title: 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, CeO2NM-212 and BaSO4upon 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 CeO2elicited lung effects at concentrations of 5mg/m3(burdens of 0.5mg/lung) in the preceding range-finding study, whereas nano-sized BaSO4did not induce any effect, female rats were exposed to aerosol concentrations of 0.1 up to 3mg/m3CeO2or 50mg/m3BaSO4nanomaterials (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 CeO2or BaSO4nanomaterial 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 CeO2or to a high dose of BaSO4nanomaterials does not induce genotoxicity on the rat hematopoietic system at the DNA, gene or chromosome levels.
authors: Eugenia
authors: E
authors: Cordelli
authors: Experimental Toxicology and Ecology, BASF SE, 67056 Ludwigshafen, Germany.
authors: Jana
authors: J
authors: Keller
authors: Patrizia
authors: P
authors: Eleuteri
authors: Paola
authors: P
authors: Villani
authors: Experimental Toxicology and Ecology, BASF SE, 67056 Ludwigshafen, Germany.
authors: Lan
authors: L
authors: Ma-Hock
authors: Experimental Toxicology and Ecology, BASF SE, 67056 Ludwigshafen, Germany.
authors: Markus
authors: M
authors: Schulz
authors: Experimental Toxicology and Ecology, BASF SE, 67056 Ludwigshafen, Germany.
authors: Robert
authors: R
authors: Landsiedel
authors: Francesca
authors: F
authors: Pacchierotti
mesh_terms: D000818:Animals; D001466:Barium Sulfate / Q000494:pharmacology / Q000633:toxicity; D002563:Cerium / Q000494:pharmacology / Q000633:toxicity; D002869:Chromosome Aberrations / Q000139:chemically induced*; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D005260:Female; D019570:Inhalation Exposure; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D009152:Mutagenicity Tests; D009154:Mutation; D049329:Nanostructures / Q000737:chemistry / Q000633:toxicity*; D051381:Rats
chemical_list: D001466:Barium Sulfate; D002563:Cerium; C030583:ceric oxide; D004247:DNA