Use of High-Throughput and Computational Approaches for Endocrine Pathway Screening

Abstract

The Endocrine Disruptor Screening Program (EDSP) screens and tests environmental chemicals for potential effects in the estrogen, androgen, and thyroid hormone pathways, and is one of the only regulatory programs designed around a mode of action framework. A variety of biological systems affect apical endpoints used in regulatory risk assessments and without mechanistic data, endocrine disruption cannot be determined. When the EDSP was developed in 1998, computational and high throughput approaches were intended to be part of the screening process, however, methods at that time were limited in availability and performance. Recently, the revolution in automated in vitro testing and computational toxicology has generated excellent tools that can be used for endocrine screening. Toxicity pathway and Adverse Outcome Pathway frameworks facilitate integrating diverse data for screening chemicals for potential endocrine activity. In addition, pathway frameworks can be used to evaluate performance of computational approaches as alternatives for low throughput and animal-based assays. Similarly, pathway frameworks may be used to evaluate the predictive performance of one or more computational models to predict downstream key events. Computational approaches such as these may provide an alternative to the EDSP Tier 1 battery and used for weight of evidence screening of a chemical’s potential endocrine activity.