Recent trends in statistical QSAR modeling of environmental chemical toxicity.

Abstract

Quantitative cheminformatics approaches such as QSAR modeling find growing applications in chemical risk assessment. Traditional methods rely on the use of calculated chemical descriptors of molecules and relatively small training sets. However, in recent years, there is a trend toward the increased use of in vitro biological testing approaches to reduce both the length of experimental studies and the animal use for chemical risk assessment. Furthermore, there is also much greater emphasis on model validation using external datasets to enable the reliable use of computational models as part of regulatory decision making. In this chapter, recent trends emphasizing the need for both careful curation of experimental data prior to model development and rigorous model validation are investigated. Furthermore, recent approaches to chemical toxicity prediction that employ both chemical descriptors and in vitro screening data for developing novel hybrid chemical/biological models are being reviewed. Examples of respective application studies that employ novel workflows for model developments are described and recent important efforts by several academic, nonprofit, and industrial groups to start placing both data and, especially, models in the public domain are discussed.