Table 1.

Reasons to combine tests^a

Not all possible outcomes of interest are covered in a single test

Different modes of action need to be covered, which may cause the same toxicological effect

In vivo processes usually involve a chain of events while one in vitro test often represents only a single or a few steps of this complex process

Not all classes of test substances are covered (applicability domains)

Not all severity classes of effect are covered

The positive test result is rare (low prevalence) and the number of false-positive results becomes excessive

The gold standard test is too costly or uses too many animals and substances need to be prioritized

The accuracy (human predictivity) is not satisfying and predictivity can be improved

Existing data and evidences from various tests shall be integrated

ADME (Absorption, Distribution, Metabolism and Excretion) information shall be integrated to make an in vivo extrapolation from data

^aCompiled and modified from Hartung et al. (2013) and Rovida et al. (2015)