Session 1: Chemotypes to Explore Toxcast

USING Chemotypes to Explore ToxCast/TOX21
Ann M Richard, National Center for Computational Toxicology, US EPA

Ann M Richard, Ph.D


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.