Lack of promoting effect of titanium dioxide particles on ultraviolet B-initiated skin carcinogenesis in rats

Titanium dioxide (TiO2) is used in sunscreens and cosmetics as an ultraviolet light screen. TiO2 has carcinogenic activity in the rat lung, but its effect on the skin has not been reported. We examined the promoting/carcinogenic effect of nano-size TiO2 particles using a two-stage skin model. c-Ha-ras proto-oncogene transgenic (Hras128) rats, which are sensitive to skin carcinogenesis, and their wild-type siblings were exposed to ultraviolet B radiation on shaved back skin twice weekly for 10 weeks; then the shaved area was painted with a 100 mg/ml TiO2 suspension twice weekly until sacrifice. All rats were killed at week 52 except for female Hras128 rats which were sacrificed at week 16 because of early mammary tumor development. Skin tumors developed in male Hras128 rats and mammary tumors developed in both sexes of Hras128 rats and in wild-type female rats, but tumor incidence was not different from controls. TiO2 particles were detected in the upper stratum corneum but not in the underlying skin tissue layers. TiO2 particles also did not penetrate a human epidermis model in vitro. Our data suggest that TiO2 does not cause skin carcinogenesis, probably due to its inability to penetrate through the epidermis and reach underlying skin structures.