{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:46:39Z","timestamp":1783345599871,"version":"3.54.6"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    \u03b1\u2010Arbutin, a glucoside of hydroquinone, is utilized as a skin\u2010lightening agent that inhibits human tyrosinase activity. Although it exhibits antioxidant and anti\u2010inflammatory properties, limited research exists on its toxicological effects. This research investigates the oral toxicity of \u03b1\u2010arbutin in both acute and subacute settings using Sprague\u2013Dawley rats as test subjects. Female Sprague\u2013Dawley rats underwent acute oral toxicity testing in accordance with OECD TG 425 guidelines. The rats received oral doses of 175, 550, 1750, and 2000\u2009mg\/kg. Additionally, a subacute oral toxicity study following OECD TG 407 protocols was performed on both male and female rats. In this study, the animals were given daily oral doses of 250, 500, 1000, and 2000\u2009mg\/kg for 28\u2009days. During acute and subacute oral toxicity assessments, no deaths or observable changes in behavior were noted at the administered doses. Examination of gross anatomy showed a significant decrease in the relative spleen weight of rats given \u03b1\u2010arbutin at 250\u2009mg\/kg compared to the control group. Male rats treated with \u03b1\u2010arbutin exhibited markedly non\u2010significantly increased levels of AST, ALT, and chloride ions. In contrast, mean corpuscular hemoglobin concentration levels notably decreased at lower \u03b1\u2010arbutin doses relative to the control group. Brain histopathology of male rats revealed moderate inflammation with pyknotic nuclei, whereas the cortex showed extensive epithelial cell necrosis following the administration of 2000\u2009mg\/kg of \u03b1\u2010arbutin. The results showed that when given for a short time, \u03b1\u2010arbutin is nontoxic till 2000\u2009mg\/kg. The median lethal dose (LD\n                    <jats:sub>50<\/jats:sub>\n                    ) of \u03b1\u2010arbutin is more than 2000\u2009mg\/kg. A long\u2010term toxicity study may be performed to validate the result. This study evaluated the acute and subacute oral toxicity of \u03b1\u2010arbutin in Sprague\u2013Dawley rats. No mortality or significant behavioral changes were observed up to 2000\u2009mg\/kg. However, at higher doses, male rats exhibited elevated liver enzymes and chloride ions, along with brain inflammation and cortical necrosis. Overall, \u03b1\u2010arbutin showed no remarkable toxicity at tested doses, with an LD\n                    <jats:sub>50<\/jats:sub>\n                    exceeding 2000\u2009mg\/kg, warranting further long\u2010term safety assessments.\n                  <\/jats:p>","DOI":"10.1002\/jat.4822","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T03:55:18Z","timestamp":1748577318000},"page":"2020-2041","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Acute and Subacute Toxicity Study of \u03b1\u2010Arbutin: An In\u00a0Vivo Evidence"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1110-5080","authenticated-orcid":false,"given":"Pooja","family":"Mishra","sequence":"first","affiliation":[{"name":"Department of Pharmacy Integral University  Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9613-2873","authenticated-orcid":false,"given":"Farogh","family":"Ahsan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Integral University  Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4006-2594","authenticated-orcid":false,"given":"Tarique","family":"Mahmood","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Integral University  Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1479-3152","authenticated-orcid":false,"given":"Shahzadi","family":"Bano","sequence":"additional","affiliation":[{"name":"Department of Chemistry Integral University  Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaseem\u00a0Ahamad","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Integral University  Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyoti","family":"Yadav","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Integral University  Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamal\u00a0Akhtar","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Chemistry Integral University  Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd\u00a0Masih\u00a0Uzzaman","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy Qassim University  Buraydah Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1515\/jbcpp\u20102019\u20100272"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1515\/JBCPP\u20102019\u20100272\/HTML"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/LIFE12071063"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/S11655\u2010023\u20103733\u20102"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/DISEASES11040184"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/3769933"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0278\u20106915(01)00117\u2010X"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.33263\/BRIAC132.119"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/ACS.CHEMRESTOX.5B00407"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.SCITOTENV.2019.03.275"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0045\u20106535(03)00471\u20105"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JEP.2006.12.017"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/BCPT.12622"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43188\u2010024\u201000252\u20101"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3831\/KPI.2018.21.007"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1590\/S2175\u201097902018000217459"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/S11655\u2010023\u20103734\u20109"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JOAD.2015.06.010"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.14573\/ALTEX.2008.3.213"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.FITOTE.2006.04.006"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.5772\/intechopen.72437"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/EFD2.70013"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/S42826\u2010022\u201000128\u20101"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/S12906\u2010021\u201003470\u20104"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JSPS.2023.101701"},{"key":"e_1_2_11_27_1","unstructured":"OECD 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Test No. 407: Repeated Dose 28\u2010Day Oral Toxicity Study in Rodents. OECD Guidelines for the Testing of Chemicals \u00a7.\u201d OECD."},{"key":"e_1_2_11_28_1","unstructured":"OECD 425.2022. \u201cTest No. 425: Acute Oral Toxicity: Up\u2010and\u2010Down Procedure OECD Guidelines for the Testing of Chemicals \u00a7.\u201d OECD."},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/IJERPH18115988"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JOAD.2015.08.006"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/627375"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/PTR.6769"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/NU11092133"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/PTR.7076"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.15547\/BJVM.983"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/SCIPHARM87020009"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3480"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3109\/10408444.2014.910753"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/S40816\u2010020\u201000228\u20102"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0101638"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1201\/9780429439964-30"},{"issue":"2","key":"e_1_2_11_42_1","first-page":"56","article-title":"Acute Oral Toxicity Evaluation of Ethyl Acetate Fraction of Sesbania grandiflora Linn. 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