2005 ANNUAL SCIENTIFIC SEMINAR 377 Table 2: PAN penetration in human and porcine skin after 72 hours (% total applied dose) Human Porcine Receptor fluid 0.30±0.04 0.45±0.15 Skin content 17.1±4.4 12.2±2.2 Total applied 17.4±4.4 12.7±2.2 dose penetrated Wash 91.5±6.7 96.9±7.8 Recovery 108.9±7.6 109.5±9.3 Values are mean ± SEM for human (n=8) and porcine (n=4) skin Metabolism of PAN could only be examined in extracts from pig skin samples since the levels of radioactivity that were absorbed into the receptor fluid were extremely small. In spite of the fact that large amounts of radioactivity were present in the skin at 24 h, no metabolites of PAN were detected by HPLC analysis. Metabolism of PAN to 4-aminoazobenzene in skin would require the cleavage of an azo bond. We have previously shown that several other azo colors were significantly metabolized with azo bond cleavage in mouse, hairless guinea pig and human skin (3). However, these colors had better water solubility and were more readily absorbed than PAN. Human skin samples in the current study were not analyzed for metabolism since they were fipm non-viable cadaver skin. Conclusion The skin absorption of 14 C-PAN into the receptor fluid beneath the skin was significantly less than 1 % with either human or pig skin in both the 24 and 72 h studies. Substantial amounts of 14 C-PAN {10-17 %) penetrated into human and pig skin in 24 hr. Pig receptor fluid levels of PAN did not increase in the extended absorption studies suggesting that material in the skin may not be available for systemic absorption. Human receptor fluid levels of PAN did increase significantly at 72 h but the 72 h values were still low and similar to those with pig skin. No metabolism of PAN to 4-aminoazobenzene was observed in viable pig skin. References 1. Gottschalck, T. E. and McEwen, G. N., International Cosmetic Ingredient Dictionary and Handbook, 9'h Ed., The Cosmetic Toiletry and Fragrance Association, Washington DC, 2004. 2. Bronaugh, R.L. and S.W. Collier, Protocol for in vitro percutaneous absorption studies. In In Vitro Percutaneous Absorption: Principles, Fundamentals, and Applications, ed. By R.L. Bronaugh and H.I. Maibach, pp. 23 7-241. CRC Press, Boca Raton, 1991. 3. Collier, S. W, Storm, J.E., and Bronaugh, R. L., Reduction of azo dyes during in vitro percutaneous absorption, Toxicol. Appl. Pharmacol. 118, 73-79, 1993.
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