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Flupyradifurone, a butenolide insecticide, is recognized for its minimal toxic effects on bees when applied at standard dosages; however, its potential toxicity or threat to B. mori has not been fully elucidated. This study aims to investigate and evaluate the toxicity of flupyradifurone soluble liquid (SL) on B. mori by administering various concentrations to third instar silkworm larvae through oral exposure. Results from both acute and chronic toxicity assessments demonstrated that flupyradifurone SL exhibits concentration-dependent toxic effects on B. mori, with the LC50 for third instar silkworms after 24\u2009h of treatment determined to be 21.96\u2009mg\/l. Acute toxicity testing revealed stunted larval growth, slight body shrinkage, and mortality. Chronic exposure to 17\u2009mg\/l flupyradifurone resulted in decreased cocoon and pupal weights, reduced silk production and egg laying, and mortality. Moreover, flupyradifurone SL significantly modulated the gene expression profile of B. mori, impacting genes associated with growth, development, reproduction, detoxification, stress response, and immunity. Specifically, genes encoding glutathione S-transferase delta 2, lipase 1, cuticular protein RR-1, and cecropin-B were upregulated. In contrast, genes primarily involved in detoxification, stress response, and developmental processes, such as those encoding cytochrome P450, heat shock proteins, and juvenile hormone, were notably downregulated. These findings elucidate the toxicology of flupyradifurone SL on the silkworm Bombyx mori and provide critical insights for the informed and safe application of flupyradifurone.<\/jats:p>","DOI":"10.1093\/jee\/toag231","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:34:37Z","timestamp":1788521677000},"page":"3684-3695","source":"Crossref","is-referenced-by-count":0,"title":["Unveiling the hidden threat: flupyradifurone soluble liquid\u2019s toxic impact on silkworms"],"prefix":"10.1093","volume":"119","author":[{"given":"Rui","family":"Xue","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology , Zhenjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxiao","family":"Dong","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology , Zhenjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijie","family":"Xu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology , Zhenjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiting","family":"Liu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology , Zhenjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qilong","family":"Huang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology , Zhenjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6663-1249","authenticated-orcid":false,"given":"Qiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology , Zhenjiang,","place":["China"]},{"name":"Key Laboratory of Silkworm and Mulberry Genetic Improvement, Ministry of Agriculture and Rural Affairs, Sericultural Scientific Research Center, Chinese Academy of Agricultural Sciences , Zhenjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Tang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology , Zhenjiang,","place":["China"]},{"name":"Key Laboratory of Silkworm and Mulberry Genetic Improvement, Ministry of Agriculture and Rural Affairs, Sericultural Scientific Research Center, Chinese Academy of Agricultural Sciences , Zhenjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyuan","family":"Shen","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology , Zhenjiang,","place":["China"]},{"name":"Key Laboratory of Silkworm and Mulberry Genetic Improvement, Ministry of Agriculture and Rural Affairs, Sericultural Scientific Research Center, Chinese Academy of Agricultural Sciences , Zhenjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2165-5434","authenticated-orcid":false,"given":"Heying","family":"Qian","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of 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