{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:10:54Z","timestamp":1792696254405,"version":"4.5.0"},"reference-count":51,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Malaysia Ministry of Higher Education","doi-asserted-by":"publisher","award":["FRGS\/1\/2023\/SKK06\/AIMST\/03\/2"],"award-info":[{"award-number":["FRGS\/1\/2023\/SKK06\/AIMST\/03\/2"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology in Vitro"],"published-print":{"date-parts":[[2025,8]]},"DOI":"10.1016\/j.tiv.2025.106062","type":"journal-article","created":{"date-parts":[[2025,4,6]],"date-time":"2025-04-06T09:43:46Z","timestamp":1743932626000},"page":"106062","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Integrative toxicity assessment of tocotrienol-rich fraction from palm oil using in silico methods and zebrafish embryotoxicity model"],"prefix":"10.1016","volume":"107","author":[{"given":"Thenmoly","family":"Damodaran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najib Sani","family":"Yahaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Nizam","family":"Mordi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"54B","key":"10.1016\/j.tiv.2025.106062_bb0005","doi-asserted-by":"crossref","first-page":"106","DOI":"10.9734\/jpri\/2021\/v33i54B33771","article-title":"Tocotrienol-rich fraction modulated genes responsible for inflammation in lipopolysaccharide-stimulated RAW 264.7 macrophages","volume":"33","author":"Abd Hafid","year":"2021","journal-title":"J. Pharm. Res. Int."},{"issue":"10","key":"10.1016\/j.tiv.2025.106062_bb0010","doi-asserted-by":"crossref","DOI":"10.1002\/cbdv.202000422","article-title":"In silico and in vivo toxicological evaluation of Paeonol","volume":"17","author":"Adki","year":"2020","journal-title":"Chem. Biodivers."},{"issue":"11","key":"10.1016\/j.tiv.2025.106062_bb0015","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1016\/j.bcp.2010.07.043","article-title":"Tocotrienols, the vitamin E of the 21st century: its potential against cancer and other chronic diseases","volume":"80","author":"Aggarwal","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.tiv.2025.106062_bb0020","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.83883","article-title":"Urotensin II-related peptides, Urp1 and Urp2, control zebrafish spine morphology","volume":"11","author":"Bearce","year":"2022","journal-title":"Elife"},{"issue":"6","key":"10.1016\/j.tiv.2025.106062_bb0025","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.3390\/ijms20061372","article-title":"Biological activity and in silico study of 3-modified derivatives of betulin and betulinic aldehyde","volume":"20","author":"B\u0119benek","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.tiv.2025.106062_bb0030","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.3389\/fphar.2019.01572","article-title":"An update on the structure of hERG","volume":"10","author":"Butler","year":"2020","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.tiv.2025.106062_bb0035","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.714918","article-title":"Comparative toxicity assessment of kratom decoction, mitragynine and speciociliatine versus morphine on zebrafish (Danio rerio) embryos","volume":"12","author":"Damodaran","year":"2021","journal-title":"Front. Pharmacol."},{"issue":"4","key":"10.1016\/j.tiv.2025.106062_bb0040","doi-asserted-by":"crossref","first-page":"710","DOI":"10.3390\/ijms18040710","article-title":"Triazole fungicides inhibit zebrafish hatching by blocking the secretory function of hatching gland cells","volume":"18","author":"De la Paz","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.tiv.2025.106062_bb0045","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/nar\/gku401","article-title":"ProTox: a web server for the in silico prediction of rodent oral toxicity","volume":"42","author":"Drwal","year":"2014","journal-title":"Nucleic Acids Res."},{"issue":"2","key":"10.1016\/j.tiv.2025.106062_bb0050","doi-asserted-by":"crossref","first-page":"776","DOI":"10.3390\/molecules28020776","article-title":"Evaluation of free online ADMET tools for academic or small biotech environments","volume":"28","author":"Dulsat","year":"2023","journal-title":"Molecules"},{"key":"10.1016\/j.tiv.2025.106062_bb0055","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1023\/A:1021828132707","article-title":"Palm oil: biochemical, physiological, nutritional, hematological and toxicological aspects: a review","volume":"57","author":"Edem","year":"2002","journal-title":"Plant Foods Hum. Nutr."},{"issue":"15","key":"10.1016\/j.tiv.2025.106062_bb0060","doi-asserted-by":"crossref","first-page":"5807","DOI":"10.1021\/es8005173","article-title":"Evolutionary conservation of human drug targets in organisms used for environmental risk assessments","volume":"42","author":"Gunnarsson","year":"2008","journal-title":"Environ. Sci. Technol."},{"key":"10.1016\/j.tiv.2025.106062_bb0065","article-title":"The antioxidant activity of tocotrienols compared with some synthetic antioxidant","volume":"2014","author":"Hamdo","year":"2014","journal-title":"Pharmacol. Pharm."},{"issue":"1","key":"10.1016\/j.tiv.2025.106062_bb0070","doi-asserted-by":"crossref","first-page":"4777","DOI":"10.1038\/ncomms5777","article-title":"ptk7 mutant zebrafish models of congenital and idiopathic scoliosis implicate dysregulated Wnt signalling in disease","volume":"5","author":"Hayes","year":"2014","journal-title":"Nat. Commun."},{"issue":"1","key":"10.1016\/j.tiv.2025.106062_bb0075","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1093\/toxsci\/kfh056","article-title":"Water permeability and TCDD-induced edema in zebrafish early-life stages","volume":"78","author":"Hill","year":"2004","journal-title":"Toxicol. Sci."},{"issue":"7446","key":"10.1016\/j.tiv.2025.106062_bb0080","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/nature12111","article-title":"The zebrafish reference genome sequence and its relationship to the human genome","volume":"496","author":"Howe","year":"2013","journal-title":"Nat"},{"issue":"2","key":"10.1016\/j.tiv.2025.106062_bb0085","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2174\/156720207780637234","article-title":"The zebrafish model: use in studying cellular mechanisms for a spectrum of clinical disease entities","volume":"4","author":"Hsu","year":"2007","journal-title":"Curr. Neurovasc. Res."},{"issue":"2","key":"10.1016\/j.tiv.2025.106062_bb0090","doi-asserted-by":"crossref","first-page":"166","DOI":"10.3923\/jpt.2011.166.173","article-title":"Subacute and subchronic toxicity studies of palm vitamin E in mice","volume":"6","author":"Ima-Nirwana","year":"2011","journal-title":"J. Pharmacol. Toxicol."},{"issue":"3","key":"10.1016\/j.tiv.2025.106062_bb0095","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/aja.1002030302","article-title":"Stages of embryonic development of the zebrafish","volume":"203","author":"Kimmel","year":"1995","journal-title":"Dev Dynam"},{"key":"10.1016\/j.tiv.2025.106062_bb0100","first-page":"41","article-title":"Cassia alata leaf methanolic extracts decreased melanin pigmentation in Zebrafish","volume":"47","author":"Lelina","year":"2020","journal-title":"Philipp. J. Nat. Sci."},{"issue":"16","key":"10.1016\/j.tiv.2025.106062_bb0105","doi-asserted-by":"crossref","first-page":"2942","DOI":"10.3390\/w15162942","article-title":"Developmental toxicities in zebrafish embryos exposed to tri-o-cresyl phosphate","volume":"15","author":"Li","year":"2023","journal-title":"Water"},{"issue":"21","key":"10.1016\/j.tiv.2025.106062_bb0110","doi-asserted-by":"crossref","first-page":"4632","DOI":"10.3390\/nu14214632","article-title":"Tocotrienol-rich fraction and levodopa regulate proteins involved in Parkinson\u2019s disease-associated pathways in differentiated neuroblastoma cells: insights from quantitative proteomic analysis","volume":"14","author":"Magalingam","year":"2022","journal-title":"Nutrients"},{"issue":"12","key":"10.1016\/j.tiv.2025.106062_bb0115","first-page":"385","article-title":"Modulation of melanin synthesis and its gene expression in skin melanocytes by palm tocotrienol rich fraction","volume":"3","author":"Makpol","year":"2009","journal-title":"Afr. J. Biochem. Res."},{"issue":"1","key":"10.1016\/j.tiv.2025.106062_bb0120","first-page":"e39","article-title":"Comparable down-regulation of TYR, TYRP1 and TYRP2 genes and inhibition of melanogenesis by tyrostat, tocotrienol-rich fraction and tocopherol in human skin melanocytes improves skin pigmentation","volume":"165","author":"Makpol","year":"2014","journal-title":"Clin. Ter."},{"issue":"2","key":"10.1016\/j.tiv.2025.106062_bb0125","first-page":"47","article-title":"Oxidative stress status and neuroprotection of tocotrienols in chronic cerebral hypoperfusion-induced neurodegeneration rat animal model","volume":"8","author":"Mohamed","year":"2018","journal-title":"Int. J. Nutr. Pharmacol. Neurol. Dis."},{"issue":"8","key":"10.1016\/j.tiv.2025.106062_bb0130","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/S0278-6915(01)00025-4","article-title":"Oral toxicity of a tocotrienol preparation in rats","volume":"39","author":"Nakamura","year":"2001","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.tiv.2025.106062_bb0135","doi-asserted-by":"crossref","DOI":"10.3389\/fnut.2021.754086","article-title":"An interactive review on the role of Tocotrienols in the neurodegenerative disorders","volume":"8","author":"Naomi","year":"2021","journal-title":"Front. Nutr."},{"issue":"20","key":"10.1016\/j.tiv.2025.106062_bb0140","doi-asserted-by":"crossref","first-page":"15373","DOI":"10.3390\/ijms242015373","article-title":"Tocotrienol-rich fraction attenuates blue light-induced oxidative stress and Melanogenesis in B16-F1 melanocytes via anti-oxidative and anti-Tyrosinase properties","volume":"24","author":"Neo","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.tiv.2025.106062_bb0145","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2020.113538","article-title":"Developmental toxicity of Clerodendrum cyrtophyllum turcz ethanol extract in zebrafish embryo","volume":"267","author":"Nguyen","year":"2021","journal-title":"J. Ethnopharmacol."},{"issue":"6","key":"10.1016\/j.tiv.2025.106062_bb0150","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3390\/antiox7060074","article-title":"Comparing palm oil, tocotrienol-rich fraction and \u03b1-tocopherol supplementation on the antioxidant levels of older adults","volume":"7","author":"Nor Azman","year":"2018","journal-title":"Antioxidants"},{"issue":"2","key":"10.1016\/j.tiv.2025.106062_bb0155","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s00204-023-03633-x","article-title":"Analysis of vascular disruption in zebrafish embryos as an endpoint to predict developmental toxicity","volume":"98","author":"N\u00f6th","year":"2024","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.tiv.2025.106062_bb0160","series-title":"Test No. 236: Fish Embryo Acute Toxicity (FET) Test, OECD Guidelines for the Testing of Chemicals, Section 2","author":"OECD","year":"2013"},{"key":"10.1016\/j.tiv.2025.106062_bb0165","first-page":"1","article-title":"Investigation of berberine and its derivatives in Sars Cov-2 main protease structure by molecular docking, PROTOX-II and ADMET methods: in machine learning and in silico study","volume":"0","author":"Oner","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"issue":"6","key":"10.1016\/j.tiv.2025.106062_bb0170","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.neuropharm.2004.06.029","article-title":"\u0391-Tocotrienol provides the most potent neuroprotection among vitamin E analogs on cultured striatal neurons","volume":"47","author":"Osakada","year":"2004","journal-title":"Neuropharmacology"},{"issue":"9","key":"10.1016\/j.tiv.2025.106062_bb0175","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures","volume":"58","author":"Pires","year":"2015","journal-title":"J. Med. Chem."},{"issue":"7","key":"10.1016\/j.tiv.2025.106062_bb0180","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1021\/acs.chemrestox.0c00040","article-title":"Most influential physicochemical and in vitro assay descriptors for hepatotoxicity and nephrotoxicity prediction","volume":"33","author":"Rana","year":"2020","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.tiv.2025.106062_bb0185","doi-asserted-by":"crossref","DOI":"10.3389\/fnut.2022.924596","article-title":"Blood\u2013brain barrier permeability study of potential neuroprotective compounds recovered from plants and Agri-food by-products","volume":"9","author":"S\u00e1nchez-Mart\u00ednez","year":"2022","journal-title":"Front. Nutr."},{"key":"10.1016\/j.tiv.2025.106062_bb0190","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s40572-018-0183-2","article-title":"Zebrafish as a model for toxicological perturbation of yolk and nutrition in the early embryo","volume":"5","author":"Sant","year":"2018","journal-title":"Curr. Environ. Health Rep"},{"key":"10.1016\/j.tiv.2025.106062_bb0195","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.reprotox.2011.08.003","article-title":"Feasibility study of the zebrafish assay as an alternative method to screen for developmental toxicity and embryotoxicity using a training set of 27 compounds","volume":"33","author":"Selderslaghs","year":"2012","journal-title":"Reprod. Toxicol."},{"issue":"18","key":"10.1016\/j.tiv.2025.106062_bb0200","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1016\/j.lfs.2005.12.001","article-title":"Tocotrienols: vitamin E beyond tocopherols","volume":"78","author":"Sen","year":"2006","journal-title":"Life Sci."},{"issue":"6","key":"10.1016\/j.tiv.2025.106062_bb0205","doi-asserted-by":"crossref","first-page":"828","DOI":"10.3390\/ph16060828","article-title":"Tocotrienol-rich fraction ameliorates the Aluminium chloride-induced neurovascular dysfunction-associated vascular dementia in rats","volume":"16","author":"Shaikh","year":"2023","journal-title":"Pharmaceuticals"},{"issue":"21","key":"10.1016\/j.tiv.2025.106062_bb0210","doi-asserted-by":"crossref","first-page":"13531","DOI":"10.3390\/ijms232113531","article-title":"Palm oil derived Tocotrienol-rich fraction attenuates vascular dementia in type 2 diabetic rats","volume":"23","author":"Shaikh","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"10","key":"10.1016\/j.tiv.2025.106062_bb0215","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.3390\/ijms19103022","article-title":"\u0394-Tocotrienol, isolated from rice bran, exerts an anti-inflammatory effect via MAPKs and PPARs signaling pathways in lipopolysaccharide-stimulated macrophages","volume":"19","author":"Shen","year":"2018","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.tiv.2025.106062_bb0220","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.jksus.2019.05.003","article-title":"Evaluation of the inhibitory effect of caffeic acid and gallic acid on tetR and tetM efflux pumps mediating tetracycline resistance in Streptococcus sp., using computational approach","volume":"32","author":"Sivakumar","year":"2020","journal-title":"J. King Saud Univ. - Sci."},{"issue":"3","key":"10.1016\/j.tiv.2025.106062_bb0225","first-page":"191","article-title":"Prediction of hERG inhibition of drug discovery compounds using biomimetic HPLC measurements","volume":"9","author":"Stergiopoulos","year":"2021","journal-title":"ADMET and DMPK"},{"issue":"2","key":"10.1016\/j.tiv.2025.106062_bb0230","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.reprotox.2011.06.121","article-title":"Zebrafish embryos as an alternative to animal experiments\u2014a commentary on the definition of the onset of protected life stages in animal welfare regulations","volume":"33","author":"Str\u00e4hle","year":"2012","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.tiv.2025.106062_bb0235","doi-asserted-by":"crossref","first-page":"255","DOI":"10.3389\/fphys.2012.00255","article-title":"Zebrafish: a novel research tool for cardiac (patho) electrophysiology and ion channel disorders","volume":"3","author":"Verkerk","year":"2012","journal-title":"Front. Physiol."},{"issue":"1","key":"10.1016\/j.tiv.2025.106062_bb0240","doi-asserted-by":"crossref","first-page":"38485","DOI":"10.1038\/srep38485","article-title":"Biological response of zebrafish embryos after short-term exposure to thifluzamide","volume":"6","author":"Yang","year":"2016","journal-title":"Sci. Rep."},{"issue":"6","key":"10.1016\/j.tiv.2025.106062_bb0245","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1093\/bioinformatics\/bty707","article-title":"AdmetSAR 2.0: web-service for prediction and optimization of chemical ADMET properties","volume":"35","author":"Yang","year":"2019","journal-title":"Bioinform"},{"key":"10.1016\/j.tiv.2025.106062_bb0250","doi-asserted-by":"crossref","DOI":"10.1016\/j.foodres.2022.111175","article-title":"Therapeutic potential of palm oil vitamin E-derived tocotrienols in inflammation and chronic diseases: evidence from preclinical and clinical studies","volume":"156","author":"Zainal","year":"2022","journal-title":"Food Res. Int."},{"issue":"4","key":"10.1016\/j.tiv.2025.106062_bb0255","doi-asserted-by":"crossref","DOI":"10.1016\/j.aquatox.2009.10.006","article-title":"Developmental toxicity of cartap on zebrafish embryos","volume":"95","author":"Zhou","year":"2009","journal-title":"Aquat. Toxicol."}],"updated-by":[{"DOI":"10.1016\/j.tiv.2025.106099","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000}}],"container-title":["Toxicology in Vitro"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0887233325000566?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0887233325000566?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T22:26:21Z","timestamp":1750717581000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0887233325000566"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":51,"alternative-id":["S0887233325000566"],"URL":"https:\/\/doi.org\/10.1016\/j.tiv.2025.106062","relation":{},"ISSN":["0887-2333"],"issn-type":[{"value":"0887-2333","type":"print"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Integrative toxicity assessment of tocotrienol-rich fraction from palm oil using in silico methods and zebrafish embryotoxicity model","name":"articletitle","label":"Article Title"},{"value":"Toxicology in Vitro","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tiv.2025.106062","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"106062"}}