Rager JE, Strynar MJ, Liang S, McMahen R, Richard AM, Grulke CM, Wambaugh JF, Isaacs KK, Judson R, Williams AJ, Sobus JR. 2016. Linking high resolution mass spectrometry data with exposure and toxicity forecasts to advance high-throughput environmental monitoring. Presented at the Society of Toxicology’s 55th Annual Meeting, March 13-17, New Orleans, LA.
There is a growing need for rapid chemical screening and prioritization for regulatory decision-making. Here we describe a study that links high resolution mass spectrometry (HRMS) data with exposure predictions from the U.S. EPA’s ExpoCast program and in vitro bioassay data from the Tox21 consortium. Vacuum dust samples were collected from 56 households across the U.S. Sample extracts were analyzed using liquid chromatography time-of-flight mass spectrometry (LC-TOF/MS) with electrospray ionization. On average, ~2000 molecular features were identified per sample 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 formulas were consistent with the dust molecular feature data; 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; over half of these have not been associated with dust in 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, and Tris(1,3-dichloro-2-propyl)phosphate (TDCPP). This study demonstrates a novel suspect screening methodology to prioritize emerging contaminants 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.