Top-down and bottom-up exposomics using nontargeted mass spectrometry

The exposome represents all environmental exposures to a human or organism during a lifetime [1]. The concept was developed to underline the important relationship between environment and health. Nontargeted screening (NTS) is an innovative approach involving high resolution mass spectrometry experiments aimed at identifying environmentally significant chemicals without prior knowledge of their structure [2]. Currently, large swaths of the exposome remain unknown: few of the c. 100,000 commercial substances have been investigated for their environmental and health impacts.

Novel experimental and informatics approaches [3] will be described that address some of the key analytical challenges associated with NTS, viz. prioritizing the interpretation of up to tens of thousands of mass spectra produced by state-of-the-art instrumentation; characterizing technical mixtures with myriad constituent compounds; and detecting trace level contaminants, especially in quantity-limited matrices like serum and dried blood spots. Collision-induced dissociation is a time-honoured technique to probe the structure of putative organic contaminants. This presentation will also highlight the importance of associative ion-molecule reactions that can differentiate (non)toxic isomers. This raises the intriguing possibility that such chemistry may be predictive of toxicity. Ultimately, tentative identifications of environmental toxicants must be confirmed with genuine analytical standards, which may be impractical (or prohibitively expensive). The potential for computational chemistry to bridge the gap will be discussed.

Throughout the presentation, vignettes of exposomic studies will be described that apply the above analytical (and computational) methodologies. The results have led to the (tentative) identification of new exposures to firefighters; in biota from the Laurentian Great Lakes; and a cohort of pregnant mothers.

References.
[1] C.P. Wild, Int. J. Epidemiol., 41 (2012) 24
[2] R.A. Hites, K. Jobst, ES&T 52 (2018) 11975-11976.
[3] For recent examples, see: (a)Zhang et al., Env. Int. 132 (2019) 104808; (b)Di Lorenzo et al., Anal. Chim. Acta, 1056 (2019) 70; (b)Fernando et al., Anal. Chem. 88 (2016) 5205