Datasets

In vitro estrogenic activity of perfluorinated diols of different chain lengths

Per- and polyfluoroalkyl substances (PFAS) are a diverse class of synthetic fluorinated chemicals that are currently ubiquitous in the environment due to their diverse usage in both consumer and industrial products. To help prioritize data poor PFAS, previous work evaluated 142 PFAS using an in vitro screening platform. To further evaluate effectiveness of the assays in identifying PFAS capable of inducing estrogenic responses in fish our lab group conducted in vivo exposures using fathead minnows (Pimephales promelas). 1H,1H,8H,8H-perfluorooctane-1,8-diol [FC8-diol], 1H,1H,10H,10H-perfluorodecane-1,10-diol [FC10-diol], and 1H,1H,8H,8H-perfluoro-3,6-dioxaoctane-1,8-diol [FC8-DOD] were found to be estrogenic in fathead minnows. The data stored here builds off these studies and was aimed to examine the ability of similar PFAS, primarily PFAS with the same structure but different chain lengths, to induce estrogenic responses in vitro. One PFAS with a high similarity score to FC10-diol (the most potent of the tested PFAS) but different structure was also included. Presented here are the data from Indigo ER bioassays along with data from a rainbow trout liver slice assay which measured estrogen receptor-regulated gene expression. Data sheets include the raw data from the plate reader (presented in blue under luminescence) and resulting data (E2 equivalence) and figures from PRISM analysis. Data sheets are labeled by date and chemicals tested. The second folder includes data sheets from rainbow trout liver slice assays. This folder includes RNA concentrations and purities from all exposures, normalized RNA used for qPCR, plate layouts, raw data from qPCR runs, and preliminary figures from qPCR.

US EPA, ORD, GLTED Newton Creek, Superior, WI Studies, conducted fall 2017

In 2017 the Wisconsin DNR reported observation of a high incidence of fish with fin erosion in Newton Creek, which originates near the site of the Calumet (later Husky) oil refinery and flows approximately 2 miles through the city of Superior, WI, before discharging at the Hog Island Inlet of the Superior Bay. In fall 2017, the United States Environmental Protection Agency’s (US EPA) Office of Research and Development (ORD), Mid-Continent Ecology Division (now Great Lakes Toxicology and Ecology Division; GLTED) conducted several studies (two caged fish exposures and one resident fish collection) aimed at elucidating potential causes of the fin erosion phenotype reported. These studies were conducted in coordination and cooperation with both the Wisconsin DNR and Calumet/Husky refinery.

Bioactivity of the ubiquitous tire preservative 6PPD and degradant, 6PPD-quinone in fish and mammalian-based assays

6PPD-quinone (N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone), a transformation product of the antiozonant 6PPD (N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine) is a likely causative agent of coho salmon (Oncorhynchus kisutch) pre-spawn mortality. Stormwater runoff transports 6PPD-quinone into freshwater streams, rapidly leading to neurobehavioral and respiratory distress and rapid mortality in laboratory exposed coho salmon (LC50 41 – 95 ng/L) but causing no mortality in many (6 of 11) laboratory-tested species. Given this identified hazard, and potential for environmental exposure, we evaluated a set of U.S. Environmental Protection Agency’s high throughput assays for their capability to detect the large potency difference between 6PPD and 6PPD-quinone observed in coho salmon and screen for bioactivities of concern. Assays included transcriptomics in larval fathead minnow (FHM), developmental and behavioral toxicity in larval zebrafish, phenotypic profiling in a rainbow trout gill cell line, acute and developmental neurotoxicity in mammalian cells, and reporter transcription factor activity in HepG2 cells (Attagene). 6PPD was more consistently bioactive across tested assays, with distinct activity in the developmental neurotoxicity assay (mean 50th centile activity concentration =0.91 µM). 6PPD-quinone was less potent in FHM and zebrafish, and displayed minimal neurotoxic activity in mammalian cells, it was highly potent in altering organelle morphology in RTgill-W1 cells (phenotype altering concentration 0.024 µM [7.2 µg/L] compared to 0.96 µM [260 µg/L] for 6PPD). Although in vitro sensitivity of RTgill-W1 cells may not be as sensitive as Coho salmon exposed in vivo, the assay may be a promising approach to test chemicals for 6PPD-quinone-like activities. The other assays each identified unique bioactivities of 6PPD, with neurobehavioral and developmental neurotoxicity being most affected, indicating a need for further assessment of this chemical.

Test-post_file_tags

Assay Description Documents

This documentation for the ToxCast assay endpoints is in a format outlined by the OECD Guidance Document 211 (GD211) for describing non-guideline in vitro test methods and their interpretation. The intent of GD 211 is to harmonize non-guideline, in vitro method descriptions to allow assessment of the relevance of the test method for biological responses of interest and the quality of the data produced. This dataset contains reports for 809 assay endpoints accompanying the invitrodb v4.2 release (Sept 2024). Compiled report is available here: https://clowder.edap-cluster.com/files/66e2e177e4b0a7c65d2f7a8b. These reports are a work in progress and will be iteratively updated as more information becomes available. Please cite as: "US EPA (2024). ToxCast Assay Description Documentation. EPA Publication Number 601B24001. https://doi.org/10.23645/epacomptox.6328037.v11"

MMDB v1.0 Scripts

Contains all scripts associated with the v1.0 release of MMDB. These were previously organized into the following datasets: MMDB Processing Scripts, Sample Queries (example queries for exploring the MMDB database), & MMDB Correction Scripts (a set of SQL commands to run to update the associated MMDB SQL dump version - these help fix minor curation issues identified after the dump file was created).

Release_Note

This .html output from Rmarkdown that describes the update of invitrodb between versions 4.1 and 4.2. Invitrodb v4.2 represents the second full release of the ToxCast database in a new schema designed to accommodate the R package dependency, tcplFit2, which is used in curve-fitting and hit-calling of multi-concentration response data. This invitrodb schema was beta-tested with our research release of invitrodb v4.0 that accompanied the publication "The ToxCast Pipeline: Updates to Curve-Fitting Approaches and Database Structure" (Feshuk et al., 2023 https://www.frontiersin.org/journals/toxicology/articles/10.3389/ftox.2023.1275980) and release of tcpl v3.0.1.

MySQL_Data

This includes a sql dump of invitrodb v4.2 with installation instructions available in README.

Summary_Files

This includes a zip file of summary files with descriptions available in README. Corrections: -Upload v4.2 tcplVarMat output (variable matrices of hitcalls, ACCs and AC50s) -Upload analytical qc file for convenience -Upload sample mapping key for Attagene mixtures data -Upload new analytical qc version to include chemicals without OPERA predicted physico-chemical properties

Plots

This includes a zip file of plots by assay source. Note: X axis of "Concentration (.M)" should be "Concentration (μM)" on all plots.

Previous Data

Abstract Sifter Plus

Files and videos for Abstract Sifter Plus.