Percutaneous absorption of aromatic amines - a contribution for human health risk assessment.

Several aromatic amines (AA) are human carcinogens. AA are widely-used, e.g., in the rubber industry. The uptake of AA at the workplace occurs by inhalation and percutaneous absorption. At present there are no risk assessment studies for percutaneous AA absorption using occupationally relevant concentrations. We conducted diffusion cell experiments for aniline (ANI), o-toluidine (OT), 4,4'-methylenedianiline (MDA) and N-phenyl-2-naphthylamine (PBNA). Excised human skin was exposed to different AA concentrations in vehicles containing water and solvents. Recovery for ANI in receptor fluid was about 20-38% and for MDA 15% over 24h. PBNA could not be detected in the receptor fluid. Further data for OT and beta-naphthylamine (BNA) were considered from our recent study. A semi-quantitative percutaneous absorption ranking for AA was derived: BNA>OT>ANI>MDA>PBNA. For aqueous ANI solutions up to saturation a linear relationship of exposed dose and penetrated amount was observed. However, a linear extrapolation of the flux of neat compounds, as often recommended for risk assessment policies, underestimates considerably the percutaneous uptake. The in vitro data support our recent findings in rubber industry workers that the percutaneous absorption may significantly contribute to overall exposure of AA.