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This systematic review synthesizes preclinical evidence on the association between fluoride exposure and changes in metal and semi\u2010metal concentrations across biological matrices. A comprehensive search strategy was conducted across major databases without language or date restrictions, following SyRF, CAMARADES and PRISMA 2020 guidelines. Thirty\u2010one animal studies were included, encompassing multiple species, exposure conditions and analytical approaches. Despite substantial methodological heterogeneity, consistent patterns emerged. Fluoride exposure was associated with element\u2010specific redistribution of the metallome rather than uniform change. Essential elements were predominantly depleted, most consistently zinc, copper and manganese, whereas the toxic metals lead and cadmium tended to be retained. This contrast between homeostatically regulated essential elements that are lost and non\u2010regulated toxic metals that accumulate supports the hypothesis that fluoride differentially modifies the distribution and retention of co\u2010existing elements. The novelty of this review lies in integrating metallomic outcomes across experimental models, highlighting fluoride as a potential systemic modulator rather than a tissue\u2010specific agent. Although variability in study design and risk of bias limits causal inference, the consistent directionality of findings across models reinforces their biological plausibility and translational relevance.<\/jats:p>","DOI":"10.1111\/bcpt.70295","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T09:00:47Z","timestamp":1788512447000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fluoride as a Modifier of Metallome Homeostasis: A Systematic Review of Animal Studies"],"prefix":"10.1111","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9114-7977","authenticated-orcid":false,"given":"Natalia","family":"Macedo\u2010Ribeiro","sequence":"first","affiliation":[{"name":"Department of Basic and Oral Biology, Faculty of Dentistry of Ribeirao Preto University of Sao Paulo (FORP\/USP)  Ribeirao Preto Sao Paulo 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