Exposome-scale Exposure Reconstruction

John Wambaugh*, Nathaniel Charest, Gabriel Sinclair, Heather Whitehead, Troy Ferland. and Kristin Isaacs

Exposomics uses tools such as suspect screening/non-targeted analysis (SSA/NTA) to detect a range of potential exposure biomarkers in biological tissues that might be associated with health effects. Depending on sample preparation and analysis instrumentation, hundreds of features potentially indicating chemical presence may be identified. Tools to relate these features to plausible chemical exposures scenarios must have the capacity to provide information for hundreds of potentially novel features. Available high throughput tools for exposure reconstruction include statistical exposure models, high throughput exposure models, chemical pathway analysis, and high throughput toxicokinetics. These tools rely on chemical-specific physico-chemical and biological properties that often must be predicted using quantitative structure-property relationship (QSPR) models. Recent evaluations comparing QSPR-based prediction of exposure properties with in vivo-derived data have indicated that exposure reconstruction can be conducted on the exposome scale with appropriate caution. Examples will be provided where exposure reconstruction has been coupled with exposomic data. We will identify important caveats to the current methods, as they represent targets for future research.