Figure 2.

A general schematic framework adapted from Kenna and co-workers [133] outlining the mechanisms underlying dose-dependent hepatotoxicity. The chemical insult is affected by exposure (e.g., the extent of exposure) and by ADME and biokinetic processes (e.g., balance between bioactivation and detoxification of reactive intermediates). Chemical insults to cells may lead to different biological responses, which may be protective to limit and control the cell damage, or they may be amplified and progress to toxicity.