National Research Council. (1971). Fluorides. Committee on Biological Effects of Atmospheric Pollutants. National Academy of Sciences. Washington, D.C.
Chapter 9: Effects of Fluoride on Human Health
NERVOUS SYSTEM (pp. 205-206)
There are very few data available related to the effect of fluoride on the central nervous system (CNS). With regard to man, we are forced to fall back on data from studies of mortality statistics, which merely indicate that ingested fluoride did not lead to an increase in deaths attributed to diseases of the CNS.
The situation is not much better with regard to animal studies. Lu et al. (1961) reported that rats given sodium fluoride by intraperitoneal injection (10 mg/kg daily) for 4-14 weeks or 7 or 70 ppm of fluoride in the diet (which contained 50-60 ppm of fluoride chiefly as bone meal) for 15-19 weeks were more sensitive to chemical stimulation of the CNS by pentylenetetrazole or strychnine and to electric shock. The animals were also more sensitive to the CNS depressant effect of diphenylhydantoin (reduction of incidence of electroshock) and showed a prolonged pentobarbital-induced sleeping time. The effect of fluoride on the activity of pentylenetetrazole and of pentobarbital disappeared 2-3 weeks after the animals were returned to a normal fluoride intake. F. A. Smith and L. C. K. Wong (unpublished data) attempted to reproduce the results of Lu et al. on pentobarbital sleeping time. They administered 8 and 63 ppm of fluoride in the drinking water to rats maintained for 8 months on a diet containing 18 ppm of fluoride, but the sleeping time was unaffected. Elliott (1967) also was unable to confirm the observation of Lu et al.
Rice and Lu (1963) showed that a diet of 70 ppm of sodium fluoride for 16 weeks caused an increase in sensitivity to the paralytic effects of succinylcholine in rats, which they attributed to the inhibition of cholinesterase activity. They also showed that rats receiving 1.68 or 3.36 mg of fluoride per 100 g of body weight daily for 30 days by stomach tube showed a heightened sensitivity to the cholinesterase inhibitors, parathion and demeton.
Lu et al. (1965) have also investigated the effect of intravenous lethal doses of sodium fluoride on the CNS of rhesus monkeys. The electroencephalogram changed from fast low-amplitude to slow high-amplitude activity. Depression and alternate periods of wakefulness and sleep were noted. Muscle fasciculations and clonic convulsions were occasionally seen. Pupils were of normal size and reactive to light until shortly before death, when they became dilated and fixed.
Apparently, only two reports in the literature have examined the behavioral effects of fluorides. Elliott (1967) studied the effects of 150 ppm of sodium fluoride added to a standard laboratory diet on the ability of rats to learn a multiple T-maze. No differences were attributable to the added fluoride either in time taken to run the maze or in errors made while learning it. It should be pointed out, however, that there was no positive control group, so the sensitivity of the test is not known.
Sadilova (1968) studied the much more toxic hydrogen fluoride. She reported on a series of conditioned-reflex studies in rats. Hydrogen fluoride was administered to the rats for 5 months in concentrations of 0. 10, 0.03, and 0.01 mg/m3. Her highest dosage produced an increase in the latency of some of the learned responses. She also found a disruption of some of the discriminations that the animals had been taught. These effects were greatest with the highest concentration but were detectable even with the 0.03-mg/m3 dosage. Rats exposed to the latter concentration returned to control levels of performance after a 1-month recovery period. These behaviorally active dosages also were reported to have depressed cholinesterase activity. In addition, those exposed to the 0.10 mg/m3 concentration showed, on histologic examination of the brains, changes ranging from hyperemia of the membrane capillaries to structural changes in the nerves themselves. Sadilova also reported on human sensory thresholds to hydrogen fluoride. She estimated the minimal concentration for odor perception at 0.03-0.11 mg/m3. About the same concentrations increased the sensitivity of the eye to light.
The presence of only those two studies makes any firm conclusion about behavioral effects of fluorides premature. In addition, the reader should keep in mind the absence of any data on the sensitivity of the maze test used by Elliott in his negative study of sodium fluoride and the absence of confirmatory replications of the Sadilova studies on hydrogen fluoride.
Elliot, L. Lack of effect of administration on the central nervous system of rats. Acta Pharmacol. (Kobenhavn) 25:323:328. 1967.
Lu, F.C., R.S. Grewal, W.B. Rice, R.C.B. Graham, and M.G. Allmark. Acute toxicity of sodium fluoride for rhesus monkeys and other laboratory animals. Acta. Pharmacol. (Kobenhavn) 22:99-106, 1965.
Lu. F.C., I.M. Mazurkiewicz, R.S. Grewal, M.G. Allmark, and P. Boivin. The effects of sodium fluoride on responses to various central nervous system agents in rats. Toxicol. Appl. Pharmacol. 3:31-38, 1961.
Rice, W.B., F.C. Lu. The effects of sodium fluoride on the actions of succinylcholine, parathion, and demeton in rats. Acta. Pharmacol. (Kobenhavn) 20:39-42, 1963.
Sadilova, M.S. Studies in the standardization of maximum allowable hydrogen fluoride concentrations in the air of inhabited areas, pp. 118-128. In U.S.S.R. Literature on Air Pollution and Related Occupations. Vol. 17. Book 10. Translated by B.S. Levine. Moscow: Medgiz, 1968. (available from National Technical Information Service, Springfield, Va., as report TT 64-11767)
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