Statistical relationship between metabolic decomposition and chemical uptake predicts bioconcentration factor data for diverse chemical exposures

Michael A. Rowland, Hannah Wear, Karen Watanabe-Sailor, Kurt A. Gust, Michael L. Mayo

Research output: Contribution to journalArticle


BACKGROUND: A challenge of in vitro to in vivo extrapolation (IVIVE) is to predict the physical state of organisms exposed to chemicals in the environment from in vitro exposure assay data. Although toxicokinetic modeling approaches promise to bridge in vitro screening data with in vivo effects, they are often encumbered by a need for redesign or re-parameterization when applied to different tissues or chemicals. RESULTS: We demonstrate a parameterization of reverse toxicokinetic (rTK) models developed for the adult zebrafish (Danio rerio) based upon particle swarm optimizations (PSO) of the chemical uptake and degradation rates that predict bioconcentration factors (BCF) for a broad range of chemicals. PSO reveals a relationship between chemical uptake and decomposition parameter values that predicts chemical-specific BCF values with moderate statistical agreement to a limited yet diverse chemical dataset, and all without a need to retrain the model to new data. CONCLUSIONS: The presented model requires only the octanol-water partitioning ratio to predict BCFs to a fidelity consistent with existing QSAR models. This success begs re-evaluation of the modeling assumptions; specifically, it suggests that chemical uptake into arterial blood may be limited by transport across gill membranes (diffusion) rather than by counter-current flow between gill lamellae (convection). Therefore, more detailed molecular modeling of aquatic respiration may further improve predictive accuracy of the rTK approach.

Original languageEnglish (US)
Number of pages1
JournalBMC systems biology
Issue number1
Publication statusPublished - Aug 7 2018
Externally publishedYes



  • Bioconcentration factors
  • Physiologically based toxicokinetics
  • Reverse toxicokinetics

ASJC Scopus subject areas

  • Structural Biology
  • Modeling and Simulation
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics

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