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. 2017 Jan;155(1):22-31.
doi: 10.1093/toxsci/kfw194. Epub 2016 Oct 25.

FutureTox III: Bridges for Translation

Daland R Juberg  1 , Thomas B Knudsen  2 , Miriam Sander  3 , Nancy B Beck  4 , Elaine M Faustman  5 , Donna L Mendrick  6 , John R Fowle 3rd  7 , Thomas Hartung  8 , Raymond R Tice  9 , Emmanuel Lemazurier  10 , Richard A Becker  4 , Suzanne Compton Fitzpatrick  11 , George P Daston  12 , Alison Harrill  13 , Ronald N Hines  2 , Douglas A Keller  14 , John C Lipscomb  15 , David Watson  16 , Tina Bahadori  17 , Kevin M Crofton  2
Affiliations

FutureTox III: Bridges for Translation

Daland R Juberg et al. Toxicol Sci. 2017 Jan.

Abstract

Future Tox III, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in November 2015. Building upon Future Tox I and II, Future Tox III was focused on developing the high throughput risk assessment paradigm and taking the science of in vitro data and in silico models forward to explore the question-what progress is being made to address challenges in implementing the emerging big-data toolbox for risk assessment and regulatory decision-making. This article reports on the outcome of the workshop including 2 examples of where advancements in predictive toxicology approaches are being applied within Federal agencies, where opportunities remain within the exposome and AOP domains, and how collectively the toxicology community across multiple sectors can continue to bridge the translation from historical approaches to Tox21 implementation relative to risk assessment and regulatory decision-making.

Keywords: in vitro and alternatives; predictive toxicology; regulatory/policy; risk assessment; testing alternatives..

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Figures

FIG. 1
FIG. 1
High throughput assays integrated into an ER predictive pathway model. Graphical representation of the computational network used in the in vitro analysis of the ER pathway across assays and technology platforms for EDSP Pivot. Colored arrow nodes represent “receptors” with which a chemical can directly interact. Colored circles represent intermediate biological processes that are not directly observable. White stars represent the in vitro assays that measure activity at the biological nodes. Arrows represent transfer of information. Gray arrow nodes are the pseudo-receptors. Each in vitro assay (with the exception of A16) has an assay-specific pseudo-receptor, but only a single example is explicitly shown, for assay A1. Source: Judson et al. 2015 (reuse permission license number 3903120062524).
FIG. 2
FIG. 2
Tier 1 alternative models in the endocrine disruptor screening program (EDSP). Estrogen receptor (ER) model is currently available; androgen receptor (AR), steroidogenesis (STR), thyroid (THY) models are still in development stages. The progression of testing is demonstrated at the time of the conference: Current (published), Anticipated (data on hand but not yet published), and Anticipated 2 (data being collected).
FIG. 3
FIG. 3
Comprehensive in vitro proarrhythmia assay: 4 components. The goal is to develop a new in vitro paradigm for cardiac safety evaluation of new drugs that provides a more accurate and comprehensive mechanistic-based assessment of proarrhythmic potential.
FIG. 4
FIG. 4
Moments of change. (A) The Sisyphus effect tipping over to the Snowball effect. (B) Keeping pace with changing scientific technologies that continue to overcome multiple tipping points toward high-throughput risk assessment (HTRA).
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References

    1. Andersen M. E., Krewski D. (2010). The vision of toxicity testing in the 21st century: Moving from discussion to action. Toxicol. Sci. 117, 17–24. - PubMed
    1. Ankley G. T., Bennett R. S., Erickson R. J., Hoff D. J., Hornung M. W., Johnson R. D., Mount D. R., Nichols J. W., Russom C. L., Schmieder P. K., et al. (2010). Adverse outcome pathways: A conceptual framework to support ecotoxicology research and risk assessment. Environ. Toxicol. Chem. 29, 730–741. - PubMed
    1. Boekelheide K., Campion S. N. (2010). Toxicity testing in the 21st century: Using the new toxicity testing paradigm to create a taxonomy of adverse effects. Toxicol. Sci. 114, 20–24. - PMC - PubMed
    1. Bouhifd M., Beger R., Flynn T., Guo L., Harris G., Hogberg H. T., Kaddurah-Daouk R., Kamp H., Kleensang A., Maertens A., et al. (2015). Quality assurance of metabolomics. ALTEX 32, 319–326. - PMC - PubMed
    1. Browne P., Judson R. S., Casey W. M., Kleinstreuer N. C., Thomas R. S. (2015). Screening chemicals for estrogen receptor bioactivity using a computational model. Environ. Sci. Technol. 49, 8804–8814. - PubMed

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