Reconstructed human epidermis for skin absorption testing: results of the German prevalidation study.
Exposure to chemicals absorbed by the skin can threaten human health. In order to standardise the predictive testing of percutaneous absorption for regulatory purposes, the OECD adopted guideline 428, which describes methods for assessing absorption by using human and animal skin. In this study, a protocol based on the OECD principles was developed and prevalidated by using reconstructed human epidermis (RHE). The permeation of the OECD standard compounds, caffeine and testosterone, through commercially available RHE models was compared to that of human epidermis and animal skin. In comparison to human epidermis, the permeation of the chemicals was overestimated when using RHE. The following ranking of the permeation coefficients for testosterone was obtained: SkinEthic > EpiDerm, EPISKIN > human epidermis, bovine udder skin, pig skin. The ranking for caffeine was: SkinEthic, EPISKIN > bovine udder skin, EpiDerm, pig skin, human epidermis. The inter-laboratory and intra-laboratory reproducibility was good. Long and variable lag times, which are a matter of concern when using human and pig skin, did not occur with RHE. Due to the successful transfer of the protocol, it is now in the validation process.
Schäfer-Korting
Monika
M
Freie Universität Berlin, Institut für Pharmazie, Königin-Luise-Strasse 2-4, 14195 Berlin, Germany. msk@zedat.fu-berlin.de
Bock
Udo
U
Gamer
Armin
A
Haberland
Annekathrin
A
Haltner-Ukomadu
Eleonore
E
Kaca
Monika
M
Kamp
Hennicke
H
Kietzmann
Manfred
M
Korting
Hans Christian
HC
Krächter
Hans-Udo
HU
Lehr
Claus-Michael
CM
Liebsch
Manfred
M
Mehling
Annette
A
Netzlaff
Frank
F
Niedorf
Frank
F
Rübbelke
Maria K
MK
Schäfer
Ulrich
U
Schmidt
Elisabeth
E
Schreiber
Sylvia
S
Schröder
Klaus-Rudolf
KR
Spielmann
Horst
H
Vuia
Alexander
A
D000328:Adult; D000368:Aged; D000826:Animal Testing Alternatives / Q000379:methods*; D000818:Animals; D002110:Caffeine / Q000493:pharmacokinetics; D002417:Cattle; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D005858:Germany; D006801:Humans; D008875:Middle Aged; D009924:Organ Culture Techniques; D015203:Reproducibility of Results; D012869:Skin Absorption / Q000502:physiology*; D013552:Swine; D013739:Testosterone / Q000493:pharmacokinetics
D002110:Caffeine; D013739:Testosterone