Long-term effects of inhaled nanoparticles in rats: Ceriumdioxide and bariumsulphate
Ceriumdioxide (NM212) and bariumsulphate (NM220) nanoparticles were tested according to the OECD test guideline no. 453; additions were made to the standard protocol to find evidence of inflammation and potential lung tumours with high sensitivity. Aerosol concentrations were concentrations 0.1, 0.3, 1 and 3 mg/m3 and 50 mg/m³ was tested, respectively. Levels of cerium measured in the organs increased with higher exposure concentrations and over time. However, the accumulation only reached a very low level. Lung burdens of barium were unexpectedly low during the first three months of exposure, due to fast clearance most probably by dissolution in vivo. Barium lung burdens increased thereafter. Animals in all exposure groups showed chronic inflammation of the lungs, with stronger inflammation at higher exposure concentrations. The level of particles present in the lungs was higher for bariumsulphate than for the highest level of ceriumdioxide. The nature of the inflammatory tissue changes varied between the two nanoparticles. Ceriumdioxide already triggered a chronic inflammation effect at the lowest dose, which was unexpected for insoluble nanoparticles without inherent toxicity. Despite chronic inflammation at all dose levels, no lung tumours were found which could be attributed to ceriumdioxide or bariumsulphate exposure. This may indicate that a particle-related, low-level chronic inflammation is not sufficient to cause tumour formation. Low-level accumulation in extrapulmonary organs did not lead to any pathological changes. No evidence of further health impacts was found for ceriumdioxide and bariumsulphate beyond those already known for granular particles. Acknowledgement: The project was carried out and funded jointly by the German Federal Environment Ministry, the Federal Environment Agency, the Federal Institute for Occupational Safety and Health and BASF SE as well as the EU project NanoREG and Cefic LRI. Histopathological examinations were performed by Fraunhofer Institute for Toxicology and Experimental Medicine and the biodistribution was analysed by the Federal Institute for Risk Assessment.