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EPA’s Concentration versus Time Database: A resource for extrapolating toxicokinetic parameters across chemicals
Citation:
Cook, C., L. Albrecht, G. Cary, B. Edwards, D. Haggard, N. Hanley, M. Hughes, A. Jarnagin, T. Kodavanti, E. Korol-Bexell, A. Kreutz, M. Ngo, C. Patullo, C. Ring, R. Sayre, B. Sharma, J. Wall, H. Yamazaki, AND J. Wambaugh. EPA’s Concentration versus Time Database: A resource for extrapolating toxicokinetic parameters across chemicals. North Carolina Society of Toxicology, Virtual, North Carolina, January 19, 2022. https://doi.org/10.23645/epacomptox.18624749
Impact/Purpose:
N/A
Description:
The Concentration versus Time Database (CvTdb) is a public repository of toxicokinetic (TK) data developed by the Center for Computational Toxicology and Exposure at the U.S. Environmental Protection Agency (EPA). The CvTdb contains manually curated experimental time-course data of chemical compound concentrations in body fluids and tissues, along with descriptive metadata, from hundreds of publications. The CvTdb is a “living” repository, to which new data can be added as they become available. Recent efforts have been made to 1) Expand the scope of in-house data curation and 2) Integrate sets of CvT data shared by other institutions. To standardize the format of data extracted from numerous publications, by several curators, we developed an R Shiny application that checks completed template curation files for bother format and data correctness. New data sets include those from collaborators of Showa Pharmaceutical University with more than 200 compounds. Standardized data reporting allows for analysis of TK trends across studies. For example, we observe that among replicate observations (those with common chemical/reference/dose/route/timepoint data), 84.9% are within two-fold of the mean concentration. When the data are subset by route, we observe that 83.3% of oral administration observations, and 87.5% of intravenous administration observations, are within two-fold of the mean concentration. Data are systematically analyzed using invivoPKfit, an R package that fits standardized 1- and 2- compartmental TK models to all data associated with a particular compound, including data that spans multiple references. We used invivoPKfit to fit models and estimate TK parameters, such as volume of distribution and elimination half-life. Overall, the CvTdb serves as a platform for assessing TK trends across a large and standardized set of data, as well as for calibrating and validating TK models.
URLs/Downloads:
DOI: EPA’s Concentration versus Time Database: A resource for extrapolating toxicokinetic parameters across chemicals
COOK_SOT_POSTER.PDF (PDF, NA pp, 2616.353 KB, about PDF)