Metabolomic Analysis of the Secretome of Human Embryonic Stem Cells Following Methyl Parathion and Methyl Paraoxon Exposure Phase 2: Metabolite Downselection for Structural Confirmation

This technical report is the second of three reports from the U.S. Army Edgewood Chemical Biological Center ECBC In- House Laboratory Independent Research funded project, Molecular Toxicology of toxic industrial chemicals TICs in Human Embryonic Stem Cells hESC. One of the goals of the study was to identify metabolites from the secretome of hESC exposed to the TICs methyl parathion and methyl paraoxon. A nontargeted liquid chromatography followed by mass spectrometry LCMS approach was used in the Phase I work Sekowski, J.W., et al. Metabolomic Analysis of the Secretome of WA09 Human Embryonic Stem Cells following Methyl Parathion and Paraoxon Exposure, Phase I Initial Nontargeted LC-MS ECBC-TR- 1177 U.S. Army Edgewood Chemical Biological Center Aberdeen Proving Ground, MD, 2013. In the Phase I work, hundreds of human metabolites and multiple metabolic pathways altered as a result of exposure to both chemicals were putatively identified. The purpose of this Phase II study was to downselect putatively identified metabolites for structural confirmation analysis by liquid chromatography followed by tandem mass spectrometry LC-MS-MS. This report describes the subset of mass features that were downselected based on the following criteria 1 impact on the arginine-proline metabolism pathway, 2 involvement with reactive oxygen species, and 3 good quality mass features suitable for structure confirmation by LC-MS-MS.