Percutaneous absorption of trinitrobenzene: animal models for human skin

The percutaneous absorption of 1,3,5-trinitrobenzene (TNB) was studied in viable skin from hairless guinea pigs (HGP), Fischer 344 rats and humans. Skin was dermatomed and assembled in flow-through diffusion cells followed by TNB application in either an acetone or a water vehicle. Skin absorption was expressed as the percentage of applied dose absorbed into skin and receptor fluid within 24 h. Rapid absorption of TNB by rodent skin was obtained with both vehicles. For HGP skin, TNB absorption was 72.7+/-5.5% in the acetone vehicle and 82.3+/-4.5% in the water vehicle. For rat skin, TNB absorption was 61.0+/-4.1% (acetone) and 66.5+/-4.1% (water). Absorption of TNB from acetone was significantly reduced (38.0+/-11.0%, P = 0.0118) in human skin, but absorption from water remained high (75.5+/-10.8%). Little TNB remained in skin when a thin (200 microm) dermatome section was used (HGP and human skin). A thicker dermatome section was required (350 microm) with haired rat skin, and 13-21% of the absorbed radioactivity remained in the skin at 24 h. Rodent skin did not simulate satisfactorily the barrier properties of human skin when TNB absorption was reduced by application in a volatile solvent.