Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

The test itemshowed negative results in a study for the induction of gene mutations (bacterial reverse mutation assay) by frameshift or base-pair substitutions with and without metabolic activation. The study was performed with the test strains S. typhimurium TA 98, TA 100, TA 1535, TA 1537, TA 1538 and E. coli WP2 uvr A. Test concentrations up to 5,000 µg/plate were tested in the experiment. The test compound proved to be not mutagenic to the bacterial strains.

The test item was tested for its potential to induce chromosome aberrations using V79 Chinese hamster cells with and without metabolic activation in the dose range of 0.05-25 µg/ml. The substance was cytotoxic in the absence of metabolic activation. In contrast, in the presence of S9 mix no clear cytotoxicity was observed up to the highest scorable concentration. With and without metabolic activation, the aberration rates were statistically significant and biologically relevant increased exceeding clearly the control data at the top values.

The test item was also assessed in the micronucleus assay for its potential to induce micronuclei in polychromatic erythrocytes (PCE) in the bone marrow of the mouse. 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 treatment with the test item. The mean values of micronuclei observed after treatment were below or near to the value of the vehicle control group using dose levels up to 2000 mg/kg bw.

In conclusion, the test substance is not mutagenic in the bacterial reverse mutation assay. An in vitro chromosome aberration study performed in V79 showed positive results. However, in an in vivo chromosome aberration study in mice, which is considered to be most relevant model for investigation of cytogenic effects since it examines the mode of action in relation to the whole organism, the substance failed to induce microcnuclei.


Justification for selection of genetic toxicity endpoint
This in vivo study is selected as key study according to the information requirement REACH Regulation, Annex VII. All available genotoxicity studies were performed according to the current OECD Guidelines and GLP.

Short description of key information:
Mutagenic activity of the substance was investigated in a bacterial reverse mutation assay (Ames test; test strains used: S. typhimurium TA 98, TA 100, TA 1535, TA 1537 and E. coli WP2 uvr A), in one in vitro chromosome aberration study in mammalian cells (V79) and in one in vivo micronucleus assay in mice. Negative results were obtained in the Ames tests with and without metabolic activation and the in vivo MNT.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The substance does not have to be classified for mutagenicity since it did not reveal any mutagenic or cytogenic effect nor in the bacterial reverse mutation assay in the presence or absence of metabolic activation in concentrations up to 5,000 µg/plate nor in thein vivochromosome aberration study in concentrations up to 2000 mg/kg bw/d.