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Key value for chemical safety assessment

Additional information

Gene Mutation in vitro

Bacteria

TFE did not induce gene mutation in the Ames test (Longstaff and Ashby, 1976; Rickard et al 1986). The latter test system conducted in the presence and absence of the S9 metabolic activation system. A cysteine conjugate of TFE, S-1,1,2,2 -tetrafluoroethyl-L-cysteine, was also without mutagenic activity in the Ames test with and without (Aroclor induced rat kidney S9) metabolic activation. The conjugate was tested in strains TA 1537, TA 1535, TA 100, TA 98, and TA 97 at concentrations reaching 500 ug/plate (Green and Odum 1985). Kidney S-9 was used for metabolic activation because of the marked nephrotoxicity noted in rats exposed to TFE.

Mammalian cells

TFE did not induce gene mutations at the HPRT locus in cultured Chinese hamster ovary (CHO) cells with or without metabolic activation (Rickard et al 1986). The negative results with metabolic activation were subsequently confirmed at the request of the US EPA (Stahl, 1988).

Chromosome aberration

Mammalian cells in vitro

TFE did not induce structural chromosome aberrations (clastogenicitiy) in CHO cells with and without metabolic activation (Vlachos, 1987).

Mammalian cells in vivo

Small but statistically significant increases in micronucleated polychromatic erythrocytes (MPE) were seen in the bone marrow of male mice 72 hours following single exposure to 5 000 and 12 000 ppm TFE but not in the corresponding 19 000ppm exposed animals. Following further evaluation and consideration of the historical database, these small increases in MPE were determined not to be of biological significance (Sheldon et al 1988).

In a 13 -week inhalation study, groups of mice were exposed to TFE at atmospheric concentrations of up to 5 000 ppm. At the end of the exposure period, peripheral blood cells of male and female animals were isolated and the frequency of micronucleated erythrocytes assessed. There were no biologically significant increases in micronucleated cells in either sex above control levels (NTP, 1997).

Unscheduled DNA synthesis (UDS) in vivo

Following exposure of mice to single TFE concentrations up to 40 000ppm, hepatocytes were isolated and examined for DNA excision repair. TFE did not induce UDS in mouse liver cells (Fox, 1998).

Other studies

The frequency of H-ras mutations was investigated in hepatocellular tumours taken from the B6C3F1 mice in the NTP carcinogenicity study. A low frequency of these mutations (15%) was observed compared to that in controls (59%) and in spontaneous liver tumours in this mouse strain (56%). This frequency is similar to that from liver tumours induced by the structurally-related chemical, tetrachloroethylene (24%). Although a few tumours in the tetrachloroethylene study were found to have a K-ras mutation, none were found in the liver tumours induced by TFE. These data indicate that TFE and tetrachloroethylene induce liver tumours by a ras-independent pathway (NTP, 1997).


Short description of key information:
TFE has been assessed for its genotoxic potential in a number of studies. It does not induce gene mutations in bacteria and mammalian cells in vitro and is not clastogenic in CHO cells in vitro or in two micronucleus tests in mice. Hepatocytes isolated from mice exposed to TFE showed no evidence of unscheduled DNA synthesis (UDS). Therefore, TFE is not genotoxic both in vitro and in vivo. A cysteine conjugate of TFE, S-1,1,2,2-tetrafluoroethyl-L-cysteine, a nephrotoxic metabolite activated by renal C-S lyases, is also without mutagenic activity in vitro.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

In view of the lack of evidence for mutagenicity in a range of studies covering the important in-vitro and in vivo endpoints, classification for mutagenicity is not warranted according to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2000.