In vitro to in vivo Extrapolation:Facilitating Alternatives to Animal Testing in Chemical Health Risk Assessment
Data gap in both hazard and exposure is a formidable challenge which hinders the advance of chemical risk assessment.It has been increasingly expected to accelerate the pace of non-animal testing methods replacing animal tests since the 21st Century.New approach methodologies(NAMs),including in vitro assays,in silico models,read-across,and in vitro-in vivo extrapolation(IVIVE),are being effectively implemented to identify and address health risks of chemicals of concern.In the NAMs framework,toxicokinetic(absorption,distribution,metabolism and excretion,ADME)features play a crucial role,which need to be combined with the most valuable(sensitive)in vivo toxicity data through the IVIVE process,and thus leverage in vitro bioactivities to predict the corresponding in vivo exposures and thresholds of concern,and to enhance the optimum design strategies for chemical hazard assessment.In this review,focusing on the physiologically based toxicokinetic model-in vitro-in vivo extrapolation(PBTK-IVIVE)method,we propose the methodology connotation and strategy,as well as the technical framework and operational workflow of IVIVE,present case studies for typical applications,and highlight their implications to better support scientific and regulatory developments in chemical health risk.
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