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Administrative data

Key value for chemical safety assessment

Additional information

Read-across concept (human health) for tin bis(tetrafluoroborate):

Substance-specific toxicity data for the substance tin bis(tetrafluoroborate) (water solubility >50 % w/w) are not available.However, since upon dissolution in water, full dissociation of the highly water-soluble tin bis(tetrafluoroborate) to (i) Sn2+cations and (ii) tetrafluoroborate anions occurs, read-across to (i) inorganic tin(II) substances and (ii) inorganic salts of tetrafluoroboric acid is made, respectively.

This read-across is considered fully justified in view of the comparable water solubilities of the similarly soluble read-across substances, such as (i) tin(II)chloride, water solubility 178 g/L at 20°C, and (ii) potassium tetrafluoroborate, water solubility 5.4 g/L at 22°C.

Whereas it is noted that upon dilution of aqueous solutions, “clouding” and precipitation of basic tin salts occurs , which can be described by the following equation:

SnX2+ H2O <--> "SnXOH"(s) + HX

this Sn2+-specific behaviour is not considered to restrict the read-cross since oral bioavailability of inorganic tin(II) substances is generally very low.

Potassium tetrafluoroborate is currently not classified according to the criteria specified by Directive 67/548/EEC and subsequent regulations, and is correspondingly considered not to require classification according to the criteria set forth by EC Regulation No. 1272/2008 and subsequent regulations, neither for HH or ENV hazards.

Any toxicological or ecotoxicological hazards (if any) are therefore assumed to be related to Sn2+only.

In vitro:

Tin(II) bis(methanesulfonate):

The bacterial gene mutation study (Grötsch, 1987) was limited by solubility with precipitation at 313 µg / plate. There was no apparent toxicity at the maximum applied concentrations of 5000 µg/plate with or without S-9. Based on the read-across approach and the assumption that possible genotoxic effects are related to tin only, tin bis(tetrafluoroborate) has no apparent toxicity in the Ames test.

Chromosome aberration:

One reliable chromosome aberration test (1987) with tin bis(methanesulfonate) according to OECD 473 is available. The peaked dose response found in the absence of S9 is considered a good dose response curve, although there was decreased damage at 200ug/ml compared with 100ug/ml. Therefore Tin-MSA is considered to be a clastogen in the absence of S9.

In the presence of S9, no statistical significance was found at any dose point, and positive result was not, therefore, obtained.

Although Tin-MSA gave an overall positive result in this study, the nature of the result suggests that it may not be mutagenic in in-vivo situations, e.g. in man.

Based on the read-across approach and the assumption that possible genotoxic effects are related to tin only, tin bis(tetrafluoroborate) is suggested to have no mutagenic potential in man.

Potassium tertafluoroborate:

Gene mutation assay :

In a GLP compliant gene mutation test performed according to OECD guideline 476, potassium tetrafluoroborate was examined for its potential to induce gene mutations at the TK-locus of cultured mouse lymphoma L5178Y cells, in both the absence and the presence of a metabolic activation system (S9-mix) (TNO Triskelion BV, 2012). One test was conducted. In this test 6 duplicate cultures were treated for 24 hours and 4 hours in the absence and presence of S9-mix, respectively. The test substance was dissolved in dimethylsuphoxide (DMSO). The highest concentration tested and evaluated for mutagenicity was 10 mmol/L. The test substance was slightly toxic to the cells in the absence of S9 -mix. A slight decrease by 24% of the relative growth (RTG) was observed at the highest dose of 10 mmol/L. In the presence of S9 -mix no cytotoxicity was observed. In both the absence and presence of S9-mix no increase in mutant frequency was observed at any test substance concentration evaluated. All data were within the range of the negative control and the historical background. Methyl methanesulphonate (MMS) and 3-methylcholanthrene (MCA) were used as positive control substances in the absence and presence of the S9-mix, respectively; DMSO served as negative control. The negative controls were within historical background ranges and treatment with the positive control yielded the expected significant increase in mutant frequency compared to the negative controls. It is concluded that under the conditions used in this study, the test substance potassium tetrafluoroborate is not mutagenic at the TK-locus of mouse lymphoma L5178Y cells in both the absence and presence of metabolic activation (S9-mix).

Micronucleus test :

In a GLP-compliant micronucleus test, performed according to OECD Guideline 487, potassium tetrafluoroborate was examined for its potential to induce micronuclei in cultured binucleated human lymphocytes, in both the absence and presence of a metabolic activation system (S9 -mix) (TNO Triskelion BV, 2012). Two independent in vitro micronucleus tests were conducted for which blood was obtained from two different donors. Dimethylsulfoxide (DMSO) was used as solvent for the test substance. Dose levels ranging from 2.5 to 1260 μg/mL were tested as final concentrations in the culture medium. Cytotoxicity was calculated from the Cytokinesis-Block Proliferation Index (CBPI). In the first test, in the presence and absence of metabolic activation (S9-mix) the treatment/recovery time was 4/20 hours (pulse treatment). In the second test, in the absence of metabolic activation, the treatment/recovery time was 20/28 hours (continuous treatment group). In the first test, in the presence of metabolic activation, a trend towards slightly decreased CBPI-values was observed at all dose levels. In the absence of metabolic activation, no cytotoxicity was observed. In the pulse treatment test, analysis of micronuclei formation was carried out at three dose levels (1260, 630 and 315 μg/mL), in the cultures of the solvent control and in the cultures of the positive controls. In the second test, no cytotoxicity was observed at any of the dose levels analysed. In the continuous treatment group, analysis of micronuclei formation was carried out in the cultures of three dose levels (1260, 1000 and 800 μg/mL) of the test substance, the cultures of the solvent control and the cultures of the positive controls. In both the first and the second test, the negative controls were within the historical data. Treatment with the positive controls, cyclophosphamide, vinblastine sulphate and mitomycin C, resulted in statistically significant increases in the numbers of binucleated cells containing micronuclei, when compared to the numbers observed in the cultures treated with the solvent control. This demonstrates the validity of the study. In both the first and second test, the test substance did not cause a significant increase in the number of binucleated cells containing micronuclei, at any of the dose levels analysed, when compared to the numbers found in the concurrent negative control. From the results obtained in the first and second in vitro micronucleus test it is concluded that, under the conditions used in this study, the test substance potassium tetrafluoroborate was not clastogenic and/or aneugenic to cultured human lymphocytes.

In vivo:

Tin(II) bis(methanesulfonate):

In vivo micronucleus test:

One reliable in vivo study according to OECD 474 with the read-across substance tin(II) bis(methanesulfonate) is available. No evidence of toxicity or genetic toxicity were observed in the in vivo micronucleus study (test performed at the maximum dose noted in the test guideline).

Based on the read-across approach and the assumption that possible genotoxic effects are related to tin only, tin bis(tetrafluoroborate) is suggested to have no genetic toxicity potential in man.


Justification for selection of genetic toxicity endpoint
Read-across information

Short description of key information:
Tin(II) bis(methanesulfonate):
No evidence of mutagenic effects from bacterial gene mutation, chromosome aberration (in vitro) and mouse micronucleus study. Based on the read-across approach and the assumption that possible genotoxic effects are related to tin only, tin bis(tetrafluoroborate) is suggested to have no mutagenic potential in man.

Potassium tetrafluoroborate:
The substance gave negative results in the reverse mutation assay, the in vitro gene mutation assay, and the in vitro micronucleus test both with and without metabolic activation.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Genetic toxicity in vivo:

One reliable study (1989) performed with the read-across substance tin bis(methanesulfonate) is considered as key study for in vivo genetic toxicity and will be used for classification. No genetic toxicity was observed.

According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the substance does not require classification for genetic toxicity/mutagenicity. According to EC Regulation No. 1272/2008 and subsequent regulations, the test item also does not require

classification for genetic toxicity/mutagenicity.

Based on the read-across approach, the test item tin bis(tetrafluoroborate) does not require classification for genetic toxicity/mutagenicity according to Directive 67/548/EEC and subsequent regulations and according to EC Regulation No. 1272/2008 and subsequent regulations.

Genetic toxicity in vitro:

None of the in vitro studies performed with the read-across substance tin bis(methanesulfonate), rated as reliable, showed any indications of genotoxicity whatsoever, rendering the test item void of genotoxicity. The classification criteria according to Directive 67/548/EEC and subsequent regulations and according to EC Regulation No. 1272/2008 and subsequent regulations as germ cell mutagen are also not met.

Based on the read-across approach, the test item tin bis(tetrafluoroborate) does not require classification for genetic toxicity/mutagenicity according to Directive 67/548/EEC and subsequent regulations and according to EC Regulation No. 1272/2008 and subsequent regulations. The classification criteria as germ cell mutagen are also not met.