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Description of key information

Short description of key information on bioaccumulation potential result: 
Various sources of data show that fluoride is bioavailable from fluorosilicate; the availability of fluoride from hexaflurosilicic acid is comparable to that from sodium fluoride.
Short description of key information on absorption rate:
No data are available. Significant dermal absorption of hexafluorosilic acid is not predicted under normal conditions of exposure, but may be increased in accidental exposures where the integrity of the skin is compromised (chemical burns).

Key value for chemical safety assessment

Additional information

Toxicokinetics

The available data indicate that fluoride is bioavailable from hexafluorosilicate administered in the diet or drinking water due to the ionisation of the hexafluorosilicate salt and the subsequent hydrolysis of hexafluorosilcate to form fluoride and silicate. Studies show elevated blood levels of fluoride following the administreation of or accidental exposure to hexafluorosilicate and also show elevated urinary excretion of fluoride and the retention of fluoride in the skeleton and teeth. Comparative studies show that the retention of fluoride is comparable when administered in the form of sodium fluoride, sodium hexafluorosilicate or hexafluorosilicic acid.

Dermal absorption

No data are available, however significant dermal absorption of hexafluorosilic acid is not predicted under normal conditions of exposure. Absorption may be increased in accidental exposures where the integrity of the skin is compromised (i.e. in burns cases).

The significant literature on the toxicokinetics of HF and fluoride has been reviewed in the EU RAR and is summarised below.

Absorption

Hydrogen fluorideisabsorbed into the body and will ionise (>99.99%) to form the hydrogen (hydronium) and fluoride ions under physiological conditions. The absorption of inorganic fluoride across mucous membranes is passive and is independent of the fluoride source. Following inhalation exposure to HF, experiments in various species including man have demonstrated that the large majority of inhaled HF does not reach the lungs but is absorbed via the upper respiratory tract mucosa. Plasma fluoride levels are directly related to HF inhalation and peak at between 60-120 hours after the start of exposure. Following dermal exposure to HF, absorption is of fluoride likely to be minimal expect in cases where the normal skin structure is compromised as a consequence of the corrosive effects of the substance. The absorption of fluoride following oral administration of HF has not been investigated, but is likely to be rapidly absorbed.

Distribution

Absorbed fluoride is distributed primarily in the blood, 75% in the plasma and 25% associated with erythrocytes. Half of the plasma fluoride may be bound to organic molecules. Fluoride is rapidly distributed and is sequestered in the bones and teeth, where exchange with hydroxyl groups results in incorporation into the bone and tooth structure. Levels of fluoride in bones and teeth are directly correlated with exposure levels.

Excretion

Fluoride is excreted rapidly as a consequence of glomerular filtration, with a plasma half-life of 2-9 hours. The half-life for skeletal fluoride in humans is reported to be 8-20 years.

Discussion on bioaccumulation potential result:

The effects of different fluoride salts on the uptake and retention of fluoride were investigated in female rats. A comparison between the retention of sodium fluoride, fluorosilicic acid, and sodium fluorosilicate did not find significant differences in the proportion of intake retained in the body of female rats exposed to 24 ppm fluoride in the diet for 5 months; fluoride retentions were 66.2, 68.1, and 64.8, respectively (Whitford & Johnson, 2003).

Rats were fed a diet containing 0.16% sodium hexafluorosilicate supplemented in a corn-soybean oilmeal-casein ration ad libitum for 22-23 days. The excretion of fluoride was measured and retention estimated. The average amounts of fluorine were 94.4 mg in faeces and 91.9 mg in urine. The mean amount of fluorine absorbed was 65.1% and that retained was 31.0%. The results of this study demonstrate the bioavailability of fluorine from fluorosilicate administered in the diet (Kick et al, 1935).

Egyed & Shlosberg (1975) report investigations of fluoride levels in poisoned animals and also in sheep following gavage dosing. From 1965 to 1974, 170 cases of suspected fluorosilicate poisoning were reported in domestic animals. For positive cases, the animals were poisoned from ingestion of bait, which had not been disposed of after use. Of these, 27 cases were used in the chemical diagnosis of sodium hexafluorosilicate poisoning (13 for cattle, 11 for sheep, and 1 each for horse, pigeon and sheep). In cattle and sheep, measured fluorine concentrations ranged from 120 to 2900 ppm (wet weight) in stomach/rumen contents and up to 75 ppm in urine. In blood serum, 8 and 3 ppm fluorine were determined in one animal from the groups of poisoned cattle and sheep, respectively. When sheep were given sodium hexafluorosilicate via stomach tube (25, 50, 200, 1500, and 2000 mg/kg; 0.13, 0.27, 1.06, 7.976, and 10.63 mmol/kg), blood serum concentrations and urine levels of fluoride initially significantly increased and then decreased with time. For example, the low dose group had blood serum concentrations ranging from 0.1-0.165 ppm fluoride prior to treatment and 4.2 ppm fluoride six hours after dose administration. By day 4, levels dropped to 0.38 ppm fluoride. Corresponding urine levels of fluoride were 1.35-6.75, 175, and 25 ppm, respectively. The results of this study demonstrate the bioavailability of fluoride in animals administered hexafluorosilicate. The results of this study demonstrate the bioavailability of fluoride in animals administered hexafluorosilicate.

For the same fluorine content, sodium fluoride, sodium hexafluorosilicate, cryolite (Na3AlF6), and barium sulphate were observed to have the same extent of chronic fluorine intoxication in rats. Ammonium fluoride, potassium fluoride, barium fluorosilicate, potassium fluorosilicate, and sodium fluorosilicate exhibited the same acute toxicity as sodium fluoride in the animals. In a comparative study of absorption and excretion of fluorine in rats fed sodium fluoride, calcium fluoride, and sodium hexafluorosilicate, the percent fluorine retained was the same for the two sodium compounds. Several experiments on growing rats orally given 5, 10, 15, 25, and 50 ppm fluorine as sodium fluoride or sodium hexafluorosilicate for 90-100 days found no differences in the quantity of fluorine deposited and the contents of ash, calcium, and phosphorus in the incisor teeth, molar teeth, mandibles, and femurs. Furthermore, there were no differences in the percent of ingested fluorine retained in the body, and a combination of sodium silicate (15 ppm silicon) with sodium fluoride (25 ppm fluorine) did not affect the amount of fluorine deposited. The growth rate was normal in all rats. A separate study using litters of female weanling Osborne-Mendel rats that were given 50 ppm fluorine as sodium fluoride or ammonium fluorosilicate in drinking water for 99 days observed similar results. The results of the reviewed studies indicate that the uptake and retention of fluoride from sodium fluoride and sodium hexafluorosilicate in the rat is essentially the same. The results of these studies therefore justifiy the read-across from hexafluorosilicic acid to sodium fluoride (NTP, 2001).

Discussion on absorption rate:

No data are available. Significant dermal absorption of hexafluorosilic acid is not predicted under normal conditions of exposure, but may be increased in accidental exposures where the integrity of the skin is compromised (i.e. in burns cases).