Dihydrogen bis(acetato-O)difluoroborate(1-)

Endpoint summary

Additional information

No in vitro data are available for dihydrogen bis(acetato-O)difluoroborate.

But studies are available for acetic acid and BF3 dihydrate.

Here, acetic acid (> 99 %) was tested in the Salmonella mutation assay using the four strains of Salmonella typhimurium TA1535, TA97, TA98, TA100 with and without metabolic activation (S9 -mix). tested concentrations were 100 - 1000 ug/plate. The pre-incubation assay was used with a 20 min pre-incubation time before plating, and with doses up to 10 mg/plate (Zeiger et al., 1992). Acetic acid was not mutagenic.

Boron trifluoride dihydrate was tested in histidine-dependent auxotrophic mutants of Salmonella typhimurium (strains TA1535, TA1537, TA98 and TA100), and a tryptophan-dependent mutant of Escherichia coli (strain WP2 uvrA (pKM101)) under GLP according to OECD 471. Test was performed in the presence and absence of liver preparations (S9 mix) with concentrations of up to 5000 ug/plate. No evidence of mutagenic activity was seen at any concentration of boron trifluoride dihydrate in either mutation test.

In two supporting studies it could also be shown that BF3 complexes showed negative results. Here, BASF (1989) reported a bacterial reverse mutation assay (Ames test) with diethyl ehter boron trifluoride (CAS: 109-63-7). Salmonella typhimurium strains used were TA 1535, TA 1537, TA 98 and TA 100. Test concentrations used were 4 - 5000 ug/plate. This test was done with and without metabolic activation. A negative result was reported.

In another BASF study (1989), borfluorid methyletherat (CAS: 353-42-4) was tested in a bacterial reverse mutation assay (Ames test). Test concentrations were 4 - 5000 ug/plate; Salmonella typhimurium strains were TA 1535, TA 1537, TA 98 and TA 98. This test was done with and without metabolic activation. A negative result was reported.

Huntingdon Life Sciences (210) report an in vitro mammalian cell gene mutation assay with boron trifluoride dihydrate (CAS: 13319-75-0). Mouse lymphoma L5178Y cells were used for this experiment. The study consisted of a preliminary toxicity test and two main tests comprising three independent mutagenicity assays. The cells were exposed for either 3 hours or 24 hours in the absence of exogenous metabolic activation (S9 mix) or 3 hours in the presence of S9 mix. Boron trifluoride dihydrate was found to be soluble at 67.8 mg/mL in water. A final concentration of 450 mg/mL, dosed at 1%v/v, was used as the maximum concentration in the preliminary toxicity test, in order to test up to the highest concentration that does not cause a fluctuation in pH of more than 1.0 unit. Toxicity was observed in the preliminary toxicity test. Following a 3 hour exposure to boron trifluoride dihydrate at concentrations from 0.9 to 450 mg/mL, relative suspension growth (RSG) was reduced from 107 to 71% and from 113 to 68% in the absence and presence of S9 mix respectively. Following a 24 hour exposure in the absence of S9 mix RSG was reduced from 114 to 1%. The concentrations assessed for determination of mutant frequency in the main test were based upon these data, the objective being to assess concentrations which span the complete toxicity range of approximately 10 to 100% relative total growth (RTG), or to assess exposure up to the highest concentration that does not cause a fluctuation in pH of more than 1.0 unit. Following 3 hour treatment in the absence and presence of S9 mix, there were no clear increases in the mean mutant frequencies of any of the test concentrations assessed that exceeded the sum of the mean concurrent vehicle control mutant frequency and the Global Evaluation Factor (GEF), within acceptable levels of toxicity. The maximum concentrations assessed for mutant frequency in the 3 hour treatment in the absence and presence of S9 mix was 450mg/mL. In the absence and presence of S9 mix RTG was reduced to 51 and 46% respectively.

Huntingdon Life Sciences (2010) reported an in vitro mammalian chromosome aberration test with borin trifluoride dihydrate (CAS: 13319-75-0). Human lymphocytes were exposed to the test substance both in the absence and presence of S9 mix. Solvent and positive control cultures were also included. Two hours before the end of the incubation period, cell division was arrested using Colcemid®, the cells harvested and slides prepared, so that metaphase cells could be examined for chromosomal damage. In order to determine the toxicity of Boron trifluoride dihydrate to cultured human lymphocytes, the mitotic index was assessed for all cultures treated with the test substance and the solvent control, water. A final concentration of 450 mg/mL, dosed at 1%v/v, was used as the maximum concentration, in order to test up to the highest concentration that does not cause a fluctuation in pH of more than 1.0 unit. On the basis of these data, the following concentrations were selected for metaphase analysis: First test: In the absence of S9 mix - 3 hour treatment, 18 hour recovery: 162, 270 and 450 µg/mL. In the presence of S9 mix (2% v/v) - 3 hour treatment, 18 hour recovery: 162, 270 and 450 µg/mL. Second test: In the absence of S9 mix - 21 hour continuous treatment: 97.2, 162 and 270 µg/mL. In the presence of S9 mix (5% v/v) - 3 hour treatment, 21 hour recovery: 162, 270 and 450 µg/mL. In the absence of S9 mix, boron trifluoride dihydrate caused statistically significant increases in the proportion of metaphase figures containing chromosomal aberrations at 450 µg/mL (3 hour treatment, including gaps; no significant increase if excluding gaps) and at 162 µg/mL (21 hour treatment, including gaps) and 270 µg/mL (21 hour treatment, excluding and including gaps), when compared with the concurrent solvent control. In the presence of S9 mix, boron trifluoride dihydrate caused no statistically significant increases in the proportion of metaphase figures containing chromosomal aberrations, at any concentration, when compared with the solvent control, in either test. No statistically significant increases in the proportion of polyploid cells were observed during metaphase analysis, in either test. All positive control compounds caused statistically significant increases in the proportion of aberrant cells, demonstrating the sensitivity of the test system and the efficacy of the S9 mix. In conclusion, boron trifluoride dihydrate has shown evidence of causing an increase in the frequency of structural chromosome aberrations, in the absence of S9 mix after 21-hour exposure period, in this in vitro cytogenetic test system, under the experimental conditions described. 

 

in vivo:

No data/information is available for effects on in vivo mutagenicity. Severe toxicity is expected to be observed after exposure well before effects on mutagenicity are induced (for further details see attachement). For this reason, any in vivo mutagenicity study is scientifically unjustified.

Endpoint Conclusion:

Justification for classification or non-classification

Based on the available data of boron trifluoride and acetic acid, no classification is proposed.