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 absorption data to link environmental contamination to potential systemic dose. Human absorption data are not readily available, so absorption models are used. In vitro diffusion systems are easy to use but have proved to be somewhat unreliable and are not validated to man. This study compares percutaneous absorption in the isolated perfused porcine skin flap (IPPSF) system with that in man in vivo. The study design utilized the same compounds and the same dose concentration and vehicle in both systems. Methodology for each system was that which is routinely used ineach system. The skin surface was not protected during the absorption dosing period. Percutaneous absorption values were, for man and 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-dimethylamine (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 wash recovery postapplication was similar for salicylic acid in man (53.4 +/- 6.3%) and the IPPSF system (48.2 +/- 4.9%). With the other compounds the majority of surface chemical was recovered in the surface wash and skin tape strip in the IPPSF system. With man, other than salicylic acid, only a few percent applied dose was recovered with surface washing and tape stripping. Since the wash procedure was effective with pig skin, we can assume that these chemicals in man were lost to adsorption 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 human skin in solvent vehicle did so in the period of time before the chemical was removed. The IPPSF system appears to be a good model for predicting percutaneous absorption relative to man. This study design should be used to validate other systems to humans in vivo.
Department of Dermatology, University of California School of Medicine, San Francisco, California.
R C
RC
Wester
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J
Melendres
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L
Sedik
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H
Maibach
J E
JE
Riviere
D010129:4-Aminobenzoic Acid / Q000008:administration & dosage / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D002250:Carbon Radioisotopes; D004051:Diethylhexyl Phthalate / Q000008:administration & dosage / Q000378:metabolism*; D004123:Dimethylamines / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D012459:Salicylates / Q000008:administration & dosage / Q000378:metabolism*; D020156:Salicylic Acid; D012869:Skin Absorption / Q000502:physiology*; D013552:Swine; D013806:Theophylline / Q000008:administration & dosage / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D002250:Carbon Radioisotopes; D004123:Dimethylamines; D012459:Salicylates; C034516:dimethylamine; D013806:Theophylline; D004051:Diethylhexyl Phthalate; D020156:Salicylic Acid; D010129:4-Aminobenzoic Acid