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Database of pharmacokinetic time-series data and parameters for environmental chemicals
Citation:
Sayre, R., J. Wambaugh, AND Chris Grulke. Database of pharmacokinetic time-series data and parameters for environmental chemicals. Presented at SOT Annual Meeting, Baltimore, MD, March 10 - 14, 2019. https://doi.org/10.23645/epacomptox.7844492
Impact/Purpose:
This is a poster being submitted for the 2019 Society of Toxicology annual meeting in Baltimore, MD. It describes the content and assembly method of a database of pharmacokinetics data.
Description:
Time courses of compound concentrations in plasma are used in chemical safety analysis to evaluate the relationship between external administered doses and internal tissue exposures. This type of data is experimentally generated for chemicals like pharmaceuticals or cosmetics, but is not usually available for the thousands of other chemicals to which people may potentially be exposed. An understanding of the pharmacokinetics for these chemicals can be developed using in vitro assays and in silico models, but the certainty of the quantitative application of these estimates to chemical safety evaluations cannot be determined without in vivo data for external validation. To address this need, we present a public database of time-series from almost 600 studies in humans or test animals for over 150 environmentally-relevant chemicals and their metabolites by all major administration routes with concentrations measured in blood/plasma, tissues, and excreta. All information was sourced from either open databases or published literature identified using a suite of classifiers from SciKitLearn trained on the term frequency-inverse document frequency (TD-IDF) of the documents’ abstracts. Both the identified sources and the extracted pharmacokinetic time-series are stored in a MySQL data model with detailed, manually curated metadata. Concentration-time points were manually captured using the webtool WebPlotDigitizer. Data in all fields are normalized to facilitate comparisons, but original values are retained for transparency. Plots of the data will be viewable on the US EPA CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard), along with optimized pharmacokinetic summary parameters (e.g. area under the curve, volume of distribution) calculated using the R package invivopkfit. In addition to model calibration and validation, this set may be used for analyses of differential chemical distribution across chemicals, species, doses, or routes, and for meta-analyses on pharmacokinetic studies. The database can also host data and metadata needed for metabolism and pharmacokinetics test guideline studies. To facilitate data sharing we can accommodate and encourage submissions of structured published data on any compound. The views expressed in this presentation are those of the presenters and do not necessarily reflect the views or policies of the US EPA.
URLs/Downloads:
DOI: Database of pharmacokinetic time-series data and parameters for environmental chemicals
RRSAYRESOTPOSTER_01MAR2019.PDF (PDF, NA pp, 1052.399 KB, about PDF)