Impacts of 17α-ethynylestradiol exposure on metabolite profiles of zebrafish (Danio rerio) liver cells.

Endocrine disrupting chemicals (EDCs) that are frequently detected in bodies of water downstream from sewage treatment facilities can have adverse impacts on fish and other aquatic organisms. To properly assess risk(s) from EDCs, tools are needed that can establish linkages from chemical exposures to adverse outcomes. Traditional methods of testing chemical exposure and toxicity using experimental animals are excessively resource- and time-consuming. In line with EPA's goal of reducing animal use in testing, these traditional screening methods may not be sustainable in the long term, given the ever increasing number of chemicals that must be tested for safety. One of the most promising ways to reduce costs and increase throughput is to use cell cultures instead of experimental animals. In accordance with National Research Council's vision on 21st century toxicity testing, we have developed a cell culture-based metabolomics approach for this application. Using a zebrafish (Danio rerio) liver cell line (ZFL), we have applied NMR-based metabolomics to investigate responses of ZFL cells exposed to 17α-ethynylestradiol (EE2). This analysis showed that metabolite changes induced by EE2 exposure agree well with known impacts of estrogens on live fish. The results of this study demonstrate the potential of cell-based metabolomics to assess chemical exposure and toxicity for regulatory application.