- 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%.
MetadatenAuthor: | Karsten R. Mewes, Adam Fischer, Nadja Nicole ZöllerORCiDGND, Vesselina LaubachGND, August BerndORCiDGND, An Jacobs, An van Rompay, Manfred Liebsch, Ralph Pirow, Dirk Petersohn |
---|
URN: | urn:nbn:de:hebis:30:3-426073 |
---|
DOI: | https://doi.org/10.1016/j.tiv.2016.07.007 |
---|
ISSN: | 1879-3177 |
---|
ISSN: | 0887-2333 |
---|
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/27432483 |
---|
Parent Title (English): | Toxicology in vitro |
---|
Publisher: | Elsevier Science |
---|
Place of publication: | Amsterdam [u. a.] |
---|
Document Type: | Article |
---|
Language: | English |
---|
Date of Publication (online): | 2017/05/04 |
---|
Year of first Publication: | 2016 |
---|
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
---|
Release Date: | 2017/05/04 |
---|
Tag: | Catch-up validation study; Cross-contamination; OECD performance standards; Open source concept; Reconstructed human epidermis; Skin irritation test |
---|
Volume: | 36 |
---|
Page Number: | 16 |
---|
First Page: | 238 |
---|
Last Page: | 253 |
---|
Note: | © 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/). |
---|
HeBIS-PPN: | 432157964 |
---|
Institutes: | Medizin / Medizin |
---|
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
---|
Sammlungen: | Universitätspublikationen |
---|
Licence (English): | Creative Commons - Namensnennung-Nicht kommerziell 4.0 |
---|