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.
Schäfer-Korting
Monika
M
Freie Universität Berlin, Institut für Pharmazie, Berlin, Germany. msk@zedat.fu-berlin.de
Bock
Udo
U
Diembeck
Walter
W
Düsing
Hans-Jürgen
HJ
Gamer
Armin
A
Haltner-Ukomadu
Eleonore
E
Hoffmann
Christine
C
Kaca
Monika
M
Kamp
Hennicke
H
Kersen
Silke
S
Kietzmann
Manfred
M
Korting
Hans Christian
HC
Krächter
Hans-Udo
HU
Lehr
Claus-Michael
CM
Liebsch
Manfred
M
Mehling
Annette
A
Müller-Goymann
Christel
C
Netzlaff
Frank
F
Niedorf
Frank
F
Rübbelke
Maria K
MK
Schäfer
Ulrich
U
Schmidt
Elisabeth
E
Schreiber
Sylvia
S
Spielmann
Horst
H
Vuia
Alexander
A
Weimer
Michaela
M
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