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. 2020 Jun 19;177(1):281–299. doi: 10.1093/toxsci/kfaa088

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© The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Toxicology.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

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Figure 1. — Covalent protein binding (CPB) in human hepatocytes is not predictive of drug-induced liver injury (DILI) risk. A, The relationship between CPB measured in human hepatocytes and maximal human daily dose for compounds with a lack of (green circles) or the ability to cause (red x’s) liver injury in humans. Dashed line indicates CPB burden (CPB × maximum daily clinical dose) threshold of 0.75. B, CPB burden (CPB × maximum daily clinical dose) is plotted for the same compounds in (A). Dashed line indicates CPB burden threshold of 0.75. C, Matrix (2 × 2) of the association of DILI risk and CPB burden > 0.75. Red highlights number of true positives, green the number of true negatives. Abbreviations: Sens, sensitivity; Spec, specificity.