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Administrative data

Key value for chemical safety assessment

Additional information

Ames test

In the Salmonella typhimurium and E.coli reverse mutation test performed according to OECD 471 FAT 41043/A TE was tested up to precipitating concentrations.

In the absence of S9-mix, FAT 41043/A TE induced dose related increases of mutants in two out of the five tester strains (TA1537 and TA98). The increases observed in these tester strains were above the laboratory historical control data range and 9.7- and 65-fold the concurrent control. In addition in tester strain TA100, increases above the historical control data range were observed. However, these increases are just above the historical control data range and not more than a 1.6-fold increase was observed, which is below the 2 -fold increase relative to concurrent control that is considered toxicologically relevant.

In the presence of S9-mix, FAT 41043/A TE induced dose related increases of mutants in two out of the five tester strains (TA1537 and TA98). The increases observed in these tester strains were above the laboratory historical control data range and 9.8- and 39-fold the concurrent control. In addition, in tester strain TA100, increases just above the historical control data range were observed. However, these increases are just above the historical control data range and not more than a 1.5-fold increase was observed, which is below the 2 -fold increase relative to concurrent control that is considered toxicologically relevant. The results of the solvent control were within historical control data.

Based on the observed increase in TA1537 and TA98, both in the absence and presence of mutagenic activity, FAT 41043/A TE is considered mutagenic.

Chromosome aberration test

A chromosome aberration study with FAT 41043/A TE tested up to precipitating concentrations was performed according to OECD 473 in cultured peripheral human lymphocytes in two independent experiments. The number of cells with chromosome aberrations found in the solvent control cultures was within the laboratory historical control data range. Positive control chemicals, mitomycin C and cyclophosphamide, both produced a statistically significant increase in the incidence of cells with chromosome aberrations, indicating that the test conditions were adequate and that the metabolic activation system (S9-mix) functioned properly.

FAT 41043/A TE did not induce a statistically significant or biologically relevant increase in the number of cells with chromosome aberrations in the absence and presence of S9-mix, in either of the two independently repeated experiments.

Based on these results, It is concluded that FAT 41043/A TE is not clastogenic in human lymphocytes.

Mouse lymphoma study

In a mouse lymphoma study performed according to OECD 476 FAT 41043/A TE was tested up to cytotoxic concentrations without metabolic activation and up to precipitating concentrations with metabolic activation.

The spontaneous mutation frequencies in the solvent-treated control cultures were within the historical control data range and within the acceptability criteria of this assay, except for the response of one of the solvent control cultures in the first experiment in the presence of S9-mix. However since this response was just below the lower limit of the range and clear negative results were obtained, the validity of the test was considered to be not affected. Mutation frequencies in cultures treated with positive control chemicals were appropriate. Although the mutation frequency of the positive control in the absence of S9-mix (second experiment) was not within the acceptability criteria,the mutagenic response was 8 times greater than the concurrent solvent control values, therefore the validity of the test was considered to be not affected

In the absence of S9-mix, FAT 41043/A TE did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in an independent repeat experiment with modifications in the duration of treatment time. In the presence of S9-mix, FAT 41043/A TE did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in an independent repeat experiment with modifications in the concentration of the S9 for metabolic activation.

Based on these results, it is concluded that FAT 41043/A TE is not mutagenic.


Justification for selection of genetic toxicity endpoint
The Ames was positive with and without metabolic activation and has a Klimisch criterium 1.

Short description of key information:
A reliable Ames test, in vitro chromosome aberration and mouse lymphoma test, all performed according to OECD/EC guidelines, are available. The Ames test was positive, both in the absence and in the presence of metabolic activation in several Salmonella typhimurium strains. The chromosome aberration and mouse lymphoma test were negative with and without metabolic activation.

Endpoint Conclusion: Adverse effect observed (positive)

Justification for classification or non-classification

Based on the data available no classification is needed according to EC 1272/2008 awaiting further in vivo testing.