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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No genotoxicity data on cesium tetrafluoroaluminate are available. The read-across candidate cesium fluoro aluminate complex did not induce an increased mutation frequency in a GLP-compliant bacterial reverse mutation assay, performed according to OECD guideline 471. In a GLP-compliant in vitro mammalian chromosome aberration test, performed according to OECD guideline 473, it was concluded that cesium fluoro aluminate complex is clastogenic in human lymphocytes in the absence of a metabolic activation system at the continuous treatment times of 24 and 48 h at the highest tested concentration of 333 μg/ml.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (positive)

Genetic toxicity in vivo

Description of key information

A negative in vivo bone marrow chromosome aberration assay is available. Consequently, it is concluded that cesium tetrafluoroaluminate is not genotoxic in vivo.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

No genotoxicity studies are available on cesium tetrafluoroaluminate. 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 other than vertebrate animal tests, i. e., applying alternative methods such as in vitro tests, QSARs, grouping and read-across.

In vitro and in vivo genotoxicity data are available on a structural analogue, cesium fluoro aluminate complex. CsAlF-complex is a multi-constituent substance containing ca. 70% of CsAlF4 and ca. 30% of higher homological penta- and hexafluoroaluminic acids, Cs2AlF5 and Cs3AlF6. The presence of these higher homological salts is, however, not expected to alter significantly the physico-chemical and toxicological properties of cesium fluoro aluminate complex in comparison to cesium tetrafluoroaluminate.

In vitro genotoxicity

The mutagenic activity of cesium fluoro aluminate complex (CsAlF-complex) was investigated in the Salmonella typhimurium reverse mutation assay and the Escherichia coli reverse mutation assay according to OECD testing guideline 471 and under GLP.

CsAlF-complex was tested in the Salmonella typhimurium reverse mutation assay with four histidine-requiring strains of Salmonella typhimurium (TA1535 TA1537, TA100 and TA98) and in the Escherichia coli reverse mutation assay with one tryptophan-requiring strain of Escherichia coli (WP2uvrA) in two independent experiments. CsAlF-complex was tested up to concentrations of 5000 µg/plate in the absence and presence of S9 -mix.

The test substance did not induce a 2-fold and/or dose-related increase in the number of revertant (His+) colonies in each of the four tester strains (TA1535 TA1537, TA98 and TA100) and in the number of revertant (Trp+) colonies in tester strain WP2uvrA both in the absence and presence of S9-metabolic activation. These results were confirmed in an independently repeated experiment. The strain-specific positive control values were at least three times the concurrent vehicle control group mean indicating that the test conditions were adequate.

Based on the results of this study it is concluded that cesium fluoroaluminate complex is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.

The ability of cesium fluoro aluminate complex to induce chromosome aberrations in cultured peripheral human lymphocytes (with repeat experiment) was investigated in a study performed according to the OECD Testing Guideline 473 and under GLP. In the absence of S9-mix CsAlF-complex was tested up to 333 µg/ml for a 3h treatment time with a 24h fixation time in the first experiment. In the second experiment CsAlF-complex was tested up to 333 µg/ml for a 24h treatment time with a 24h fixation time and for a 48h treatment time with a 48h fixation time.

In the presence of 1.8% (v/v) S9-fraction CsAlF-complex was tested up to 333 µg/ml for a 3h treatment time with a 24h fixation time in the first experiment. In the second experiment CsAlF-complex was tested up to 333 µg/ml for a 3h treatment time with a 48h fixation time. Positive control chemicals, mitomycin C and cyclophosphamide, both produced a statistically significant increase in the incidence of cells with chromosome aberrations, indicating that the test conditions were adequate and that the metabolic activation system (S9-mix) functioned properly.

Experiment 1

Both in the absence and presence of S9-mix CsAlF-complex did not induce a statistically or biologically significant increase in the number of cells with chromosome aberrations.

Experiment 2

In the absence of S9-mix, at the 24h and 48h treatment CsAlF-complex induced statistically significant increase in the number of cells with chromosome aberrations at the highest tested concentration of 333 µg/ml both when gaps were included and excluded. In the presence of S9-mix,CsAlF-complex did not induce a statistically or biologically significant increase in the number of cells with chromosome aberrations.

It is concluded that cesium fluoro aluminate complex is clastogenic under the experimental conditions of this test in the absence of a metabolic activation system at the continuous treatment times of 24 and 48h at the highest tested concentration of 333 µg/ml.

In vivo genotoxicity

Cesium fluoro aluminate complex was tested in the Micronucleus Test in mice, to evaluate its genotoxic effect in developing erythrocytes (polychromatic erythrocytes) in the bone marrow. The test was performed according to the OECD Testing Guideline 474 and under GLP.

Six groups comprising 5 males and 5 females, received a single oral intubation. Two groups (A and B) were dosed with 1000 mg/kg body weight, two groups (C and D) were dosed with 500 mg/kg body weight, two groups (E and F) dosed with 250 mg/kg body weight.

One group (G) treated with a single oral intubation of cyclophosphamide (CP) at 50 mg/kg body weight served as positive control.

Bone marrow was sampled 24 or 28 hours after dosing. Bone marrow from the positive control group (G), was harvested at 48 hours after dosing only.

Cyclophosphamide, the positive control substance, induced a statistically significant increase in the number of micronucleated polychromatic erythrocytes in both sexes. No increase in the frequency of micronucleated polychromatic erythrocytes was observed in the polychromatic erythrocytes of the bone marrow of animals treated with Cesium fluoro aluminate complex.

The groups that were treated with CsAlF-complex and the positive control showed no decrease in the ratio of polychromatic to normochromatic erythrocytes (in controls in the region of 1), which reflects a lack of toxic effects of this compound on the erythropoiesis. It is concluded that cesium fluoro aluminate complexis not mutagenic in the micronucleus test under the experimental conditions described in this report.

Discussion

Cesium fluoro aluminate complex was negative in the Ames test with S. typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and E. coli strain WP2 uvrA at dose levels up to 5000 µg/plate, with and without metabolic activation. Although the test result of the in vitro chromosome aberration test is positive under the experimental conditions in the absence of a metabolic activation system, the in vivo micronucleus assay was negative indicating that the substance is not genotoxic. Therefore classification for genotoxicity is not warrented in accordance to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. Consequently, it is concluded that cesium tetrafluoroaluminate also does not need to be classified for genotoxicity.

Justification for classification or non-classification

Based on the available data on the read-across candidates cesium fluoro aluminate complex, and in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification of cesium tetrafluoroaluminate is not necessary for genotoxicity.