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Key value for chemical safety assessment

Additional information

In vitro

The potential of the test material to cause gene mutation was investigated in a bacterial reverse mutation assay (e.g. Ames test) using the plate incorporation method in accordance with the standardised guidelines OECD 471 and EU Method B.13/14 under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria for assessing data quality set forth by Klimisch et al. (1997).

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvr A were exposed to the test material in dimethyl sulphoxide at concentrations of 50, 150, 500, 1500 and 5000 μg/plate in the presence and absence of mammalian metabolic activation.

The test material was tested up to a limit concentration of 5000 μg/plate, based on a lack of cytotoxic responses exhibited in a preliminary study. The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background.

The results of this study were negative and the substance was found to be non-mutagenic.

 

The potential of the test material to cause chromosome aberration was investigated in an in vitro mammalian chromosome aberration test conducted in accordance with the standardised guidelines OECD 473 and US EPA OPPTS 870.5375 under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria for assessing data quality set forth by Klimisch et al. (1997).

Human lymphocyte cultures from healthy, non-smoking male blood donors were exposed to the test material in DMSO at a range of concentrations up to and including 800 µg/mL both with and without metabolic activation.

The test material caused no statistically significant increases in the proportion of cells with chromosomal aberrations at any dose level, when compared with the solvent control.

Under the conditions of this study, the test material is non clastogenic.

 

The potential of the test material to cause gene mutation was investigated in a mammalian cell gene mutation assay conducted in accordance with the standardised guidelines OECD 476, EU Method B.17 and US EPA OPPTS 870.5300 under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria for assessing data quality set forth by Klimisch et al. (1997).

This test system is based on detection and quantitation of forward mutation in the subline 3.7.2c of mouse lymphoma L5178Y cells, from the heterozygous condition at the thymidine kinase locus (TK +/-) to the thymidine kinase deficient genotype (TK -/-). Two independent tests in the absence of exogenous metabolic activation (S9 mix) and two independent tests in the presence of S9 mix were carried out.

 The highest concentration tested was 1000 µg/mL, based on the test substance in DMSO precipitating in medium at concentrations of 500 µg/mL and higher. Little toxicity was observed after treatment in any test, in the absence or the presence of S9 mix.

No significant increases in mutant frequency were observed in any of the tests, either in the absence or presence of S9 mix. In all tests the positive control substances increased mutant frequencies significantly. 

Under the conditions of this study, the test material did not demonstrate mutagenic potential.


Justification for selection of genetic toxicity endpoint
No single key study was selected on the basis that the available studies all address different aspects of genetic toxicity and the data should be considered as a whole. All three studies were conducted in accordance with standardised guidelines under GLP conditions.

Short description of key information:
IN VITRO
- Non mutagenic with and without metabolic activation (Ames test); OECD 471 and EU Method B.13/14
- Non clastogenic with and without metabolic activation (chromosome aberration test); OECD 473 and US EPA OPPTS 870.5375
- Non mutagenic with and without metabolic activation (mouse lymphoma assay); OECD 476, EU Method B.17 and US EPA OPPTS 870.5300

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to genetic toxicity.