No evidence for carcinogenicity of titanium dioxide nanoparticles in 26-week inhalation study in rasH2 mouse model

Abstract

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. We performed a 26-week inhalation exposure studies of titanium dioxide nanoparticles (TiO2 NPs) using CByB6F1-Tg(HRAS)2Jic (rasH2) mice model for detecting carcinogenicity. Male and female rasH2 mice were exposed to 2, 8 or 32 mg/m3 of TiO2 NPs for 6 h/day, 5 days/week for 26 weeks. All tissues and blood were collected and subjected to biological and histopathological analyses. TiO2 NPs exposure induced deposition of particles in lungs in a dose-dependent manner in each exposure group. Exposure to TiO2 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 alveolar epithelial type 2 cells was examined, and it was not increased by exposure to TiO2 NPs. This is the first report showing the lack of pulmonary fibrogenicity and carcinogenicity (no evidence of carcinogenic activity) of TiO2 NPs in 26-week inhalation study in rasH2 mice exposed up to 32 mg/m3, which is considered to be a high concentration.

Carcinogenicity and testicular toxicity of 2-bromopropane in a 26-week inhalation study using the rasH2 mouse model

“…Statistical analysis was performed as previously described 26 . All statistical analysis, except for the Poly-k test, was carried out by the BAIS system (Hitachi Social Information Services Ltd., Tokyo, Japan) and GraphPad Prism 5 (GraphPad Software, San Diego, CA).…”

“…Hematological and blood chemistry tests. Hematological examination was performed as previously described 26 . Briefly, blood samples collected at the time of each autopsy were analyzed with an automated hematology analyzer (ADVIA120, Siemens Healthcare Diagnostics Inc. Tarrytown, NY).…”

“…Histopathological analysis. Histopathological analysis was performed as previously described 26 . Briefly, tissue sections were cut from paraffin-embedded specimens of all organs required by OECD TG451 29 , and the Sections (2-μm thick) were stained with hematoxylin and eosin (HE) for histological examination.…”

Photocatalytic degradation of methylene blue by anatase TiO 2 coating

“…While TiO 2 was previously classified as a potential carcinogen, due to a lack of evidence confirming this supposition in numerous in-depth studies, the opposite view is increasingly held. As a result, its EU classification of TiO 2 as a potential carcinogen has also recently been withdrawn [10][11][12]. The discovery of the photocatalytic properties of TiO 2 has led to great interest in its potential for environmental applications [13].…”

Carcinogenicity and testicular toxicity of 2-bromopropane in a 26-week inhalation study using the rasH2 mouse model

“…We have previously conducted systemic inhalation exposure studies of various chemicals in rodents, including rasH2 mice, and have examined various toxicities, including carcinogenicity and pulmonary fibrosis [25][26][27] . In this study, we conducted a 26-week systemic inhalation exposure study of 2-BP using rasH2 mice and comprehensively evaluated carcinogenicity in each organ and reproductive organ toxicity.…”