Potential for metabolism locally in the skin of dermally absorbed compounds.
Dermally absorbed chemicals can be locally metabolized in the skin during absorption but it is difficult to distinguish this metabolism from liver metabolism by biological monitoring in vivo. Studies with sub-cellular fractions have showed the presence of metabolizing enzymes in the skin but with loss of cellular localization. Studies in HaCat cells in culture maintain cellular localization and in skin, in short-term culture, the chemical can be applied to the skin surface and metabolism during absorption can be monitored. Flow though diffusion systems with tissue culture medium as receptor fluid have maintained the viability of skin and supported metabolism, but dilution of the metabolites in the receptor fluid has limited detection. This article uses data derived by a range of techniques from the Newcastle laboratory to discuss the importance of local metabolism in the skin of butoxyethanol to butoxyacetic acid and parabens to p-hydroxybenzoic acid during dermal absorption, following application to the skin surface.
Williams
F M
FM
Toxicology Unit, Newcastle University, Newcastle upon Tyne, UK. f.m.williams@ncl.ac.uk
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D043182:Carboxylesterase / Q000378:metabolism; D002458:Cell Fractionation; D002460:Cell Line; D005026:Ethylene Glycols / Q000493:pharmacokinetics*; D006801:Humans; D010226:Parabens / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*
D005026:Ethylene Glycols; D010226:Parabens; D000426:Alcohol Dehydrogenase; D043182:Carboxylesterase; C017096:n-butoxyethanol