Long-term Inhalation Study with Nanomaterials: Effects and lung burdens after chronic inhalation with Ceria and Barium sulfate

R. Landsiedel, L. Ma-Hock, J. Keller, P. Laux, T. Gebel

Keywords: long-term inhalation study, nanomaterials, chronic effects, inhalation exposure, OECD TG 453


Lung carcinogenicity and putative systemic effects of low-dose life-time inhalation exposure to biopersistent nanoparticles were examined in a chronic inhalation study performed according to OECD test guideline no. 453 with several protocol extensions. Female rats (100/group) were exposed to cerium dioxide (NM-212, 0.1; 0.3; 1; 3 mg/m³) and barium sulfate (NM-220; 50 mg/m³) for two years; a control group was exposed to clean air. Lung burdens and burdens in extrahepatic tis-sues were measured at various time-point. The two year exposure period was successfully terminated and 50 animals per dose group were examined for organ burden and histopathology. The remaining animals currently are kept exposure-free for maximally 6 additional months. Up to two years exposure to both nanoparticles did not lead to body weight reduction compared to control ani-mals. The mortality rates were in an acceptable range. Macroscopically evident tumors were not detected after two years. The CeO2 lung burdens were maximally 3.5 mg/g lung tissue at the highest exposure concentration of 3 mg/m³. In comparison, highest CeO2 burdens in organs remote to expo-sure were liver and spleen with maximally roughly 1 x 10-3 g/g tissue. In brain, maximum CeO2 levels were 7x10-6 mg/g lung tissue. BaSO4 lung burdens were comparatively low (1 mg/g) within the first 13 weeks of exposure and steeply increased to 6 mg/g lung tissue after one year. The comprehen-sive histopathological examinations of lungs and other tissues will be finalized in 2017.