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Development and Distribution of Test Method Documentation for ToxCast HTT Assays
Citation:
Flood, S. AND K. Houck. Development and Distribution of Test Method Documentation for ToxCast HTT Assays. Presented at SETAC North America Focused Topic Meeting : High-Throughput Screening, Durham, NC, April 16 - 18, 2018. https://doi.org/10.23645/epacomptox.6948023
Impact/Purpose:
Presentation at SETAC North America Focused Topic Meeting : High-Throughput Screening April 2018
Description:
Major concerns exist for the large number of environmental chemicals which lack toxicity data. The tens of thousands of commercial substances in need of screening for potential human health effects would cost millions of dollars and take several decades to test in traditional animal-based guideline studies, and these concerns have led many researchers to increasingly rely on alternative screening methods. High-throughput testing (HTT) methods have been developed to evaluate the hazard potential of diverse chemical libraries and are helpful in prioritizing the compounds of greatest concern for adverse effects. As part of a larger multiagency project to identify substances for prioritized testing, the U.S. EPA’s National Center for Computational Toxicology (NCCT) ToxCastTM program has, to date, screened >3800 unique compounds for biological activity in some or all of over 800 assays. These efforts are designed to inform decision-makers of the bioactivity and/or toxicity of chemicals, but there remains a need to establish confidence in the applicability of these novel technologies to regulatory agencies. Here we describe the status of the NCCT’s development of descriptive ToxCast assay documentation designed to implement OECD Guidance Document No. 211 recommendations for describing non-guideline in vitro test methods to diverse audiences. These annotations are designed to offer a clear and comprehensive depiction of all aspects of the ToxCast and Tox21 assays - from the development of novel methods, to the technological relevancy for examinating chemical-target interactions, through the interpretation of the >1600 different analytical endpoints. Alterations and additions to the OECD Guidance template were necessary to a limited extent to accommodate existing data infrastructure supporting the ToxCast program. Integrating detailed context-based textual information with structured ontology-based annotations into a publicly available database will facilitate the evaluation of these assays for regulatory applications. Our current work will provide critical feedback useful in future improvements to the OECD reporting template. This work is concurrent with efforts to deposit ToxCast data into other publicly accessible repositories (e.g., PubChem BioAssay and DB-ALM) and will help fulfill NCCT’s commitment to increasing transparency and public accessibility to information produced by HTT studies conducted under the ToxCast program. This abstract does not reflect EPA policy.
URLs/Downloads:
DOI: Development and Distribution of Test Method Documentation for ToxCast HTT Assays
SETAC_HTSFTM__SFLOOD_12APR2018.PDF (PDF, NA pp, 1725.638 KB, about PDF)