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• W4200247130 abstract "Abstract Background With the rapid development of alternative methods based on the spirit of animal welfare, the publications of animal studies evaluating endpoints such as cancer have been extremely reduced. There have been no systemic inhalation exposure studies of titanium dioxide nanoparticles (TiO 2 NPs) using CByB6F1-Tg(HRAS)2Jic (rasH2) 26-week study mice model for detecting carcinogenicity. Methods Male and female rasH2 mice were exposed to 2, 8 or 32 mg/m 3 of TiO 2 NPs for 6 hours/day, 5 days/week for 26 weeks using a whole-body inhalation exposure system, with reference to the Organization for Economic Co-operation and Development principles of Good Laboratory Practice. All tissues including lungs, and blood were collected and subjected to biological and histopathological analyses. Additionally, Ki67 positive index were evaluated in mice lung alveolar epithelial type 2 cell (AEC2). Results This study established a stable method for generating and exposing TiO 2 NPs aerosol, and clarified the dose-response relationship by TiO 2 NPs inhalation to rasH2 mice. TiO 2 NPs exposure induced deposition of particles in lungs and mediastinal lymph nodes in a dose-dependent manner in each exposure group. Additionally, alveolar inflammation was only observed in 32 mg/m 3 exposure group in both the sexes. Exposure to TiO 2 NPs, as well as other organs, did not increase the incidence of lung tumors in any group, and pulmonary fibrosis and pre-neoplastic lesions were not observed in all groups. Finally, the cell proliferative activity of AEC2 was examined, and it was not increased by exposure to TiO 2 NPs. Conclusions This is the first report showing the lack of pulmonary fibrogenicity and carcinogenicity (no evidence of carcinogenic activity) of TiO 2 NPs in 26-week inhalation study in rasH2 mice exposed up to 32 mg/m 3 , which is considered to be a high concentration. Macrophages undergoing phagocytosis due to TiO 2 NPs exposure formed inflammatory foci in the alveolar regions of exposed mice but did not develop fibrosis or hyperplasia or tumors. Moreover, the cell proliferative ability of AEC2 in lesions was not increased. In addition, no carcinogenicity was observed for any organs other than the lungs in this study." @default.
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• W4200247130 date "2021-12-23" @default.
• W4200247130 modified "2023-10-18" @default.
• W4200247130 title "Lack of pulmonary fibrogenicity and carcinogenicity of titanium dioxide nanoparticles in 26-week inhalation study in rasH2 mouse model" @default.
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• W4200247130 doi "https://doi.org/10.1101/2021.12.23.473959" @default.
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