The use of reconstructed human epidermis for skin absorption testing: Results of the validation study.
A formal validation study was performed, in order to investigate whether the commercially-available reconstructed human epidermis (RHE) models, EPISKIN, EpiDerm and SkinEthic, are suitable for in vitro skin absorption testing. The skin types currently recommended in the OECD Test Guideline 428, namely, ex vivo human epidermis and pig skin, were used as references. Based on the promising outcome of the prevalidation study, the panel of test substances was enlarged to nine substances, covering a wider spectrum of physicochemical properties. The substances were tested under both infinite-dose and finite-dose conditions, in ten laboratories, under strictly controlled conditions. The data were subjected to independent statistical analyses. Intra-laboratory and inter-laboratory variability contributed almost equally to the total variability, which was in the same range as that in preceding studies. In general, permeation of the RHE models exceeded that of human epidermis and pig skin (the SkinEthic RHE was found to be the most permeable), yet the ranking of substance permeation through the three tested RHE models and the pig skin reflected the permeation through human epidermis. In addition, both infinite-dose and finite-dose experiments are feasible with RHE models. The RHE models did not show the expected significantly better reproducibility, as compared to excised skin, despite a tendency toward lower variability of the data. Importantly, however, the permeation data showed a sufficient correlation between all the preparations examined. Thus, the RHE models, EPISKIN, EpiDerm and SkinEthic, are appropriate alternatives to human and pig skin, for the in vitro assessment of the permeation and penetration of substances when applied as aqueous solutions.
Freie Universität Berlin, Institut für Pharmazie, Berlin, Germany. msk@zedat.fu-berlin.de
Monika
M
Schäfer-Korting
Udo
U
Bock
Walter
W
Diembeck
Hans-Jürgen
HJ
Düsing
Armin
A
Gamer
Eleonore
E
Haltner-Ukomadu
Christine
C
Hoffmann
Monika
M
Kaca
Hennicke
H
Kamp
Silke
S
Kersen
Manfred
M
Kietzmann
Hans Christian
HC
Korting
Hans-Udo
HU
Krächter
Claus-Michael
CM
Lehr
Manfred
M
Liebsch
Annette
A
Mehling
Christel
C
Müller-Goymann
Frank
F
Netzlaff
Frank
F
Niedorf
Maria K
MK
Rübbelke
Ulrich
U
Schäfer
Elisabeth
E
Schmidt
Sylvia
S
Schreiber
Horst
H
Spielmann
Alexander
A
Vuia
Michaela
M
Weimer
D000826:Animal Testing Alternatives / Q000379:methods*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D004817:Epidermis / Q000187:drug effects / Q000502:physiology; D005439:Flufenamic Acid / Q000494:pharmacology; D006801:Humans; D007559:Ivermectin / Q000494:pharmacology; D008353:Mannitol / Q000494:pharmacology; D009924:Organ Culture Techniques; D019651:Plastic Surgery Procedures; D015203:Reproducibility of Results; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*; D023422:Skin Irritancy Tests / Q000379:methods; D013552:Swine
D002110:Caffeine; D008353:Mannitol; D005439:Flufenamic Acid; D007559:Ivermectin