Abstract
Dental fluorosis (DF) remains a global public health challenge traditionally attributed to elevated water fluoride F-. However, the Halo Effect and environmental factors now complicate this dose-response relationship. Following PRISMA 2020 guidelines, this systematic review identified 20 observational studies (n = 21,780) via PubMed, Scopus, and Web of Science. Inclusion logic utilized the PICOS framework, specifically selecting human studies that reported quantitative water F- levels alongside environmental or dietary confounders. Quality was assessed via the Newcastle-Ottawa Scale. Synthesis revealed that in optimal fluoridated areas (0.7 mg/L), mild DF prevalence reached 15-20% in cohorts with high "Halo Effect" exposure (infant formula, processed beverages) a twofold increase over historical benchmarks. High altitude (>2000 m) and arid climates further exacerbated toxicity by altering renal clearance. These factors sustain systemic fluoride levels that inhibit protease activity (MMP-20/KLK4) and induce endoplasmic reticulum stress during enamel maturation, causing hypomineralization. Current water-centric monitoring is insufficient for modern risk assessment. A transition toward Total Daily Intake (TDI) models and context-specific standards accounting for altitude and dietary diffusion is essential to balance caries prevention with systemic safety.