Linking high resolution mass spectrometry data with exposure and toxicity forecasts to advance high-throughput environmental monitoring

Abstract

There is a growing need in the field of exposure science for monitoring methods that rapidly screen environmental media for suspect contaminants. Measurement and analysis platforms, based on high resolution mass spectrometry (HRMS), now exist to meet this need. Here we describe results of a study that links HRMS data with exposure predictions from the U.S. EPA's ExpoCast™ program and in vitro bioassay data from the U.S. interagency Tox21 consortium. Vacuum dust samples were collected from 56 households across the U.S. as part of the American Healthy Homes Survey (AHHS). Sample extracts were analyzed using liquid chromatography time-of-flight mass spectrometry (LC-TOF/MS) with electrospray ionization. On average, approximately 2000 molecular features were identified per sample (based on accurate mass) in negative ion mode, and 3000 in positive ion mode. Exact mass, isotope distribution, and isotope spacing were used to match molecular features with a unique listing of chemical formulas extracted from EPA's Distributed Structure-Searchable Toxicity (DSSTox) database. A total of 978 DSSTox formulas were consistent with the dust LC-TOF/molecular feature data (match score≥90); these formulas mapped to 3228 possible chemicals in the database. Correct assignment of a unique chemical to a given formula required additional validation steps. Each suspect chemical was prioritized for follow-up confirmation using abundance and detection frequency results, along with exposure and bioactivity estimates from ExpoCast and Tox21, respectively. Chemicals with elevated exposure and/or toxicity potential were further examined using a mixture of 100 chemical standards. A total of 33 chemicals were confirmed present in the dust samples by formula and retention time match; nearly half of these do not appear to have been associated with house dust in the published literature. Chemical matches found in at least 10 of the 56 dust samples include Piperine, N,N-Diethyl-m-toluamide (DEET), Triclocarban, Diethyl phthalate (DEP), Propylparaben, Methylparaben, Tris(1,3-dichloro-2-propyl)phosphate (TDCPP), and Nicotine. This study demonstrates a novel suspect screening methodology to prioritize chemicals of interest for subsequent targeted analysis. The methods described here rely on strategic integration of available public resources and should be considered in future non-targeted and suspect screening assessments of environmental and biological media.

Use of high-throughput in vitro toxicity screening data in cancer hazard evaluations by IARC Monograph Working Groups

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Trends in the application of high-resolution mass spectrometry for human biomonitoring: An analytical primer to studying the environmental chemical space of the human exposome

“…Tackling the exposome requires state-of-the-art analytical techniques and tools (Jones, 2016, Rager et al, 2016). Exposome studies involve multidisciplinary approach requiring efforts from exposure scientists, epidemiologists, clinicians, statisticians, bioinformaticians, and analytical chemists.…”

An expanded conceptual framework for solution-focused management of chemical pollution in European waters

“…In several case studies, panels of these tools were tested successfully for their applicability on environmental samples [39–41]. A key component for the identification of hazard drivers in complex mixture exposure is the EDA approach, where combinations of non-target/target screening [31] with bioanalytical tools can be applied in different tiers to identify drivers of toxicity or in combination with toxicity information or hazardous properties of encountered substances [35, 42]. Stepwise approaches for the use of bioanalytical tools, which details the developing methodologies for innovative monitoring also including mixtures, have been presented [5, 22, 43].…”