In Vitro and Integrated In Vivo Strategies to Reduce Animal Use in Genotoxicity Testing

Scientific, financial, and ethical drivers have led to unprecedented interest in implementing human-relevant, mechanistic in vitro and in silico testing approaches. Further, as non-animal approaches are being developed and validated, researchers are interested in strategies that can immediately reduce the use of animals in toxicology testing. Here, we outline a testing strategy for assessing genotoxicity beginning with standard in vitro methods, such as the bacterial reverse mutation test and the in vitro micronucleus test, followed by a second tier of in vitro assays including those using advanced 3-dimensional tissue models. Where regulatory agencies require in vivo testing, one demonstrated strategy is to combine genotoxicity studies traditionally conducted separately into a single test or to integrate genotoxicity studies into other toxicity studies. Standard setting organizations and regulatory agencies have encouraged such strategies, and examples of their use can be found in the scientific literature. Employing approaches outlined here will reduce animal use as well as study time and costs.

GROFF Katherine;  EVANS Stephen J.;  DOAK Shareen H.;  PFUHLER Stefan;  CORVI Raffaella;  SAUNDERS Samantha;  STODDART Gilly; 

2021-11-30

OXFORD UNIV PRESS

JRC126091

0267-8357 (online),   

https://publications.jrc.ec.europa.eu/repository/handle/JRC126091,   

10.1093/mutage/geab035 (online),