Challenges and directions for regulatory use of QSARs for predicting active pharmaceutical ingredients environmental...

Regulators globally are facing increasing challenges to make decisions regarding subtle effects and risks of pharmacodynamic compounds found in the environment. There is a recognized need for rapid screening tools as well as development of methods to support the further prioritization and testing of these compounds. It is becoming evident that the current standardized experimental designs and predictive models are not specific enough to predict the chronic and long term toxicity of active pharmaceutical ingredients. Novel approaches to firstly screen and prioritize the compounds e.g. by (quantitative) structure-activity relationship modeling and inter-species extrapolation tools are currently proving difficult to develop for chronic effects. Novel toxicogenomic high through-put screening tools may be useful for more rapidly developing toxicogenomic hypothesis and molecular initiating events especially for pharmacodynamic compounds with relatively well described mechanisms of action. The molecular initiating events can then be entered into the proposed adverse outcome pathway which can then indicate the relevant test design to demonstrate the anticipated adverse chronic effects.