Investigating the Relationship between in Vitro–in Vivo Genotoxicity: Derivation of Mechanistic QSAR Models for in Vivo Liver Genotoxicity and in Vivo Bone Marrow Micronucleus Formation Which Encompass Metabolism
2012
Strategic testing as part of an
integrated testingstrategy (ITS) to maximize information and avoid the use of animals where possible is fast becoming the norm with the advent of new legislation such as REACH.
Genotoxicityis an area where regulatory testing is clearly defined as part of ITS schemes. Under REACH, the
specific informationrequirements depend on the
tonnagemanufactured or imported. Two types of test systems exist to meet these information requirements, in vivo
genotoxicityassays, which take into account the whole animal, and in vitro assays, which are conducted outside the living mammalian organism using microbial or mammalian cells under appropriate culturing conditions. Clearly, with these different broad experimental categories, results for a given chemical can often differ, which presents challenges in the interpretation as well as in attempting to model the results in silico. This study attempted to compare the differences between in vitro and in vivo
genotoxicityresults, to rationa...
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