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Roadmap for Animal-free Reproductive Toxicity Testing: Predictive Toxicology and Computational Embryology
Citation:
KNUDSEN, T. B. Roadmap for Animal-free Reproductive Toxicity Testing: Predictive Toxicology and Computational Embryology. Presented at Scientific Roadmap for the Future of Animal-free Systemic Toxicity Testing Workshop (CAAT): U.S. Food and Drug Administration's Wiley Building, College Park, MD, May 30 - 31, 2013.
Impact/Purpose:
Hypothesis: A computer model that simulates cellular function in the growing embryo can be used to predict the potential impact of chemical exposure during pregnancy and lactation. Problem Statement: Scale: tens of thousands of chemicals, most lack toxicity information especially for reproduction and development. Paradigm: animal testing paradigm does not scale to the throughput needed for coverage of the chemical landscape. Sensitivity: current paradigm focuses on apical endpoints (malformations - tip of the iceberg for developmental toxicity). Robustness: developmental endpoints can have high background variability (even among controls), only ~61% species concordance. Summary: Multiscale modeling and simulation of biological complex system can be used to rapidly sweep many ‘what-if’ scenarios in silico: predictive toxicology - new way to model high-dimensional data; hypothesis generation - select the most plausible ideas for study temporal analysis - identify key events and causal relationships dose predictivity – predict dose-time exposure for an adverse effect
Description:
See attached Power Point Presentation.