La fluoration

2. What happens to fluoride in your body?

The SCHER opinion states:

Hexafluorosilicic acid and hexafluorosilicates are the most commonly used agents in drinking water fluoridation and it has been claimed that incomplete dissociation of these agents in drinking water may result in human exposure to these chemicals. The toxicology of these compounds is incompletely investigated. Recent studies have addressed the equilibrium of the free fluoride ion and fluorosilicate species in aqueous solutions over a wide concentration and pH range. In the pH-range and at the concentrations of hexafluorosilicates/fluoride relevant for drinking water, hydrolysis of hexafluorosilicates to fluoride was rapid and the release of the fluoride ion was essentially complete. Residual fluorosilicate intermediates were not observed by sensitive 19F-NMR. Other hydrolysis products of hexafluorosilicate such as Si(OH)4 are rapidly transformed to colloidal silica (Finney et al. 2006). Si(OH)4 is present naturally in drinking water in large quantities and is not considered a risk. In summary, these observations suggest that human exposure to fluorosilicates due to the use of hexafluorosilicic acid or hexafluorosilicate for drinking water fluoridation, if any, is very low as fluorosilicates in water are rapidly hydrolyzed to fluoride, as illustrated in the following equation:
H 2 SiF6 ( aq ) + 6OH − ( aq ) ⇔ 6 F − ( aq ) + Si( OH )4 ( aq ) + 2 H 2 O( l ) Studies on Na2SiF6 and H2SiF6, compounds used to fluoridate drinking water, show a pharmacokinetic profile for fluoride identical to that of sodium fluoride (NaF) (Maguire et al. 2005, Whitford et al. 2008). It therefore seems unlikely that the rate and degree of absorption, fractional retention, balance and elimination of fluoride will be affected if these fluoride compounds are added artificially in low concentrations, or if fluoride is naturally present in drinking water.

Hexafluorosilicic acids used as fluoridating agents may contain some impurities. Concerns have been raised about several heavy metals present as low-concentration impurities in commercial hexafluorosilicic acid. The average concentrations of arsenic, mercury, lead and cadmium present in hexafluorosilicic acid are low – between 10 and 400 mg/kg H2SiF6 (CEN 12175-2006). Therefore, fluoridation of drinking water only contributes to a limited extent to the total exposure to these contaminants (expected drinking water concentrations are between 3.0 and 16.2 ng/L). These calculated concentrations are at least two orders of magnitude below drinking water guideline values for these metals established by WHO and other organizations, and therefore are not regarded as an additional health risk.

It has been claimed that fluoridated drinking water increases human exposure to lead due to solubilisation of lead from drinking water pipes by formation of highly soluble lead complexes. The claim was based on relationships of drinking water fluoridation and blood lead concentrations observed in a case study (Coplan et al. 2007).

Based on the available chemistry of fluoride in solution, the chemistry of lead and lead ions, and the concentrations of fluoride in tap water, it is highly unlikely that there would be an increased release of lead from pipes due to hexafluorosilicic acid. The added concentrations of hexafluorosilicic acid do not influence the pH of tap water, and do not form soluble lead complexes at the low concentrations of hexafluorosilicic acid present in the gastrointestinal tract after consumption of fluoridated drinking water (Urbansky and Schock 2000).

Physico-chemical properties

the main substance of concern is the fluoride ion (F-) and therefore the identification and the physico-chemical properties of sodium fluoride (NaF) given in Table 1 are considered applicable.

Table 1: Main physico-chemical properties of sodium fluoride (NaF). SCHER agreed to use these physico-chemical properties where relevant in this opinion.

Substance
Sodium fluoride
Elemental symbol
NaF
Ionic form
Na+, F-
CAS-number
7681-49-4
EINECS-number
231-667-8
Molecular weight (M)
42 g/mol (Na: 23; F: 19)
Melting point (MP)
ca. 1,000°C
Boiling point (BP)
1,700°C
Vapour pressure (VP)
133 Pa at 1077°C
Vapour pressure at 25°C (VP)
1.97E-5 Pa (conversion by EUSES)
Water solubility (WS)
40,000 mg/L at 20°C
Water solubility at 25°C (WS)
42,900 mg/L (conversion by EUSES)
Octanol-water partition (log Kow)
Not appropriate
Henry’s Law constant (H)
1.93E-8 Pa.m3/mol (calculation by EUSES)
Sorption capacity (Kd)
0.0006–0.03 dm3/kg (estimation) (Bégin et al. 2003) (see 3.1)
Removal rate (R)
1.39E-06 d-1 at 12°C (default)
Bioconcentration factor (BCF)
Not relevant

Oral uptake

In humans and animals, ingested fluoride occurs as hydrogen fluoride (HF) in the acidic environment of the stomach and is effectively absorbed from the gastrointestinal tract, although there is no proved absorption from the oral cavity. Peak plasma levels are typically seen within 30–60 minutes after ingestion. Highly soluble fluoride compounds, such as NaF present in tablets, aqueous solutions and toothpaste are almost completely absorbed, whereas compounds with lower solubility, such as CaF2, MgF2, and AlF3, are less well absorbed. Ingestion of fluoride with milk or a diet high in calcium will decrease fluoride absorption.

Dermal absorption

No experimental data on the extent of dermal absorption of fluoride from dilute aqueous solutions are available. As fluoride is an ion it is expected to have low membrane permeability and limited absorption through the skin from dilute aqueous solutions at near neutral pH (such as water used for bathing and showering). This exposure pathway is unlikely to contribute to the fluoride body burden.

Inhalation

No systematic experimental data on the absorption of fluoride after inhalation are available. A few older occupational studies have shown uptake of fluoride in heavily exposed workers from fluoride-containing dusts, but it is unlikely that inhalation exposure will contribute significantly to the body burden of fluoride in the general population.

Fluoride distribution, metabolism and excretion

Once absorbed, fluoride is rapidly distributed throughout the body via the blood. The short term plasma half-life is normally in the range of 3 to 10 hours. Fluoride is distributed between the plasma and blood cells, with plasma levels being twice as high as blood cell levels. The saliva fluoride level is about 65% of the level in plasma (Ekstrand 1977). Plasma fluoride concentrations are not homeostatically regulated, but rise and fall according to the pattern of fluoride intake. In adults, plasma fluoride levels appear to be directly related to the daily exposure of fluoride. Mean plasma levels in individuals living in areas with a water fluoride concentration of 0.1 mg/L or less are normally 9.5 μg /L, compared to a mean plasma fluoride level of 19-28.5 μg/L in individuals living in areas with a water fluoride content of 1.0 mg/L. In addition to the level of chronic fluoride intake and recent intake, the level of plasma fluoride is influenced by the rates of bone accretion and dissolution, and by the renal clearance rate of fluoride. Renal excretion is the major route of fluoride removal from the body. The fluoride ion is filtered from the plasma by the glomerulus and then partially reabsorbed; there is no tubular secretion of fluoride. Renal clearance rates of fluoride in humans average at 50 mL/minute. A number of factors, including urinary pH, urinary flow, and glomerular filtration rate, can influence urinary fluoride excretion. There are no apparent age related differences in renal clearance rates (adjusted for body weight or surface area) between children and adults. However, in older adults (more than 65 years of age), a significant decline in renal clearance of fluoride has been reported consistent with the age-related decline in glomerular filtration rates.

Approximately 99% of the fluoride in the human body is found in bones and teeth. Fluoride is incorporated into tooth and bone by replacing the hydroxyl ion in hydroxyapatite to form fluorohydroxyapatite. The level of fluoride in bone is influenced by several factors including age, past and present fluoride intake, and the rate of bone turnover. Fluoride is not irreversibly bound to bone and is mobilized from bone through bone remodelling.

Soft tissues do not accumulate fluoride, but a higher concentration has been reported for the kidney due to the partial re-absorption. The blood-brain barrier limits the diffusion of fluoride into the central nervous system, where the fluoride level is only about 20% that of plasma. Human studies have shown that fluoride is transferred across the placenta, and there is a direct relationship between fluoride levels in maternal and cord blood. In humans, fluoride is poorly transferred from plasma to milk. The fluoride concentration in human milk is in the range of 3.8–7.6 μg/L.