IADR Abstract Archives
8:2 Fluorotelomer Alcohol Causes Enamel Hypoplasia in a Rodent Model
Objectives: Per- and polyfluoroalkyl substances (PFAS) are a large group of artificial forever organofluorine chemicals, which have been reported to have potential adverse health effects. One of the PFAS, 8:2 fluorotelomer alcohol (FTOH) is degraded into Perfluorooctanoic acid (PFOA) to release fluorine. Previously we reported that PFOA caused apoptosis and necrosis via ROS mediates MAPK/ERK signaling in ameloblast-like cells. However, the effects of 8:2 FTOH (a precursor of PFOA) on amelogenesis remain unexplained. Here, we demonstrate that oral repeated-dose systemic 8:2 FTOH administration caused enamel hypoplasia in the mouse incisor.
Methods: C57BL/6 mice (Six-weeks-old male) were randomly divided into three groups (8:2 FTOH; 0, 50 or 125 mg/kg/weight/day, n=6/group). Mice were treated with 8:2 FTOH daily by oral gavage for 90 days. Thereafter, maxillary and mandibular incisors were collected. Enamel phenotype (morphological, histological, structural, and mechanical) changes were evaluated using light microscopy, Quantitative light-induced fluorescence (QLF), IHC, micro-CT, SEM, and microhardness test.
Results: Mice treated with 8:2 FTOH (125 mg/kg) displayed enamel hypoplasia in maxillary and mandibular incisors manifested as chalky white enamel. µCT results revealed that the high-dose group significantly decreased enamel mineral density and Vickers microhardness value significantly decreased compared to the control group (0 mg/kg). IHC analysis showed ameloblast disruption. These results suggest that 8:2 FTOH could cause ameloblast degeneration via apoptosis or necrosis during enamel development resulting in enamel hypoplasia. These enamel phenotype changes were observed only in incisors (in the process of amelogenesis), but not in molars (of which enamel formation has been completed before 8:2 FTOH administration).
Conclusions: This study is the first report to demonstrate enamel hypoplasia in mouse incisors caused by oral systemic 8:2 FTOH administration. Our results indicate that FTOH can cause enamel malformation, especially in children. This study warrants further investigation to identify mechanisms of FTOH's adverse effects during amelogenesis.
Methods: C57BL/6 mice (Six-weeks-old male) were randomly divided into three groups (8:2 FTOH; 0, 50 or 125 mg/kg/weight/day, n=6/group). Mice were treated with 8:2 FTOH daily by oral gavage for 90 days. Thereafter, maxillary and mandibular incisors were collected. Enamel phenotype (morphological, histological, structural, and mechanical) changes were evaluated using light microscopy, Quantitative light-induced fluorescence (QLF), IHC, micro-CT, SEM, and microhardness test.
Results: Mice treated with 8:2 FTOH (125 mg/kg) displayed enamel hypoplasia in maxillary and mandibular incisors manifested as chalky white enamel. µCT results revealed that the high-dose group significantly decreased enamel mineral density and Vickers microhardness value significantly decreased compared to the control group (0 mg/kg). IHC analysis showed ameloblast disruption. These results suggest that 8:2 FTOH could cause ameloblast degeneration via apoptosis or necrosis during enamel development resulting in enamel hypoplasia. These enamel phenotype changes were observed only in incisors (in the process of amelogenesis), but not in molars (of which enamel formation has been completed before 8:2 FTOH administration).
Conclusions: This study is the first report to demonstrate enamel hypoplasia in mouse incisors caused by oral systemic 8:2 FTOH administration. Our results indicate that FTOH can cause enamel malformation, especially in children. This study warrants further investigation to identify mechanisms of FTOH's adverse effects during amelogenesis.