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Key value for chemical safety assessment

Additional information

In the key bacterial reverse mutation assay (equivalent toOECD guideline 471), CTFE was tested at dose levels of 12.5%, 15%, 25%, 30% and 50% in presence and in the absence of exogenous metabolic activation (from the livers of Sprague-Dawley adult male rates induced by Aroclor 1254 - S9) in Salmonella typhimurium strains TA 98, TA 100, TA 1535 and TA 1537. Positive controls were included in all incubations. Although the results showed a slight increase in revertants at the 25% dose level with strain TA 100, subsequent testing at this and higher dose levels showed that this result was not reproducible; CTFE did not induce a mutagenic response in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 in the presence or absence of rat liver activating enzyme. Incubation with positive control substances in the absence or presence of metabolic activation resulted in anticipated increases in reverse mutation rates.

In a key mammalian chromosome aberration test (equivalent to OECD guideline 473), CTFE was tested at doses of 5%, 10%, 20% 50%, 70% and 100% (v/v) within the gas phase of tight capped culture vessels in the presence and absence of liver metabolic activation (S9). Incubations at each concentration were done in duplicate. Since the test article was applied via gas phase in culture vessels only a negative control with medium was performed. Ethylmethanesulfonate (EMS) without metabolic activation and Cyclophosphamide (CPA) with metabolic activation were used as the positive control compounds. No chromosome damage was noted at any CTFE concentration. Incubations with the positive control compound resulted in anticipated increases in chromatid damage.

In the key mammalian gene mutation assay (equivalent to OECD guideline 476), CTFE was tested in a GLP study at doses of 14%, 50%, 70% and 100% (v/v) within the gas phase of tight capped culture vessels in the presence and absence of liver metabolic activation (S9).

The experiment was conducted in duplicate. Ethylmethanesulfonate (EMS) and 7,12-dimethylbenz[a]anthracene(DMBA) were used as the positive control compounds in the absence and presence of metabolic activation, respectively. Under the experimental conditions reported CTFE did not induce point mutation at the HGPRT locus in the V79 cells at any tested concentrations in the absence or presence of metabolic activation. Incubation with positive control substances in the absence or presence of metabolic activation resulted in anticipated increases in the mutation frequencies. In the supportive non GLP study Sister Chromatid Exchange (SCE), SCE frequencies were determined in peripheral lymphocytes of experimental rats and rabbits before, during and after the period of time during which the animals were being exposed to CTFE by inhalation. Student’s t-test was used to compare SCE frequencies observed after the start of treatment in each animal with the highest value observed prior to treatment in the same animal. Statistically significant increases in SCE frequency were observed only in positive control animals, with one exception being negative control animal 905 on day 10. Despite the absence of positive statistical findings using Student’s t-test, the X2-analysis was carried out as well. It was again clear from these analyses that CTFE did not induce SCEs in peripheral lymphocytes of either rats or rabbits, and so no further statistical tests were performed. Test animals were observed at 2-3 day intervals for signs of overt toxicity. No such signs were observed, despite the cumulative dose of 10,800 ppm-days.

Short description of key information:
The genetic toxicity of chlorotrifluoroethylene (CTFE) has been assessed in 3 in vitro studies (including 1 bacterial reverse mutation assay, a mammalian chromosome aberration test, and a mammalian gene mutation assay) and an in vivo assay Sister Chromatid Exchange (SCE). Negative results were reported in all the studies.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The substance does not meet the criteria for classification and labelling for this endpoint, as set out in Regulation (EC) No. 1272/2008.