5th dialogue phase: Expert Dialogue 3 | Risk research, risk communication and risk management of nanomaterials exemplified by "Nano-In-Vivo" long-term research project

From 2012 to 2018, BASF, the Federal Institute for Occupational Safety and Health (BAuA), the Federal Environment Agency (UBA), the Federal Institute for Risk Assessment (BfR) and the Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) jointly assessed the long-term effects of nanomaterials using the example of nanoscale cerium dioxide. The long-term research cooperation project "Nano-In-Vivo", organised under the auspices of the Federal Environment Ministry, is globally unique.

The project examined the potential long-term effects of nanomaterials on the lungs and other organs of rats. Particular focus was placed on the analysis of effects at low doses and over longer time periods in order to detect chronic effects of nanomaterials. To this end, the entire lifetime of the rats was analysed. The material used in the analysis was nanoscale cerium dioxide. Nanoscale barium sulphate, considered insoluble before then, was used to reliably demonstrate what happens when there is no effect ("negative control"). Both substances are used frequently in industry and included in the OECD list of nanomaterials recommended for use in research projects.

A range of concentrations of these substances was dispersed into the air in order to examine a possible link between nanoparticle-specific lung overload, inflammation and the development of tumours. The study strictly complied with the OECD Test Guideline 453.

The Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM) developed and carried out the histopathological examination on the rats. The Federal Institute for Occupational Safety and Health (BAuA), the Federal Environment Agency (UBA) and the Federal Institute for Risk Assessment (BfR) provided technical support throughout the project and evaluated the findings of the project upon its completion. External international experts comprising high-ranking, internationally renowned, independent scientists accompanied the development stage of the study and the analyses.

• The long-term study revealed a number of things, including: nanoscale cerium dioxide also caused chronic pulmonary inflammation when the pulmonary clearance mechanism was not overloaded.
• Nanoscale cerium dioxide caused these inflammations at each dose level and therefore also at the lowest dose.
• While nanoscale cerium dioxide did lead to chronic inflammation, it did not have any other effects nor did it cause tumours. In this study, it did not prove to be carcinogenic.
• Contrary to expectations, the data suggested that cerium dioxide has its own substance-specific toxicity.
• Contrary to assumptions made prior to the study, barium sulphate proved to be soluble.

The project results were presented and viewed within the overarching regulatory context at the Expert Dialogue in April 2018. In addition, there was an in-depth discussion of aspects of research cooperation and the transparent communication of research results. Representatives from civil society organisations in particular were invited to participate in the Expert Dialogue.