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In Vitro to In Vivo Extrapolation

A key issue encountered with high throughput, in vitro testing methods is how to accurately relate chemical concentrations that induce in vitro responses to in vivo exposure concentrations that result in human or animal illness or injury. This relationship is established through in vitro to in vivo extrapolation, the focus of a NICEATM webinar series. Subsequently, scientists interested in the use of IVIVE for chemical screening and risk decision-making met in February 2016 at a workshop co-organized by NICEATM and the U.S. Environmental Protection Agency to develop best practices and identify areas for further research.

Workshop report: Bell SM, Chang X, Wambaugh JF, Allen DG, Bartels M, Brouwer KLR, Casey WM, Choksi N, Ferguson SS, Fraczkiewicz G, Jarabek AM, Ke A, Lumen A, Lynn SG, Paini A, Price PS, Ring C, Simon TW, Sipes N, Sprankle CS, Strickland J, Troutman J, Wetmore BA, Kleinstreuer NC. 2018. In vitro to in vivo extrapolation for high throughput prioritization and decision making. Toxicology In Vitro 47:213-227.

NICEATM's computational toxicologists are developing methods for conducting IVIVE analyses. Current work is focused on understanding the impact of various parameters, such as using free plasma concentration as a surrogate for the total plasma concentration and comparing multiple modeling approaches. 

Chang X, Kleinstreuer N, Ceger P, Hsieh J-H, Allen D, Casey W. 2014. Application of reverse dosimetry to compare in vitro and in vivo estrogen receptor activity. Applied In Vitro Toxicology 1(1):33-44

Application of these IVIVE approaches to predicting the potential of chemicals to cause developmental toxicity and interact with the endocrine system was described in a poster presented at the 2017 SOT Annual Meeting (Chang et al.). A workflow for conducting these analyses is planned for a future release of the Integrated Chemical Environment resource.