THE COLIPA SKIN METABOLISM PROJECT: DO IN VITRO ALTERNATIVES COMPRISE ADEQUATE DETOXIFICATION CAPACITIES FOR CHEMICAL TESTING IN SKIN?

• TR Number: 605
• Authors: Gotz2, C., Ruwiedel2, K., Pfeiffer2, R., Hubenthal2, U., Edwards2, R., Carmichael1, P., Aeby4, P., Goebel5, C., Pease1, C., Fritsche2,6, E. 1Unilever, Safety & Environmental Assurance Centre, Sharnbrook, Bedford, UK. 2Institute for Environmental Health Research (IUF gGmbH), Dusseldorf, Germany. 3Imperial College London, Hammersmith Campus, London UK. 4Procter and Gamble, Cosmital, Marly, Switzerland. 5Procter and Gamble, Darmstadt, Germany. 6Clinic of Dermatology, RWTH Aachen, Germany.
• Materials Tested: 3-Methylcholanthrene

Background: The aim of this study is to characterize the specific enzymatic activity of Phase I and II detoxification enzymes in human ex vivo skin compared to skin cell-derived in vitro models. Emphasis was here put on the determination of basal enzyme activity. Conclusions: Basal CYP1A, 1B1 and CYP2B activity is below detection limit in human skin microsomes and skin equivalents, but in-ducible. CYP3A is present at basal level, but was not inducible in this setup. Phase II enzymes are far more prominent in skin than Phase I CYP enzymes. Phase II activity is not dependent on donor, but shows slight activity decrease depending on cultivation time. Phase II enzymes were not inducible in this setup by the model genotoxin 3-Methylcholantrene. Phase II: 3-D models (EPI-200) resemble skin metabolism well.