has there been any investigation of the relationship between pineal fluoride concentrations and either recent or cumulative fluoride intakes.

In Vitro Studies

Few studies have examined the effects of fluoride on pineal function. NaF (2.5-20 mM, or fluoride at 47.5-380 mg/L) produces markedly increased adenylyl cyclase activity (up to four times control activity) of rat pineal homogenates in vitro (Weiss 1969a,b), as it does in other tissues (Weiss 1969a); ATPase activity in the homogenates was inhibited by up to 50% (Weiss 1969a). Potassium fluoride (7-10 mM, or fluoride at 133-190 mg/L) has been used experimentally to increase adenylyl cyclase activity in rat pineal glands in vitro (Zatz 1977, 1979).

Animal Studies

Details of the effect of fluoride on pineal function are presented in Appendix E, Table E-15. Luke (1997) examined melatonin production as a function of age and time of day in Mongolian gerbils (Meriones unguiculatus). On an absolute basis, melatonin production by the low-fluoride group was constant at ages 7-28 weeks, with no difference between males and females. Relative to body weight, melatonin output declined progressively with age until adulthood (by 11.5 weeks in females and 16 weeks in males). In contrast, prepubescent gerbils fed the high-fluoride diet had significantly lower pineal melatonin production than prepubescent gerbils fed the low-fluoride diet. Relative to body weight, the normal higher rate of melatonin production in sexually immature gerbils did not occur.

Sexual maturation in females occurred earlier in the high-fluoride animals (Luke 1997); males had increases in melatonin production relative to body weight between 11.5 and 16 weeks (when a decrease normally would occur), and testicular weight at 16 weeks (but not at 9 or 28 weeks) was significantly lower in high-fluoride than in low-fluoride animals. The circadian rhythm of melatonin production was altered in the high-fluoride animals at 11.5 weeks but not at 16 weeks. In high-fluoride females at 11.5 weeks, the nocturnal peak (relative to body weight) occurred earlier than in the low-fluoride animals; also, the peak value was lower (but not significantly lower) in the high-fluoride animals. In males, a substantial reduction (P < 0.00001) in the nocturnal peak (relative to body weight) was observed in the high-fluoride animals.



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