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1858 chemicals in EPA's ToxCast program were analyzed for endocrine assay targets.ToxPi model utilizes 85 in vitro HTS assays and 2 physicochemical properties.We focused on estrogen, androgen, thyroid, glucocorticoid, PPARs and monoamines.Many chemicals showing activity in the in vitro assays have not been studied for potential endocrine disruption.Additional research is required to confirm these screening level analyses.Identifying chemicals, beyond those already implicated, to test for potential endocrine disruption is a challenge and high throughput approaches have emerged as a potential tool for this type of screening. This review focused the Environmental Protection Agency's (EPA) ToxCast™ high throughput in vitro screening (HTS) program. Utility for identifying compounds was assessed and reviewed by using it to run the recently expanded chemical library (from 309 compounds to 1858) through the ToxPi™ prioritization scheme for endocrine disruption. The analysis included metabolic and neuroendocrine targets. This investigative approach simultaneously assessed the utility of ToxCast, and helped identify novel chemicals which may have endocrine activity. Results from this exercise suggest the spectrum of environmental chemicals with potential endocrine activity is much broader than indicated, and that some aspects of endocrine disruption are not fully covered in ToxCast.