{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:13:24Z","timestamp":1789172004466,"version":"build-2803163510"},"reference-count":86,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"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>Following EU restrictions on dental amalgam from January 1, 2025, and the Minamata Convention's COP\u20106 decision to phase out dental amalgam globally by 2034, the era of amalgam restorations is drawing to a close. However, populations with historical mercury exposure may retain persistent, species\u2010dependent tissue mercury burdens, particularly within the kidney and brain. This persistent body burden may prolong internal mercury exposure after cessation or substantial reduction of the external source. We propose \u201cMercury Debt\u201d as a conceptual construct describing residual, species\u2010specific internal mercury exposure after external exposure has ceased or substantially declined. We hypothesize that Mercury Debt could be operationalized as a species\u2010 and organ\u2010specific time\u2010integrated internal exposure metric incorporating empirically derived weighting factors. Framed within the exposome paradigm, this review synthesizes recent mechanistic advances in mercury toxicology. We highlight representative molecular pathways, including oxidative stress, calcium dysregulation involving CaM\/CaMKII signaling, DRP1\u2010mediated mitochondrial fission, disruption of selenium\u2010dependent biology and selenoprotein function, and mercury\u2010associated epigenetic alterations characterized by DNA methylation changes. Furthermore, we integrate these molecular mechanisms with emerging physiologically based pharmacokinetic (PBPK) modeling, adverse outcome pathway (AOP) networks, and machine learning toxicity predictors. Finally, we outline a five\u2010stage methodological roadmap encompassing speciation biomonitoring, multiomic exposome mapping, PBPK and AOP coupling, explainable AI risk stratification, and carefully controlled biomarker\u2010guided clinical studies. This framework proposes a testable approach for future quantification of persistent internal mercury exposure, requiring validation through longitudinal biomonitoring, PBPK calibration, and mechanistic endpoint integration.<\/jats:p>","DOI":"10.1002\/jat.70436","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:39:48Z","timestamp":1789169988000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mercury Debt: Molecular Mechanisms and Exposome Mapping of Persistent Post\u2010Amalgam Exposure"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6100-3182","authenticated-orcid":false,"given":"Ghassan","family":"Sonji","sequence":"first","affiliation":[{"name":"Pharmaceutical Sciences Department, School of Pharmacy Lebanese International University  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3792-4763","authenticated-orcid":false,"given":"Nada","family":"Sonji","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Department, School of Pharmacy Lebanese International University  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1756-5298","authenticated-orcid":false,"given":"Afaf","family":"El Katerji","sequence":"additional","affiliation":[{"name":"American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2026.111924"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph14010093"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/etc.34"},{"key":"e_1_2_16_5_1","volume-title":"Toxicological Profile for Mercury","author":"ATSDR","year":"2024"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202413405"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsenvironau.1c00022"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356\u2010025\u201037354\u20108"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1289\/EHP3904"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0109\u20105641(97)80099\u20101"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/460508"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/10937404.2017.1289834"},{"key":"e_1_2_16_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/10937404.2016.1243501"},{"key":"e_1_2_16_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2014.04.010"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201000384\u20105"},{"key":"e_1_2_16_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011\u2010018\u20101380\u20104"},{"key":"e_1_2_16_17_1","volume-title":"Behavioral and Neural Genetics of Zebrafish","author":"Carvan M. 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