Yourick, J.J. and R. L. Bronaugh. In Vitro Percutaneous Absorption and Metabolism of 2-Nitro-P-Phenylenediamine in Human and Fuzzy Rat Skin. The Toxicologist 1999. 48(1S): 74. Abstract #346.

2-nitro-p-phenylenediamine - 05307-14-2;

2-Nitro-p-phenylenediamine (2NPPD) is a "coal-tar" dye used in semipermanent and permanent (tinting color) hair dye formulations. In previous work, we reported on the percutaneous absorption and metabolism of 2NPPD in fuzzy rat skin and intestinal tissue (Toxicologist 35: 188, 1997). These studies were expanded to include in vitro absorption and metabolism of 2NPPD in human skin from ethanol and from a spiked semipermanent formulation, and in fuzzy rat skin from ethanol and from a spiked permanent formulation. Dosing vehicles were applied to skin in the diffusion cells for 30 min. Absorption was measured over 24 hr by using flow-through diffusion cells (0.64 cm2) with a receptor fluid consisting of HHBSS (pH 7.4). 2NPPD metabolites were determined by HPLC. In human skin, the percentages of total applied dose absorbed (receptor fluid + skin) over 24 hr were 9.2 ± 5.7 (mean ± SD) and 9.5± 3.2 for the ethanol and semipermanent vehicles, respectively with approximately 3% remaining in skin. In rat skin, the percentages of total applied dose absorbed over 24 hr were 9.3± 1.2 (mean± SEM) and 4.2± 0.1 for the ethanol and permanent formulation, vehicles, respectively with approximately 3% remaining in skin. 2NPPD rapidly penetrated both human and fuzzy rat skin from the product formulations with 47 and 64% respectively of the total absorbed dose found in the receptor fluid within 3 hr. In humans and rat skin, 2NPPD was metabolized to triaminobenzene and N4-acetyl-2NPPD. 2NPPD was also metabolized to a sulfated 2NPPD metabolite in rat skin, but not in human skin. These results suggest that 2NPPD is rapidly absorbed and extensively metabolized in both human and rat skin. 2NPPD metabolism upon absorption appears to be species dependent.