TY  - JOUR
A1  - Groeber, Florian
A1  - Schober, Lena
A1  - Schmid, Freia F.
A1  - Traube, Andrea
A1  - Kolbus-Hernandez, Silvia
A1  - Daton, Karolina
A1  - Hoffmann, Sebastian
A1  - Petersohn, Dirk
A1  - Schaefer-Korting, Monika
A1  - Walles, Heike
A1  - Mewes, Karsten R.
T1  - Catch-up validation study of an in vitro skin irritation test method based on an open source reconstructed epidermis (phase II)
JF  - Toxicology in Vitro
N2  - To replace the Draize skin irritation assay (OECD guideline 404) several test methods based on reconstructed human epidermis (RHE) have been developed and were adopted in the OECD test guideline 439. However, all validated test methods in the guideline are linked to RHE provided by only three companies. Thus,the availability of these test models is dependent on the commercial interest of the producer. To overcome this limitation and thus to increase the accessibility of in vitro skin irritation testing, an open source reconstructed epidermis (OS-REp) was introduced. To demonstrate the capacity of the OS-REp in regulatory risk assessment, a catch-up-validation study was performed. The participating laboratories used in-house generated OS-REp to assess the set of 20 reference substances according to the performance standards amending the OECD test guideline 439. Testing was performed under blinded conditions. The within-laboratory reproducibility of 87% and the inter-laboratory reproducibility of 85% prove a high reliability of irritancy testing using the OS-REp protocol. In addition, the prediction capacity was with an accuracy of 80% comparable to previous published RHE based test protocols. Taken together the results indicate that the OS-REp test method can be used as a standalone alternative skin irritation test replacing the OECD test guideline 404.
KW  - Model
KW  - Chemicals
KW  - Assay
KW  - Episkin
KW  - Vivo
KW  - RHE
KW  - In vitro skin irritation testing
KW  - Open source reconstructed epidermis
KW  - Validation
KW  - Alternative test methods
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187311
VL  - 36
ER  - 
TY  - JOUR
A1  - Alepee, Natalie
A1  - Bahinski, Anthony
A1  - Daneshian, Mardas
A1  - De Weyer, Bart
A1  - Fritsche, Ellen
A1  - Goldberg, Alan
A1  - Hansmann, Jan
A1  - Hartung, Thomas
A1  - Haycock, John
A1  - Hogberg, Helena T.
A1  - Hoelting, Lisa
A1  - Kelm, Jens M.
A1  - Kadereit, Suzanne
A1  - McVey, Emily
A1  - Landsiedel, Robert
A1  - Leist, Marcel
A1  - Lübberstedt, Marc
A1  - Noor, Fozia
A1  - Pellevoisin, Christian
A1  - Petersohn, Dirk
A1  - Pfannenbecker, Uwe
A1  - Reisinger, Kerstin
A1  - Ramirez, Tzutzuy
A1  - Rothen-Rutishauser, Barbara
A1  - Schäfer-Korting, Monika
A1  - Zeilinger, Katrin
A1  - Zurich, Marie-Gabriele
T1  - State-of-the-Art of 3D Cultures (Organs-on-a-Chip) in Safety Testing and Pathophysiology
JF  - ALTEX - Alternatives to Animal Experimentation
N2  - Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.e., they aim to reproduce major functions of an organ or organ system. This implies in many cases that more than one cell type forms the 3D structure, and often matrix elements play an important role. This review summarizes the state of the art concerning commonalities of the different models. For instance, the theory of mass transport/metabolite exchange in 3D systems and the special analytical requirements for test endpoints in organotypic cultures are discussed in detail. In the next part, 3D model systems for selected organs liver, lung, skin, brain are presented and characterized in dedicated chapters. Also, 3D approaches to the modeling of tumors are presented and discussed. All chapters give a historical background, illustrate the large variety of approaches, and highlight up- and downsides as well as specific requirements. Moreover, they refer to the application in disease modeling, drug discovery and safety assessment. Finally, consensus recommendations indicate a roadmap for the successful implementation of 3D models in routine screening. It is expected that the use of such models will accelerate progress by reducing error rates and wrong predictions from compound testing.
KW  - 3D models
KW  - organotypic
KW  - organ-on-a-chip
KW  - multicellular tumor spheroids
KW  - primary human hepatocytes
KW  - embryonic stem cell
KW  - reconstructed human epidermis
KW  - in-vitro models
KW  - full thickness skin
KW  - necrosis-factor-alpha
KW  - metabolic flux analysis
KW  - long-term
KW  - human liver cells
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117826
VL  - 31
IS  - 4
ER  -