Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

The aims of testing for genotoxicity are to assess the potential of substances to induce genotoxic effects which may lead to cancer or cause heritable damage in humans.

According to the intelligent testing strategy proposed in the ECHA Guidance on information requirements and chemical safety assessment Chapter R.7a the first test to conduct is a Bacterial Reverse Mutation Assay (Ames Test). In this test, two of the five tester strains used gave positive results after incubation with the test material without metabolic activation. The respective tester strains were S. typhimurium TA98, being sensitive for frame-shift mutations, and TA100, indicating base-pair substitutions.

To confirm this finding, a mutation assay on mammalian cells (HPRT Test) was performed on V79 (Chinese hamster lung fibroblast) cells. In this assay, FAT40850/ATE did not induce gene mutations at the HPRT locus, contradicting the aforementioned results.As the results of mammalian tests may be considered of higher significance than results from bacterial tests, one can conclude that the potential of FAT40850/A TE to induce mutations in mammals is quite low.

 

Beside gene mutations, chromosomal aberrations may be the cause of many human genetic diseases. In an in vitro mammalian cell chromosomal aberration test, FAT40850/A TE was found to induce structural chromosome aberrations in V79 cells. As mentioned in REACH Regulation Annex IX, it is proposed to perform an in vivo micronucleus test to further investigate the clastogenic potential of the test material.


Short description of key information:
To date, three different in vitro studies on genotoxicity/mutagenicity of the test material are available:

Sokolowski (2010): In a Salmonella typhimurium and Escherichia coli Reverse Mutation Assay (Ames Test), FAT40850/A TE showed positive results without metabolic activation in two of the five tester strains used, i.e. TA98 and TA100, which indicate frame-shift mutations and base-pair substitution, respectively.

Hall (2010): The test item FAT40850/A TE induced structural chromosome aberrations in V79 cells (Chinese hamster cell line) in vitro.

Wollny (2010): The test item FAT40850/A TE did not induce gene mutations at the HPRT locus in V79 cells.

Endpoint Conclusion:

Justification for classification or non-classification

Classification of a substance as germ cell mutagen is mainly based on the results of in vivo tests. To date, only results from in vitro tests are available. These indicate that the test material may not be a mutagen according to the negative findings in the HPRT test (Wollny 2010). Regarding clastogenicity, no unequivocal result can be given that satisfies the needs of the respective classification regulations. It has to be stated that the in vitro chromosomal aberration test in mammalian cells was positive but this finding has first to be confirmed with the proposed in vivo micronucleus test.

Taken together, the test material is not yet classified as germ cell mutagen but due to the ambiguous results and the in vivo study to be performed “inconclusive” is entered as reason for no classification.