Dataset consists of high throughput in vitro bioactivity data and exposure predictions from the U.S. EPA’s Toxicity and Exposure Forecaster (ToxCast and ExpoCast) project. This dataset is associated with the following publication: Wegner, S., C. Pinto, C. Ring, and J. Wambaugh. High-throughput screening tools facilitate calculation of a combined exposure-bioactivity index for chemicals with endocrine activity. ENVIRONMENT INTERNATIONAL. Elsevier B.V., Amsterdam, NETHERLANDS, 137: 105470, (2020).

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. This dataset is associated with the following publication: Rager, J.E., M. Strynar , S. Liang, R.L. McMahen, A. Richard , C.M. Grukle, J. Wambaugh , K. Isaacs , R. Judson , A. Williams , and J. Sobus. Linking high resolution mass spectrometry data with exposure and toxicity forecasts to advance high-throughput environmental monitoring. ENVIRONMENT INTERNATIONAL. Elsevier Science Ltd, New York, NY, USA, 88: 269-280, (2016).

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. This dataset is associated with the following publication: Rager, J.E., M. Strynar , S. Liang, R.L. McMahen, A. Richard , C.M. Grukle, J. Wambaugh , K. Isaacs , R. Judson , A. Williams , and J. Sobus. Linking high resolution mass spectrometry data with exposure and toxicity forecasts to advance high-throughput environmental monitoring. ENVIRONMENT INTERNATIONAL. Elsevier Science Ltd, New York, NY, USA, 88: 269-280, (2016).

The Exposure Forecaster Database (ExpoCastDB) is EPA's database for aggregating chemical exposure information and can be used to help with chemical exposure predictions. The database currently includes biomonitoring exposure data from three studies: the American Healthy Homes Survey, the First National Environmental Health Survey of Child Care Centers and the Children's Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants study. Data include the amounts of chemicals found in food, drinking water, air, dust indoor surfaces and urine. The database will eventually include high-throughput exposure predictions for thousands of chemicals based on manufacture and use information. EPA researchers developed high-throughput exposure models to predict exposures for 1,763 chemicals using production volume, environmental fate and transport models, and a simple indicator of consumer product use.The model is being improved by adding more refined indoor and consumer use information since these are also large determinants of exposure. As these models are refined and more exposure data is collected, it will be added to ExpoCastDB.

The Exposure Forecaster Database (ExpoCastDB) is EPA's database for aggregating chemical exposure information and can be used to help with chemical exposure predictions. The database currently includes biomonitoring exposure data from three studies: the American Healthy Homes Survey, the First National Environmental Health Survey of Child Care Centers and the Children's Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants study. Data include the amounts of chemicals found in food, drinking water, air, dust indoor surfaces and urine. The database will eventually include high-throughput exposure predictions for thousands of chemicals based on manufacture and use information. EPA researchers developed high-throughput exposure models to predict exposures for 1,763 chemicals using production volume, environmental fate and transport models, and a simple indicator of consumer product use.The model is being improved by adding more refined indoor and consumer use information since these are also large determinants of exposure. As these models are refined and more exposure data is collected, it will be added to ExpoCastDB.

This study represents the first report applying IVIVE approaches and exposure comparisons using the entirety of the Tox21 federal collaboration chemical screening data, incorporating assay response efficacy and quality of concentration-response fits, and providing quantitative anchoring to first address the likelihood of human in vivo interactions with Tox21 compounds. This likelihood was assessed using a maximum blood concentration to in vitro response ratio approach (Cmax/AC50), analogous to decision-making methods for clinical drug-drug interactions. Fraction unbound in plasma (fup) and intrinsic hepatic clearance (CLint) parameters were estimated in silico and incorporated in a 3-compartment toxicokinetic (TK) model to first predict Cmax for in vivo corroboration using therapeutic scenarios. This dataset is associated with the following publication: Sipes, N., J. Wambaugh, R. Pearce, S. Auerbach, B. Wetmore, J. Hsieh, A. Shapiro, D. Sboboda, M. DeVito, and S. Ferguson. (ENVIRONMENTAL SCIENCE and TECHNOLOGY) An Intuitive Approach for Predicting Human Risk with the Tox21 10k Library. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, USA, issue}: 10786-10796, (2017).

This study represents the first report applying IVIVE approaches and exposure comparisons using the entirety of the Tox21 federal collaboration chemical screening data, incorporating assay response efficacy and quality of concentration-response fits, and providing quantitative anchoring to first address the likelihood of human in vivo interactions with Tox21 compounds. This likelihood was assessed using a maximum blood concentration to in vitro response ratio approach (Cmax/AC50), analogous to decision-making methods for clinical drug-drug interactions. Fraction unbound in plasma (fup) and intrinsic hepatic clearance (CLint) parameters were estimated in silico and incorporated in a 3-compartment toxicokinetic (TK) model to first predict Cmax for in vivo corroboration using therapeutic scenarios. This dataset is associated with the following publication: Sipes, N., J. Wambaugh, R. Pearce, S. Auerbach, B. Wetmore, J. Hsieh, A. Shapiro, D. Sboboda, M. DeVito, and S. Ferguson. (ENVIRONMENTAL SCIENCE and TECHNOLOGY) An Intuitive Approach for Predicting Human Risk with the Tox21 10k Library. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, USA, issue}: 10786-10796, (2017).

Three recent IARC Working Groups pioneered inclusion of the US Environmental Protection Agency (EPA) ToxCast program high-throughput screening (HTS) data to supplement other mechanistic evidence. In Monograph V110, HTS profiles were compared between perfluorooctanoic acid (PFOA) and prototypical activators across multiple nuclear receptors. For Monograph V112-113, HTS assays were mapped to 10 key characteristics of carcinogens identified by an IARC expert group, and systematically considered as an additional mechanistic data stream. This dataset is not publicly accessible because: The data is generated by external authors from existing public data sources. It can be accessed through the following means: Data is available in existing public data sources. Format: N/A. This dataset is associated with the following publication: Chiu, W., K. Guyton, M. Martin, D. Reif, and I. Rusyn. (ALTEX) Use of High-throughput in vitro toxicity screening data in cancer hazard evaluations by the IARC Monograph Working Groups. ALTEX. Society ALTEX Edition, Kuesnacht, SWITZERLAND, 35(1): 51-64, (2018).

Three recent IARC Working Groups pioneered inclusion of the US Environmental Protection Agency (EPA) ToxCast program high-throughput screening (HTS) data to supplement other mechanistic evidence. In Monograph V110, HTS profiles were compared between perfluorooctanoic acid (PFOA) and prototypical activators across multiple nuclear receptors. For Monograph V112-113, HTS assays were mapped to 10 key characteristics of carcinogens identified by an IARC expert group, and systematically considered as an additional mechanistic data stream. This dataset is not publicly accessible because: The data is generated by external authors from existing public data sources. It can be accessed through the following means: Data is available in existing public data sources. Format: N/A. This dataset is associated with the following publication: Chiu, W., K. Guyton, M. Martin, D. Reif, and I. Rusyn. (ALTEX) Use of High-throughput in vitro toxicity screening data in cancer hazard evaluations by the IARC Monograph Working Groups. ALTEX. Society ALTEX Edition, Kuesnacht, SWITZERLAND, 35(1): 51-64, (2018).

ToxCast is used as a cost-effective approach for efficiently prioritizing the toxicity testing of thousands of chemicals. It uses data from state-of-the-art high throughput screening (HTS) bioassay and builds computational models to forecast potential chemical toxicity in humans. ToxRefDB stores data related to ToxCast.