{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T08:29:06Z","timestamp":1765787346365,"version":"3.48.0"},"reference-count":47,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chirality"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Indoxacarb is a typical chiral pesticide composed of two enantiomers, of which only\n                    <jats:italic>S<\/jats:italic>\n                    \u2010(+)\u2010indoxacarb exhibits strong insecticidal activity. Growing interest in its enantioselective toxicology and metabolites has highlighted the need for more data on mammalian metabolism to assess human health risks. In this study, two new pairs of enantiomeric metabolites were identified from indoxacarb metabolism in rats:\n                    <jats:italic>S<\/jats:italic>\n                    \u2010IN\u2010RM493 and\n                    <jats:italic>S<\/jats:italic>\n                    \u2010IN\u2010RM541 derived from\n                    <jats:italic>S<\/jats:italic>\n                    \u2010(+)\u2010indoxacarb, and\n                    <jats:italic>R<\/jats:italic>\n                    \u2010IN\u2010RM493 and\n                    <jats:italic>R<\/jats:italic>\n                    \u2010IN\u2010RM541 derived from\n                    <jats:italic>R<\/jats:italic>\n                    \u2010(\u2212)\u2010indoxacarb. To facilitate a more comprehensive risk assessment, the toxicokinetics of both metabolite pairs (IN\u2010RM493 and IN\u2010RM541) were evaluated in rats. The results showed that IN\u2010RM493 was primarily formed in the stomach, which then entered the systemic circulation and was ultimately eliminated via feces. In contrast, IN\u2010RM541 was primarily produced in the small intestine. Only a small portion of indoxacarb was converted to IN\u2010RM541 in the small intestine, and this metabolite was poorly absorbed by the bloodstream. Consequently, IN\u2010RM541 remained largely confined to intestinal tissues (small intestine, cecum, and large intestine) and feces. Toxicokinetic comparisons revealed that the\n                    <jats:italic>S<\/jats:italic>\n                    \u2010enantiomeric metabolites were cleared more rapidly and accumulated less in tissues than their\n                    <jats:italic>R<\/jats:italic>\n                    \u2010enantiomeric counterparts. This was consistent with the inherent property of\n                    <jats:italic>S<\/jats:italic>\n                    \u2010(+)\u2010indoxacarb, which is more easily metabolized and less prone to accumulation in\u00a0vivo. Overall,\n                    <jats:italic>S<\/jats:italic>\n                    \u2010(+)\u2010indoxacarb demonstrates a more favorable safety profile than\n                    <jats:italic>R<\/jats:italic>\n                    \u2010(\u2212)\u2010indoxacarb with respect to mammals. These findings provide valuable insights into the toxicology of indoxacarb in mammals, thereby paving the way for the informed agricultural application of its optically pure\n                    <jats:italic>S<\/jats:italic>\n                    \u2010(+)\u2010indoxacarb.\n                  <\/jats:p>","DOI":"10.1002\/chir.70068","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T02:36:32Z","timestamp":1765766192000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evidence Supporting the Use of Optically Pure\n                    <i>S<\/i>\n                    \u2010(+)\u2010Indoxacarb: Discovery and Toxicokinetic Characterization of Two New Pairs of Metabolite Enantiomers in Rats"],"prefix":"10.1002","volume":"37","author":[{"given":"Jiao","family":"Ai","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Liaoning University  Shenyang Liaoning People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianxin","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Liaoning University  Shenyang Liaoning People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan\u00a0Kueichieh","family":"Chang","sequence":"additional","affiliation":[{"name":"College of Life and Environmental Sciences Wenzhou University  Wenzhou Zhejiang People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhui","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Liaoning University  Shenyang Liaoning People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Liaoning University  Shenyang Liaoning People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, College of Pharmacy Shenyang Pharmaceutical University  Shenyang Liaoning People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijiang","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Liaoning University  Shenyang Liaoning People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7838-064X","authenticated-orcid":false,"given":"Xiao","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Liaoning University  Shenyang Liaoning People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2018.07.185"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2012.09.082"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2015.09.120"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2010.04.011"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2022.463595"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx500481n"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2010.03.014"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.0c07947"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.2c07924"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2013.07.083"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2015.01.016"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfs094"},{"key":"e_1_2_7_14_1","unstructured":"\u201cNational Standards of People's Republic of China National Food Safety Standard\u2014Maximum Residue Limits for Pesticides in Food \u201d National Health and Family Planning Commission Ministry of Agriculture State Food and Drug Administration. GB (2019): 2763\u20132019."},{"key":"e_1_2_7_15_1","first-page":"1","article-title":"The European Commission Regulation (EU) No 149\/2008 of 29 January 2008 Amending Regulation (EC) No 396\/2005 of the European Parliament and of the Council by Establishing Annexes II, III and IV Setting Maximum Residue Levels for Products Covered by Annex I Thereto","volume":"58","year":"2008","journal-title":"Official Journal of the European Union"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2018.07.078"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2023.105696"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2019.04.124"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2020.127134"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2020.127920"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2017.11.038"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12161\u2010019\u201001681\u20107"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2020.122724"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/polym12051135"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ps.7412"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.22207"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf4045952"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2022.153763"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2024.106024"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2024.173475"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.2c02882"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2022.158372"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.1c00616"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2021.150454"},{"key":"e_1_2_7_35_1","unstructured":"\u201cReport of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group on Pesticide Residues \u201d Geneva Switzerland 20\u201329 September 2005."},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2023.131470"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M113.028878"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14061141"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2016.05.003"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2025.106369"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2020.104636"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116722"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2021.114872"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.2298\/JSC230714102A"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf303116p"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204\u2010019\u201002523\u20105"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498259209049904"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2011.05.049"}],"container-title":["Chirality"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chir.70068","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T08:24:09Z","timestamp":1765787049000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/chir.70068"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":47,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/chir.70068"],"URL":"https:\/\/doi.org\/10.1002\/chir.70068","archive":["Portico"],"relation":{},"ISSN":["0899-0042","1520-636X"],"issn-type":[{"type":"print","value":"0899-0042"},{"type":"electronic","value":"1520-636X"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-09-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70068"}}