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

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-weighting scheme known as “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. All data, metadata, calculated pharmacokinetic parameters, and scripts are openly available at https://github.com/USEPA/CompTox-PK-CvTdb. 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 encourage submissions through our GitHub of structured published data on any compound.

This abstract does not necessarily reflect U.S. EPA policy.