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In this study, we investigated its toxicokinetics and biotransformation in rats following oral administration. IMZ was rapidly absorbed, reaching peak plasma concentration at 0.75 h, followed by a prolonged elimination phase with minimal decrease between 12 and 48 h. Tissue distribution analysis revealed notable accumulation and slower elimination of IMZ in the kidneys, testes, and muscle. Eleven metabolites were identified, with M227, M231, and M233 being reported for the first time. Notably, metabolite M277 exhibited high relative abundance in the kidneys and liver and was predicted to have high nephrotoxic and hepatotoxic potential. Metabolites M217 and M243 were prominent in the testes, highlighting potential reproductive toxicity concerns. The study provided a comprehensive characterization of IMZ disposition in rats, underscoring its tissue distribution and the organ-specific toxicological risks associated with its key metabolites.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c04897","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:01:59Z","timestamp":1788922919000},"page":"29058-29070","source":"Crossref","is-referenced-by-count":0,"title":["Toxicokinetics, Biotransformation, and Tissue Distribution\nof Imidaclothiz in Rats"],"prefix":"10.1021","volume":"74","author":[{"given":"Yishuang","family":"Duan","sequence":"first","affiliation":[{"name":"Jianghan University , , ,","place":["Wuhan, China, 430056"]},{"name":"Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nian","family":"Xiong","sequence":"additional","affiliation":[{"name":"Jianghan University , , ,","place":["Wuhan, China, 430056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoran","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jianghan University , , ,","place":["Wuhan, China, 430056"]},{"name":"Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9003-2756","authenticated-orcid":true,"given":"Pu","family":"Wang","sequence":"additional","affiliation":[{"name":"Jianghan University , , ,","place":["Wuhan, China, 430056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2212-6694","authenticated-orcid":true,"given":"Yong","family":"Liang","sequence":"additional","affiliation":[{"name":"Jianghan University , , ,","place":["Wuhan, China, 430056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2521-100X","authenticated-orcid":true,"given":"Qunfang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Jianghan University , , ,","place":["Wuhan, China, 430056"]},{"name":"Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6335-3917","authenticated-orcid":true,"given":"Guibin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"2026092310082827800_cit1","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1146\/annurev-pharmtox-010617-052429","article-title":"Mechanism\nof neonicotinoid toxicity: Impact on oxidative stress and metabolism","volume":"58","author":"Wang","year":"2018","journal-title":"Annu. 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Pollut."},{"key":"2026092310082827800_cit26","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1007\/s00253-005-0223-3","article-title":"Microbial hydroxylation\nof imidacloprid for the synthesis of highly\ninsecticidal olefin imidacloprid","volume":"71","author":"Dai","year":"2006","journal-title":"Appl. Microbiol.\nBiotechnol."},{"key":"2026092310082827800_cit27","doi-asserted-by":"publisher","first-page":"6016","DOI":"10.1021\/jf000873c","article-title":"Neonicotinoid insecticides: Molecular\nfeatures conferring selectivity for insect versus mammalian nicotinic\nreceptors","volume":"48","author":"Tomizawa","year":"2000","journal-title":"J. Agric. Food Chem."},{"key":"2026092310082827800_cit28","doi-asserted-by":"publisher","first-page":"128579","DOI":"10.1016\/j.foodchem.2020.128579","article-title":"Comparation study on\nthe metabolism destination of neonicotinoid and organophosphate insecticides\nin tea plant (Camellia sinensis L.)","volume":"344","author":"Ge","year":"2021","journal-title":"Food Chem."},{"key":"2026092310082827800_cit29","first-page":"46","article-title":"Novel insecticide\u2500\u2500imidaclothiz\nWorld Pesticides","volume":"27","author":"Baojiang","year":"2005","journal-title":"World Pestic."},{"key":"2026092310082827800_cit30","doi-asserted-by":"publisher","first-page":"119511","DOI":"10.1016\/j.ecoenv.2025.119511","article-title":"Characteristics\nof\ntoxicokinetics and metabolic transformation of flonicamid in rats","volume":"309","author":"Zhang","year":"2026","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"2026092310082827800_cit31","doi-asserted-by":"publisher","first-page":"107823","DOI":"10.1016\/j.envint.2023.107823","article-title":"Evaluation of the risk\nof human exposure to thiamethoxam by extrapolation from a toxicokinetic\nexperiment in rats and literature data","volume":"173","author":"Yi","year":"2023","journal-title":"Environ.\nInt."},{"key":"2026092310082827800_cit32","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1021\/acs.estlett.2c00206","article-title":"Communicating confidence\nof per- and polyfluoroalkyl\nsubstance identification via high-resolution mass spectrometry","volume":"9","author":"Charbonnet","year":"2022","journal-title":"Environ. Sci. Technol. Lett."},{"key":"2026092310082827800_cit33","doi-asserted-by":"publisher","first-page":"12794","DOI":"10.1021\/acs.est.3c02156","article-title":"Nontarget\nidentification of novel organophosphorus flame retardants\nand plasticizers in rainfall runoffs and agricultural soils around\na plastic recycling industrial park","volume":"57","author":"Li","year":"2023","journal-title":"Environ.\nSci. Technol."},{"key":"2026092310082827800_cit34","doi-asserted-by":"publisher","first-page":"2097","DOI":"10.1021\/es5002105","article-title":"Identifying small molecules via high\nresolution mass spectrometry: Communicating confidence","volume":"48","author":"Schymanski","year":"2014","journal-title":"Environ. Sci. Technol."},{"key":"2026092310082827800_cit35","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5553","article-title":"Toxicokinetics in preclinical drug development of small-molecule\nnew chemical entities","volume":"37","author":"Li","year":"2022","journal-title":"Biomed. 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Food Chem."},{"key":"2026092310082827800_cit39","doi-asserted-by":"publisher","first-page":"106443","DOI":"10.1016\/j.aquatox.2023.106443","article-title":"Relationship\nbetween photolysis mechanism\nand photo-enhanced toxicity to Vibrio Fischeri for neonicotinoids\nwith cyano-amidine and nitroguanidine structures","volume":"257","author":"Fan","year":"2023","journal-title":"Aquat. Toxicol."},{"key":"2026092310082827800_cit40","doi-asserted-by":"publisher","first-page":"118317","DOI":"10.1016\/j.envpol.2021.118317","article-title":"Bio-uptake, tissue distribution and\nmetabolism of a neonicotinoid insecticide clothianidin in zebrafish","volume":"292","author":"Yang","year":"2022","journal-title":"Environ. Pollut."},{"key":"2026092310082827800_cit41","doi-asserted-by":"publisher","first-page":"7066","DOI":"10.1021\/jf034760f","article-title":"Absorption, tissue\ndistribution, excretion, and metabolism of clothianidin in rats","volume":"51","author":"Yokota","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"2026092310082827800_cit42","doi-asserted-by":"publisher","first-page":"3888","DOI":"10.1021\/acs.est.8b07062","article-title":"Toxicokinetics of\nimidacloprid-coated wheat seeds in Japanese quail (Coturnix japonica).\nand an evaluation of hazard","volume":"53","author":"Bean","year":"2019","journal-title":"Environ. Sci. Technol."},{"key":"2026092310082827800_cit43","doi-asserted-by":"publisher","first-page":"152935","DOI":"10.1016\/j.tox.2021.152935","article-title":"An integrated\napproach, based on\nmass spectrometry, for the assessment of imidacloprid metabolism and\npenetration into mouse brain and fetus after oral treatment","volume":"462","author":"Passoni","year":"2021","journal-title":"Toxicology"},{"key":"2026092310082827800_cit44","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1002\/tox.22132","article-title":"Evaluation of ameliorative effect\nof curcumin on imidacloprid-induced male reproductive toxicity in\nWistar rats","volume":"31","author":"Lonare","year":"2016","journal-title":"Environ. Toxicol."},{"key":"2026092310082827800_cit45","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1016\/j.envpol.2016.03.037","article-title":"Enantioselective\nabsorption and transformation of a novel chiral neonicotinoid [14C]-cycloxaprid in rats","volume":"213","author":"Wu","year":"2016","journal-title":"Environ. Pollut."},{"key":"2026092310082827800_cit46","doi-asserted-by":"publisher","first-page":"106786","DOI":"10.1016\/j.pestbp.2025.106786","article-title":"Subchronic hepatorenal toxicity induced\nby low-dose neonicotinoid\npesticide imidaclothiz exposure in mice","volume":"216","author":"Cai","year":"2026","journal-title":"Pestic.\nBiochem. Physiol."},{"key":"2026092310082827800_cit47","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-22-0247","article-title":"RISING STARS:\nSex differences in toxicant-associated fatty liver disease","volume":"258","author":"Wahlang","year":"2023","journal-title":"J. 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