摘要：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(TM) 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.
关键词：HT; high; throughput; HTS; high; throughput screening; LC; Si; liquid; chromatography/silica; LC; TOF/MS; liquid chromatography time; of; flight mass spectrometry; HRMS; high resolution mass spectrometry; MFE; Molecular Feature Extraction; MS; mass spectrometry; MW; molecular weight; NF@kB1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1; NHANES; U.S;National Health and Nutrition Examination Survey; PPAR@c; peroxisome proliferator; activated receptor gamma; RSD; relative standard deviation; RT; retention time; SPE; solid; phase extraction; ToxPi; Toxicological Priority Index; Non; targeted; Suspect screening; Exposome; ExpoCast; ToxCast; Dust; ACToR; EPA's Aggregated Computational Toxicology Resource; AHHS; American Healthy Homes Survey; AhR; aryl hydrocarbon receptor; AR; androgen receptor; CASRN; Chemical Abstract Services Registry Number; DI; deionized; DSSTox; EPA's Distributed Structure; Searchable Toxicity database; ER@a; estrogen receptor alpha; GCxGC; TOF/MS; two; dimensional gas chromatography coupled with time; of; flight mass spectrometry; HPLC; high performance liquid chromatograph; HPV; high; production volume
