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IVIVE: Facilitating the use of in vitro toxicity data in risk assessment and decision making



Xiaoqing Chang, Yu-Mei Tan, David Allen, Shannon Bell, Paul Brown, Lauren Browning, Patricia Ceger, Jeffery Gearhart, Pertti Hakkinen, Shruti Kabadi, Nicole Kleinstreuer, Annie Lumen, Joanna Matheson, Alicia Paini, Heather Pangburn, Elijah Petersen, Emily Reinke, Alexandre Ribeiro, Nisha Sipes, Lisa Sweeney, John Wambaugh, Ronald Wange, Barbara Wetmore, Moiz Mumtaz


During the past few decades, the science of toxicology has been undergoing transformation from an observational to a predictive science. New approach methodologies (NAMs) including in vitro, in silico models, read across, and in vitro to in vivo extrapolation (IVIVE) are being developed to reduce, refine or replace whole animal testing encouraging judicious use of time and resources. Some of these methods have advanced past the exploratory research stage and are beginning to gain acceptance for risk assessment of chemicals. Review of the recent literature reveals a burst of IVIVE publications over the past decade. In this review we proposed operational definitions for IVIVE, present specific case histories for several common toxicity endpoints and highlight their implications in decision making processes across various federal agencies, as well as international organizations including European Union (EU). The translational application of these methods to toxicity assessment and associated uncertainties are presented. In addition to refining and reducing the use of animals in traditional toxicity testing protocols and being used for prioritizing chemical testing, the goal to use IVIVE to facilitate replacement of animal models can be achieved through their continued evolution and development including a strategic plan of qualification towards acceptance.


Chang, X. , Tan, Y. , Allen, D. , Bell, S. , Brown, P. , Browning, L. , Ceger, P. , Gearhart, J. , Hakkinen, P. , Kabadi, S. , Kleinstreuer, N. , Lumen, A. , Matheson, J. , Paini, A. , Pangburn, H. , Petersen, E. , Reinke, E. , Ribeiro, A. , Sipes, N. , Sweeney, L. , Wambaugh, J. , Wange, R. , Wetmore, B. and Mumtaz, M. (2022), IVIVE: Facilitating the use of in vitro toxicity data in risk assessment and decision making, Toxics, [online], (Accessed May 28, 2024)


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Created May 1, 2022, Updated November 29, 2022