Methods to Expand and Improve CvTdb: A Publicly Available Resource of Toxicokinetic Data
Citation:
Rowan, E., J. Aboabdo, R. Casey, V. Correa, M. Huse, B. Kesic, C. Ring, P. Schlosser, J. Wall, J. Wambaugh, AND R. Sayre. Methods to Expand and Improve CvTdb: A Publicly Available Resource of Toxicokinetic Data. Presented at SOT, Salt Lake City, UT, March 10 - 14, 2024.
Impact/Purpose:
N/A
Description:
Background and Purpose: Time series data for environmentally relevant chemicals in body fluids and tissues after an exposure is rarely made available despite their importance for risk assessment. Further, access to in vivo data is crucial for chemical safety evaluation estimates and other quantitative applications. The Concentration versus Time Database (CvTdb) contains manually curated time-series data and associated metadata for in vivo studies on organic chemicals available in the scientific literature. These data inform chemical safety analysis and allow evaluation of the relationship between administered doses and internal concentrations of a substance. These data can also be used to build or evaluate physiologically-based pharmacokinetic (PBPK) models, which simulate the absorption, distribution, metabolism, and elimination of a chemical. The database also contains toxicokinetic parameters, including volume of distribution and elimination half-life, which are calculated across all data associated with a particular compound using the publicly available pharmacokinetic curve-fitting software invivoPKfit. Methods: A previous version of the database included time-series data for plasma concentrations of 144 environmentally relevant chemicals and their metabolites. Updates to the database since its launch in 2020 include the addition of six new datasets, which comprise hundreds of chemicals and include oral, intravenous, dermal, and inhalation routes of exposure, updated data identification and extraction processes, and adding a quality control process to the workflow. Additional updates include improved representation of dermal and inhalation CvT data, a more efficient inter-curator review process, and significant updates to the curation process and associated standard operating procedure documents, creating clear and consistent guidelines for data curation and quality control efforts. Results: The most recent data load added upwards of 200 new chemicals to the database, more than doubling the size of the CvTdb. Improvements to data curation and extraction processes and the addition of a quality control process have increased the quality of data being added to the database. Expansion of occupationally relevant administration routes (inhalation and dermal) captured by the database, improved document identification processes, and increased participation by collaborators have increased the number of time-series data records being loaded into the database. Conclusions: The CvT database can be used by researchers to assess trends or perform meta-analyses across various chemicals, administration routes, dose levels, and species from a variety of data sources. Researchers and scientists may contribute new data to the database to continue expanding upon the types of data the team is able to extract or download data using the GitHub site for CvTdb (https://github.com/USEPA/CompTox-PK-CvTdb). A process for automated data identification and extraction utilizing recent advances in Natural Language Processing techniques is also in progress to streamline the document identification and curation process. These efforts will continue to bolster and expand the previous analysis, modeling, and validation capabilities of the database. Additionally, the database can be used to calibrate and evaluate pharmacokinetic models, therefore helping to improve pharmacokinetic models. In particular, the database facilitates efforts for quantitative assessment of in vitro – in vivo extrapolation (IVIVE). The public, open-source nature of the database is especially relevant to human health since it offers a means of sharing toxicokinetic data to improve transparent risk assessment of environmentally and occupationally relevant chemicals and exposure routes. This abstract does not necessarily represent the views or policies of the U.S. Environmental Protection Agency.