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Administrative data

Key value for chemical safety assessment

Additional information

In a GLP conform study according to OECD guideline 471, the potential of the test substance to induce gene mutations using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, and TA 100, and the Escherichia coli strain WP2 uvrA and WP2 was investigated in two independent experiments (CCR 1992).

In the first mutation assay, the test substance was tested up to concentrations of 5000 µg/plate in the absence and presence of S9-mix.

In the second mutation assay, the test substance was tested up to concentrations of 5000 µg/plate in the absence and presence of S9-mix. The bacterial background lawn was not reduced at all concentrations tested and no decrease in the number of revertants was observed.

The test substance did not induce a dose-related, two-fold, increase in the number of revertant (His+) colonies in each of the four tester strains (TA1535, TA1537, TA98 and TA100) and in the number of revertant (Trp+) colonies in tester strains WP2uvrA and WP2 both in the absence and presence of S9-metabolic activation. These results were confirmed in an independently repeated experiment.

Based on the results of this study it is concluded that the test substance is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.

 

Cytogenicity in mammalian cells:

In a GLP conform study according to OECD guideline 473, the substance was assessed for its potential to induce structural chromosome aberrations in V79 cells (CCR 1993a and b). The possible clastogenicity of the test substance was tested in two independent experiments. Preparation of chromosomes was done 18 h (0.6; 3.0; 6.0

µg/ml

), and 28 h (6

µg/ml

) after

start of treatment with the test article which was formulated in DMSO. The treatment interval was 4 h. In each experimental group two parallel cultures were set up. Per culture 100 metaphases were scored for structural chromosomal aberrations except for the

positive control cultures where 25 metaphases were scored. The concentration range of the test article applied was limited by its solubility. The solubility of the test article in aqueous solutions (eg. culture medium, aqua dest.) and other organic solvents (eg. DMSO, acetone, ethanol) was very poor. Therefore, a suspension of the test article has to be prepared. The evaluation of cultures treated with concentrations higher than 6.0 µg/ml was prevented due to a very strong precipitation of the test article. There was no reproducible reduction of the mitotic indices at any fixation interval (with and without S9 mix) up to the highest

concentration used. In both independent experiments, there were no statistically relevant increases in cells with structural aberrations after treatment with the test article at both fixation intervals with and without S9 mix. The test substance did not induce a statistically significant or biologically relevant increase in the number of cells with chromosome aberrations in the absence and in the presence of S9-mix, in two independently repeated experiments. There was no increase in the polypoloidy index.

A micronucleus study in Chinese Hamster was performed with the lower molecular weight DPP pigment (EC no. 401-540-3) (Ciba 1986). Instead of the two diphenyl substituents, it carries two 4 -chlor-phenyl substituents. The read-across justification is given in the toxicokinetic part in section 5.1.3. The micronucleus study is assigned a reliability of 2 because it was performed according to an outdated version of the OECD testing guideline 474 with a reduced number of scored cells per dose group. It gives however additional evidence, as the tested dose of 5000 mg/kg bw exceeds the current limit dose of 2000 mg/kg bw. No indication of toxicity and no indication of genotoxicity was observed.

 


Short description of key information:
in vitro:
Gene mutation in bacteria:
Ames test, S. typhimurium/ E.coli, with and without metabolic activation: negative (GLP, OECD 471)

Gene mutation in mammalian cells:
no data.

Cytogenicity in mammalian cells:
Chromosome aberration, V79 cells with and without metabolic activation: negative (GLP, OECD 473)

in vivo:
A read-across substance was not genotoxic in the micronucleus assay in Chinese hamster at 5000 mg/kg bw. (GLP, OECD 474)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC):

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for mutagenicity under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

 

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008:

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for mutagenicity under Regulation (EC) No. 1272/2008.