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Description of key information

The available literature data indicate that fluoride is orally bioavailable from sodium 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 have shown elevated blood levels of fluoride following the administration 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 toxicokinetic studies show that the retention of fluoride is comparable when administered in the form of sodium fluoride, disodium hexafluorosilicate or hexafluorosilicic acid.

Dermal absorption is possible based on physicochemical properties and also supported by the corrosive properties, which will enhance penetration. Taking into account that hydrolysis takes place in humid conditions to hydrogen fluoride, complete dermal absorption cannot be excluded.

Absorption by inhalation is not expected, which is also founded by literature data on silicate compounds hydrolysing to hydrogen fluoride, which does not reach the lungs.

Key value for chemical safety assessment

Bioaccumulation potential:
high bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
100
Absorption rate - inhalation (%):
10

Additional information

A. Literature data

The available literature 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 administration 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.

 

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).

Fluorosilicate poisoning in domestic animals (cattle, sheep, horse, pigeon and sheep) showed fluorine concentrations in stomach/rumen contents, urine and blood. Sheep given sodium hexafluorosilicate via stomach tube showed blood and urine levels of fluoride initially significantly increased and then decreased with time (Egyed & Shlosberg, 1975).

 

For the same fluorine content, sodium fluoride, and sodium hexafluorosilicate were observed to have the same extent of chronic fluorine intoxication in rats. 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: Haneke & Carson, 2001).

 

Toxicokinetics of HF and fluoride has been reviewed in the EU RAR (2001). Hydrogen fluoride is absorbed 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 except 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. 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.

 

B. Basic toxicokinetics assessment

According to chapter R.7C (Version 3.0- June 2017) of the endpoint specific guidance of REACH, physicochemical and toxicological data may be used for a qualitative TK assessment.

Absorptionof Hexafluorosilic acid was assessed as follows based on physicochemical/toxicological data:

- Hexafluorosilicic acid is a transparent, colourless, fuming liquid with a sour, pungent odour. It has a molecular weight of 144.0898 g/mol and is known to be miscible with water.

- Based upon the ionisable/hydrophilic properties and expected hydrolysis of Hexafluorosilicic acid,oral absorption is considered to be possible. This is supported by the toxicokinetics literature data on silicate compounds and the oral toxicity observed with sodium fluoride.   

- Based on the rather low vapor pressure and high hydrophilicity of Hexafluorosilicic acid, deposition in the airways and absorption by inhalation is not expected. This is supported by the toxicokinetics literature data on silicate compounds hydrolysing to hydrogen fluoride, which does not reach the lungs.

- Based on the fact that Fluorosilic acid is a liquid with low molecular weight and rather low vapour pressure, dermal absorption is possible. This is further supported by the corrosive properties, which will enhance penetration. Taking into account that hydrolysis takes place in humid conditions to hydrogen fluoride, complete dermal absorption cannot be excluded.

 

For the assessment of distribution, metabolism and excretion physicochemical and toxicological properties are taken into account.

- Based upon the low molecular weight and solubility in water, hexafluorosilic acid is expected to be distributed in the body. This is supported by the expected hydrolysis to HF and observed target organs and toxicity (thickening and ulceration of the gastric mucosa, dental fluorosis, nephrosis and skeletal effects) observed with read-across substance NaF.

- Hydrolysis to HF is expected in watery solution. Fluoride is known to be 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 via the urine is however expected because hexafluorisilic acid is miscible in water. Taking into account the hydrolysis to HF in watery solution, fluoride can be excreted rapidly as a consequence of glomerular filtration.