Data for a single chemical endpoint pair for thousands of chemicals and 821 assay endpoints for 20 variables such as the activity or hit call/activity concentrations/whether the chemical was tested in a specific assay/etc.

ToxCast high-throughput assay information including assay annotation user guide, assay target information, study design information and quality statistics on the assays.Science Inventory, CCTE products: https://cfpub.epa.gov/si/si_public_search_results.cfm?advSearch=true&showCriteria=2&keyword=CCTE&TIMSType=&TIMSSubTypeID=&epaNumber=&ombCat=Any&dateBeginPublishedPresented=07/01/2017&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&DEID=&personName=&personID=&role=Any&journalName=&journalID=&publisherName=&publisherID=&sortBy=pubDate&count=25

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.

Background: Chemical toxicity testing is being transformed by advances in biology and computer modeling, concerns over animal use and the thousands of environmental chemicals lacking toxicity data. EPA's ToxCast program aims to address these concerns by screening and prioritizing chemicals for potential human toxicity using in vitro assays and in silico approaches. Objectives: This project aims to evaluate the use of in vitro assays for understanding the types of molecular and pathway perturbations caused by environmental chemicals and to build initial prioritization models of in vivo toxicity. Methods: We tested 309 mostly pesticide active chemicals in 467 assays across 9 technologies, including high-throughput cell-free assays and cell-based assays in multiple human primary cells and cell lines, plus rat primary hepatocytes. Both individual and composite scores for effects on genes and pathways were analyzed. Results: Chemicals display a broad spectrum of activity at the molecular and pathway levels. Many expected interactions are seen, including endocrine and xenobiotic metabolism enzyme activity. Chemicals range in promiscuity across pathways, from no activity to affecting dozens of pathways. We find a statistically significant inverse association between the number of pathways perturbed by a chemical at low in vitro concentrations and the lowest in vivo dose at which a chemical causes toxicity. We also find associations between a small set in vitro assays and rodent liver lesion formation. Conclusions: This approach promises to provide meaningful data on the thousands of untested environmental chemicals, and to guide targeted testing of environmental contaminants.

A spreadsheet of EPA's analysis of the chemicals screened through ToxCast and the Tox21 collaboration which includes EPA's activity calls from the screening of over 8000 chemicals.

HR-machine/ToxCast dataset hosted on Hugging Face and contributed by the HF Datasets community

Title: ToxCast Cytotoxicity-Associated Burst Paragraph: Chemical toxicity can arise from disruption of specific biomolecular functions or through more generalized cell stress and cytotoxicity-mediated processes. Evaluating the ToxCast high-throughput screening library, many chemicals show activation of large numbers of assays over a narrow range of concentrations in which cell stress and cytotoxicity are also seen. We term this phenomenon the cytotoxicity-associated “burst”. Whereas some of the assay activity in this concentration range may represent chemical effects on the intended target of the assay, some of it is not. In such situations, activity represents a false positive response that can be ascribed to assay interference processes. This phenomenon raises the need to establish a concentration threshold at which each chemical begins to drive activity across multiple and diverse cell stress and cytotoxicity assays by initiating this cytotoxicity-associated burst of activity. Judson R, et al . Analysis of the Effects of Cell Stress and Cytotoxicity on In Vitro Assay Activity Across a Diverse Chemical and Assay Space. Toxicol Sci. 2016 Oct;153(2):409. doi: 10.1093/toxsci/kfw148. Epub 2016 Sep 7. Erratum for: Toxicol Sci. 2016 Aug;152(2):323-39. PMID: 27605417; PMCID: PMC7297301.

These data are based on ToxCast invitroDBv3.5

ToxCast high-throughput assay information including assay annotation user guide, assay target information, study design information and quality statistics on the assays.

Supplemental datafiles for journal article 'High-Throughput Transcriptomics Screen of ToxCast Chemicals in U-2 OS Cells'.

ToxCast high-throughput assay information including assay annotation user guide, assay target information, study design information and quality statistics on the assays. This version is Mac compatible.

liuganghuggingface/toxcast dataset hosted on Hugging Face and contributed by the HF Datasets community

Thousands of chemicals are directly added to or come in contact with food, many of which have undergone little to no toxicological evaluation. The landscape of the food-relevant chemical universe was evaluated using cheminformatics, and subsequently the bioactivity of food-relevant chemicals across the publicly available ToxCast highthroughput screening program was assessed. In total, 8659 food-relevant chemicals were compiled including direct food additives, food contact substances, and pesticides. Of these food-relevant chemicals, 4719 had curated structure definition files amenable to defining chemical fingerprints, which were used to cluster chemicals using a selforganizing map approach. Pesticides, and direct food additives clustered apart from one another with food contact substances generally in between, supporting that these categories not only reflect different uses but also distinct chemistries. Subsequently, 1530 food-relevant chemicals were identified in ToxCast comprising 616 direct food additives, 371 food contact substances, and 543 pesticides. Bioactivity across ToxCast was filtered for cytotoxicity to identify selective chemical effects. Initiating analyses from strictly chemical-based methodology or bioactivity/cytotoxicity-driven evaluation presents unbiased approaches for prioritizing chemicals. Although bioactivity in vitro is not necessarily predictive of adverse effects in vivo, these data provide insight into chemical properties and cellular targets through which foodrelevant chemicals elicit bioactivity. This dataset is associated with the following publication: Karmaus , A., D. Filer , M. Martin , and K. Houck. (FOOD AND CHEMICAL TOXICOLOGY) Evaluation of food-relevant chemicals in the ToxCast high-throughput screening program. FOOD AND CHEMICAL TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 92: 188-196, (2016).

Abbreviations and data for manuscript Figures in the main text and supplemental. This dataset is associated with the following publication: Stoker, T., J. Want, A. Murr, J. Bailey, and A.R. Buckalew. High-Throughput Screening of ToxCast PFAS Chemical Library for Potential Inhibitors of the Human Sodium Iodide Symporter. CHEMICAL RESEARCH IN TOXICOLOGY. American Chemical Society, Washington, DC, USA, 36(3): 380-389, (2023).

The tcpl package was developed to process high-throughput and high-content screening data generated by the ToxCast program. ToxCast is screening thousands of chemicals with hundreds of assays coming from numerous and diverse biochemical and cell-based technology platforms. The diverse data, received in heterogeneous formats from numerous vendors, are transformed to a standard computable format and loaded into the tcpl database by vendor-specific R scripts. Once data is loaded into the database, ToxCast utilizes the generalized processing functions provided in this package to process, normalize, model, qualify, flag, inspect, and visualize the data. While developed primarily for ToxCast, we have attempted to make the tcpl package generally applicable to chemical-screening community.

The tcpl package provides a set of tools for processing and modeling high-throughput and high-content chemical screening data.

This dataset is associated with the following publication: Filer, D.L., P. Kothiya, R.W. Setzer, R.S. Judson, and M.T. Martin. (BIOINFORMATICS) tcpl: The ToxCast Pipeline for High-Throughput Screening Data. BIOINFORMATICS. Oxford University Press, Cary, NC, USA, 1-3, (2016).

Introduction: The US Environmental Protection Agency Toxicity Forecaster (ToxCast) program makes in vitro medium- and high-throughput screening assay data publicly available for prioritization and hazard characterization of thousands of chemicals. The assays employ a variety of technologies to evaluate the effects of chemical exposure on diverse biological targets, from distinct proteins to more complex cellular processes like mitochondrial toxicity, nuclear receptor signaling, immune responses, and developmental toxicity. The ToxCast data pipeline (tcpl) is an open-source R package that stores, manages, curve-fits, and visualizes ToxCast data and populates the linked MySQL Database, invitrodb.Methods: Herein we describe major updates to tcpl and invitrodb to accommodate a new curve-fitting approach. The original tcpl curve-fitting models (constant, Hill, and gain-loss models) have been expanded to include Polynomial 1 (Linear), Polynomial 2 (Quadratic), Power, Exponential 2, Exponential 3, Exponential 4, and Exponential 5 based on BMDExpress and encoded by the R package dependency, tcplfit2. Inclusion of these models impacted invitrodb (beta version v4.0) and tcpl v3 in several ways: (1) long-format storage of generic modeling parameters to permit additional curve-fitting models; (2) updated logic for winning model selection; (3) continuous hit calling logic; and (4) removal of redundant endpoints as a result of bidirectional fitting.Results and discussion: Overall, the hit call and potency estimates were largely consistent between invitrodb v3.5 and 4.0. Tcpl and invitrodb provide a standard for consistent and reproducible curve-fitting and data management for diverse, targeted in vitro assay data with readily available documentation, thus enabling sharing and use of these data in myriad toxicology applications. The software and database updates described herein promote comparability across multiple tiers of data within the US Environmental Protection Agency CompTox Blueprint.

Previous work identified a ‘cytotoxic burst’ (CTB) phenomenon wherein large numbers of the ToxCast assays begin to respond at or near test chemical concentrations that elicit cytotoxicity, and a statistical approach to defining the bounds of the CTB was developed. To focus AOP development on the molecular targets corresponding to ToxCast assays indicating pathway-specific effects, we conducted a meta-analysis to identify which assays most frequently respond at concentrations below the CTB. A preliminary list of potentially important, target-specific assays was determined by ranking assays by the fraction of chemical hits below the CTB compared to the number of chemicals tested. Additional priority assays were identified using a diagnostic-odds-ratio approach which gives greater ranking to assays with high specificity but low responsivity. Combined, the two prioritization methods identified several novel targets (e.g., peripheral benzodiazepine and progesterone receptors) to prioritize for AOP development, and affirmed the importance of a number of existing AOPs aligned with ToxCast targets (e.g., thyroperoxidase, estrogen receptor, aromatase).

This dataset is associated with the following publication: Fay, K., J. Swintek, D. Villeneuve, S. Edwards, M. Nelms, B. Blackwell, and G. Ankley. Differentiating pathway-specific from non-specific effects in high-throughput toxicity data: A foundation for prioritizing adverse outcome pathway development. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 163(2): 500-515, (2018).

amirhallaji/Toxicity-Prediction-Task-ToxCast dataset hosted on Hugging Face and contributed by the HF Datasets community

These are the raw data files for TOXSCI manuscript 19-0578 entitled, “Respirometric Screening and Characterization of Mitochondrial Toxicants Within the ToxCast Phase I and II Chemical Libraries”: Description from readme.txt file: 1) sc_seahorse.lvl0.merged.data.csv- contains all mapped raw OCR data from tier 1 single-concentration RSA screening of 1,042 Toxcast Phase I and II chemicals 2) mc_seahorse.lvl0.merged.data.csv- contains all mapped raw OCR data from tier 2 multi-concentration RSA screening of 249 actives from tier 1 3) EFA.lvl0.merged.data.csv- contains all mapped raw OCR data from tier 3 EFA screening of 149 putative electron transport chain inhibitors 4) mc5_mc6_ncct_mito_nov2019.csv- level 5 and 6 outputs from ToxCast pipeline (tcpl) analysis 5) RawMC3_ToxCast_by_aeid.csv- level 3 tcpl outputs for all mitochondrial ToxCast assays 6) RawMC5_ToxCast_by_aeid.csv- level 5 tcpl outputs for all mitochondrial ToxCast assays 7) ref.set.chems.csv- sixty reference chemicals used to compared assay performance 8) study_code.R- R script used to analyze data and generate figures and tables. This dataset is associated with the following publication: Hallinger, D., H. Lindsay, K. Friedman, D. Suarez, and S. Simmons. Respirometric Screening and Characterization of Mitochondrial Toxicants Within the ToxCast Phase I and II Chemical Libraries. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 176(1): 175-192, (2020).

A data set of 500 chemicals evaluated for their ability to induce cleft palate in animal prenatal developmental studies was compiled from Toxicity Reference Database and the biomedical literature, which included 63 cleft palate active and 437 inactive chemicals. To characterize the potential molecular targets for chemical‐induced cleft palate, we mined the ToxCast high‐throughput screening database for patterns and linkages in bioactivity profiles and chemical structural descriptors. The following datasets can be obtained via the links and files in the Data section: Phase II ToxCast assay data results (Judson et al., 2010); The Gene Score data set derived from ToxCast; ToxRefDB version 1 (Knudsen et al., 2009; Martin, Judson, et al., 2009); The ToxPrint chemotypes (Yang et al., 2015). This dataset is associated with the following publication: Baker, N., N. Sipes, J. Franzosa, D. Belair, B. Abbott, R. Judson, and T. Knudsen. Characterizing cleft palate toxicants using ToxCast data, chemical structure, and the biomedical literature. Birth Defects Research. John Wiley & Sons, Inc., Hoboken, NJ, USA, 1-21, (2019).