{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:10:00Z","timestamp":1788844200302,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["scijournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pest Management Science"],"abstract":"Abstract<\/jats:title>\n \n BACKGROUND<\/jats:title>\n \n Prothioconazole (PTC) is one of the most widely used triazole fungicides worldwide, while its major metabolite, prothioconazole\u2010desthio (dPTC), exhibits enhanced toxicological potential. However, the metabolic perturbations induced by chronic PTC exposure and sensitive biomarkers for exposure monitoring remain poorly understood. This study aimed to elucidate the metabolic toxicity mechanisms of PTC and identify reliable biomarkers using integrated\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n metabolomics.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Cytotoxicity assays demonstrated significant differences in the toxicity of eight representative pesticides toward L\u201002 hepatocytes, with half\u2010maximal inhibitory concentration (IC\n 50<\/jats:sub>\n ) values of 102.8 and 167.3\u2009\u03bcmol\u2009L\n \u22121<\/jats:sup>\n for PTC and dPTC, respectively. Untargeted metabolomics revealed that PTC exposure significantly disturbed lipid metabolism, nicotinate metabolism, amino acid metabolism, and mitochondrial energy homeostasis. Corticosterone, equol, and uric acid exhibited excellent discriminatory performance (area under the curve (AUC)\u2009>\u20090.95) and were identified as potential cellular biomarkers of exposure. In C57BL\/6J mice, chronic PTC exposure for 28\u2009days induced systemic metabolic disturbances involving the tricarboxylic acid cycle, lysine degradation, and host\u2013microbiota co\u2010metabolism. Targeted metabolomics further validated significant increases in succinic acid, heptanedioic acid, and 2\u2010oxohexanedioic acid, together with a marked decrease in indole\u20103\u2010propionic acid, consistent with the untargeted metabolomics results. These metabolites demonstrated high sensitivity and specificity for discriminating PTC exposure.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n This study demonstrates that chronic PTC exposure disrupts mitochondrial energy metabolism and multiple metabolic pathways, leading to systemic metabolic dysfunction. The identified metabolic biomarkers provide promising tools for pesticide biomonitoring and mechanistic toxicity assessment, improving exposure surveillance and health risk evaluation of triazole fungicides. \u00a9 2026 Society of Chemical Industry.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ps.71286","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:23:20Z","timestamp":1788841400000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated cell\u2013mouse metabolomics reveals toxicity mechanisms and biomarkers of prothioconazole exposure"],"prefix":"10.1002","author":[{"given":"Linlin","family":"Shi","sequence":"first","affiliation":[{"name":"Key Laboratory of Agri\u2010products Quality and Biosafety (Anhui Agricultural University), Ministry of Education Hefei China"},{"name":"School of Plant Protection, Anhui Province Key Laboratory of Integrated Pest Management on Crops Anhui Agricultural University Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Agri\u2010products Quality and Biosafety (Anhui Agricultural University), Ministry of Education Hefei China"},{"name":"School of Plant Protection, Anhui Province Key Laboratory of Integrated Pest Management on Crops Anhui Agricultural University Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiandan","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Plant Protection, Anhui Province Key Laboratory of Integrated Pest Management on Crops Anhui Agricultural University Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Agri\u2010products Quality and Biosafety (Anhui Agricultural University), Ministry of Education Hefei 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Province Key Laboratory of Integrated Pest Management on Crops Anhui Agricultural University Hefei China"},{"name":"Joint Research Centre for Food Nutrition and Health of IHM Anhui Agricultural University Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7278-9766","authenticated-orcid":false,"given":"Qingkui","family":"Fang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Agri\u2010products Quality and Biosafety (Anhui Agricultural University), Ministry of Education Hefei China"},{"name":"School of Plant Protection, Anhui Province Key Laboratory of Integrated Pest Management on Crops Anhui Agricultural University Hefei China"},{"name":"Joint Research Centre for Food Nutrition and Health of IHM Anhui Agricultural University Hefei China"},{"name":"Anhui Provincial Key Laboratory of Hazardous Factors and Risk Control of Agri\u2010food Quality Safety Anhui Agricultural University Hefei 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