Title
Xenobiotic metabolism in human skin and 3D human skin reconstructs: A review
Author
Gibbs, S.
van de Sandt, J.J.M.
Merk, H.F.
Lockley, D.J.
Pendlington, R.U.
Pease, C.K.
TNO Kwaliteit van Leven
Publication year
2007
Abstract
In this review, we discuss and compare studies of xenobiotic metabolism in both human skin and 3D human skin reconstructs. In comparison to the liver, the skin is a less studied organ in terms of characterising metabolic capability. While the skin forms the major protective barrier to environmental chemical exposure, it is also a potential target organ for adverse health effects. Occupational, accidental or intended-use exposure to toxic chemicals could result in acute or delayed injury to the skin (e.g. inflammation, allergy, cancer). Skin metabolism may play a role in the manifestation or amelioration of adverse effects via the topical route. Today, we have robust testing strategies to assess the potential for local skin toxicity of chemical exposure. Such methods (e.g. the local lymph node assay for assessing skin sensitisation; skin painting carcinogenicity studies) incorporate skin metabolism implicitly in the in vivo model system used. In light of recent European legislation (i.e. 7th Amendment to the Cosmetics Directive and Registration Evaluation and Authorisation of existing Chemicals (REACH)), non-animal approaches will be required to reduce and replace animal experiments for chemical risk assessment. It is expected that new models and approaches will need to account for skin metabolism explicitly, as the mechanisms of adverse effects in the skin are deconvoluted. 3D skin models have been proposed as a tool to use in new in vitro alternative approaches. In order to be able to use 3D skin models in this context, we need to understand their metabolic competency in relation to xenobiotic biotransformation and whether functional activity is representative of that seen in human skin. © 2007 Bentham Science Publishers Ltd.
Subject
Biology
3D skin reconstructs
Cytochrome P450
IDO expression
In vitro skin absorption
Microarray
Peptidases
1 chloro 2,4 dinitrobenzene
2 nitro 1,4 phenylenediamine
4 aminophenol
alcohol dehydrogenase
aldehyde dehydrogenase
alpha tocopherol
atrazine
azo reductase
carnitine
cinnamaldehyde
cinnamyl alcohol
clobetasol propionate
cytochrome P450
esterase
hydrogen peroxide
messenger RNA
nicotinic acid ethyl ester
oxygenase
phenylenediamine
propoxur
propranolol
resorufin
retinoic acid
retinol palmitate
T 2 toxin
toxic substance
triclosan
triolein
unindexed drug
xenobiotic agent
biotransformation
chemical carcinogenesis
environmental exposure
enzyme assay
ex vivo study
human
immunohistochemistry
in vitro study
nonhuman
Northern blotting
occupational exposure
protein expression
protein function
review
skin absorption
skin allergy
skin cancer
skin carcinogenesis
skin inflammation
skin sensitization
skin toxicity
toxicokinetics
Western blotting
xenobiotic metabolism
Biotransformation
Humans
Models, Biological
Skin
Xenobiotics
To reference this document use:
http://resolver.tudelft.nl/uuid:2cd94baf-d34f-4d61-8f29-6cc67dcef31f
DOI
https://doi.org/10.2174/138920007782798225
TNO identifier
240329
ISSN
1389-2002
Source
Current Drug Metabolism, 8 (8), 758-772
Document type
article