessment of NMs. NorNANoREG has developed tools for innovative test strategies and hazard and risk assessment. The aim was also to establish close collaboration with authorities and industry for efficient risk management and safe and responsible development of nanomaterials. There is a need for appropriate and validated test methods that address specific features of NMs related to their physico-chemical properties. A common challenge is interference between the test material and the readout of the assay due to the high reactivity of the nanoscaled particles. NorNanoREG has contributed significantly to validation and standardization of test methods suitable for toxicity testing of NMs, and has given substantial knowledge about ecotoxicity and human related toxicity of a range of repository NMs. Tools for innovative test strategies and hazard and risk assessment in a regulatory aspect has been delivered for more efficient risk management and safe and responsible development of NMs, supporting the safe-by-design principle, with toxicity testing in parallel with nanotechnological development of new products. The importance of physio-chemical characterization and dependency of toxicity on properties such as size, surface coating, and shape have been demonstrated and is emphasized for the testing strategy for NMs. Standard operating procedures (SOPs) have been developed and validated for a lot of different test methods for toxicity testing, as well as for preparation of NM dispersion and physio-chemical characterization of NMs. Within the project, more than 15 JRC repository nanomaterials have been investigated for cytotoxicity, genotoxicity (DNA damage and gene mutations) and carcinogenicity in vitro, as well as underlying mechanisms for toxicity. Both human toxicity and ecotoxicity has been tested. Toxicity ranking of the tested NMs was performed. NorNanoREG has importantly strengthened the national collaboration between seven strong Norwegian NANoREG partners within nanotoxicology and nanosafety, NILU, SINTEF, UiB, STAMI, NMBU, GenØK, CometBiotech (CBT)/NorGenoTech (NTG), and has given the research groups the possibility for positioning Norway in the research front within the field. The project promised to deliver in total 13-17 papers, a policy brief and a workshop, and all were delivered beyond the original plan. The consortium has been very successful, as demonstrated by the resulting 23 scientific papers published in peer-review journals, 5 book chapters, 5 monographs, 1 policy brief and 68 presentations. The project has delivered far more than promised, and results have been extensively disseminated, including one successful workshop with stakeholders. Additionally, new methodology has been developed and new business area has been explored. A lot of nanotoxicity data have been produced within NorNanoREG, and 18 more papers are already planned or in progress.

Possible negative impacts on human health and the environment from increasing exposure to manufactured nanomaterials (MNMs) is a growing concern. A sound scientific basis to assess potential risks to workers, consumers and ecosystems is urgently needed but poses serious challenges. Characterisation of MNMs in terms of their size, shape, surface chemistry, solubility and aggregation state are crucial, as these factors can account for biological effects that differ (qualitatively and quantitatively) from those of bulk materials. The physicochemical state and biological activity of MNMs are, however, influenced by the medium or matrix in which they are tested. In this project we will evaluate the adequacy of existing standardised methods for assessing impacts from MNMs, and where necessary, develop novel models and methods, particularly emphasising high throughput techniques to allow rapid testing of the large and growing number of MNMs. Information gained will be used to inform risk assessment and regulatory decision-making. Potential adverse health effects will be studied using assays for oxidative stress, cytotoxicity, genotoxicity, carcinogenicity, as well as molecular biomarkers, in model cell systems closely simulating in vivo conditions of MNM exposure. Environmental impacts will be assessed with toxicity tests including analytical and metabolomic assays on sentinel organisms: algae, soil nematodes,bacteria, daphnia and fish. This project is also committed to developing effective transdisciplinary communication with both the scientific community and stakeholders (regulatory bodies, industry, concerned public) to enable producers and consumers to balance information on risks and benefits of MNMs. NorNANoREG partners participate in the EC FP7 project NANoREG and this proposal aims to secure national financing to complement the restricted (20%) funding from the EC. However, the research in this project(e.g. on novel methods) also goes beyond the scope of NANoREG