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Key value for chemical safety assessment

Additional information

Mammalian chromosomal aberration test

In order to assess the potential of the test item to induce structural chromosomal aberrations in cultured human lymphocytes, Bohnenberg 2014 conducted a study following recent guidelines and in compliance with GLP. In each experimental group two parallel cultures were analysed, in the absence and presence of an exogenous metabolic activation system (liver S9 mix from phenobarbital / beta-naphthoflavone treated male rats). In Experiment I in the absence and presence of S9 mix, no clear cytotoxicity was observed up to the highest applied concentration. However, the mitotic indices were markedly reduced to about or below 60 % of control. In Experiment II in the absence of S9 mix clear cytotoxic effects were observed at the highest evaluated concentration. In Experiment II in the presence of S9 mix concentrations showing clear cytotoxicity were not evaluable for cytotoxic damage.

Either with or without metabolic activation, no clastogenicity was observed at the concentrations evaluated. No evidence of an increase in polyploid metaphases was noticed after treatment with the test substance as compared to the control cultures. Appropriate mutagens were used as positive controls. They induced statistically significant increases (p < 0.05) in cells with structural chromosome aberrations.

Based on the available data which is considered to be adequate, reliable and conclusive for Genetic toxicity, the substance is considered to be non-clastogenic.

Bacterial Reverse Mutation Test (Ames)

This study was performed to investigate the potential of the substance to induce gene mutations in the plate incorporation test (experiment I) and the pre-incubation test (experiment II) using Salmonella typhimurium strains, and Escherichia coli strains. The plates incubated with the test substance showed reduced background growth in all strains used. Cytotoxic effects, evident as a reduction in the number of revertants (below the indication factor of 0.5), occurred in all strains with and without metabolic activation in both independent experiments. No increase in revertant colony numbers of any of the six tester strains was observed following treatment with the test item at any concentration level, neither in the presence nor absence of metabolic activation (S9 mix). Appropriate reference mutagens were used as positive controls. They showed a distinct increase of induced revertant colonies.

It can be stated that during the described mutagenicity test and under the experimental conditions reported, the test substance did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used.

Based on the available data which is considered to be adequate, reliable and conclusive for Genetic toxicity, the substance is considered to be non-mutagenic.

In accordance with Regulation (EC) No. 1907/2006, Annex VII, 8.4.1, the available data is considered relevant, reliable and adequate for the purposes of risk assessment and classification.


Justification for selection of genetic toxicity endpoint
Both available studies provide valid information on genotoxicity and chromosome aberration.

Short description of key information:
Negative with/without metabolic activation, Chromosome aberration, OECD 473, Bohnenberger 2014
Negative with/without metabolic activation, Ames test, OECD 471, Skolowski 2014

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Genetic toxicity in vitro

A chromosome aberration study and a bacterial reverse mutation test were conducted following OECD guidelines and in compliance with GLP Directive 2004/10/EC. The result are valid, reliable and adequate for the purpose of risk assessment, classification and labelling.

The substance does not meet the criteria for classification as a germ cell mutagenic substance according to Regulation (EC) 1272/2008, 3.5.2.