US-EPA CompTox Chemicals Research Articles

Personal External Exposomes from Around the World

BACKGROUND AND AIM: Industrial advances have led to a plethora of anthropogenic chemicals in our air, water, and soil. Exposures to a subset of these chemicals can lead to illnesses including respiratory illnesses, auto-immune disorders, inhibited immune response, and various cancers. Most studies focus on particulate matter or a select set of chemicals, missing chemicals of potential concern. Therefore, we have developed a personal exposure monitoring technology and workflow to comprehensively determine airborne chemical exposures of concern in populations across the globe. METHODS: Polydimethylsiloxane (PDMS) passive samplers placed in wristbands were deployed in South Africa, China, United States, Canada, and India, both in rural and urban regions. Samplers were shipped to Yale University and analyzed by direct thermal desorption gas-chromatography high-resolution mass spectrometry using a Q-Exactive orbitrap mass spectrometer. A software was developed to rank suspect screening annotations in terms of confidence, normalize for batch effects, filter out chemicals from background contamination, and remove redundant chemical annotations. Furthermore, a workflow implementing tools on the US EPA CompTox Chemicals Dashboard and prototype Hazard Comparison Dashboard was developed to automatically determine chemicals of most concern from a health perspective. RESULTS:Unique chemicals of concern, including pesticides used for malaria control in South Africa and for household pest control in China, fungicides deployed in the United States, and anti-microbial agents found in all populations, were determined. Participants were likely inhaling some of these chemicals, which poses health concerns. Chemical exposures were dynamic, with seasonal variation predominating any other factor among studies in different locations. CONCLUSIONS:We are finding that people around the world, from children in rural South African villages to the elderly in Chinese metropolis, to college students at Yale, are inhaling chemicals of concern, including biocides. These chemical exposures are dynamic, with season seeming to have the greatest influence on exposure profiles. KEYWORDS: Air pollution, external exposome, exposure assessment, omics technologies, mixtures, pesticides

An annotation database for chemicals of emerging concern in exposome research

BackgroundChemicals of Emerging Concern (CECs) include a very wide group of chemicals that are suspected to be responsible for adverse effects on health, but for which very limited information is available. Chromatographic techniques coupled with high-resolution mass spectrometry (HRMS) can be used for non-targeted screening and detection of CECs, by using comprehensive annotation databases. Establishing a database focused on the annotation of CECs in human samples will provide new insight into the distribution and extent of exposures to a wide range of CECs in humans. ObjectivesThis study describes an approach for the aggregation and curation of an annotation database (CECscreen) for the identification of CECs in human biological samples. MethodsThe approach consists of three main parts. First, CECs compound lists from various sources were aggregated and duplications and inorganic compounds were removed. Subsequently, the list was curated by standardization of structures to create “MS-ready” and “QSAR-ready” SMILES, as well as calculation of exact masses (monoisotopic and adducts) and molecular formulas. The second step included the simulation of Phase I metabolites. The third and final step included the calculation of QSAR predictions related to physicochemical properties, environmental fate, toxicity and Absorption, Distribution, Metabolism, Excretion (ADME) processes and the retrieval of information from the US EPA CompTox Chemicals Dashboard. ResultsAll CECscreen database and property files are publicly available (DOI: https://doi.org/10.5281/zenodo.3956586). In total, 145,284 entries were aggregated from various CECs data sources. After elimination of duplicates and curation, the pipeline produced 70,397 unique “MS-ready” structures and 66,071 unique QSAR-ready structures, corresponding with 69,526 CAS numbers. Simulation of Phase I metabolites resulted in 306,279 unique metabolites. QSAR predictions could be performed for 64,684 of the QSAR-ready structures, whereas information was retrieved from the CompTox Chemicals Dashboard for 59,739 CAS numbers out of 69,526 inquiries. CECscreen is incorporated in the in silico fragmentation approach MetFrag. DiscussionThe CECscreen database can be used to prioritize annotation of CECs measured in non-targeted HRMS, facilitating the large-scale detection of CECs in human samples for exposome research. Large-scale detection of CECs can be further improved by integrating the present database with resources that contain CECs (metabolites) and meta-data measurements, further expansion towards in silico and experimental (e.g., MassBank) generation of MS/MS spectra, and development of bioinformatics approaches capable of using correlation patterns in the measured chemical features.