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Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The substance was found to be negative in an Ames test, in an in-vitro chromosomal aberration test in mammalian cells and in an in-vitro gene mutation study in mammalian cells

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

An in vitro chromosome aberration test in cultured mammalian cells (CHL/IU cells) was performed to assess the potential of 1,1,2,2-tetrafluoroethyl-2,2,2-trifluoroethyl ether to induce chromosome aberrations. Since cell growth inhibition in both short-term and continuous exposure experiments were not observed at 5.0mg/mL (max concentration) in the results of the cell growth inhibition test, the concentrations of 50% cell growth inhibition for this test substance were more than 5.0mg/mL. Therefore, the maximum concentration of test substance in short term and continuous exposure experiments was 5.0mg/mL, and 3 applied concentrations which were prepared with dilution by a common ratio of 2 were set up and examined.

In the results of the chromosome aberration test in short-term and continuous exposure experiments, the frequency of cells carrying structural chromosome aberrations or polyploidy were not increased at any concentration compared with negative (untreated and solvent) controls.

Based on the above results, it was concluded that 1,1,2,2-tetrafluoroethyl-2,2,2-trifluoroethyl ether did not induce chromosomal aberrations in CHL/IU cells.

The mutagenic potential of 1,1,2,2-tetrafluoroethyl-2,2,2-trifluoroethyl ether was assessed by a bacterial reverse mutation assay, using 5 bacterial strains. Metabolic activation was also used, and four known mutagens were used as positive controls. The results show that that test compound does not have any mutagenic potential, both with and without metabolic activation. It can therefore be considered not to be mutagenic.

The mutagenic potential of1,1,2,2-tetrafluoroethyl-2,2,2-trifluoroethyl etherwas examined in an in vitro mammalian cell mutation assay conducted in accordance with OECD Guideline 476, EU Method B.17 and EPA OPPTS 870.5300. In this test system, Chinese hamster ovary (CHO-K1) cells are used to detect forward mutations at the functionally hemizygous hypoxanthine phosphoribosyl transferase (HPRT) locus.

The test item in vehicle (dimethylsulfoxide (DMSO)) was tested from 15.63 µg/mL up to a limit concentration of 2000 µg/mL (as recommended by the regulatory guidelines) in a preliminary toxicity test. No precipitate was observed by eye at the end of treatment at 2000 µg/mL. Cytotoxicity was measured as Day 1 relative survival (RS). After exposure to1,1,2,2-tetrafluoroethyl-2,2,2-trifluoroethyl etherfor 3 hours the RS values ranged from 108 to 68% and from 126 to 89% in the absence and presence of S9 respectively. 

In the additional main test in the absence of S9 mix, cultures were exposed to1,1,2,2-tetrafluoroethyl-2,2,2-trifluoroethyl etherfor 3 hours at concentrations ranging from 62.5 to 2000 µg/mL. No precipitate was observed. No reduction in mean RS values were observed. No significant increases in mutant frequency were observed at any concentration. Treated groups at 62.5, 125 and 2000 µg/mL induced mutant frequencies marginally above the laboratory historical control 95% confidence limit, while the remaining treated groups and vehicle control induced mutant frequencies within the laboratory historical 95% confidence limit. Tests for linear trend and non-linearity were not statistically significant. The positive control (EMS) induced a significant increase in mutant frequency. The experiment was negative.

In the additional main test in the presence of S9 mix, cultures were exposed to1,1,2,2-tetrafluoroethyl-2,2,2-trifluoroethyl etherfor 3 hours at concentrations ranging from 62.5 to 2000 µg/mL. No precipitate was observed. No reduction in mean RS values were observed. No significant increases in mutant frequency were observed at any concentration. The vehicle control and treated groups induced mutant frequencies above the laboratory historical 95% confidence limits. The linear trend test was statistically significant (p= 0.015) while the test for non-linearity was not statistically significant. The positive control (3MC) induced a significant increase in mutant frequency. The experiment was considered equivocal, and a second experiment in the presence of S9 mix was conducted.

In the second additional main test in the presence of S9 mix, cultures were exposed to1,1,2,2-tetrafluoroethyl-2,2,2-trifluoroethyl etherfor 3 hours at concentrations ranging from 62.5 to 2000 µg/mL. No precipitate was observed. No reduction in mean RS values were observed. No significant increases in mutant frequency were observed at any concentration. The vehicle control and treated groups induced mutant frequencies within the historical 95% confidence limits. Tests for linear trend and non-linearity were not statistically significant. The positive control (3MC) induced a significant increase in mutant frequency. The experiment was concluded to be negative.

Under the experimental conditions described in this in vitro HPRT cell mutation assay,1,1,2,2-tetrafluoroethyl-2,2,2-trifluoroethyl etherdid not demonstrate mutagenic potential.

Justification for classification or non-classification

As 1,1,2,2-tetrafluoroethyl-2,2,2-trifluoroethyl ether was demonstrated to give a negative result in an Ames test, in an in-vitro chromosomal aberration test in mammalian cells and in an in-vitro gene mutation study in mammalian cells, it is not necessary to classify it for mutagenic effects.