Use of in vitro 3D tissue models in genotoxicity testing: Strategic fit, validation status and way forward. Report of the working group from the 7th International Workshop on Genotoxicity Testing (IWGT)

Use of three-dimensional (3D) tissue equivalents in toxicology has been increasing over the last decade as novel preclinical test systems and alternatives to animal testing. In the area of genetic toxicology particular progress with establishing robust protocols has been made for skin, lung and liver tissue equivalents. In light of these advancements, a “Use of 3D Tissues in Genotoxicity Testing” working group (WG) met at the 7th IWGT meeting in Tokyo, November 2017 to discuss the progress of these models and how they may fit into a genotoxicity testing strategy. The workshop demonstrated that extensive progress has been made in the last years in relation to 3D genotoxicity models. While skin models have reached an advanced state of validation following over 10 years of development, liver-and lung model-based genotoxicity assays show promise but are at an early stage of development. Further effort in liver-and lung model-based assays is needed to address the lack of coverage of the three key endpoints of genotoxicity (mutagenicity, clastogenicity and aneugenicity), and information on metabolic competence. The IWGT WG believes that the 3D skin comet and micronucleus assays are now sufficiently validated to first undergo an independent peer review of the validation study and then move towards the development of individual OECD Test Guidelines.

PFUHLER Stefan;  VAN BENTHEM Jan;  CURREN R;  DOAK Shareen H.;  DUSINSKA Maria;  HAYASHI Makoto;  HEFLICH Bob;  KIDD Darren;  KIRKLAND David;  LUAN Yang;  OUEDRAOGO G;  REISINGER K;  SOFUNI Toshio;  VAN ACKER Frederique;  YANG Ying;  CORVI Raffaella; 

2021-07-27

ELSEVIER SCIENCE BV

JRC118112

1383-5718 (online),   

https://www.sciencedirect.com/science/article/pii/S138357182030005X?via%3Dihub,    https://publications.jrc.ec.europa.eu/repository/handle/JRC118112,   

10.1016/j.mrgentox.2020.503135 (online),