In Silico Toxicology

The chapter describes in silico methodologies and models based on structure-activity relationships to predict toxicological endpoints. It provides an overview of relevant in silico toxicology concepts including databases, prediction methodologies, and items to consider when identifying and selecting in silico models. An increasingly important element of any in silico assessment is an expert review of the model output. Here a summary of current best practices is provided. There is also a discussion on the importance of using protocols (i.e., standardized procedures) to improve acceptance and use of in silico approaches. The chapter also reviews the state of the science in predicting a variety of safety-related endpoints, including genetic toxicity, skin sensitization, irritation/corrosion, acute toxicity, endocrine activity, reproductive and developmental toxicity, carcinogenicity, organ toxicity, biomolecule reactivity, abuse liability, and bioactivation. Finally, how in silico toxicology can support several applications throughout drug discovery will be reviewed based on a variety of methodologies and models. These applications cover discovery, pre-clinical, manufacturing, and regulation.