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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Additional information

In Vitro studies

- In vitro gene mutation (bacteria)

The test substance was evaluated for its mutagenic potential according to the OECD test guideline 471 (BASF SE, 2010), based on the ability to induce point mutations in selected loci of several bacterial strains, i.e. Salmonella typhimurium and Escherichia coli, in a reverse mutation assay. TA 1535, TA 100, TA 1537, TA 98 and E. coli WP2 uvrA were used and the doses rage from 33 μg/plate to 5000 μg/plate (standard plate test [SPT] and preincubation test [PIT]), both with and without metabolic activation (liver S9 mix from induced rats). No precipitation of the test substance was found up to 5000 µg/plate and a weak bacteriotoxic effect was occasionally observed at 5000 μg/plate. A relevant increase in the number of his+ or trp+ revertants was not observed in the standard plate test or in the preincubation test either without S9 mix or after the addition of a metabolizing system. Thus, under the experimental conditions of this study, the test substance is not mutagenic in the Salmonella typhimurium/Escherichia coli reverse mutation assay in the absence and the presence of metabolic activation.

The study was conducted according to the OECD test guideline 471 (GLP, Val 1), without any deviations, and is therefore considered reliable to assess the gene mutation potential of the test substance.

 

- In vitro mammalian gene mutation

The potential of the test substance to induce gene mutation is also evaluated in mammalian CHO cells according to the OECD test guideline 476 (BASF SE, 2011). The evaluated concentrations ranged from 1.6 to 5100 µg/mL for 4 hours (both with and without metabolic activation), or 24 hours (without metabolic activation) exposure times, about 6-8 days expression phase, and about 1 week selection period. The colonies of each test group were fixed with methanol, stained with Giemsa and counted.

Steep dose-effect related cytotoxic effects indicated by clearly reduced cloning efficiencies of below 20% of control were observed in the 1st and 2nd Experiment under all test conditions, but only at clearly precipitating concentrations (from 30 µg/mL onward). In both experiments after 4 and 24 hours treatment with the test substance the values for the corrected mutation frequencies (MFcorr.: 0.00 – 9.99 per 10E6 cells) were close to the respective vehicle control values (MFcorr.: 1.86 – 5.06. per 10E6 cells) and clearly within the range of the historical negative control data (without S9 mix: MFcorr.: 0.00 – 15.95 per 10E6 cells; with S9 mix: MFcorr.: 0.00 – 15.68 per 10E6 cells). The positive control substances induced clearly increased mutant frequencies as expected. The values of the corrected mutant frequencies (without S9 mix: MFcorr.: 151.54 – 392.00 per 10E6 cells; with S9 mix: MFcorr.: 81.04 – 105.35 per 10E6 cells) were clearly within the historical positive control data range (without S9 mix: MFcorr.: 48.83 – 1 338.10 per 10E6 cells; with S9 mix: MFcorr.: 26.29 – 413.54 per 10E6 cells).

The test substance did not lead to a relevant increase in the number of mutant colonies either without S9 mix or after the addition of a metabolizing system in two experiments performed independently of each other. Thus, under the experimental conditions chosen here, the test substance is not a mutagenic substance in the HPRT locus assay using CHO cells in the absence and the presence of metabolic activation.

The test was conducted according to the OECD TG 476 and clearly shows no evidence that the test substance could have a gene mutation potential in mammalian CHO cells. Taken together with the negative Ames test, a mutagenic potential for the test substance is not anticipated.

 

- In vitro mammalian chromosome aberration

The potential of the test substance to induce structural chromosomal aberrations (clastogenic activity) and/or changes in the number of chromosomes (aneugenic activity) was assessed in V79 cells in vitro both in the absence and the presence of a metabolizing system (BASF SE, 2011), according to the OECD TG 473. Because test substance precipitation in medium (in the absence of any cytotoxicity) was observed in the initial range-finding test up to the highest required concentration, 5100 μg/mL (approx. 5000 μg/mL of the active ingredient), the main test was performed with test substance concentrations up to 320 µg/mL in medium.

According to the results, the test substance did not lead to a biologically relevant increase in the number of structural chromosomal aberrations incl. and excl. gaps either without and/or with S9 mix in three scorable experiments performed independently of each other at different exposure times (4 and 18 hours) and sampling times (18 and 28 hours). The types and frequencies of structural chromosome aberrations were close to the range of the concurrent negative control values at both sampling times and within the range of the historical negative control data.

Single increased endoreduplication indices exceeding the historical negative control data range (0.0% - 5.2%) were observed in the 2nd and the 3rd Experiment in the presence of S9 mix after 4 hours treatment at 18 hours or 28 hours preparation, but occurred non-homogeneously within the test group without any additional indication (increased number of aneuploid, polyploid or endopolyploid metaphase cells) for an aneugenic potential of the test substance in any other experimental part of this study. This observation was therefore regarded as artifact of cell preparation, and, thus, considered as biologically irrelevant.

The increase in the frequencies of structural chromosome aberrations induced by the positive control substancesand CPP clearly demonstrated the sensitivity of the test system and of the metabolic activity of the S9 mix employed. The values were within the range of the historical positive control data and, thus, fulfilled the acceptance criteria of this study. Thus, under the experimental conditions chosen here, the conclusion is drawn that the test substance is not a chromosome-damaging (clastogenic) substance under in vitro conditions using V79 cells in the absence and the presence of metabolic activation.

The study was conducted according to the OECD TG 473 without any deviation and is clearly sufficient for assessment of in vitro chromosomal aberration potential of the test substance in mammalian cells. Taken together with the available negative bacterial and mammalian gene mutations assays and with the absence of any further indication for such effect, a genetic toxicity potential for the test substance is not anticipated.

 

In vivo studies

No data available.


Short description of key information:
- Bacterial gene mutation: negative; OECD test guideline 471, GLP (BASF SE, 2010);
- Mammalian gene mutation: negative; OECD test guideline 476 (CHO/HPRT assay), GLP (BASF SE, 2011);
- In vitro mammalian chromosome aberration test: negative; OECD test guideline 473, GLP (BASF SE, 2011).

Endpoint Conclusion:

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available experimental test data are considered reliable and suitable for the purpose of classification. No classification is warranted.

 

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

The available experimental test data are considered reliable and suitable for the purpose of classification. No classification is warranted.