The LCGC Blog:The Exposome: Is It Too Vast to Tackle?

I run into scientists all the time who have never heard the term exposome. Most are not intimately connected in the analytical world; these days, analytical scientists seemingly expect “ome” and “omics” to be tacked onto pretty much anything. I’ll even admit to have previously co-authored a conference poster on sakeomics. Yes, that would be the characterization of all constituents that make up the sakeome; the evaluation of everything in sake. If you are rolling your eyes right now, I am sure you are not alone. But “omics” is certainly more than a fad, and most in the business can connect with common concepts like proteomics, metabolomics, lipidomics, and genomics.

The exposome is a different beast, and it is decidedly a beast. It refers to everything, from birth, to which a person has been exposed, including both chemical and biological constituents. Exposure could be environmental, occupational, or habitual. It includes the air we breathe and the food we eat. It even seeks to incorporate knowledge of genetic predispositions of severity of responses to different exposures. This could be something like an allergy, or it could also refer to someone who was exposed to a fungus, which made them more susceptible to deleterious effects of some inhaled chemical. There is no shortage of hypotheticals that could be imagined; exposomics could actually subsume virtually all of the other “omics” concepts.

There are so many pieces to the puzzle, could we ever hope to create a complete picture? Perhaps it is a good guiding concept for designing research – more on that in a moment. The problem is that we are likely not yet in possession of all of the puzzle pieces. And even when you have a large number of pieces, how do you put them all together? I am not sure what that puzzle box cover even looks like.

Judging whether we can assess human exposures to different environmental contaminants, I cannot help but think of some of the topics that are so prominent today. For many of these, we do not even have sufficient analytical capabilities to provide comprehensive exposure assessments.

Per- and polyfluoroalkyl substances (PFAS) have received no shortage of attention in the past couple of years (1).  This class of compounds represents thousands of different variants of size and functionality that have been used as flame retardant additives and as other industrial additives and surfactants. Recent evidence suggests that many are carcinogenic or have endocrine disrupting properties. The main problem is that we do not have adequate chemical standards available to aptly identify and determine all PFAS constituents to which we might come into contact. I have heard first-hand of the difficulty for commercial labs to handle such analyses – the time and complexity PFAS analysis includes makes it a difficult area to make money. Such determinations also require exceptional analytical sensitivity, since PFAS can be present and persist at very low levels.

Mineral oil saturated hydrocarbons and mineral oil aromatic hydrocarbons (MOSH/MOAH) are another class of compounds, which have been the focus of food scientists. MOSH/MOAH include residual mixtures of hydrocarbons of varying sizes that can be transmitted to ingested food based on contact with other materials. For example, MOSH/MOAH may be deposited on packaging material through its preparation; when the materials are used, food becomes contaminated. While the saturated hydrocarbons are not considered particularly unhealthy, the aromatic compound are believed to be carcinogenic. As such, it is desirable to determine the aromatic content. The difficulty is that the dangerous aromatic mineral oil hydrocarbons often exist in the presence of a much higher amount of saturates. It has been shown that multidimensional separations (2), and even detection systems with special capabilities, like vacuum ultraviolet spectroscopy (3), are needed to well speciate these potential exposure compounds. The more complicated the instrumentation needed, the less accessible it will be for routine determinations; this could ultimately limit the ability to collect sufficient exposure data.

Microplastics in the environment is another hot topic (4). In this case, we know that microplastics exist as vehicles for food and beverage contamination. Plastic is ubiquitous in the environment and eventually it is degraded and ground-down into micrometer size particles, to which a myriad of different chemical compounds can be adsorbed and transported through the environment. At this point, it is not even clear what is the best way to collect microplastic particles for analysis from the environment, much less decide what adsorbed chemicals are of the most concern for exposure to organisms. PFAS certainly is one of the adsorbed compound classes of interest; thus, we arrive at the same problem of identification and quantification of a widely variable analyte set, most of for which no standards exist to aid analytical determinations.

Some huge industrial processes have, as to now, still not been fully characterized in terms of their potential environmental and health impacts. My research group has spent considerable effort working to characterize the potential impact of unconventional oil and gas extraction, which includes the process of hydraulic fracturing (5–7). Our research has shown that there can be deleterious consequences to groundwater, air, and soil quality, but these are mainly episodic and not necessarily systemic. Still, our group is one of a small handful focused on such efforts. These efforts are limited by funding. We have yet to see a viable federal grant program, which is aimed to support the generation of a better understanding of the exposure risk from unconventional oil and gas extraction. Instead, we have piecemeal studies, which ultimately may be ignored or not considered comprehensive enough to draw general conclusions (8). It can be a frustrating area in which to work, but studies on this scale will be needed to fully characterize an exposome to individuals living in and around such industrial activities.

The examples go on and on. I have three boys who play sports every season. Much of that is on newly installed (and also, older) turf fields. These turf fields use ground-up old tires as filler for the surface material. The floor inside our back door always has this stuff around as the boys take off their cleats. More importantly, there have been reports of the potential for soccer goalies, who are constantly diving to the ground in this material, to develop cancer as a result of repeated exposure to this material. Seems like a no brainer to me; from a commercial stance, it is a great way to use old tires, but creating the potential for people to inhale small particles of rubber laced with polyaromatic hydrocarbons and who knows what else is not smart. By the way, older fields are likely to be worse than newer fields, since time, play, and weathering will cause the creation of more smaller particles, which are more dangerous inhalants.

Now, looking past the sheer vastness of the exposome, and how difficult it might be to glean meaningful connections, perhaps there is also opportunity to consider. For example, if you were designing a study, either human health or more environmentally-focused, might you design your study differently if you knew that your data was going to be inputted into some larger exposomics model? Such a model would most certainly utilize some kind of artificial intelligence or machine learning to detect correlations and make predictions. It would also provide a framework for the most efficient design of experiments, to maximize information generated from as limited numbers of samples as possible. Additionally, quality control and, to some extent, methodology would likely be normalized to be consistent among different studies. 

Surely, people are already thinking along these lines, and some exposomics initiatives are already underway. I am still an outsider, looking in, but it is an attractive umbrella under which both health and environmental research could be directed. Solving significant methodological and logistical challenges, making these methods widely available and affordable, and close interfacing between analytical chemists and data scientists will be key to some success. It is too vast of an undertaking? I don’t think so. I just think it will take a long time to realize models which are broadly useful and beneficial to society.

References

(1) Z. Wang, J.C. DeWitt, C.P. Higgins, and I.T. Cousins. Environ. Sci. Technol.51, 2508–2518 (2017).

(2) M. Zoccali, P.Q. Tranchida, and L. Mondello. Anal. Chim. Acta1048, 221–226 (2019).

(3) A.R. Garcia-Cicourel and H.-G. Janssen. J. Chromatogr. A1590, 113–120 (2019).

(4) A.B. Silva, A.S. Bastos, C.I.L. Justino, J.P. da Costa, A.C. Duarte, T.A.P. Rocha-Santos. Anal. Chim. Acta1017, 1–19 (2018).

(5) B.E. Fontenot, L.R. Hunt, Z.L. Hildenbrand, D.D. Carlton Jr., H. Oka, J.L. Walton, D. Hopkins, A. Osorio, B. Bjorndal, Q. Hu, and K.A. Schug, Environ. Sci. Technol.47, 10032–10040 (2013).

(6) Z.L. Hildenbrand, D.D. Carlton Jr., B.E. Fontenot, J.M. Meik, J. Walton, J.T. Taylor, J.B. Thacker, S. Korlie, C.P. Shelor, D. Henderson, A.F. Kadjo, C.E. Roelke, P. Hudak, T. Burton, H.S. Rifai, and K.A. Schug, Environ. Sci. Technol. 49, 8254–8262 (2015).

(7) Z.L. Hildenbrand, D.D. Carlton Jr., B.E. Fontenot, J.M. Meik, J. Walton, J.B. Thacker, S. Korlie, C.P. Shelor, A.F. Kadjo, A. Clark, S. Usenko, J. Hamilton, P. Mach, G. Verbeck IV, P. Hudak, and K.A. Schug, Sci. Tot. Environ.562, 906–913 (2016).

(8) K.A. Schug, The LCGC Blog. August 11, 2015. http://www.chromatographyonline.com/lcgc-blog-environmental-effects-unconventional-drilling-why-we-need-comprehensive-study

Kevin A. Schug is a Full Professor and Shimadzu Distinguished Professor of Analytical Chemistry in the Department of Chemistry & Biochemistry at The University of Texas (UT) at Arlington. He joined the faculty at UT Arlington in 2005 after completing a Ph.D. in Chemistry at Virginia Tech under the direction of Prof. Harold M. McNair and a post-doctoral fellowship at the University of Vienna under Prof. Wolfgang Lindner. Research in the Schug group spans fundamental and applied areas of separation science and mass spectrometry. Schug was named the LCGC Emerging Leader in Chromatography in 2009 and the 2012 American Chemical Society Division of Analytical Chemistry Young Investigator in Separation Science. He is a fellow of both the U.T. Arlington and U.T. System-Wide Academies of Distinguished Teachers.