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Description of key information

Short description of key information on absorption rate: 
A dermal absorption percentage for workers of 0.07% is assumed. For the general population a dermal absorption percentage of 0.2% is assumed.

Key value for chemical safety assessment

Additional information

Oral route

For cryolite information on absorption mainly comes from fluoride determination (F-) in excrements (animal or human studies) after oral application. Very little is known on the absorption and bioavailability of the aluminium-containing moiety.

Oral uptake of cryolite, followed as retention and excretion of fluoride ion, has been studied in a number of animal and human volunteer studies. Available data indicate that cryolite hydrolyses to produce fluoride anion instantaneously under acidic or basic conditions. Due to the acidic and aqueous conditions in the stomach, fluoride ions, which are liberated from cryolite, are present in the form of hydrogen fluoride and then behave as fluoride from any other inorganic source, readily penetrating biological membranes by passive diffusion both in stomach and intestines.

Largent and Heyroth (1949) investigated absorption, retention and excretion of cryolite administered to human volunteers as either solid in small gelatin capsules, or a solution in distilled water after repeated oral exposure. When solid cryolite was ingested, 62.2-70% of the average daily intake was absorbed on the average per day. With cryolite solution, the average daily absorbed amount was 93%. With solid cryolite 34.1-45.4% of the average daily intake was retained in the body. With cryolite solution, retention was 37%. Urinary and faecal excretion of fluoride was dose-dependent. With solid cryolite, 29.9-37.9% of the fluoride intake was excreted via faeces on a daily average basis and 36-45% was excreted via urine. With a cryolite solution, lower faecal (7%) and higher urinary (59%) excretion levels could be observed.

In available animal studies, 85% uptake of fluoride was reported by Wright and Thompson (1978) who administered cryolite in diet to rats for 7 consecutive days. 30% of the amount of fluoride that had been taken up with the diet was excreted with the urine, 15% was excreted with faeces and approximately 55% was retained.

In summary, the way in which oral administration takes place influences the amount of absorption of fluoride ions from cryolite: when administered in solution or via drinking water, higher rates of absorption (up to 20% higher) can be found compared to the intake of the solid material via diet. Based on the study of Largent and Heyroth (1949), 60% oral absorption in humans is assumed as a worst case estimate, while 85% oral absorption is established for rats, based on the study of Wright and Thompson (1978).

Inhalation route

In animals and humans, cryolite can be absorbed after inhalation exposure as could be concluded from acute inhalation studies in rats and from cryolite exposed workers, in which serum and urinary fluoride had been quantified. The extent of inhalation absorption can be assumed to be dependent on the size of the cryolite particles. In occupationally cryolite exposed workers (crushing, separation and grinding of dry cryolite, particle size has not been determined; it might be possible that during crushing non-respirable particles have been formed in addition to respirable particles), based on maximal achievable values, up to 31% of the inhaled amount of fluoride was excreted via urine (Grandjean et al, 1990).

For the risk characterisation a default value of 100% inhalation absorption is taken as:

- intake might have been higher if only fine ground cryolite had been applied;

- from oral studies it is known that comparable quantities of fluoride from cryolite that are excreted via urine may be retained in the body.

Dermal route

Experimental data on dermal uptake of cryolite are not available. Based on the low solubility and the type of compound (inorganic salt), dermal absorption of cryolite could be anticipated to be quite low. Cryolite is insoluble in organic solvents and thus will not easily pass the lipophilic stratum corneum of the skin. A dermal absorption percentage of 0.07% will be used for risk assessment for workers, while for the general population a dermal absorption percentage of 0.2% is assumed.

Discussion on absorption rate:

Solids substances will only penetrate the skin in (aqueous) solution. Cryolite is a salt with a water solubility of 0.6 g/L. Once solved, the salt is hydrolysed to its ions F-, Al3+ and Na+. The ions are hydrophylic and due to lack of lipophilicity, they will not have any affinity to skin(lipids). Therefore, skin absorption can only occur through the water that penetrates the skin and the maximum skin absorption is defined by the maximum water solubility of the salts and the maximum amount of water that can penetrate the skin.

 

The maximum amount of water that can penetrate the skin is determined to be 17 µL per 1 cm2 per 24 hours (Ten Berge, W. A simple dermal absorption model: derivation and application.Chemosphere 2009; 75(11):1440-5), which equals 6 µL per cm2 per 8 hours.

As already stated, the maximum amount of cryolite that can be solved in water is 0.6 g/L (= 0.6 µg/µL).

Skin penetration, dermal absorption percentage for workers

Since 6 µL of water can maximally penetrate 1 cm2 of skin per 8 hours, 6 x 0.6 = 3.6 µg of hydrolysed salt may penetrate 1 cm2 of skin per 8 hours. In an in vitro skin absorption experiment (according to OECD guideline 428), the application should mimic human exposure, normally 1-5 mg/cm2 (1000-5000 µg/cm2). Thus, in case the skin penetration of cryolite would be experimentally be determined according to OECD guideline 428 using 5 mg/cm2 as exposure condition, a skin penetration of 0.07% (3.6/5000) would be observed maximally. Assuming a skin penetration of cryolite of 0.07% is considered a worse-case situation.

Skin penetration, dermal absorption percentage for general population

Since 17 µL of water can maximally penetrate 1 cm2 of skin per 24 hours, 17 x 0.6 = 10.2 µg of hydrolysed salt may penetrate 1 cm2 of skin per 24 hours. In an in vitro skin absorption experiment (according to OECD guideline 428), the application should mimic human exposure, normally 1-5 mg/cm2 (1000-5000 µg/cm2). Thus, in case the skin penetration of cryolite would be experimentally be determined according to OECD guideline 428 using 5 mg/cm2 as exposure condition, a skin penetration of 0.2% (10.2/5000) would be observed maximally. Assuming a skin penetration of cryolite of 0.2% is considered a worse-case situation.