NOEL and NOAEL: A retrospective analysis of mention in a sample of recently conducted safety pharmacology studies

The concept of characterizing adversity in relation to administered test article dose and/or exposure within toxicology studies has long been considered a normal aspect of the drug safety evaluation enterprise. The typical way this is done in drug safety investigations is by examining study data, often with focus on clinical signs, clinical pathology and histopathology, to determine a No-Observable-Effect-Level (NOEL) and/or a No-Observable-Adverse-Effect-Level (NOAEL). Once established, these, with other information, may be used to identify a safe starting dose in human clinical trials. Although safety pharmacology (SP) is concerned to identify and characterize potentially “adverse” functional effects, NOEL, and particularly NOAEL, traditionally do not have application in SP study interpretation and reporting. An anonymized survey of a contract research laboratory master schedule was undertaken to appreciate recent usage of these concepts in GLP (Good Laboratory Practice) cardiovascular, respiratory, and neurobehavioral safety studies. Results across the sample of studies (N = 635) generally confirmed application of appropriate dose selection strategies, as there was a very low proportion (