Quantitative in vitro to in vivo extrapolation of stem cell-based toxicity data to predict developmental toxicity dose levels

2014 ◽  
Vol 229 ◽  
pp. S13
Author(s):  
Jochem Louisse
Keyword(s):  
Stem Cell ◽  
Developmental Toxicity ◽  
Toxicity Data ◽  
Dose Levels ◽  
In Vivo Extrapolation

scholarly journals 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

2010 ◽  
Vol 118 (2) ◽  
pp. 470-484 ◽  
Author(s):  
Jochem Louisse ◽  
Esther de Jong ◽  
Johannes J. M. van de Sandt ◽  
Bas J. Blaauboer ◽  
Ruud A. Woutersen ◽  
...  
Keyword(s):  
Kinetic Modeling ◽  
Dose Response ◽  
Developmental Toxicity ◽  
In Vitro Toxicity ◽  
Toxicity Data ◽  
Glycol Ethers ◽  
Response Curves ◽  
Physiologically Based

scholarly journals Profiling the ToxCast Library With a Pluripotent Human (H9) Stem Cell Line-Based Biomarker Assay for Developmental Toxicity

2020 ◽  
Vol 174 (2) ◽  
pp. 189-209 ◽  
Author(s):  
Todd J Zurlinden ◽  
Katerine S Saili ◽  
Nathaniel Rush ◽  
Parth Kothiya ◽  
Richard S Judson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Animal Studies ◽  
Developmental Toxicity ◽  
Embryonic Stem ◽  
High Specificity ◽  
Chemical Exposure ◽  
Toxicity Screening ◽  
In Silico Models

Abstract The Stemina devTOX quickPredict platform is a human pluripotent stem cell-based assay that predicts the developmental toxicity potential based on changes in cellular metabolism following chemical exposure [Palmer, J. A., Smith, A. M., Egnash, L. A., Conard, K. R., West, P. R., Burrier, R. E., Donley, E. L. R., and Kirchner, F. R. (2013). Establishment and assessment of a new human embryonic stem cell-based biomarker assay for developmental toxicity screening. Birth Defects Res. B Dev. Reprod. Toxicol. 98, 343–363]. Using this assay, we screened 1065 ToxCast phase I and II chemicals in single-concentration or concentration-response for the targeted biomarker (ratio of ornithine to cystine secreted or consumed from the media). The dataset from the Stemina (STM) assay is annotated in the ToxCast portfolio as STM. Major findings from the analysis of ToxCast_STM dataset include (1) 19% of 1065 chemicals yielded a prediction of developmental toxicity, (2) assay performance reached 79%–82% accuracy with high specificity (> 84%) but modest sensitivity (< 67%) when compared with in vivo animal models of human prenatal developmental toxicity, (3) sensitivity improved as more stringent weights of evidence requirements were applied to the animal studies, and (4) statistical analysis of the most potent chemical hits on specific biochemical targets in ToxCast revealed positive and negative associations with the STM response, providing insights into the mechanistic underpinnings of the targeted endpoint and its biological domain. The results of this study will be useful to improving our ability to predict in vivo developmental toxicants based on in vitro data and in silico models.

scholarly journals Biotransformation in vitro: An essential consideration in the quantitative in vitro-to-in vivo extrapolation (QIVIVE) of toxicity data

Toxicology ◽  
2015 ◽  
Vol 332 ◽  
pp. 8-19 ◽  
Author(s):  
Iwona Wilk-Zasadna ◽  
Camilla Bernasconi ◽  
Olavi Pelkonen ◽  
Sandra Coecke
Keyword(s):  
Toxicity Data ◽  
In Vivo Extrapolation

Use of physiologically based kinetic modeling-facilitated reverse dosimetry of in vitro toxicity data for prediction of in vivo developmental toxicity of tebuconazole in rats

2017 ◽  
Vol 266 ◽  
pp. 85-93 ◽  
Author(s):  
Hequn Li ◽  
Mengying Zhang ◽  
Jacques Vervoort ◽  
Ivonne M.C.M. Rietjens ◽  
Bennard van Ravenzwaay ◽  
...  
Keyword(s):  
Kinetic Modeling ◽  
Developmental Toxicity ◽  
In Vitro Toxicity ◽  
Toxicity Data ◽  
Reverse Dosimetry ◽  
Physiologically Based
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