There are three principal pressures driving the development of in vitr
o toxicology: (1) the need for more efficient testing systems to cope
with the large number of xenobiotics currently being developed; (2) pu
blic pressure to reduce animal experimentation; and (3) a need for a b
etter understanding of the mechanisms of toxicity. Within this, in vit
ro toxicology is focused on local, systemic, and target-organ toxicity
. It is becoming increasingly apparent that a step or decision-tree ap
proach using input of a variety of experimental data (physicochemical
properties, biokinetics, cytotoxicity) provides the most efficient sys
tem for predicting toxicity. Examples of the use of in vitro toxicity
systems for prediction of systemic toxicity and target-organ (liver) t
oxicity are presented.