title: Genotoxicity analysis of cerium oxide micro and nanoparticles in Wistar rats after 28 days of repeated oral administration.
abstract: The applications of cerium oxide nanoparticles (CeO2 NPs; nanoceria) extend to polishing agents, diesel fuel additives and as a putative antioxidant in therapeutics. Therefore, understanding the long-term toxic effects of CeO2 NPs is of particular importance. This study investigated the 28 days of repeated toxicity of 30, 300 and 600 mg/kg body weight (bw)/day of nanoceria and CeO2 microparticles (MPs) in Wistar rats after oral exposure. Genotoxicity was analysed using comet, micronucleus (MN) and chromosomal aberration (CA) assays. The results demonstrated a significant increase in DNA damage in peripheral blood leukocytes and liver, MN and CA in bone marrow as well as MN in peripheral blood after exposure to CeO2 NPs at 300 and 600 mg/kg bw/day. Significant alterations were observed in alkaline phosphatase and lactate dehydrogenase activity in serum and reduced glutathione content in the liver, kidneys and brain at 300 and 600 mg/kg bw/day in a dose-dependent manner. Conversely, CeO2 MPs did not induce any significant toxicological changes. A much higher absorptivity and significant tissue distribution of CeO2 NPs was perceived in comparison to CeO2 MPs in a dose-dependent manner. A substantial fraction of CeO2 NPs was cleared by urine and faeces. Histopathological analysis revealed that CeO2 NPs caused alterations in liver, spleen and brain. Further, distinct difference in the data among genders was not obvious. In general, the results suggested that prolonged oral exposure to nanoceria has the potential to cause genetic damage, biochemical alterations and histological changes after retention in vital organs of rats at high concentrations.
authors.affiliation: Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad 500007, Andhra Pradesh, India and Department of Genetics, Osmania University, Osmania University Main Road, Hyderabad 500007, Andhra Pradesh, India.
authors.forename: Monika
authors.initials: M
authors.lastname: Kumari
authors.affiliation: Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad 500007, Andhra Pradesh, India and.
authors.forename: Srinivas Indu
authors.initials: SI
authors.lastname: Kumari
authors.affiliation: Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad 500007, Andhra Pradesh, India and paramgrover@gmail.com.
authors.forename: Paramjit
authors.initials: P
authors.lastname: Grover
mesh_terms: D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002563:Cerium / Q000008:administration & dosage / Q000633:toxicity*; D002869:Chromosome Aberrations; D020552:Comet Assay; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000633:toxicity* / Q000648:ultrastructure; D009929:Organ Size / Q000187:drug effects; D009928:Organ Specificity / Q000187:drug effects; D017208:Rats, Wistar; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D009153:Mutagens; D002563:Cerium; C030583:ceric oxide; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; D005978:Glutathione