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Identification of xenobiotic metabolites using in silicotools and non-targeted analysis
Citation:
Boyce, M., K. Favela, A. Chao, G. Patlewicz, J. Sobus, A. Williams, AND J. Wambaugh. Identification of xenobiotic metabolites using in silicotools and non-targeted analysis. Non-Target Analysis for Environmental Risk Assessment, Durham, NC, May 22 - 26, 2022. https://doi.org/10.23645/epacomptox.20216666
Impact/Purpose:
This is a contributed presentation for the SETAC North America Focused Topic Meeting: Nontarget Analysis for Environmental Risk Assessment in Durham, NC on 22-26 May 2022.
Description:
Efforts to estimate chemical risk to public health require information on both inherent hazard and public exposure. Tools for high-throughput exposure (HTE) predictions often rely on exposure inferences drawn from targeted data sets such as the National Health and Nutrition Examination Survey (NHANES). Broad suspect screening analysis (SSA) and non-targeted analysis (NTA) may potentially provide greater evaluation of and reduce uncertainty in HTE models. SSA/NTA using both two-dimensional gas chromatography and liquid chromatography time-of-flight/mass spectrometry (GCxGC-TOF/MS and LC-QTOF) was performed on three replicates each of 16 pooled serum samples (25 individuals each) obtained from the National Institute of Environmental Health Sciences Clinical Research Unit. Separate workflows were used for LC (NTA) and GC (SSA). Tentative chemical identifications (IDs) were only assumed if a compound peak was identified in two of the three technical replicates. To support identification of likely sources of chemicals found in biological media through SSA/NTA, this work-in-progress annotates chemicals with likely origin categories. We identify five categories of chemical origin of small molecules found in human blood biomonitoring samples: 1) endogenous metabolites, 2a) exogenous nutrients, 2b) metabolites of exogenous nutrients, 3a) xenobiotics (pharmaceuticals, pesticides, and others), and 3b) metabolites of xenobiotics. Roughly half of the 120 compounds tentatively identified by GC were categorized as xenobiotics. Targeted chemical analysis of select xenobiotics is underway to confirm tentative chemical identifications. Based on our preliminary findings, it appears that NTA tools are sufficiently developed for training high-throughput exposure models and nominating chemicals for human biomonitoring programs. This abstract may not reflect U.S. EPA policy.
URLs/Downloads:
DOI: Identification of xenobiotic metabolites using in silicotools and non-targeted analysis
SETAC_2022_NTAMETABOLITE.PDF (PDF, NA pp, 1764.833 KB, about PDF)