Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

In Vitro:

The test substance was tested in an Ames Salmonella/ microsome assay. The bacterial strains used were: TA98, TA100, TA102, TA1535, TA1537, TA1538 and Escherichia coli WP2uvrA and WP2uvrA/pKM101. The test substance was tested without metabolic activation and with S-9 mix from male Sprague-Dawley rats. The following standard mutagens served as positive controls: AF2: 2 -(2 -furyl)-3 -(5 -nitro-2 -furyl)acrylamide, NaN3: sodium azide, 9AA: 9 -aminoacridine, 2NF: 2 -nitrofluorene, 4NQO: 4 -nitroquinoline-N-oxide, BLM: bleomycin, PA: pyruvic aldehyde, 2AA: 2 -amino anthracene. Al chemicals except BLM and PA were dissolved in DMSO. BLM and PA were dissolved in sterile destilled water.

The test substance was found to be mutagenic for strain TA 100 with metabolic activation (JETOC, 1996).

In a Chromosome Aberration study in Chinese Hamster Lung-cells the test substance was tested with and without metabolic activation. The number of cells with chromosomal aberrations from 100 metaphases were counted per each culture bottle. The incidence of polyploid cells in the 100 metaphases was recorded. For the evaluation of the frequencies of structural aberrations and of polyploid, the following criteria were used: Negative: less than 5% Equivocal: from 5% to less than 10% Positive: 10% and more When a test was positive, the D20 values were calculated from the result. The D20 value is the concentration (mg/ml) required to induce any aberration in 20% of metaphases. Thus, a low D20 value indicates that the agent induces chromosomal aberrations at relatively low dose levels. The calculated D20 value for the test substance was 0.076 mg/ml. The genotoxicity therefore was positive (JETOC, 1996)

Additionally, the test substance was assessed for its mutagenic potential in vitro in the chromosome-aberration-test with two independent cell cultures without metabolic activation and two independent cell cultures with metabolic activation. No relevant enhancement of chromosome mutations were observed without S9 -mix but a relevant and reproducible enhancement of metaphases with aberrations over the range of the negative control was found with any of the concentrations at all treatment time used with metabolic activation theese data were found significantly enhanced in the Fisher's exact test. The sensitivity of the test system was demonstrated by the enhanced mutation frequency in the cell cultures treated with positive control substances...

Justification for selection of genetic toxicity endpoint
No study was selected because the key studies including point mutations in Ames test and clastogenic activity in mammalian cell system show that the test substance elicit mutagenic activity. These studies are performed in compliance with therespective guidelines and are evaluated with Klimisch score 2

Short description of key information:
Based on the available data the test compound is mutagenic

Endpoint Conclusion: Adverse effect observed (positive)

Justification for classification or non-classification

Due to a positive in vitro chromosome aberration assay the compound might be classified as a category 3 mutagen; R68: possible risk of irreversible effects according to Regulation 67/548/EEC. With respect to Regulation (EC) No. 1272/2008 the substance should be allocated to category 2 of the mutagenic substances (H341)