Theme 3 – Hazard
The hazard theme is comprised of three workpackages – WP9, WP10 and WP11 – aimed at developing harmonized and standardized reference methods for hazard assessment of engineered nanomaterials for both human health and the environment culminating in an integrated testing strategy. Dr. Bengt Fadeel, Karolinska Institutet, Sweden, acts as the hazard theme leader in MARINA.
(WP Leader: Dr. Kai Savolainen, Finland) – development of an integrated testing strategy suitable for the assessment of engineered nanomaterial toxicity based on comprehensive in vitro, in vivo and ex vivo testing of representative ENMs.
- In WP9, researchers have identified and evaluated existing in vitro test methods for the assessment of acute toxicity of a panel of representative ENMs obtained from the JRC repository (see WP3) and assessed the reliability of existing and newly developed in vitro test methods. The in vitro testing approach included the use of twelve different cellular models representing six different target organs/systems.
- In addition, existing in vivo and ex vivo test methods were identified and evaluated and the responses to selected ENMs were studied in terms of organ specific toxicity, biodistribution and barrier-crossing after inhalation and oral exposure.
- Finally, the development of an intelligent (or: integrated) testing strategy serving or ITS was initiated for human risk assessment utilizing in vitro and in vivo test systems above according to a tiered approach.
(WP Leader: Dr. Kerstin Hund-Rinke, Germany) – comprehensive evaluation of aquatic, sediment and terrestrial eco-toxicity of engineered nanomaterials including assessment of the validity of existing OECD guidelines.
- In this WP, researchers evaluated the practical use and fundamental validity of current eco-toxicity tests, i.e., OECD test systems, for the assessment of ENM’s and identified specific requirements for testing ENM’s. In addition, studies were conducted to determine dosing strategies and exposure conditions. Different compartments (water, sediment, soil), the main test organisms, and the most relevant impact parameters were addressed. Compilation of the eco-toxicity data thus far offered a general overview of eco-toxicity effects and allowed for a ranking of the ENMs tested with respect to the sensitivity of the test organisms and the influence of the physico-chemical properties of the nanoparticles on ecotoxicity. This information will be forwarded to the relevant standardization organizations to improve test guidelines for the testing of ENMs.
Systems Toxicology (WP11)
(WP Leader: Dr. Knut Reinert, Germany) – implementation of methods for toxicological profiling of engineered nanomaterials using toxicogenomics, proteomics and metabolomics along with computational analyses.
- Considerable attention has been devoted to the preparation of protocols in order to ensure high quality transcriptomics, metabolomics, and proteomics measurements of the samples from WP9 and WP10. In addition, the preparation of a data analysis platform that allows a parallel analysis of all three data sources.
- The experimental procedures were successfully applied to different samples generated in WP9 and WP10. This has yielded a first set of results for further computational analysis using an integrative approach.
- Implementation of the MARINA methods for toxicological profiling using transcriptomics, proteomics, and metabolomics for ENMs will enable the identification of (novel) ENM specific Modes of Action, MOA.