Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Genetic toxicity in vitro, Chromosomal aberration test:

In a GLP compliant chromosome aberration test, tested according to OECD guideline 473, Chinese hamster V79 cells, were exposed to the test substance, with and without metabolic activation by S9 mix (RCC 2005). The exposure period was 4 hours with and without metabolic activation. In each experimental group two parallel cultures were set up. Per culture 100 metaphase plates were scored for structural chromosome aberrations. Dose selection of the main experiments was based on a pretest. Toxic effects indicated by reduced mitotic indices or reduced cell numbers were observed after treatment with the test item. However, concentrations showing clear cytotoxicity were not scorable for cytogenetic damage. In the absence of S9 mix, a dose-related increase in the number of cells carrying structural chromosomal aberrations was observed with a statistically significant and biologically relevant value after treatment with the test item in the highest evaluable concentration (250 µg/mL), clearly exceeding historical control data range. In addition, the number cells carrying exchanges was distinctly increased. No relevant increase in the frequencies of polyploid metaphases was found after treatment with the test substance as compared to the frequencies of the controls. In conclusion, it can be stated that under the experimental conditions reported, the test item did induce structural chromosome aberrations. Therefore, the test substance is considered to be clastogenic.

Genetic toxicity in vitro, Gene mutation assay:

In a GLP-compliant mammalian cell gene mutation test, performed according to OECD guideline 476, V79 cells of the Chinese hamster were exposed to the test substance with and without metabolic activation to investigate the potential of the test substance to induce gene mutations at the HPRT locus (RCC 2005). The assay was performed in two independent experiments. The cells were exposed to the test item for 4 hours in the first experiment with and without metabolic activation. The second experiment was solely performed in the absence of metabolic activation with a treatment period of 24 hours. No substantial and reproducible dose dependent increase in mutant colony numbers was observed in both main experiments. In conclusion it can be stated that under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells. Therefore, the test substance is considered to be non-mutagenic in this HPRT assay.

Genetic toxicity in vivo, Micronucleus test:

In a GLP-compliant erythrocyte micronucleus test, tested according to OECD guideline 474, 6 NMRI mice per sex were treated once by oral gavage with the test substance (500, 1000, 2000 mg/kg bw) dissolved in water followed by a 24 or 48 hours post exposure period (RCC 2006). Ten animals (5 males, 5 females) per test group were evaluated for the occurrence of micronuclei and at least 2000 polychromatic erythrocytes (PCEs) per animal were scored. The mean number of polychromatic erythrocytes (PCEs) was not decreased after treatment with the test substance as compared to the mean value of PCEs of the vehicle control indicating that the test substance had no cytotoxic properties in the bone marrow. In comparison to the corresponding vehicle controls there was no statistically significant or biologically relevant enhancement in the frequency of the detected micronuclei at any preparation interval and dose level after administration of the test substance. The mean values of micronuclei observed after treatment with the test substance were below or near to the value of the vehicle control group. Therefore, it can be stated that during the study described and under the experimental conditions reported, the test item did not induce micronuclei in the bone marrow cells of the mouse.


Short description of key information:
The test substance is considered to be mutagenic in the in vitro chromosome aberration. However, the test substance was not mutagenic in the in vitro gene mutation assay and the in vivo micronucleus test.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available genotoxicity studies, the test substance does not need to be classified for genotoxicity according to the Directive 67/548/EEC and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008