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Several epidemiological studies, beginning with those of Dean and co-workers in the 1940's, clearly demonstrate the relationship between dental fluorosis in humans and the level of fluoride in water supplies. These studies and others have shown that, in a population, there is a direct relationship among the degree of enamel fluorosis, plasma and bone fluoride levels, and the concentration of fluoride in drinking water. However, dental fluorosis is a reflection of fluoride exposure only during the time of enamel formation, somewhat limiting its use as a biomarker. In addition, the degree of fluorosis is dependent not only on the total fluoride dose, but also on the timing and duration of fluoride exposure. At the level of an individual response to fluoride exposure, factors such as body weight, activity level, nutritional factors, and the rate of skeletal growth and remodeling are also important. These variables, along with an individual variability in response to similar doses of fluoride, indicate that enamel fluorosis cannot be used as a biological marker of the level of fluoride exposure for an individual.

It is now well-established that a linear relationship exists between fluoride dose and enamel fluorosis in human populations. With increasing severity, the subsurface enamel all along the tooth becomes increasingly porous (hypomineralized), and the lesion extends toward the inner enamel. In dentin, hypomineralization results in an enhancement of the incremental lines. After eruption, the more severe forms are subject to extensive mechanical breakdown of the surface. The continuum of fluoride-induced changes can best be classified by the TF index, which reflects, on an ordinal scale, the histopathological features and increases in enamel fluoride concentrations. Human and animal studies have shown that it is possible to develop dental fluorosis by exposure during enamel maturation alone. It is less apparent whether an effect of fluoride on the stage of enamel matrix secretion, alone, is able to produce changes in enamel similar to those described as dental fluorosis in man. The clinical concept of post-eruptive maturation of erupting sound human enamel, resulting in fluoride uptake, most likely reflects subclinical caries. Incorporation of fluoride into enamel is principally possible only as a result of concomitant enamel dissolution (caries lesion development). At higher fluoride concentrations, calcium-fluoride-like material may form, although the formation, identification, and dissolution of this compound are far from resolved. It is concluded that dental fluorosis is a sensitive way of recording past fluoride exposure because, so far, no other agent or condition in man is known to create changes within the dentition similar to those induced by fluoride. Since the predominant cariostatic effect of fluoride is not due to its uptake by the enamel during tooth development, it is possible to obtain extensive caries reductions without a concomitant risk of dental fluorosis.

The developing enamel from three-day-old hamster first maxillary (M1) molar tooth germs exposed to fluoride (F-) in vitro was analyzed for its mineral content by means of the energy-dispersive x-ray microanalysis technique. The aim of this study was to obtain semi-quantitative data on the F(-)-induced hypermineralization patterns in the enamel and to confirm that the increase in electron density observed in micrographs of F(-)-treated enamel (Lyaruu et. al., 1986, 1987b) is indeed due to an increase in mineral content in the fluorotic enamel. The tooth germs were explanted during the early stages of secretory amelogenesis and initially cultured for 24 hr in the presence of 10 ppm F- in the culture medium. The germs were then cultured for another 24 hr without F-. In order to compare the ultrastructural results directly with the microprobe data, we used the same specimens for both investigations. The net calcium counts (measurement minus background counts) in the analyses were used as a measure of the mineral content in the enamel. The aprismatic pre-exposure enamel, deposited in vivo before the onset of culture, was the most hypermineralized region in the fluorotic enamel, i.e., it contained the highest amount of calcium measured. The degree of the F(-)-induced hypermineralization gradually decreased (but was not abolished) in the more mature regions of the enamel. The unmineralized enamel matrix secreted during the initial F- treatment in vitro mineralized during the subsequent culture without F-. The calcium content in this enamel layer was in the same order of magnitude as that recorded for the newly deposited enamel in control tooth germs cultured without F-.(ABSTRACT TRUNCATED AT 250 WORDS)