title: Genotoxicity assessment of cerium oxide nanoparticles in female Wistar rats after acute oral exposure.
abstract: Cerium oxide nanoparticles (CeO2 NPs; nanoceria) have demonstrated excellent potential for commercial use in various arenas, such as in biomedical industry in cosmetics and as a fuel additive. However, limited knowledge exists regarding their potential toxicity. In this study, acute oral toxicity of CeO2 NPs and their microparticles (MPs; bulk) was carried out in female albino Wistar rats. The CeO2 NPs and CeO2 MPs were characterized utilizing transmission electron microscopy (TEM), dynamic light scattering (DLS) and laser Doppler velocimetry (LDV) for the size, distribution and surface charge respectively. The genotoxicity studies were conducted using micronucleus test (MNT), comet and chromosomal aberration (CA) assays. Results revealed that at high dose (1000mg/kg bw) CeO2 NPs induced significant DNA damage in peripheral blood leukocytes (PBL) and liver cells, micronucleus formation in bone marrow and blood cells and total cytogenetic changes in bone marrow. However, significant genotoxicity was not observed at 500 and 100mg/kg bw of CeO2 NPs. The findings from biochemical assays depicted significant alterations in ALP and LDH activity in serum and GSH content in liver, kidneys and brain only at the high dose of CeO2 NPs. Tissue biodistribution of both particles was analyzed by inductively coupled plasma optical emission spectrometer (ICP-OES). Bioaccumulation of nanoceria in all tissues was significant and dose-, time- and organ-dependent. Moreover, CeO2 NPs exhibited higher tissue distribution along with greater clearance in large fractions through urine and feces than CeO2 bulk, whereas, maximum amount of micro-sized CeO2 got excreted in feces. The histopathological examination documented alterations in the liver due to exposure with CeO2 NPs only. Hence, the results suggest that bioaccumulation of CeO2 NPs may induce genotoxic effects. However, further research on long term fate and adverse effects of CeO2 NPs is warranted.
authors.affiliation: Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad 500 007, Andhra Pradesh, India; 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 500 007, Andhra Pradesh, India.
authors.forename: Srinivas Indu
authors.initials: SI
authors.lastname: Kumari
authors.affiliation: Defence Metallurgical Research Laboratory, Kanchanbagh, Hyderabad 500058, Andhra Pradesh, India.
authors.forename: Sarika Srinivas Kalyan
authors.initials: SS
authors.lastname: Kamal
authors.affiliation: Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad 500 007, Andhra Pradesh, India. Electronic address: paramgrover@gmail.com.
authors.forename: Paramjit
authors.initials: P
authors.lastname: Grover
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002563:Cerium / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D002869:Chromosome Aberrations / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D009928:Organ Specificity; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D002563:Cerium; C030583:ceric oxide
keywords: Biochemical; Biodistribution; CeO(2) microparticles; CeO(2) nanoparticles; Genotoxicity; Wistar rats