Citation:

Krewski, D., M. Andersen, M. Tyshenko, K. Krishnan, T. Hartung, K. Boekelheide, J. Wambaugh, D. Jones, M. Whelan, R. Thomas, C. Yauk, T. Barton-Maclaren, AND I. Cote. (Archives of Toxicology) Toxicity Testing in the 21st Century: Progress in the Past Decade and Future Perspectives. Archives of Toxicology. Springer, New York, NY, 94(1):1-58, (2020). https://doi.org/10.1007/s00204-019-02613-4

Impact/Purpose:

In 2007, the US National Research Council (NRC) published a landmark report on Toxicity Testing in the 21st Century, which put forward a long-term strategy designed to take advantage of new tools and technologies to increase the efficiency of toxicity testing in order to permit the assessment of the large numbers of environmental agents to which human populations may be exposed (NRC 2007). Key elements of the use of this strategy included increased use of high-throughput in vitro test systems and methods in computational toxicology, with less reliance on more time-consuming and costly toxicological studies using experimental animals. The NRC vision has received widespread support internationally, and has provided a blueprint for change in toxicological science. A subsequent NRC report on Exposure Science in the 21st Century provided a parallel vision for the advance of exposure science (NRC 2012) emphasising high-throughput exposomics and computational methods for exposure assessment. The US Environmental Protection Agency’s NexGen initiative subsequently integrated new developments in toxicological risk assessment within an overarching framework for the Next Generation of Risk Science (EPA 2014). This paper provides a review and update on the NRC vision, including concomitant advances in risk science, and applications in assessing the risks of environmental agents.

Description:

Advances in the biological sciences have led to an ongoing paradigm shift in toxicity testing, based on expanded application of high-through put 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 also 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 appears to be both substantial and even ahead of schedule. 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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