Session 1: Chemotypes to Explore Toxcast
National Center for Computational Toxicology, US EPA
Abstract does not reflect EPA policy.
The ToxCast and Tox21 chemical libraries currently exceed 3000 and 9000 unique chemicals, respectively, and span a broad diversity of chemical use-types, functionality, and toxicity mechanism and endpoint space.
These libraries function as probes of diverse biological responses across hundreds of high-throughput screening (HTS) in vitro bioassays that are potentially informative of toxicity mechanisms.
Structure-activity relationship (SAR) models and structure alerts that carry historical chemical-toxicity inferences can be projected onto this chemical landscape as a way of incorporating prior knowledge, thereby aiding in the detection of significantly enriched patterns and associations within and across the in vitro and in vivo data landscapes.
A set of public ToxPrint chemotypes are being used to create a common platform for storing and communicating such associations, and for profiling and comparing structure inventories.
Several examples will be presented using such knowledge-informed features to convey associations within a chemical use category (flame retardants), and various HTS and in vivo activity subsets.
The large and growing in vitro, in vivo, and computed property data profiles associated with ToxCast/Tox21 chemicals are also providing a means to expand the concept of molecular similarity beyond that of chemical structure alone, to build on prior knowledge and inform read-across approaches.