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Identifying known unknowns using the US EPA's CompTox Chemistry Dashboard
Citation:
McEachran, A., J. Sobus, AND A. Williams. Identifying known unknowns using the US EPA's CompTox Chemistry Dashboard. Analytical and Bioanalytical Chemistry. Springer, New York, NY, 409(7):1729-1735, (2017).
Impact/Purpose:
• Agency Research Drivers - The Frank R. Lautenberg Chemical Safety for the 21st Century Act requires the Agency to initiate rulemaking on chemicals that have an unreasonable risk of injury to health or the environment. These Agency standards should be based on exposure to chemical under its conditions of use; therefore, understanding the intended, known, or foreseeable sources of chemical exposure is critical for the Agency’s mission. • Science Challenge – Thousands of chemicals are present in the environment, but only a few are routinely monitored. Methods and tools are needed to characterize the totality of chemical exposures to ensure public and environmental health. • Research Approach – Candidate chemicals not included monitoring efforts but contained within a reference database were selected as "known unknown" chemicals. The performance of the U.S. EPA’s CompTox Chemistry Dashboard in identifying "known unknowns" was against another of the online chemistry database. • Results – The U.S. EPA’s CompTox Chemistry Dashboard is a curated and freely available resource for chemistry and computational toxicology research, containing more than 720,000 chemicals of relevance to environmental health science. Using multiple previously studied datasets, 162 chemicals were compared between EPA's CompTox Chemistry Dashboard and ChemSpider. These chemicals were examined using both applications via molecular formula and monoisotopic mass searches followed by rank-ordering of candidate compounds by associated data sources. A greater percentage of chemicals ranked in the top position when using EPA's Dashboard, indicating an advantage of this application over ChemSpider for identifying known unknowns using data source ranking. • Anticipated Impact/Expected use – This work shows the potential for use of the EPA's CompTox Chemistry Dashboard in exposure assessment and risk decision-making.
Description:
Chemical features observed using high-resolution mass spectrometry can be tentatively identified using online chemical reference databases by searching molecular formulae and monoisotopic masses and then rank-ordering of the hits using appropriate relevance criteria. The most likely candidate “known unknowns,” which are those chemicals unknown to an investigator but contained within a reference database or literature source, rise to the top of a chemical list when rank-ordered by the number of associated data sources. The U.S. EPA’s CompTox Chemistry Dashboard is a curated and freely available resource for chemistry and computational toxicology research, containing more than 720,000 chemicals of relevance to environmental health science. In this research, the performance of the Dashboard for identifying “known unknowns” was evaluated against that of the online ChemSpider database, one of the primary resources used by mass spectrometrists, using multiple previously studied datasets reported in the peer-reviewed literature totaling 162 chemicals. These chemicals were examined using both applications via molecular formula and monoisotopic mass searches followed by rank-ordering of candidate compounds by associated references or data sources. A greater percentage of chemicals ranked in the top position when using the Dashboard, indicating an advantage of this application over ChemSpider for identifying known unknowns using data source ranking. Additional approaches are being developed for inclusion into a non-targeted analysis workflow as part of the CompTox Chemistry Dashboard. This work shows the potential for use of the Dashboard in exposure assessment and risk decision-making through significant improvements in non-targeted chemical identification.
URLs/Downloads:
MCEACHRAN ET AL - IDENTIFYING KNOWN UNKNOWNS IN THE DASHBOARD - ACCEPTED.PDF (PDF, NA pp, 174.471 KB, about PDF)http://dx.doi.org/10.1007/s00216-016-0139-z
