{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T02:53:18Z","timestamp":1781491998135,"version":"3.54.1"},"reference-count":51,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In recent years, olaflur, mainly containing three amine hydrofluorides (compounds\n                    <jats:bold>1\u20133<\/jats:bold>\n                    ), has been widely used as a cariostatic agent in children's toothpaste. However, there is no report on the systematic toxic evaluation of olaflur thus far. Therefore, acute and 28\u2010day repeated dose oral toxicity studies of commercial olaflur and\n                    <jats:bold>1\u20133<\/jats:bold>\n                    were conducted in rats. Two inorganic fluorides, sodium fluoride (NaF) and sodium monofluorophosphate (SMFP), were selected as positive controls in the 28\u2010day study. The acute oral LD\n                    <jats:sub>50<\/jats:sub>\n                    values were determined as 35.0, 28.3, 36.5, and 30.7\u2009mg\u2009F\/kg for commercial olaflur and\n                    <jats:bold>1\u20133<\/jats:bold>\n                    , respectively, indicating higher toxicity than inorganic fluorides. In the 28\u2010day study, olaflur and\n                    <jats:bold>1\u20133<\/jats:bold>\n                    primarily induced hepatic, splenic, pulmonary, and gastrointestinal toxicity. In particular, at doses of 4 and 10\u2009mg\u2009F\/kg, the spleen exhibited punctate necrosis and the duodenum and jejunum exhibited edema of the intestinal villi, whereas these toxic effects were not observed in all NaF\/SMFP groups. Structural\u2010toxicity analysis of these amine hydrofluorides and inorganic fluorides reveals that the protonated alkylamine moiety contributes significant additional gastrointestinal toxicity beyond the fluoride ion. These findings strongly urge caution in the use of olaflur and its constituents as dentifrice additives, particularly for children's toothpaste.\n                  <\/jats:p>","DOI":"10.1002\/jat.70288","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T02:36:13Z","timestamp":1781490973000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acute and 28\u2010Day Repeated Dose Oral Toxicity Studies of Olaflur, a Common Cariostatic Agent in Children's Toothpaste"],"prefix":"10.1002","author":[{"given":"Xue\u2010Min","family":"Shan","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences (Shenzhen) Sun Yat\u2010sen University  Shenzhen People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao\u2010Hang","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences (Shenzhen) Sun Yat\u2010sen University  Shenzhen People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences (Shenzhen) Sun Yat\u2010sen University  Shenzhen People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Jiang","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences (Shenzhen) Sun Yat\u2010sen University  Shenzhen People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9578-2986","authenticated-orcid":false,"given":"Xing\u2010Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences (Shenzhen) Sun Yat\u2010sen University  Shenzhen People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.20945\/2359\u20104292\u20102023\u20100521"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472\u20106831\u20106\u20108"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472\u20106831\u20107\u201014"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.21058"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2010.07.011"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468\u20102494.2008.00425.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jebdp.2014.02.004"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14232"},{"key":"e_1_2_8_10_1","volume-title":"Safety and Technical Standards for Cosmetics (2015 Edition)","author":"China Food and Drug Administration","year":"2015"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/eos.12177"},{"key":"e_1_2_8_12_1","first-page":"15","article-title":"Study on the Biofilm\u2010Inhibiting Performance of Amine Fluoride Toothpaste","volume":"34","author":"Dai J.","year":"2024","journal-title":"Oral Care Industry"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cod.12664"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2903\/j.efsa.2025.9478"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910408301s08"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/B978-0-12-801238-3.10923-7","volume-title":"Comprehensive Toxicology","author":"Gelberg H.","year":"2018"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03178271"},{"key":"e_1_2_8_18_1","unstructured":"Heckendorn R. andJ.Gosteli.2002. \u201cN\u2010Alkyldiethanolamine Hydrofluorides and Oral Hygiene Compositions Containing Them.\u201d U.S. Patent 6 464 962B2.http:\/\/www.uspto.gov\/web\/menu\/patdata.html."},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010\u2010006\u20109405\u20102"},{"key":"e_1_2_8_20_1","volume-title":"Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride","author":"Institute of Medicine","year":"1997"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2022\u2010060417"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579\u2010018\u20100089\u2010x"},{"key":"e_1_2_8_23_1","unstructured":"Liang Y. 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Y.Ding N.Liu andS.Wang.2025. \u201cAn Analytical Method for Olaflur and Its Related Components.\u201d China Patent CN119335103B."},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00284\u2010025\u201004365\u20100"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2023.115239"},{"key":"e_1_2_8_47_1","first-page":"60","article-title":"Study on the Enamel Remineralization Effect of Amine Fluoride Toothpaste","volume":"47","author":"Wang W.","year":"2024","journal-title":"Daily Chemicals Science"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1159\/000261252"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/vec.13299"},{"key":"e_1_2_8_50_1","volume-title":"Nutrients in Drinking Water","author":"World Health Organization","year":"2005"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2015.03.007"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2024.117385"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.70288","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jat.70288","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.70288","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T02:36:37Z","timestamp":1781490997000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.70288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,14]]},"references-count":51,"alternative-id":["10.1002\/jat.70288"],"URL":"https:\/\/doi.org\/10.1002\/jat.70288","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,14]]},"assertion":[{"value":"2026-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"jat.70288"}}