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Toxicity testing in the 21st century: progress in the past decade and future perspectives

Abstract

Advances in the biological sciences have led to an ongoing paradigm shift in toxicity testing based on expanded application of high-throughput in vitro screening and in silico methods to assess potential health risks of environmental agents. This review examines progress on the vision for toxicity testing elaborated by the US National Research Council (NRC) during the decade that has passed since the 2007 NRC report on Toxicity Testing in the 21st Century (TT21C). Concomitant advances in exposure assessment, including computational approaches and high-throughput exposomics, are also documented. A vision for the next generation of risk science, incorporating risk assessment methodologies suitable for the analysis of new toxicological and exposure data, resulting in human exposure guidelines is described. Case study prototypes indicating how these new approaches to toxicity testing, exposure measurement, and risk assessment are beginning to be applied in practice are presented. Overall, progress on the 20-year transition plan laid out by the US NRC in 2007 has been substantial. Importantly, government agencies within the United States and internationally are beginning to incorporate the new approach methodologies envisaged in the original TT21C vision into regulatory practice. Future perspectives on the continued evolution of toxicity testing to strengthen regulatory risk assessment are provided.

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Adapted from NIH BioSystems #83115 (KEGG: hsa05219, 2015) (color figure online)

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Acknowledgements

The authors gratefully acknowledge the input of Drs. Patrick McMullen and Miyoung Yoon to parts of this article. The authors would also like to thank Drs. Maureen Gwinn and Sean Collins for helpful comments, which served to improve the original draft of this article. We also thank Abdallah Alami for assistance in the final formatting of the manuscript and supplementary material. D. Krewski is the Natural Sciences and Engineering Research Council of Canada Chair in Risk Science at the University of Ottawa.

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Krewski, D., Andersen, M.E., Tyshenko, M.G. et al. Toxicity testing in the 21st century: progress in the past decade and future perspectives. Arch Toxicol 94, 1–58 (2020). https://doi.org/10.1007/s00204-019-02613-4

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Keywords

  • Toxicity testing
  • New approach methodologies
  • Computational toxicology
  • High-throughput in vitro testing
  • High-throughput exposomics
  • High-throughput pharmacokinetics
  • In vitro to in vivo extrapolation