Exposure to Per- and Polyfluoroalkyl Substances (PFAS) Causes Dental Developmental Anomalies: Underrecognized Risk of Fluoride Bioaccumulation.

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and have potential health risks. Among them, 8:2 fluorotelomer alcohol (FTOH) undergoes microbial biotransformation in the environment into perfluorooctanoic acid (PFOA) and releases fluoride. While PFOA's toxic effects have been well-studied, the impact of PFOA (and its precursor 8:2 FTOH) on dental health is largely unknown. Moreover, it is not established whether, and to what extent, defluorination and fluoride bioaccumulation occur during the in vivo 8:2 FTOH metabolism. This study is the first to comprehensively demonstrate the pathophysiology of PFAS-associated developmental dental anomalies─enamel and dentin hypoplasia─in the context of fluoride bioaccumulation after exposure to 8:2 FTOH in mice. Over 90 days, mice (male and female C57BL/6J) received daily oral doses of 8:2 FTOH. At the high dose, the levels of PFOA and 7:3 FTCA (the main 8:2 FTOH metabolites) in blood increased significantly, reaching PFOA concentrations comparable to those in occupationally exposed humans, underscoring the relevance of high-exposure scenarios. Fluoride levels significantly increased in the blood, urine, and bone, approaching levels linked to dental fluorosis in animal models. Dental defects included enamel and dentin hypoplasia, discoloration, reduced mineral density, and structural abnormalities, including damaged ameloblasts and immature mineral composition. Although some features resembled fluorosis, the defects were distinct. 8:2 FTOH and other PFAS capable of similar metabolic conversion may represent an understudied source of fluorine accumulation and a potential, previously unrecognized contributor to cryptogenic odontogenic abnormalities.