title: In vivo genotoxicity study of titanium dioxide nanoparticles using comet assay following intratracheal instillation in rats.
abstract: Titanium dioxide (TiO₂) is widely used as a white pigment in paints, plastics, inks, paper, creams, cosmetics, drugs and foods. In the present study, the genotoxicity of anatase TiO₂ nanoparticles was evaluated in vivo using the comet assay after a single or repeated intratracheal instillation in rats. The nanoparticles were instilled intratracheally at a dosage of 1.0 or 5.0 mg/kg body weight (single instillation group) and 0.2 or 1.0 mg/kg body weight once a week for 5 weeks (repeated instillation group) into male Sprague-Dawley rats. A positive control, ethyl methanesulfonate (EMS) at 500 mg/kg, was administered orally 3 h prior to dissection. Histopathologically, macrophages and neutrophils were detected in the alveolus of the lung in the 1.0 and 5.0 mg/kg TiO₂ groups. In the comet assay, there was no increase in % tail DNA in any of the TiO₂ groups. In the EMS group, there was a significant increase in % tail DNA compared with the negative control group. TiO₂ nanoparticles in the anatase crystal phase are not genotoxic following intratracheal instillation in rats.
authors.affiliation: Research Institute of Science for Safety and Sustainability, National Institute of Advanced Industrial Science and Technology (AIST), 16-1 Onogawa, Tsukuba, Ibaraki 305-8569, Japan. masato.naya@aist.go.jp
authors.forename: Masato
authors.initials: M
authors.lastname: Naya
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Ema
authors.forename: Sawako
authors.initials: S
authors.lastname: Kasamoto
authors.forename: Masahito
authors.initials: M
authors.lastname: Fukumuro
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Takami
authors.forename: Madoka
authors.initials: M
authors.lastname: Nakajima
authors.forename: Makoto
authors.initials: M
authors.lastname: Hayashi
authors.forename: Junko
authors.initials: J
authors.lastname: Nakanishi
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D020552:Comet Assay; D008297:Male; D053758:Nanoparticles / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014025:Titanium / Q000633:toxicity*; D023382:Toxicity Tests, Acute; D059551:Toxicity Tests, Subacute
chemical_list: C009495:titanium dioxide; D014025:Titanium