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EVALUATION OF XENOBIOTIC METABOLISM IN HUMAN RECONSTRUCTED SKIN MODELS FOR GENOTOXICITY TESTING.

Jackh1, C, Blatz1, V., Fabian1, E., Reisinger2 , K., van Ravenzwaay1 , B., Trappe3, S., Landsiedel1, R.  1Experimental Toxicology and Ecology, BASF SE, 67056 Ludwigshafen, Germany. 2Henkel AG & CO. KGaA, 40191 Düsseldorf, Germany.  3Federal Institute for Risk Assessment (BfR), 14195 Berlin, Germany.
Abstract

Skin penetration and absorption is a major route of xenobiotic uptake. Skin maintains furthermore capacities to transform chemical substances which was previously shown by transcriptional expression analysis of metabolizing enzymes including CYPs, Flavin-dependent monooxygenases (FMO), N- Acetyltransferases (NAT) and UDP-Glucuronyltransferases (UDP-GT) [1-3]. Their catalytic activity in skin tissue however was rarely specified. Human reconstructed skin models are under investigation to be used as in vitro alternative for in vivo animal testing. As metabolic processing is required for chemical induced effects, i.e. genotoxicity, characterization of enzymatic competence of in vitro skin models is demanded for their usage in toxicity testing.

Keywords

Cytochrome P450 (CYPs), EFT-400, EPI-200, Flavin-dependent monooxygenases, N-Acetyltransferases (NAT), UDP-Glucuronyltransferases (UDP-GT), Xenobotic metabolism

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