Fluorosis fluoride

Because of the corrosive effects and discomfort associated with inhalation of fluorine, chronic toxicity does not occur. Although the metaboHc fate of fluorine is not clear, it does not seem that much is converted to fluoride ion in the body (107). Therefore comparisons to effects of fluoride ion poisoning, known as fluorosis, are probably incorrect. 

Fluorides ia small (1 ppm ia water, 0.1% ia dentifrices) quantities have been shown to provide dramatic reduction ia dental decay. Fluorides also show promise for bone treatment and ia pharmaceuticals (qv) (see also Chemotherapeutics, anticancer Steroids). However, larger quantities of fluorides can lead to dental fluorosis, bone fracture, and even death. The oral LD q for free fluoride ion ia rats appears to be 50 to 100 mg/kg body weight based on LD q values for several fluorides. 

Health and Safety Factors. Boron trifluoride is primarily a pulmonary irritant. The toxicity of the gas to humans has not been reported (58), but laboratory tests on animals gave results ranging from an increased pneumonitis to death. The TLV is 1 ppm (59,60). Inhalation toxicity studies in rats have shown that exposure to BF at 17 mg/m resulted in renal toxicity, whereas exposure at 6 mg/m did not result in a toxic response (61). Prolonged inhalation produced dental fluorosis (62). High concentrations bum the skin similarly to acids such as HBF and, if the skin is subject to prolonged exposure, the treatment should be the same as for fluoride exposure and hypocalcemia. No chronic effects have been observed in workers exposed to small quantities of the gas at frequent intervals over a period of years. 

Health and Safety Factors. The low solubiUty of calcium fluoride reduces the potential problem of fluoride-related toxicity. Water saturated with calcium fluoride has a fluoride concentration of 8.1 ppm as compared to the recommended water fluoridation level of 1 ppm fluoride ion. However, because the solubiUty of calcium fluoride ia stomach acid is higher, continued oral ingestion of calcium fluoride could produce symptoms of fluorosis. The adopted TWA limit for fluorides as F is 2.5 mg/m (68,69). 

Tolerance of animals for fluorides varies, dairy cattle being most sensitive and poultry least (Table 8-3). Fluorosis of animals in contaminated areas can be avoided by keeping the intake levels below those listed by incorporating clean feeds with those high in fluorides. It has also been determined... 

Toxicology. Fluoride causes irritation of the eyes and respiratory tract and gastrointestinal effects absorption of excessive amounts of fluoride over a long period of time results in skeletal fluorosis. 

Repeated exposure to excessive concentrations of fluoride over a period of years results in increased radiographic density of bone and eventually may cause skeletal fluorosis. Crip-... 

Repeated exposure to excessive concentrations of hydrogen fluoride over a period of years may result in an increased radiographic density of bone and eventually may cause crippling fluorosis (osteosclerosis due to deposition of fluoride in bone)/ The early signs of increased bone density from fluoride deposition are most apparent in the lumbar spine and pelvis and can be detected by X ray. 

Both anhydrous hydrogen fluoride gas and hydrofluoric acid are highly corrosive and dangerous. Skin contact by even dilute aqueous HF can be severely injurious, causing deep ulceration with delayed effect. The acid can penetrate the skin and destroy tissues. It also is damaging to eyes, nose and lungs. Inhalation can cause fluorosis and pulmonary edema. 

Under neutral conditions, fluoride is also able to induce nucleation and growth of apatite crystals without the involvement of OCP [72]. This requires fluoride concentrations of 0.5 ppm or higher, which are rarely achieved in vivo except in cases where fluorosis may result. It is significant that in severe cases of fluorotic enamel, ultra-structural studies [73] have shown the occurrence of a proliferation of apatite nuclei, suggesting that the presence of fluoride may act to encourage precipitation of crystals of fluorapatite. 

Fluorosis affects the enamel of the tooth, causing it to become hypominera-lised. This is detected as visual changes in the opacity, and it is only in extreme cases that this leads to an adverse appearance as mottling of the tooth surface [86]. The severity of the discolouration depends on the dose of fluoride, its duration and timing of consumption. 

The risk of fluorosis is only of concern for children below about 8 years of age, because enamel can no longer be affected once pre-eruptive maturation has occurred [89]. As far as cosmetic effects are concerned, the critical age is somewhat younger because at this age the central incisors are undergoing development, and hence are at a stage that makes them susceptible to fluorosis. For children at the age likely to be affected, the main sources of fluoride are drinking water, processed food and beverages, toothpaste and other dental products (i.e., tablets or drops). 

In general, moderate and severe fluorosis is rare. However, mild fluorosis has been detected at significant levels, for example, in 26% of subjects in one recent study [93]. However, the mildness of the fluorosis detected is associated with only very slight changes in the appearance of the teeth, which suggests that, even at these levels, it is not a major public health problem. Nonetheless, it is appropriate to ensure that parents or guardians of children continue to receive sound advice on safe levels of fluoride for those in their care to be exposed to and, since the cariostatic effect of fluoride is known to occur well after enamel formation during tooth development, treatment to reduce caries should concentrate on those measures that carry the lowest possible risks of fluorosis [91]. 

In most cases, fluoridated toothpastes are acceptable substances for use, but even for these products, there is some risk of fluorosis. For example, children who began using them before the age of 2 were shown to be at higher risk of developing fluorosis than children who do not use it at all [94,95]. However, the relative importance of the various factors that govern exposure to fluoride from this source (age of starting to use fluoridated toothpastes, amount used and frequency) is not known. 

One contributor to this risk of fluorosis in children is the lack of control in the swallowing reflex, particularly in children younger than 3 years of age [96], Children are also known to like the taste of toothpaste, and hence to swallow it deliberately. A small toothbrush of the size appropriate for use by a child holds in the region of 0.75-1.0 g of toothpaste, which means that an individual blob of toothpaste provides between 0.75 and 1.0 mg of fluoride. It has been estimated that children below the age of six swallow a mean of 0.3 of toothpaste per brushing and this may be sufficient to lead to ingestion of enough fluoride to cause the mottling associated with fluorosis [97]. 

R.D. Jackson, S.A. Kelly, B. Katz, E. Brizendine, G.K. Stookey, Dental fluorosis in children residing in communities with different water fluoride levels 33 month followup, Pediatr. Dent. 21 (1999) 248-254. 

S.O. Griffen, E.D. Beltran, S.A. Lockwood, L.K. Barker, Esthetically objectionable fluorosis attributable to water fluoridation. Common. Dent. Oral Epidemiol. 30 (2002) 199-209. 

S.A. Ekiund, B.A. Burt, A.I. Ismail, J.J. Calderone, High fluoride drinking water, fluorosis, and dental caries in adults, J. Am. Dent. Assoc. 114 (1987) 324-328. 

L.W. Ripa, A critique of topical fluoride methods (dentifrices, mouthrinses, operator-, and self-applied gels) in an era of decreased caries and increased fluorosis prevalence, J. Public Health Dent. 51 (1991) 23-41. 

Because of the low natural levels of fluoride in some water supplies and correspondingly high levels of dental caries, many authorities worldwide have permitted, or instigated, fluoridation of water supplies, although this has met some opposition, partly because of the potential health or dental effects including fluorosis. In order to prevent dental caries, fluoride is deliberately added to salt or milk in some countries. 

This paper is written with the aim of providing sufficient background to help understand the mechanism of action of fluoride ion on humans. The main focus is on the effects of fluoride on dental health, in-depth discussion of skeletal fluorosis and use of fluoride for treating osteoporosis being outside the scope of this paper. Current information on the main sources of human exposure to fluoride and current recommendations for adequate intake (Al) of fluoride, as well as methods for assessing exposure, will be reviewed. 

Fig. 1. Areas of the world with endemic fluorosis and areas with high concentrations of fluoride in water.

The primary adverse effects associated with chronic, excess fluoride intake are skeletal, and dental or enamel, fluorosis. Other effects, including hypersensitivity reactions, renal insufficiency, immunological effects, possible association with repetitive strain injury, birth defects and cancer have been observed and discussed [17,41-45]. 

Dental or enamel fluorosis is an irreversible dose-response effect caused by fluoride ingestion during the pre-eruptive development of teeth. The pre-eruptive maturation of crowns of the anterior permanent teeth, which are of most concern aesthetically, is complete and, together with the risk of fluorosis, is over by the age of 7-8 years [46,47]. After the enamel has completed its pre-eruptive maturation, it is no longer susceptible. Therefore, fluoride intake up to the age of 7-8 years is of most interest. Although it is usually the permanent teeth that are affected, occasionally the deciduous teeth may be also involved. 

Fig. 2. Teeth demonstrating fluorosis. A high level of dietary fluoride has resulted in much of the enamel becoming opaque in patches, giving a mottled appearance. (Reprinted with permission from [48]. Copyright 2002 Mosby International Limited.) (See Colour Plate Section at the end of this book.)...

Due to ubiquitous exposure to fluoride sources other than drinking water, it is not possible to draw firm conclusions regarding the independent effects of fluoride in drinking water on dental caries and its prevention. It has been estimated that moderate dental fluorosis occurs in 1-2% of the population exposed to fluoride at 1 mg/L in drinking water and in about 10% of the population at 2 mg/L moderate/severe fluorosis occurs in variable percentages ranging up to 33% of the population exposed to fluoride at 2.4-4.1 mg/L [52]. 

Skeletal fluorosis can be defined as excessive deposition of fluoride in bone. This is a pathological condition that is by far the most important aspect of chronic exposure to elevated levels of fluoride, either by inhalation or by ingestion. The skeletal deformities may be associated with or accentuated by nutritional deficiencies or even malnutrition and hard manual work or, possibly, other conditions found in areas of long-term social and nutritional deprivation [6]. See, for instance Fig. 1 of [54]. The situation is specific also for populations consuming large volumes of water, such as athletes or people with certain medical conditions or... 

Endemic crippling skeletal fluorosis is confined in temperate climates to individuals exposed continuously over many years to very high levels of fluoride these cases are associated with industrial situations, with unusually high levels of fluoride in drinking water (e.g., 10 mg/L) or the use of high fluoride coal for cooking and drying foodstuffs indoors [6,17,55]. 

Most epidemiological research has indicated that an intake of at least 10 mg/day for 10 or more years is needed to produce clinical signs of the milderforms of osteosclerosis [8]. Water fluoride concentrations of 4-8 mg/L in temperate climates have not been found to be associated with any signs or symptoms of skeletal fluorosis [6]. This data should be regarded with scepticism in view of reports from a number of developing countries that endemic skeletal fluorosis occurs in individuals whose drinking water contains more than 6 mg/L of fluoride [6]. 

---