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      EPA’s DSSTox database: History of development of a curated chemistry resource supporting computational toxicology research

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          Abstract

          The US Environmental Protection Agency’s (EPA) Distributed Structure-Searchable Toxicity (DSSTox) database, launched publicly in 2004, currently exceeds 875 K substances spanning hundreds of lists of interest to EPA and environmental researchers. From its inception, DSSTox has focused curation efforts on resolving chemical identifier errors and conflicts in the public domain towards the goal of assigning accurate chemical structures to data and lists of importance to the environmental research and regulatory community. Accurate structure-data associations, in turn, are necessary inputs to structure-based predictive models supporting hazard and risk assessments. In 2014, the legacy, manually curated DSSTox_V1 content was migrated to a MySQL data model, with modern cheminformatics tools supporting both manual and automated curation processes to increase efficiencies. This was followed by sequential auto-loads of filtered portions of three public datasets: EPA’s Substance Registry Services (SRS), the National Library of Medicine’s ChemID, and PubChem. This process was constrained by a key requirement of uniquely mapped identifiers (i.e., CAS RN, name and structure) for each substance, rejecting content where any two identifiers were conflicted either within or across datasets. This rejected content highlighted the degree of conflicting, inaccurate substance-structure ID mappings in the public domain, ranging from 12% (within EPA SRS) to 49% (across ChemID and PubChem). Substances successfully added to DSSTox from each auto-load were assigned to one of five qc_levels, conveying curator confidence in each dataset. This process enabled a significant expansion of DSSTox content to provide better coverage of the chemical landscape of interest to environmental scientists, while retaining focus on the accuracy of substance-structure-data associations. Currently, DSSTox serves as the core foundation of EPA’s CompTox Chemicals Dashboard [ https://comptox.epa.gov/dashboard], which provides public access to DSSTox content in support of a broad range of modeling and research activities within EPA and, increasingly, across the field of computational toxicology.

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          Most cited references 38

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          Trust, but verify: on the importance of chemical structure curation in cheminformatics and QSAR modeling research.

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            The Toxicity Data Landscape for Environmental Chemicals

            Objective Thousands of chemicals are in common use, but only a portion of them have undergone significant toxicologic evaluation, leading to the need to prioritize the remainder for targeted testing. To address this issue, the U.S. Environmental Protection Agency (EPA) and other organizations are developing chemical screening and prioritization programs. As part of these efforts, it is important to catalog, from widely dispersed sources, the toxicology information that is available. The main objective of this analysis is to define a list of environmental chemicals that are candidates for the U.S. EPA screening and prioritization process, and to catalog the available toxicology information. Data sources We are developing ACToR (Aggregated Computational Toxicology Resource), which combines information for hundreds of thousands of chemicals from > 200 public sources, including the U.S. EPA, National Institutes of Health, Food and Drug Administration, corresponding agencies in Canada, Europe, and Japan, and academic sources. Data extraction ACToR contains chemical structure information; physical–chemical properties; in vitro assay data; tabular in vivo data; summary toxicology calls (e.g., a statement that a chemical is considered to be a human carcinogen); and links to online toxicology summaries. Here, we use data from ACToR to assess the toxicity data landscape for environmental chemicals. Data synthesis We show results for a set of 9,912 environmental chemicals being considered for analysis as part of the U.S. EPA ToxCast screening and prioritization program. These include high-and medium-production-volume chemicals, pesticide active and inert ingredients, and drinking water contaminants. Conclusions Approximately two-thirds of these chemicals have at least limited toxicity summaries available. About one-quarter have been assessed in at least one highly curated toxicology evaluation database such as the U.S. EPA Toxicology Reference Database, U.S. EPA Integrated Risk Information System, and the National Toxicology Program.
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              ToxCast Chemical Landscape: Paving the Road to 21st Century Toxicology

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                Author and article information

                Journal
                101708081
                46674
                Comput Toxicol
                Comput Toxicol
                Computational toxicology (Amsterdam, Netherlands)
                2468-1113
                25 November 2020
                1 November 2019
                07 January 2021
                : 12
                Affiliations
                [a ]National Center for Computational Toxicology, Office of Research & Development, US Environmental Protection Agency, Mail Drop D143-02, Research Triangle Park, NC 27711, USA
                [b ]Senior Environmental Employment Program, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
                Author notes
                [* ]Corresponding author. richard.ann@ 123456epa.gov (A.M. Richard).
                Article
                EPAPA1647193
                10.1016/j.comtox.2019.100096
                7787967

                This is an open access article under the CC BY license ( http://creativecommons.org/licenses/BY/4.0/).

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