Time courses of compound concentrations in plasma and other tissues are used to evaluate the relationship between external administered doses and internal tissue exposures. As internal exposure is relevant when assessing the potential risk a chemical poses in the environment. This type of data is usually unavailable for the thousands of chemicals in the environment. Understanding the pharmacokinetics for such 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 requires in vivo data for external evaluation. To address this need, we present a workflow for the extraction of pharmacokinetic time-series data from publications and the resulting public database of time-series from almost 600 studies in humans or test animals. This database currently contains over 150 environmentally-relevant chemicals and their metabolites, all major administration routes, and concentrations measured in blood/plasma, tissues, and/or excreta. All information in the database 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 database 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 are intended for dissemination through the US EPA CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard), along with this associated optimized pharmacokinetic summary parameters (e.g. area under the curve, volume of distribution) calculated using the R package invivopkfit (https://github.com/USEPA/CompTox-ExpoCast-invivoPKfit). To facilitate data sharing we can accommodate and encourage submissions of structured published data on any compound. This abstract does not necessarily reflect U.S. EPA policy.

Database of pharmacokinetic time-series data and parameters for evaluating the safety of environmental chemicals

2019 Spring National Meeting

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