New Publication: A Study of Inter-Individual Variability in the Phase II Metabolism Xenobiotics in Human Skin


Understanding skin metabolism is key to improve in vitro to in vivo extrapolations used to inform risk assessments of topically applied products. However, published literature is scarce and usually covers a limited and non-representative number of donors. We developed a protocol to handle and store ex vivo skin samples post-surgery and prepare skin S9 fractions to measure the metabolic activity of Phase II enzymes. The addition of an excess of cofactors immediately after preparation, before pre-incubation at 37°C for fifteen minutes before introducing the testing probe, greatly increased the stability of the enzymes. Using this standardised assay, the rates of sulphation (SULT) and glucuronidation (UGT) of 7-hydroxycoumarin, methylation (COMT) of dopamine and N-acetylation (NAT) of procainamide were measured in the ng/mg protein/h range in ninety individuals. Glutathione conjugation (GST) of 1-chloro-2,4-dinitrobenzene was assessed in a smaller pool of fifty donors. The metabolic rate was much faster and measured over six minutes using a different methodology to express rates in µg metabolite formed/mg protein/min. A comprehensive statistical analysis of these results was carried out, separating donors by age, gender and metabolic rate measured to estimate skin metabolism in the general population.

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