{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T13:19:19Z","timestamp":1789823959006,"version":"4.0.1"},"reference-count":33,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000038","name":"US Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology and Applied Pharmacology"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1016\/j.taap.2026.117832","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T16:05:23Z","timestamp":1776701123000},"page":"117832","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Translating in vitro mechanistic findings to in vivo toxicity outcomes: A case study of Usnic acid hepatotoxicity"],"prefix":"10.1016","volume":"512","author":[{"given":"Yitong","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiugong","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Eckstrum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla","family":"Campasino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyra","family":"Headrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.taap.2026.117832_bb0005","doi-asserted-by":"crossref","first-page":"315","DOI":"10.3390\/toxics9110315","article-title":"Update and evaluation of a high-throughput in vitro mass balance distribution model: IV-MBM EQP v2.0","volume":"9","author":"Armitage","year":"2021","journal-title":"Toxics"},{"key":"10.1016\/j.taap.2026.117832_bb0010","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1002\/em.22521","article-title":"Quantitative in vitro to in vivo extrapolation of genotoxicity data provides protective estimates of in vivo dose","volume":"64","author":"Beal","year":"2023","journal-title":"Environ. Mol. Mutagen."},{"key":"10.1016\/j.taap.2026.117832_bb0015","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/s41573-025-01182-9","article-title":"Application of new approach methodologies for nonclinical safety assessment of drug candidates","volume":"24","author":"Beilmann","year":"2025","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.taap.2026.117832_bb0020","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1002\/bdr2.2019","article-title":"Quantitative in vitro to in vivo extrapolation for developmental toxicity potency of valproic acid analogues","volume":"114","author":"Chang","year":"2022","journal-title":"Birth Defects Res"},{"key":"10.1016\/j.taap.2026.117832_bb0025","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3390\/toxics10050232","article-title":"IVIVE: facilitating the use of in vitro toxicity data in risk assessment and decision making","volume":"10","author":"Chang","year":"2022","journal-title":"Toxics"},{"key":"10.1016\/j.taap.2026.117832_bb0030","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/toxsci\/kfu154","article-title":"The role of autophagy in usnic acid-induced toxicity in hepatic cells","volume":"142","author":"Chen","year":"2014","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.taap.2026.117832_bb0035","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1093\/toxsci\/kfv075","article-title":"Endoplasmic reticulum stress and store-operated calcium entry contribute to usnic acid-induced toxicity in hepatic cells","volume":"146","author":"Chen","year":"2015","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.taap.2026.117832_bb0040","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1007\/s00204-016-1775-y","article-title":"Activation of the nrf2 signaling pathway in usnic acid-induced toxicity in HepG2 cells","volume":"91","author":"Chen","year":"2017","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.taap.2026.117832_bb0045","first-page":"1","article-title":"Hepatotoxicity of usnic acid and underlying mechanisms","volume":"43","author":"Chen","year":"2025","journal-title":"J Environ Sci Health C Toxicol Carcinog"},{"key":"10.1016\/j.taap.2026.117832_bb0050","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00114-002-0305-3","article-title":"A review on usnic acid, an interesting natural compound","volume":"89","author":"Cocchietto","year":"2002","journal-title":"Naturwissenschaften"},{"key":"10.1016\/j.taap.2026.117832_bb0055","doi-asserted-by":"crossref","DOI":"10.1016\/j.fct.2022.112828","article-title":"Evaluation of the utility of the beta human liver emulation system (BHLES) for CFSAN\u2019S regulatory toxicology program","volume":"161","author":"Eckstrum","year":"2022","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.taap.2026.117832_bb0060","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1080\/00498250701802514","article-title":"Metabolism and related human risk factors for hepatic damage by usnic acid containing nutritional supplements","volume":"38","author":"Foti","year":"2008","journal-title":"Xenobiotica"},{"key":"10.1016\/j.taap.2026.117832_bb0065","doi-asserted-by":"crossref","DOI":"10.1016\/j.tox.2025.154189","article-title":"Enantiospecific hepatotoxicity of usnic acid in vitro, and the attempt to modify the toxic effect","volume":"516","author":"Galanty","year":"2025","journal-title":"Toxicology"},{"key":"10.1016\/j.taap.2026.117832_bb0070","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s10565-017-9383-z","article-title":"A transcriptomic study suggesting human iPSC-derived hepatocytes potentially offer a better in vitro model of hepatotoxicity than most hepatoma cell lines","volume":"33","author":"Gao","year":"2017","journal-title":"Cell Biol. Toxicol."},{"key":"10.1016\/j.taap.2026.117832_bb0075","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1002\/jat.4620","article-title":"Oxidative DNA damage contributes to usnic acid-induced toxicity in human induced pluripotent stem cell-derived hepatocytes","volume":"44","author":"Gao","year":"2024","journal-title":"J. Appl. Toxicol."},{"key":"10.1016\/j.taap.2026.117832_bb0080","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1124\/dmd.105.007658","article-title":"Binding of drugs to hepatic microsomes: comment and assessment of current prediction methodology with recommendation for improvement","volume":"34","author":"Hallifax","year":"2006","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.taap.2026.117832_bb0085","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/S0031-9422(02)00383-7","article-title":"Usnic acid","volume":"61","author":"Ingolfsdottir","year":"2002","journal-title":"Phytochemistry"},{"key":"10.1016\/j.taap.2026.117832_bb0090","doi-asserted-by":"crossref","DOI":"10.1016\/j.yrtph.2019.104515","article-title":"State of the science on alternatives to animal testing and integration of testing strategies for food safety assessments: workshop proceedings","volume":"110","author":"Karmaus","year":"2020","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.taap.2026.117832_bb0095","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/S0090-9556(25)08813-0","article-title":"Pharmacokinetics of d(+)-usnic acid in rabbits after intravenous and oral administration","volume":"20","author":"Krishna","year":"1992","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.taap.2026.117832_bb0100","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.yrtph.2007.12.001","article-title":"Application of PBPK modeling in support of the derivation of toxicity reference values for 1,1,1-trichloroethane","volume":"50","author":"Lu","year":"2008","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.taap.2026.117832_bb0105","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s40262-019-00741-9","article-title":"Physiologically based pharmacokinetic modelling for first-in-human predictions: An updated model building strategy illustrated with challenging industry case studies","volume":"58","author":"Miller","year":"2019","journal-title":"Clin. Pharmacokinet."},{"key":"10.1016\/j.taap.2026.117832_bb0110","doi-asserted-by":"crossref","first-page":"1373325","DOI":"10.3389\/ftox.2024.1373325","article-title":"Use of quantitative in vitro to in vivo extrapolation (QIVIVE) for the assessment of non-combustible next-generation product aerosols","volume":"6","author":"Moreau","year":"2024","journal-title":"Front Toxicol"},{"key":"10.1016\/j.taap.2026.117832_bb0115","unstructured":"OECD, 2025. Principles of quantitative in vitro to in vivo extrapolation (QIVIVE) - as example applied to the DNT IVB. In OECD,OECD series on testing and assessment no 411."},{"key":"10.1016\/j.taap.2026.117832_bb0120","first-page":"714","article-title":"Ways to broaden the awareness, consideration and adoption of new approach methodologies (NAMs)","volume":"42","author":"Oyetade","year":"2025","journal-title":"ALTEX"},{"key":"10.1016\/j.taap.2026.117832_bb0125","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.fct.2018.07.005","article-title":"Usnic acid reactive metabolites formation in human, rat, and mice microsomes. Implication for hepatotoxicity","volume":"120","author":"Piska","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.taap.2026.117832_bb0130","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0041-008X(88)90155-X","article-title":"Physiologically based pharmacokinetic modeling with methylchloroform: implications for interspecies, high dose\/low dose, and dose route extrapolations","volume":"95","author":"Reitz","year":"1988","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.taap.2026.117832_bb0135","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1002\/jat.1721","article-title":"Effects of usnic acid exposure on human hepatoblastoma HepG2 cells in culture","volume":"32","author":"Sahu","year":"2012","journal-title":"J. Appl. Toxicol."},{"key":"10.1016\/j.taap.2026.117832_bb0140","doi-asserted-by":"crossref","DOI":"10.1093\/toxres\/tfae044","article-title":"New approach methodologies (NAMs): identifying and overcoming hurdles to accelerated adoption","volume":"13","author":"Sewell","year":"2024","journal-title":"Toxicol. Res."},{"key":"10.1016\/j.taap.2026.117832_bb0145","doi-asserted-by":"crossref","DOI":"10.1289\/EHP1289","article-title":"A web-based system for bayesian benchmark dose estimation","volume":"126","author":"Shao","year":"2018","journal-title":"Environ. Health Perspect."},{"key":"10.1016\/j.taap.2026.117832_bb0150","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1021\/acs.chemrestox.5c00161","article-title":"Applying new approach methods for toxicokinetics for chemical risk assessment","volume":"38","author":"Wambaugh","year":"2025","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.taap.2026.117832_bb0155","doi-asserted-by":"crossref","DOI":"10.1002\/bmc.4139","article-title":"Simultaneous determination of usnic, diffractaic, evernic and barbatic acids in rat plasma by ultra-high-performance liquid chromatography-quadrupole exactive orbitrap mass spectrometry and its application to pharmacokinetic studies","volume":"32","author":"Wang","year":"2018","journal-title":"Biomed. Chromatogr."},{"key":"10.1016\/j.taap.2026.117832_bb0160","doi-asserted-by":"crossref","first-page":"7469","DOI":"10.3390\/molecules27217469","article-title":"Advances in research on bioactivity, toxicity, metabolism, and pharmacokinetics of usnic acid in vitro and in vivo","volume":"27","author":"Wang","year":"2022","journal-title":"Molecules"},{"key":"10.1016\/j.taap.2026.117832_bb0165","doi-asserted-by":"crossref","first-page":"1207928","DOI":"10.3389\/fphar.2023.1207928","article-title":"Metabolism and toxicity of usnic acid and barbatic acid based on microsomes, s9 fraction, and 3T3 fibroblasts in vitro combined with a UPLC-Q-TOF-MS method","volume":"14","author":"Wang","year":"2023","journal-title":"Front. Pharmacol."}],"container-title":["Toxicology and Applied Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X26001286?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X26001286?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:40:00Z","timestamp":1784767200000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0041008X26001286"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":33,"alternative-id":["S0041008X26001286"],"URL":"https:\/\/doi.org\/10.1016\/j.taap.2026.117832","relation":{},"ISSN":["0041-008X"],"issn-type":[{"value":"0041-008X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Translating in vitro mechanistic findings to in vivo toxicity outcomes: A case study of Usnic acid hepatotoxicity","name":"articletitle","label":"Article Title"},{"value":"Toxicology and Applied Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.taap.2026.117832","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"117832"}}