Prioritizing Endocrine-Disruptor Screening Using ToxPi Visually translating the integration of ToxCast data

Prioritizing Endocrine-Disruptor Screening Using ToxPi Visually translating the integration of ToxCast data July 6, 2010 Impact Statement This research paper presents ToxPi (Toxicological Priority Index), a new weight-of-evidence framework for profiling and prioritizing chemicals. It numerically integrates various knowledge sources about chemical specific properties (biological and chemical). This numeric summation is displayed graphically in order to help further understand the chemical. ToxCast is a multiyear, multi-million dollar effort that uses advanced science tools to help efficiently ($20K per chemical) understand biological processes impacted by chemicals that may lead to adverse health effects. ToxCast currently includes 467 in vitro, high-throughput screening assays which have assessed over 300 environmental chemicals. This study applied ToxPi to ToxCast's 309 chemicals, which includes 52 of the chemicals currently undergoing screening in Tier 1 of the EDSP. In the future, ToxPi may be used to prioritize chemicals for screening in the EDSP Tier 1 battery. Understanding which chemicals can cause endocrine disruption (ability of a chemical to interact with the body’s hormonal systems and cause adverse health outcomes such as birth defects and cancer) is a high US EPA priority. EPA has developed a group of tests (the EDSP Tier I battery) capable of describing endocrine disruptor potential and is in the process of acquiring data on chemicals using these tests. EDSP assays are relatively expensive (~$0.5M per chemical) and tools are needed to help select which chemicals should be first in line for further testing. This study applied ToxPi to multiple potential endocrine disrupting measures and then ranked chemicals for additional screening. The knowledge sources used in this study included in vitro assays, chemical properties and pathways. For this study, 90 ToxCast assays relevant to endocrine activity were selected, and these assay results were then used to generate results in 27 endocrine pathways. Two chemical properties relevant to biological activity were also used. Results indicate that combining multiple ToxCast data sources into an overall, weight-of-evidence ToxPi for prioritizing further chemical screening is a robust prioritization method.