Current and Future Perspectives on the Development, Evaluation, and Application of in Silico Approaches for Predicting Toxicity

Exploiting non-testing approaches to predict toxicity early in the drug discovery development cycle is a helpful component in minimizing expensive drug failures due to toxicity being identified in late development or even during clinical trials. Changes in regulations in the industrial chemicals and cosmetics sectors in recent years have prompted a significant number of advances in the development, application, and assessment of non-testing approaches, such as (Q)SARs. Many efforts have also been undertaken to establish guiding principles for performing read-across within category and analogue approaches. This review offers a perspective, as taken from these sectors, of the current status of non-testing approaches, their evolution in light of the advances in high-throughput approaches and constructs such as adverse outcome pathways, and their potential relevance for drug discovery. It also proposes a workflow for how non-testing approaches could be practically integrated within testing and assessment strategies.