TY  - JOUR
A1  - Mewes, Karsten R.
A1  - Fischer, Adam
A1  - Zöller, Nadja Nicole
A1  - Laubach, Vesselina
A1  - Bernd, August
A1  - Jacobs, An
A1  - Rompay, An van
A1  - Liebsch, Manfred
A1  - Pirow, Ralph
A1  - Petersohn, Dirk
T1  - Catch-up validation study of an in vitro skin irritation test method based on an open source reconstructed epidermis (phase I)
T2  - Toxicology in vitro
N2  - We have developed a new in vitro skin irritation test based on an open source reconstructed epidermis (OS-REp) with openly accessible protocols for tissue production and test performance. Due to structural, mechanistic and procedural similarity, a blinded catch-up validation study for skin irritation according to OECD Performance Standards (PS) was conducted in three laboratories to promote regulatory acceptance, with OS-REp models produced at a single production site only. While overall sensitivity and predictive capacity met the PS requirements, overall specificity was only 57%. A thorough analysis of the test results led to the assumption that some of the false-positive classifications could have been evoked by volatile skin-irritating chemicals tested in the same culture plate as the non-irritants falsely predicted as irritants. With GC/MS and biological approaches the cross-contamination effect was confirmed and the experimental set-up adapted accordingly. Retesting of the affected chemicals with the improved experimental set-up and otherwise identical protocol resulted in correct classifications as non-irritants. Taking these re-test results into account, 93% overall sensitivity, 70% specificity and 82% accuracy was achieved, which is in accordance with the OECD PS. A sufficient reliability of the method was indicated by a within-laboratory-reproducibility of 85–95% and a between-laboratory-reproducibility of 90%.
KW  - Skin irritation test
KW  - Reconstructed human epidermis
KW  - Open source concept
KW  - Catch-up validation study
KW  - Cross-contamination
KW  - OECD performance standards
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/42607
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-426073
SN  - 1879-3177
SN  - 0887-2333
N1  - © 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
VL  - 36
SP  - 238
EP  - 253
PB  - Elsevier Science
CY  - Amsterdam [u. a.]
ER  -