Lack of skin carcinogenicity of topically applied titanium dioxide nanoparticles in the mouse.
This study was conducted to examine the post-initiation carcinogenic potential of coated and uncoated titanium dioxide nanoparticles (CTDN and UCTDN) using a mouse medium-term skin carcinogenesis bioassay. For this purpose, 5, 10 and 20mg/animal doses of CTDN or UCTDN were applied to mouse skin in the post-initiation phase (up to 20 weeks) in a two-stage skin carcinogenesis model using 7 week old CD1 (ICR) female mice. 7,12-dimethylbenz[a]anthracene (DMBA) and 12-o-tetradecanoylphorbol 13-acetate (TPA) were used as the initiator and a positive control promoter, respectively. Pentalan 408 served as a vehicle control. No changes in survival rate, general condition and body weight related to the test materials were observed. On macroscopic observation, 1-2 nodules/group on the skin were observed in each group applied CTDN and UCTDN as well as the control group after DMBA initiation. The nodules were histopathologically diagnosed as squamous cell hyperplasia, sebaceous gland hyperplasia, squamous cell papilloma and keratoacanthoma. CTDN and UCTDN experiments, while enlargement of the mandibular, pancreatic, lumbar region and inguinofemoral lymph nodes, spleen and thymus was observed in mice given 5 and 10mg but not 20mg, the lack of dose-dependence suggests no biological significance. In the present study, CTDN and UCTDN applied in post-initiation stages at doses of up to 20mg/mouse did not increase the development of nodules, and thus it was concluded that titanium dioxide nanoparticles do not possess post-initiation potential for mouse skin carcinogenesis.
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi-ken 491-0113, Japan. furukawa@dims.co.jp
Fumio
F
Furukawa
Yuko
Y
Doi
Mayuko
M
Suguro
Osamu
O
Morita
Hirofumi
H
Kuwahara
Takuji
T
Masunaga
Yoshiro
Y
Hatakeyama
Fukuyoshi
F
Mori
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000287:Administration, Topical; D000818:Animals; D001835:Body Weight; D015197:Carcinogenicity Tests; D053768:Metal Nanoparticles; D051379:Mice; D008813:Mice, Inbred ICR; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000473:pathology; D015996:Survival Rate; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity*
C009495:titanium dioxide; D015127:9,10-Dimethyl-1,2-benzanthracene; D014025:Titanium; D013755:Tetradecanoylphorbol Acetate