FLUORIDE 31(2) 1998, pp 89 - 90	International Society for Fluoride Research	Table of Contents

These two papers^1,2 (see abstracts on pages 91-99) document the development of significant pathology in the brains and kidneys of rats drinking water containing fluoride at a concentration of 1 ppm. What had previously been seen by some to be a safe procedure, the addition to water supplies of fluoride in a concentration of 1 ppm, has now been demonstrated to be associated with the occurrence of serious adverse effects in rats. However, rather than acting alone, fluoride acts in conjunction with aluminium to produce this toxicity.

Although it has sometimes been simplistically thought that the fluoride ion, at 1 ppm, has the same effect irrespective of what else is present with it, the fact is that the toxicity of fluoride is affected by the degree of hardness of the water reflecting the levels of magnesium and calcium. Jolly et al³ found that, in four pairs of villages, the village in each pair with the higher level of magnesium hardness of the water had a lower skeletal fluorosis rate even though its mean water fluoride level was higher. High concentrations of dietary calcium and other cations that form insoluble complexes with fluoride can reduce fluoride absorption from the gastrointestinal tract.⁴ Magnesium fluoride and calcium fluoride are relatively insoluble, dissociating less into their respective ions, so that for a given fluoride concentration they may be less likely to produce adverse effects than the same fluoride concentration in the form of sodium fluoride.

The authors of the present studies have found both aluminium fluoride and sodium fluoride can produce significant pathology in rats with points of both similarity and difference. It appears that a complex interaction may occur between fluoride and aluminium so that when both are present in rats' drinking water, at a low concentration, 0.5 ppm of trivalent aluminium ion and 1 ppm of fluoride ion, they combine to form aluminium fluoride, AlF₃, which has the ability to penetrate the blood-brain barrier and enter the brain, and also to become deposited in the kidneys. When 2.1 ppm of sodium fluoride is present in the drinking water of rats, corresponding to 1.1 ppm of sodium ion and 1 ppm of fluoride ion, the fluoride ion appears to be able to combine with aluminium from the food resulting in a similar entry to the brain and kidneys but with some points of difference. When the fluoride is present with larger amounts of aluminium, such as 5 ppm of trivalent aluminium and about 10 ppm of fluoride or 50 ppm of trivalent aluminium and about 100 ppm of fluoride, the resulting overt toxicity is less.

These papers are extremely important because of the severity of the pathology and the replication of the situation commonly occurring with the treatment of water for public consumption when both fluoride and alum, a double sulphate of aluminium and potassium, is often added. Increased mortality occurred in the rats receiving 0.5 ppm of aluminium fluoride, containing 0.5 ppm of trivalent aluminium and about 1 ppm of fluoride, together with the deposition of increased amounts of aluminium in the kidneys, hypercellularity of the renal glomeruli, renal mesangial proliferation, and the deposition of protein in the renal tubules. The cerebral changes involved raised aluminium levels, damage to and loss of neurones, increases in -amyloid, the presence of aluminium complexes in cerebral blood vessels, and of IgM in the neural parenchyma. The vascular inclusions were seen to be likely to cause a significant functional disturbance with decreased aerobic metabolism. The localization of the changes included the hippocampus which has a role in memory, the posterolateral area of the dorsal thalamus and the areas to which it is connected in the cerebral cortex. Similarly, the addition of 2.1 ppm of sodium fluoride, resulting in 1 ppm of fluoride, was seen to lead to analogous changes involving the kidney and brain. The cerebral effects included increased aluminium levels, IgM inclusions in the cerebral vasculature, increased IgM in the neural parenchyma, neuronal abnormalities, and increased -amyloid deposition.

Although the precise manner in which aluminium exerts its toxic effects requires further study, the present papers demonstrate that cerebral and renal toxicity in rats can result from relatively low concentrations of aluminium and fluoride in the drinking water. The complexity of the problem is augmented by the finding that, although AlF3 is lipid soluble and can pass through hydrophobic membranes, it is actually more toxic at 0.5 ppm trivalent Al and 1 ppm F^– than at higher concentrations such as 5 and 50 ppm Al3+ in association with 10 and 100 ppm F^–. This surprising fact suggested to the authors that fluoride at the higher concentrations might play a neuroprotective role against elevated cerebral accumulation of aluminium. The authors acknowledged, however, that the intrinsic toxicity of fluoride militates against proposing any such use, and the possibility that other, as yet unrecognized factors and mechanisms may be involved remains to be investigated. In any event, the results in these papers clearly point to the urgency for reassessing the risks of having both aluminium and fluoride present in drinking water.

1. Isaacson RL, Varner JA, Jensen KF. Toxin-induced blood vessel inclusions caused by the chronic administration of aluminum and sodium fluoride and their implications for dementia. Neuroprotective Agents. Annals of the New York Academy of Sciences 825 152-166 1997.
2. Varner JA, Jensen KF, Horvath W, Isaacson RL. Chronic administration of aluminum-fluoride or sodium-fluoride to rats in drinking water: alterations in neuronal and cerebrovascular integrity. Brain Research 784 284-298 1998.
3. Jolly SS, Prasad S, Sharma R, Chander R. Endemic fluorosis in Punjab. 1. Skeletal aspect. Fluoride 6 4-18 1973.
4. Subcommittee on Health Effects of Ingested Fluoride. Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission on Life Sciences, National Research Council. Health Effects of Ingested Fluoride. National Academy Press, Washington, DC 1993 pp 128-129.

FLUORIDE 31(2) 1998, pp 89 - 90	International Society for Fluoride Research
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