Predictive analysis using chemical-gene interaction networks consistent with observed endocrine activity and mutagenicity of U.S. streams

In a recent U.S. Geological Survey/U.S. Environmental Protection Agency study assessing more than 700 organic compounds in 38 streams, in vitro assays indicated generally low estrogen, androgen, and glucocorticoid receptor activities, with 13 surface waters with 17β-estradiol-equivalent (E2Eq) activities greater than a 1-ng/L estimated effects-based trigger value for estrogenic effects in male fish. Among the 36 samples assayed for mutagenicity in the Salmonella bioassay (reported here), 25% had low mutagenic activity and 75% were not mutagenic. Endocrine and mutagenic activities of the water samples were well correlated with each other and with the total number and cumulative concentrations of detected chemical contaminants. To test the predictive utility of knowledge-base-leveraging approaches, site-specific predicted chemical-gene (pCGA) and predicted analogous pathway-linked (pPLA) association networks identified in the Comparative Toxicogenomics Database were compared with observed endocrine/mutageni...