pharmaceutical toxicology or safety assessment is, through and through, a translational discipline. All aspects of preclinical safety activities aim at identifying potential hazards, predicting and quantifying risks for healthy trial subjects or patients, and, if necessary, assessing suitable means for eliminating or reducing unacceptable risks. However, there are many uncertainties in this approach. For practical reasons, only a limited number of aspects can be addressed in preclinical animal and in vitro studies. Furthermore, considerable species differences leading to changes in biological activity or pharmacokinetic properties as well as individual variations in susceptibility to certain effects and compounds add to uncertainties in the risk-assessment process.