Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A fully guideline-compliant Magnusson Kligman Test (GPMT) is available (NOTOX, 1998). 1% aqueous carboxymethyl cellulose was used as a vehicle. For intradermal induction 0.1 ml of a 10% test substance formulation was injected into the skin of the scapular region. Since no dermal reactions were observed after topical induction in the pretest (cryolite concentration up to 50%), local irritation of the shaved skin of the flank was induced by topical epidermal treatment with 0.5 ml 10% sodium laurylsulfate in vaseline on day 7. On day 8, 0.5 ml of a 50% formulation of cryolite in 1% aqueous carboxymethyl cellulose was occlusively applied to the shaved flank for 48 hours. Challenge was conducted at the induced flank sites on day 22 with a 50% substance formulation. Control animals received the vehicle only during inductions (day 1 and day 8) and a 50% substance formulation at challenge. After challenge, no skin reactions were observed in treated and control animals.


Migrated from Short description of key information:
In a Magnusson Kligman Test with guinea pigs, no skin sensitisation was observed

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

No substance-specific data on respiratory tract sensitising properties of cryolite was available for assessment. However, Article 13 of the REACH legislation states that, in case no appropriate animal studies are available for assessment, information should be generated whenever possible by means of other than vertebrate animal tests, i.e. applying alternative methods such asin vitrotests, QSARs, grouping and read-across.

A reliable, GLP-compliant study with Brown Norway (BN) rats on respiratory tract sensitisation is available for a structural analogue of cryolite, aluminium potassium fluoride (KAlF4) (TNO, 2004). One group of 6 female rats was exposed to a target concentration of 100 mg/m3 for 6 hours/day for 5 consecutive days (sensitisation phase). Approximately 14 days later these animals were exposed to the same concentration for 30 min (challenge phase). Two control groups, also of 6 female rats each, were used. One group was sensitised only, the other group was exposed to air during the sensitisation phase and challenged to 100 mg/m3 for 30 min approximately 14 days later. The mean actual concentration ( ± standard deviation) of aluminium potassium fluoride in the test atmosphere during the sensitisation phase was 104.4 ( ± 6.7) mg/m3 while during the challenge it was 100.3 ( ± 1.2) mg/m3. The mean MMAD (Mass Median Aerodynamic Diameter) of the particles in the aerosol was 2.5 µm with a mean geometric standard deviation of 1.7.

The day after challenge hyperresponsiveness to methacholine was tested in all animals; two days after challenge the animals were necropsied.

To examine possible allergenicity, total and specific IgE levels, breathing pattern and frequency during challenge, hyperresponsiveness to methacholine one day after challenge, and histopathology of the respiratory tract and bronchoalveolar lavage fluid measurements two days after challenge were carried out.

No treatment-related abnormalities were observed. Also no changes in body weight gain and organ weights were noted.

No increases in specific IgE levels or treatment-related changes in cholinergic hyperresponsiveness upon methacholine challenge were noted. There were also no changes in breathing frequency and pattern during challenge, suggesting that aluminium potassium fluoride is not a respiratory tract sensitiser. Repeated inhalation of aluminium potassium fluoride induced histopathological changes in the nasal passages, larynx, and lungs. Focal olfactory epithelial degeneration, necrosis and regeneration were observed in the nasal passages. In the larynx, there was a focal granulomatous inflammation. In the lungs, alveolar bronchiolisation and typical alveolar macrophage accumulations were seen. Sensitised animals exhibited a significantly increased percentage of neutrophils and a significantly decreased percentage of ofeosinophils in bronchoalveolar lavage fluid. The tested concentration of 100 mg/m3for both sensitisation as well as challenge phases was therefore considered sufficiently high enough in view of the observed histopathological and bronchoalveolar lavage fluid changes. Based on these results and taking into account the structural similarity of cryolite and aluminium potassium fluoride, as well as their comparable physico-chemical and human toxicological properties, it is considered acceptable to conclude that cryolite also does not possess respiratory tract sensitising properties.

Migrated from Short description of key information:
Based on the study on respiratory tract sensitisation with the structural analogue of cryolite, aluminium potassium fluoride (KAlF4), it is concluded that cryolite does not induce repiratory tract sensitisation.

Justification for classification or non-classification

In accordance to Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification is not necessary for sensitisation.