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

Abstract

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 5mg/m³ (burdens of 0.5mg/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 3mg/m³ CeO₂ or 50mg/m³ BaSO₄ nanomaterials (6h/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 20mg/kg body weight ethylnitrosourea at 24h 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.