No genotoxicity in rat blood cells upon 3-or 6-month inhalation exposure to CeO2 or BaSO4 nanomaterials

In the course of a 2-year combined chronic toxicity-carcinogenicity study performed according to Organisation for Economic Co-operation and Development (OECD) Test Guideline 453, systemic (blood cell) genotoxicity of two OECD representative nanomaterials, CeO2 NM-212 and BaSO4 upon 3-or 6-month inhalation exposure to rats was assessed. DNA effects were analysed in leukocytes using the alkaline Comet assay, gene mutations and chromosome aberrations were measured in erythrocytes using the flow cytometric Pig-a gene mutation assay and the micronucleus test (applying both microscopic and flow cytometric evaluation), respectively. Since nano-sized CeO2 elicited lung effects at concentrations of 5 mg/m(3) (burdens of 0.5 mg/lung) in the preceding range-finding study, whereas nano-sized BaSO4 did not induce any effect, female rats were exposed to aerosol concentrations of 0.1 up to 3 mg/m(3) CeO2 or 50 mg/m(3) BaSO4 nanomaterials (6 h/day; 5 days/week; whole-body exposure). The blood of animals treated with clean air served as negative control, whereas blood samples from rats treated orally with three doses of 20 mg/kg body weight ethylnitrosourea at 24 h intervals were used as positive controls. As expected, ethylnitrosourea elicited significant genotoxicity in the alkaline Comet and Pig-a gene mutation assays and in the micronucleus test. By contrast, 3-and 6-month CeO2 or BaSO4 nanomaterial inhalation exposure did not elicit significant findings in any of the genotoxicity tests. The results demonstrate that subchronic inhalation exposure to different low doses of CeO2 or to a high dose of BaSO4 nanomaterials does not induce genotoxicity on the rat hematopoietic system at the DNA, gene or chromosome levels.