Quantitative in vitro to in vivo extrapolation of cell-based toxicity assay results

  title={Quantitative in vitro to in vivo extrapolation of cell-based toxicity assay results},
  author={Miyoung Yoon and Jerry L. Campbell and Melvin E. Andersen and Harvey J. Clewell},
  journal={Critical Reviews in Toxicology},
  pages={633 - 652}
The field of toxicology is currently undergoing a global paradigm shift to use of in vitro approaches for assessing the risks of chemicals and drugs in a more mechanistic and high throughput manner than current approaches relying primarily on in vivo testing. However, reliance on in vitro data entails a number of new challenges associated with translating the in vitro results to corresponding in vivo exposures. Physiologically based pharmacokinetic (PBPK) modeling provides an effective… 
Use of Physiologically Based Kinetic Modeling-Based Reverse Dosimetry to Predict in Vivo Toxicity from in Vitro Data.
Since proofs-of-principle available so far have been provided for the prediction of toxicity in experimental animals, future research should focus on the use of in vitro toxicity data obtained in human models to predict the human situation using human PBK models to facilitate human- instead of experimental animal-based approaches in risk assessment.
Biokinetics and repeated exposure in in vitro assays : A detailed study into the behaviour of chlorpromazine and diazepam in different cell systems
By studying the in vitro biokinetics of CPZ in different cell systems, it is found that the compound distributes over the different compartments present in an in vitro system: medium, cells and plastic.
Species extrapolation of life-stage physiologically-based pharmacokinetic (PBPK) models to investigate the developmental toxicology of ethanol using in vitro to in vivo (IVIVE) methods.
Benefits and challenges are demonstrated associated with use of multispecies PBPK models to estimate in vivo tissue concentrations associated with in vitro embryotoxicity studies and a model-supported linkage of in vitro concentrations with plausible exposure ranges for pregnant women is demonstrated.
Considerations for Improving Metabolism Predictions for In Vitro to In Vivo Extrapolation
Current challenges in implementation of IVIVE for prioritization and risk assessment are discussed and a path forward for addressing the most pressing needs and expanding the utility of HT-IVIVE is recommended.
Advancing In Vitro-In Vivo Extrapolations of Mechanism-Specific Toxicity Data Through Toxicokinetic Modeling.
Different available options for in vitro-in vivo extrapolation (IVIVE) of mechanism-specific effects focused on fish species are described and the implications of confounding factors during the conduction of in vitro bioassays and their influence on the optimal choice of different dose metrics are reviewed.
Modeling Exposure in the Tox21 in Vitro Bioassays.
Effective membrane concentrations indicated that the specific effects of very hydrophobic chemicals in multiple bioassays are occurring at concentrations close to baseline toxicity.


Incorporating human dosimetry and exposure into high-throughput in vitro toxicity screening.
Many chemicals in commerce today have undergone limited or no safety testing. To reduce the number of untested chemicals and prioritize limited testing resources, several governmental programs are
Integration of dosimetry, exposure, and high-throughput screening data in chemical toxicity assessment.
The incorporation of dosimetry and exposure provide necessary context for interpretation of in vitro toxicity screening data and are important considerations in determining chemical testing priorities.
The use of in vitro toxicity data and physiologically based kinetic modeling to predict dose-response curves for in vivo developmental toxicity of glycol ethers in rat and man.
An approach to predict in vivo dose-response curves for developmental toxicity by combining in vitro toxicity data and in silico kinetic modeling is shown, which could provide a means to reduce the need for animal testing in human risk assessment practices.
Biokinetic Modeling and in Vitro–in Vivo Extrapolations
  • B. Blaauboer
  • Biology
    Journal of toxicology and environmental health. Part B, Critical reviews
  • 2010
The introduction of in vitro methodologies in the toxicological risk assessment process requires a number of prerequisites regarding both the toxicodynamics and the biokinetics of the compounds under study, and the application of physiologically based biokinetic modelling is essential.
Toxicodynamic modelling and the interpretation of in vitro toxicity data.
Measuring, modeling, and increasing the free Concentration of test Chemicals in cell assays
A good correlation between basal cytotoxicity and acute toxicity data from fathead minnow of 82 industrial organic chemicals is found and significant improvements to the correlation could be made if multiple cell types and endpoints are included in an in vitro test battery and the free concentration is determined for hydrophobic and volatile chemicals.
In vitro measurements of metabolism for application in pharmacokinetic modeling.
Methods for predicting in vivo pharmacokinetics using data from in vitro assays.
Strategies for optimising in vivo predictions from in vitro data on metabolic stability and CYP inhibition are discussed and perspectives for future application and improvements in these predictions strategies are outlined.