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Key value for chemical safety assessment

Additional information

In a GLP compliant bacterial mutagenicity assay (Ames test), performed according to OECD 471, using four Salmonella typhimurium strains (TA 1535, TA 1537, TA 98, and TA 100) and two E. Coli strains (WP2 and WP2 uvrA) the test substance was evaluated at concentrations of 100, 200, 500, 1000, 2500, and 5000 µg per plate in the presence and absence of rat liver derived metabolic activation system (S9-mix). In two separate experiments (one plate incorporation test and one pre-incubation test), the test substance did not induce any significant, reproducible increases in the observed numbers of revertant colonies in any of the strains used, either in the presence or absence of S9-mix.The sensitivity of the test system, and the metabolic activity of the S9-mix, were clearly demonstrated by the increases in the numbers of revertant colonies induced by positive control substances. It is concluded that, under the conditions of this assay, the test substance gave a negative, i.e. non-mutagenic response in S.typhimurium strains TA1535, TA1537, TA98 and TA 100 and E.coli strains WP2 and WP2 uvrA in both the presence and absence of S9-mix.

In a GLP-compliant chromosome aberration test, performed according to OECD guideline 473, the test substance was evaluated for its clastogenic potential in an in vitro cytogenetic assay using human lymphocytes in two separate experiments treated in the presence and absence of a rat liver-derived metabolic activation system (S9-mix). In Experiment 1, cultures were treated for a period of 3 hours both in the presence and absence of S9 mix, followed by a recovery time of 17 hours. In Experiment 2, cultures were treated for a period of 3 hours in the presence of S9 -mix followed by a recovery time of 17 hours, and treated for a period of 20 hours in the absence of S9 -mix. Cultures were treated with test substance at concentrations of 10, 50, 100, 250, 500, 750, 1000, and 1445 µg/mL. Cultures treated with 1445, 750, and 250 µg/mL of the test substance were selected for chromosomal aberration analysis. The highest concentration selected for chromosomal aberration was 1445 µg/mL which is equivalent to 10 mM, the limit concentration for the assay. No statistically or biologically significant increases in the percentage of aberrant cells, compared to the solvent control values, were recorded in cultures from either experiment treated in either the presence or absence of S9-mix. The sensitivity of the test system, and the metabolic activity of the S9-mix employed, were clearly demonstrated by the increases in the percentage of aberrant cells induced by the positive control agents, mitomycin C and cyclophosphamide. It is concluded that, under the conditions of this assay, the test substance is not clastogenic to cultured human lymphocytes treated in vitro in either the presence or absence of S9-mix.


Short description of key information:
Ames Test, OECD 471, not mutagenic, Callander 2000.
Chromosome Aberration test, OECD 473, not clastogenic, Fox 2000.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the bacterial mutagenicity assay and the chromosome aberration test, classification for genotoxicity is not warranted according to Directive 67/548/EEC.

Based on the bacterial mutagenicity assay and the chromosome aberration test, classification for genotoxicity is not warranted according to

EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.