Fluoride Action Network


This study evaluated dental fluorosis of the incisors and immunoreactivity in the brain tissues of rats given chronic fluoride doses pre- and postnatally. Female rats were given drinking water with 0, 30 or 100 ppm fluoride ad libitum throughout gestation and the nursing period. In addition, 63 male offspring were treated with the same water regimens as the mothers after weaning and were followed for 1, 3 or 5 months. The upper and lower incisors were collected, and all teeth were examined under a stereomicroscope and scored by two blinded examiners using a modified rodent enamel fluorosis index. Cortical, hippocampal and cerebellar brain samples were evaluated morphologically and immunohistochemically. All fluoride-treated pups were born with low body weight (p = 0.001). All animals from the fluoride groups had enamel fluorosis with defects of various degrees. The increase in the dental fluorosis scores in the fluoride treatment groups was significant (p < 0.01). The catalase immunoreactivity in the 30- and 100-ppm fluoride groups was significantly higher than that in the controls after 1, 3 and 5 months (p < 0.001). In conclusion, this study showed that rats with dental fluorosis had catalase immunoreactivity in the brain tissues, which may reflect the neurobehavioral toxicity of fluoride.


At 3 months in the cerebellum, most of the neurons had normal cell structures and only a few Purkinje cell irregularities were notable, such as cell swelling and balloon-like cells in rats subjected to 30 ppm fluoride. In the cerebrum and hippocampus, no neuronal damage
was observed in rats exposed to 30 ppm fluoride. However, neurodegenerative changes were seen in the neurons of the rats exposed to 100 ppm fluoride. In the cerebellum, cell structure irregularities and Purkinje cell swelling were observed. In the cerebrum, ischemic changes such as pyknosis, loss of the nucleolus, a decrease in Nissl substance and hyperchromatic nuclei were observed (Fig. 4). In the hippocampus, neurodegenerative changes were observed in the CA1 and CA3 regions. In CA3, a group of neurons had
hyperchromatic nuclei and pyknosis. Neurons in the CA2 region had normal cell structures.

At 5 months in the 30-ppm fluoride group, Purkinje cell swelling was observed in the cerebellum. In the cerebrum, some neurons had hyperchromatic nuclei, and a reduction in the Nissl substance was observed. In the hippocampus, disorganised neurons and neurodegenerative changes such as pyknosis, hyperchromatic nuclei and a reduction in Nissl substance were seen. These neurodegenerative changes were more marked in rats exposed to
100 ppm fluoride. Purkinje cells in the cerebellum had irregular cell structures, with swelling, pyknosis, hyperchromatic nuclei and nucleoli loss. In the hippocampus, CA1 and CA2 regions neurons were hyperchromatic and shrunken with small nuclei, and vacuolisation and nucleoli loss were seen. In the CA3 region, a few cells had histological alterations.