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How omics technologies can enhance chemical safety regulation: perspectives from academia, government, and industry
Citation:
Campos, B., J. Colbourne, James Brown, M. Viant, A. Biales, K. Gallagher, T. Henry, K. Sappington, S. Marshall, AND G. Whale. How omics technologies can enhance chemical safety regulation: perspectives from academia, government, and industry. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, 37(5):1252-1259, (2018). https://doi.org/10.1002/etc.4079
Impact/Purpose:
The high dimensionality of omics data sets suggests the possibility of developing omics‐based in fingerprints for a chemical or activated biological pathway. These fingerprints can be applied to both exposure and hazard assessment in an unsupervised or non‐targeted manner to simultaneously screen all activated biological pathways within in vivo or in vitro systems, requiring no a priori information regarding MOA. This may be particularly useful for ecological risk assessments which focus on individual or population level adverse outcomes through the measure of relatively non‐specific endpoints (mortality, reproduction, and growth), which can be impacted by many chemical and non‐chemical stressors either directly or indirectly. The ability to develop MOA specific fingerprints makes this concept amenable to discovery and characterization of multiple cellular pathways simultaneously in a ingle experiment, as opposed to screening against a panel of focused bioassays, providing needed time and resource efficiency. The ability to screen for all activated MOA simultaneous has particular benefits in characterizing real‐world exposures. Environmental samples are often highly complex mixtures, with constituents that have the potential to interact altering both toxicity and exposure parameters. Mixture constituent interactions are not reflected in analytical chemistry measures; however, the omics endpoints are effects‐based measures, thus they should effectively integrate potentially confounding factors. Fingerprints can also be used for hazard assessment, where they can be used to identify MOA of untested or uncharacterized chemicals by establishing relationships among chemicals based on similarities of their omics responses (Lamb, Crawford et al. 2006). Omics‐based fingerprints can also be related to the manifestation of disease states, suggesting the potential for predictive measures of apical response. An extension of this is the ability to leverage publicly available datasets, reducing the need for additional toxicity testing. Moreover, it has been demonstrated that these relationships are conserved across experimental platforms, cell lines and species, suggesting the potential for rapidly increasing the coverage of the total chemical space without the need for further testing (Wang, Biales et al. 2016).
Description:
Despite decades of toxicological research and advances in the chemical regulatory landscape throughout the world, the need for improving the efficiency and accuracy of our chemical risk assessment process has never been greater. Characterizing chemical risk is accomplished through the linkage of measured or modeled exposure and toxicity values. The current paradigm for risk estimation has limitations based on the types of tools available, as well as the availability of data to expand existing tools and/or create new, improved tools. Traditional methods are ill equipped to robustly assess risks associated with the 70,000+ chemicals in commerce in an efficient and timely manner, let alone other perennial issues such as mixtures. It has been suggested that the various omics modalities, such as transcriptomics, proteomics, metabolomics and epigenomics, may be used to augment traditional methods, or be combined with other next generation technologies to address limitations and provide a better characterization of chemical risk (NRC 2007, NRC 2017). Alterations on the omics level are often the initial responses of organisms to a chemical exposure and are thought to be initiating events in the pathway to adverse changes on higher biological levels. Many of the technological platforms available (e.g., microarrays, GC‐MS, RNA‐seq) are able to measure changes across large proportions of the total omic response of an organism, tissue, or cell (i.e. 100s to 1000s of genes, proteins, or metabolites). The sheer number of simultaneously measured endpoints can be applied to chemical risk assessment in any number of ways (discussed below). Lastly, omics‐based approaches are amenable to high and medium throughput experimental formats, suggesting their utility for the rapid screening and characterization of untested chemicals.
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DOI: How omics technologies can enhance chemical safety regulation: perspectives from academia, government, and industry