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L S Lautz1, R Oldenkamp1, J L Dorne2

  • 1Department of Environmental Science, Institute for Water and Wetland Research, Radboud University Nijmegen, Houtlaan 4, 6525 XP Nijmegen, The Netherlands.

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|May 11, 2019
PubMed
Summary

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Physiologically based kinetic (PBK) models for farm animals are numerous but often lack transparency. Further development is needed to improve their reliability for chemical risk assessment.

Area of Science:

  • Pharmacokinetics and toxicokinetics
  • Animal modeling
  • Risk assessment

Background:

  • Physiologically based kinetic (PBK) models are crucial for understanding chemical disposition in animals.
  • A comprehensive review of existing PBK models for common farm animal species was conducted.

Purpose of the Study:

  • To identify and critically assess PBK models for farm animals using WHO evaluation criteria.
  • To determine the suitability of current PBK models for chemical risk assessment in agriculture.

Main Methods:

  • Extensive literature search to identify PBK models in 10 common farm animal species.
  • Critical assessment of 39 identified PBK models based on purpose, structure, implementation, parameterization, performance, and documentation.
  • Evaluation of model calibration, validation, code availability, and sensitivity analysis methods.
Keywords:
Chemical risk assessmentFood safety, feed safetyPhysiologically-based kinetic models, farm animalsReview

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Main Results:

  • 39 PBK models were identified, primarily for pharmaceuticals.
  • Most models were calibrated (92%) and validated (67%), but model code publication (28%) and global sensitivity analysis were limited.
  • The reliability and applicability of current PBK models for chemical risk assessment are questionable due to methodological limitations.

Conclusions:

  • Current PBK models for farm animals have limitations in transparency and reliability, restricting their use in risk assessment.
  • Future PBK models should feature flexible structures, independent parameters, and robust performance assessment tools.
  • Development of structured databases for physiological and chemical-specific data is essential for advancing species-specific quantitative in vitro to in vivo extrapolation (QIVIVE) models.