The first appearance of the term ‘safety pharmacology’ in the published literature dates back to 1980. The term was certainly in common usage in the 1980s within the pharmaceutical industry to describe nonclinical pharmacological evaluation of unintended effects of candidate drugs for regulatory submissions. Back then, it was part of a wider ‘general pharmacology’ assessment, which addressed actions of a drug candidate beyond the therapeutically intended effects. The only detailed guidelines indicating the requirements from drug regulatory authorities for general pharmacology studies were from the Ministry of Health, Labour, and Welfare. Nowadays, the term ‘general pharmacology’ is no longer used, and the ICH S7A guidelines distinguish between primary pharmacodynamics (“studies on the mode of action and/or effects of a substance in relation to its desired therapeutic target”), secondary pharmacodynamics (“studies on the mode of action and/or effects of a substance not related to its desired therapeutic target”) and safety pharmacology (“studies that investigate the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure in the therapeutic range and above.”).
A major stimulus to the discipline of safety pharmacology was the release in 1996 of a draft ‘Points to Consider’ document on QT prolongation by the European Medicines Agency's Committee for Proprietary Medicinal Products (CPMP), issued in final form the following year. This initiative had been prompted by growing concern of sudden death caused by drug-induced torsade de pointes, a potentially lethal cardiac tachyarrhythmia. Later, in 2005,  this concern was addressed by issue of the ICH S7B guidelines.