Toxicity testing in the 21st century: A vision and a strategy

Daniel Krewski, Daniel Acosta, Melvin Andersen, Henry Anderson, John C. Bailar, Kim Boekelheide, Robert Brent, Gail Charnley, Vivian G. Cheung, Sidney Green, Karl T. Kelsey, Nancy I. Kerkvliet, Abby A. Li, Lawrence McCray, Otto Meyer, Reid D. Patterson, William Pennie, Robert A. Scala, Gina M. Solomon, Martin L StephensJames D Yager, Lauren Zeise

Research output: Contribution to journalArticle

Abstract

With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal usage by transitioning from current expensive and lengthy in vivo testing with qualitative endpoints to in vitro toxicity pathway assays on human cells or cell lines using robotic high-throughput screening with mechanistic quantitative parameters. Risk assessment in the exposed human population would focus on avoiding significant perturbations in these toxicity pathways. Computational systems biology models would be implemented to determine the dose-response models of perturbations of pathway function. Extrapolation of in vitro results to in vivo human blood and tissue concentrations would be based on pharmacokinetic models for the given exposure condition. This practice would enhance human relevance of test results, and would cover several test agents, compared to traditional toxicological testing strategies. As all the tools that are necessary to implement the vision are currently available or in an advanced stage of development, the key prerequisites to achieving this paradigm shift are a commitment to change in the scientific community, which could be facilitated by a broad discussion of the vision, and obtaining necessary resources to enhance current knowledge of pathway perturbations and pathway assays in humans and to implement computational systems biology models. Implementation of these strategies would result in a new toxicity testing paradigm firmly based on human biology.

Original languageEnglish (US)
Pages (from-to)51-138
Number of pages88
JournalJournal of Toxicology and Environmental Health - Part B: Critical Reviews
Volume13
Issue number2-4
DOIs
StatePublished - Feb 2010

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Toxicity
Testing
Systems Biology
Computational Biology
Assays
Cells
Pharmacokinetics
Robotics
Extrapolation
Risk assessment
Toxicology
Screening
Animals
Blood
Throughput
Tissue
Cell Line
Population
In Vitro Techniques

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Toxicology

Cite this

Krewski, D., Acosta, D., Andersen, M., Anderson, H., Bailar, J. C., Boekelheide, K., ... Zeise, L. (2010). Toxicity testing in the 21st century: A vision and a strategy. Journal of Toxicology and Environmental Health - Part B: Critical Reviews, 13(2-4), 51-138. https://doi.org/10.1080/10937404.2010.483176

Toxicity testing in the 21st century : A vision and a strategy. / Krewski, Daniel; Acosta, Daniel; Andersen, Melvin; Anderson, Henry; Bailar, John C.; Boekelheide, Kim; Brent, Robert; Charnley, Gail; Cheung, Vivian G.; Green, Sidney; Kelsey, Karl T.; Kerkvliet, Nancy I.; Li, Abby A.; McCray, Lawrence; Meyer, Otto; Patterson, Reid D.; Pennie, William; Scala, Robert A.; Solomon, Gina M.; Stephens, Martin L; Yager, James D; Zeise, Lauren.

In: Journal of Toxicology and Environmental Health - Part B: Critical Reviews, Vol. 13, No. 2-4, 02.2010, p. 51-138.

Research output: Contribution to journalArticle

Krewski, D, Acosta, D, Andersen, M, Anderson, H, Bailar, JC, Boekelheide, K, Brent, R, Charnley, G, Cheung, VG, Green, S, Kelsey, KT, Kerkvliet, NI, Li, AA, McCray, L, Meyer, O, Patterson, RD, Pennie, W, Scala, RA, Solomon, GM, Stephens, ML, Yager, JD & Zeise, L 2010, 'Toxicity testing in the 21st century: A vision and a strategy', Journal of Toxicology and Environmental Health - Part B: Critical Reviews, vol. 13, no. 2-4, pp. 51-138. https://doi.org/10.1080/10937404.2010.483176
Krewski, Daniel ; Acosta, Daniel ; Andersen, Melvin ; Anderson, Henry ; Bailar, John C. ; Boekelheide, Kim ; Brent, Robert ; Charnley, Gail ; Cheung, Vivian G. ; Green, Sidney ; Kelsey, Karl T. ; Kerkvliet, Nancy I. ; Li, Abby A. ; McCray, Lawrence ; Meyer, Otto ; Patterson, Reid D. ; Pennie, William ; Scala, Robert A. ; Solomon, Gina M. ; Stephens, Martin L ; Yager, James D ; Zeise, Lauren. / Toxicity testing in the 21st century : A vision and a strategy. In: Journal of Toxicology and Environmental Health - Part B: Critical Reviews. 2010 ; Vol. 13, No. 2-4. pp. 51-138.
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