Host: The Japanese Society of Toxicology
Aromatic amines (AA) are widely used as dyes. Several decades ago, an increased risk for bladder cancer among male hairdressers using hair dyes containing AA was reported. While, the recent epidemiological studies have suggested the association between hairdressers and increased risk for skin cancer at the scalp and neck, sites of contact for hair dyes. In this study, we investigated the skin accumulation and genotoxicity of ortho-phenylenediamine (OPDA) as a model substance for AA used in hair dye to see if the experimental results support the epidemiological data. The skin absorption of OPDA was examined using C-14 labeled OPDA and the modified Franz diffusion cell method with a 3D reconstructed human epidermis model (3D-Skin), a cultured cell model similar to the human epidermis. We found that OPDA enters the 3D-Skin easily and time-dependently accumulates in it (about 60% of the added amount of OPDA entered the 3D-skin by 24 h, and almost no passed through the 3D-skin). In comparison to OPDA, aniline, the simplest structure of the AA, did not accumulate in the 3D-skin, and almost passed through the 3D-skin. The genotoxicity of OPDA is being investigated using 3D-Skin and HaCaT cells with γH2AX as an DNA damage indicator. Although the results are preliminary, the induction of γH2AX by OPDA has been confirmed in the concentration range that does not affect cell viability. As shown in this study, the high accumulation of OPDA, which has DNA-damaging properties, in the epidermis may cause the occurrence of skin cancer.
