Percutaneous penetration of dimethylnitrosamine through human skin in vitro: Application from cosmetic vehicles

Human skin penetration of N-dimethylnitrosamine (DMN) from three vehicles has been determined in vitro. When applied as an infinite dose in isopropyl myristate (IPM, 1 μg/μl) the average total absorption over 48 hr was 2.6 ± 1.2% of the applied dose (all data presented are expressed as means ± standard errors). When applied as a finite dose in a representative oil-in-water emulsion vehicle the average total absorption over 48 hr was 4.0 ± 0.3% of the applied dose. When applied as a finite dose in a representative shampoo vehicle for 10 min followed by rinsing (i.e. to represent in-use exposure conditions) the average total absorption over 48 hr was 1.1 ± 0.1% of the applied dose. Approximately 72% of the DMN in the applied shampoo vehicle was removed by rinsing. There was considerable evaporative loss of DMN from the IPM and oil-in-water emulsion vehicles, such that absorption was complete within 3 hr of application. The overall data indicate that DMN can penetrate the skin rapidly but that in practice the amount actually available for penetration is significantly reduced by high permeant volatility. In contrast, application of N-nitrosodiethanolamine (NDELA) at a concentration of 1 μg/μl as an infinite dose generated an average total absorption over 48 hr of 23.6 ± 6.4%, representing a total flux of 103.9 ± 28.4 μg/cm2. In the case of NDELA, no evaporative loss was evident.