Datasets

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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.

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Test-post_file_tags

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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"

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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).

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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.

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MySQL_Data

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

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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