has been found to be reduced in regions of the brain thought to be most important for mental stability and for adequate retrieval of memories.

It appears that many of fluoride’s effects, and those of the aluminofluoride complexes are mediated by activation of Gp, a protein of the G family. G proteins mediate the release of many of the best known transmitters of the central nervous system. Not only do fluorides affect transmitter concentrations and functions but also are involved in the regulation of glucagons, prostaglandins, and a number of central nervous system peptides, including vasopressin, endogenous opioids, and other hypothalamic peptides. The AlFx binds to GDP and ADP altering their ability to form the triphosphate molecule essential for providing energies to cells in the brain. Thus, AlFx not only provides false messages throughout the nervous system but, at the same time, diminishes the energy essential to brain function.

Fluorides also increase the production of free radicals in the brain through several different biological pathways. These changes have a bearing on the possibility that fluorides act to increase the risk of developing Alzheimer’s disease. Today, the disruption of aerobic metabolism in the brain, a reduction of effectiveness of acetylcholine as a transmitter, and an increase in free radicals are thought to be causative factors for this disease. More research is needed to clarify fluoride’s biochemical effects on the brain.

Anatomical Changes in the Brain

Studies of rats exposed to NaF or AlF3 have reported distortion in cells in the outer and inner layers of the neocortex. Neuronal deformations were also found in the hippocampus and to a smaller extent in the amygdala and the cerebellum. Aluminum was detected in neurons and glia, as well as in the lining and in the lumen of blood vessels in the brain and kidney. The substantial enhancement of reactive microglia, the presence of stained intracellular neurofilaments, and the presence of IgM observed in rodents are related to signs of dementia in humans. The magnitude of the changes was large and consistent among the studies. Given this, the committee concludes further research is warranted in this area, similar to that discussed at a February 2-3,1999, EPA workshop on aluminum complexes and neurotoxicity and that recommended for study by NTP (2002).

RECOMMENDATIONS

On the basis of information largely derived from histological, chemical, and molecular studies, it is apparent that fluorides have the ability to interfere with the functions of the brain and the body by direct and indirect means. To determine the possible adverse effects of fluoride, additional data from both the experimental and the clinical sciences are needed.



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