PERCUTANEOUS-ABSORPTION OF SALICYLIC-ACID, THEOPHYLLINE, 2,4-DIMETHYLAMINE, DIETHYL HEXYL PHTHALIC-ACID, AND P-AMINOBENZOIC ACID IN THE ISOLATED-PERFUSED PORCINE SKIN FLAP COMPARED TO MAN IN-VIVO

Human risk assessment for topical exposure requires percutaneous absor ption data to link environmental contamination to potential systemic d ose. Human absorption data are not readily available, so absorption mo dels are used. In vitro diffusion systems are easy to use but have pro ved to be somewhat unreliable and are not validated to man. This study compares percutaneous absorption in the isolated perfused porcine ski n flap (IPPSF) system with that in man in vivo. The study design utili zed the same compounds and the same dose concentration and vehicle in both systems. Methodology for each system was that which is routinely used in each system. The skin surface was not protected during the abs orption dosing period. Percutaneous absorption values were, for man an d the IPPSF system, respectively: salicylic acid (6.5 +/- 5.0%; 7.5 +/ - 2.6%), theophylline (16.9 +/- 11.3%; 11.8 +/- 3.8%), 2,4-dimethylami ne (1.1 +/- 0.3%; 3.8 +/- 0.6%), diethyl hexyl phthalic acid (1.8 +/- 0.5%; 3.9 +/- 2.4%), and p-aminobenzoic acid (11.5 +/- 6.3%; 5.9 +/- 3 .7%) (correlation coefficient was 0.78; p < 0.04). The skin surface wa sh recovery postapplication was similar for salicylic acid in man (53. 4 +/- 6.3%) and the IPPSF system (48.2 +/- 4.9%). With the other compo unds the majority of surface chemical was recovered in the surface was h and skin tape strip in the IPPSF system. With man, other than salicy lic acid, only a few percent applied dose was recovered with surface w ashing and tape stripping. Since the wash procedure was effective with pig skin, we can assume that these chemicals in man were lost to adso rption to any clothing or bedding with the volunteers. The absorption in man was not less than that In the IPPSF. Assuming the dose was lost in man, it seems plausible that whatever compound was to penetrate hu man skin in solvent vehicle did so in the period of time before the ch emical was removed. The IPPSF system appears to be a good model for pr edicting percutaneous absorption relative to man. This study design sh ould be used to validate other systems to humans in vivo. (C) 1998 Aca demic Press.