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Published on: August 28, 2019
FutureTox II: in vitro data and in silico models for predictive toxicology
Thomas B Knudsen1, Douglas A Keller2, Miriam Sander1
1United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, Sanofi, Bridgewater, New Jersey 08807, Page One Editorial Services, Boulder, Colorado 80304, Dow Chemical Company, Midland, Michigan 48674, Health and Environmental Sciences Institute, Washington, District of Columbia 20005, University of Washington, Seattle, Washington 98105, United States Food and Drug Administration, Silver Spring, Maryland 20993, Sanofi, Bethesda, Maryland 20814, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, University of North Carolina, Chapel Hill, North Carolina 27599, The Hamner Institutes, Research Triangle Park, North Carolina 27709, and European Commission Joint Research Centre, I-21027 Ispra, Italy.
FutureTox II explored predicting in vivo toxicity from in vitro and in silico data. Key challenges and future research needs were identified for improving toxicological risk assessment.
Area of Science:
- Toxicology
- Risk Assessment
- Computational Biology
Background:
- The workshop addressed the need to integrate new approach methodologies (NAMs) into toxicological evaluations.
- It focused on the National Research Council's 21st-century vision for predictive toxicology.
- The goal was to bridge the gap between in vitro/in silico data and in vivo outcomes.
Purpose of the Study:
- To review the current state of predictive toxicology science.
- To identify knowledge gaps and technological limitations in using non-animal testing methods.
- To define future research directions for regulatory toxicology.
Main Methods:
- Discussions and presentations at the FutureTox II workshop.
- Review of emerging technologies like stem cell models, organotypic cultures, and high-content imaging.
- Exploration of mathematical modeling and adverse outcome pathways (AOPs).
Main Results:
- Advances in predicting metabolism, cell growth, and effects on sensitive populations were discussed.
- Integration of in vitro/in silico data into risk assessment frameworks was evaluated.
- Knowledge gaps and technological limitations were identified across various toxicological endpoints.
Conclusions:
- Significant progress has been made towards an in vitro/in silico based risk assessment paradigm.
- Further research is needed in areas including hepatotoxicity, cancer prediction, and developmental toxicity.
- Recommendations were made to advance regulatory toxicology and reduce reliance on traditional animal testing.
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