Percutaneous absorption of nitroaromatic compounds: in vivo and in vitro studies in the human and monkey

The percutaneous absorption of 2-nitro-p-phenylene-diamine, 4-amino-2-nitrophenol, nitrobenzene, p-nitroaniline, and 2,4-dinitrochlorobenzene was measured through human and monkey skin. Human studies were performed with excised skin in diffusion cells. Absorption through monkey skin was measured by in vivo and in vitro techniques. Results were compared with those from previously reported human in vivo studies on 2,4-dinitrochlorobenzene and nitrobenzene. Rapid penetration was observed with all compounds, with maximum absorption occurring the first few hours. No significant differences in absorption were found in values obtained by the different procedures except for the highly volatile (and therefore difficult to compare) compound nitrobenzene. A comparison of the human and monkey in vitro data showed a trend toward increased absorption through monkey skin, but the increase was not statistically significant. The monkey in vivo and in vitro results showed that absorption of all compounds except nitrobenzene was slightly less in the in vitro studies; however, the values were not significantly different. The relative volatility of these nitroaromatic compounds was measured by the loss of compound from epidermal discs at various time intervals. The greatest loss of applied material occurred with nitrobenzene; however, substantial amounts of the other compounds were lost, particularly during the first minute after application as the acetone vehicle evaporated. Monkey skin was found to be a good model for human skin for the determination of the percutaneous absorption of these compounds, and in vitro measurements of absorption agreed reasonably well with values obtained by in vivo techniques. A good correlation was not observed between the absorption of these compounds and their solubility properties.