Registration Dossier

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Additional information

Genetic toxicity in vitro

 

The test item was investigated for mutagenicity to bacteria according to the OECD TG 471 and in compliance with GLP (Lee, 2010a). In a plate incorporation experiment (2 plates per concentration) the test material was tested in S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and in E. coli WP2 uvrA up to limit concentration with and without a metabolic activation system, except for TA 100 strain which was tested up to cytotoxic concentration. No significant increase in the number of revertants was observed in any of the tested strains with and without metabolic activation. Appropriate solvent and positive controls were included into the test and gave the expected results. Hence, the test item was considered to be not mutagenic to bacteria under the conditions of the test.

 

 

The test item was evaluated for cytogenicity to mammalian cells in a study conducted according to the OECD TG 473 and in compliance with GLP (Lee, 2010b). In order to determine the high dose for the main study, the cell growth inhibition study was conducted in Chinese Hamster Lung (CHL/IU) cells. The cell growth inhibition was less than 50% at all dose levels (6.80, 13.6, 27.2, 54.4, 109, 218, 435, 870 and 1740 µg/mL) tested for the 6 h treatment, with and without metabolic activation and for the 24 h treatment without metabolic activation. The deposition of the test substance was not evident at the time of treatment of the test substance and at the end of the incubation. Therefore, 1740 µg/mL (approximately 10 mM) in the main study was selected as the high dose in the 6 h treatment with and without metabolic activation and 24 h treatment without metabolic activation. The high dose was serially diluted by a ratio of 2 to a produce total of 3 dose levels (435, 870 and 1740 µg/mL) for the main study.

Chinese Hamster Lung (CHL/IU) cells treated with the test material up to the limit concentration with and without metabolic activation, did not exhibit any significant changes of chromosomal aberrations as compared to the control. Appropriate solvent and positive controls were included into the test and gave the expected results. Hence, the test item was considered to be not clastogenic under the conditions of the test.

Justification for selection of genetic toxicity endpoint

No study was selected, since all available studies were negative.

Short description of key information:

Genetic toxicity in vitro:

Gene mutation (Bacterial reverse mutation assay / Ames test): S. typhimurium TA 98, TA 100, TA 1535, TA 1537, and E. coli WP2 uvrA: negative with and without metabolic activation (according to OECD TG 471)

Mammalian cytogenicity (Chromosome Aberration): CHL/IU cells: negative with and without metabolic activation (according to OECD TG 473)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data on genetic toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

Categories Display