Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Gene mutation in bacteria

A bacterial gene mutation assay with the test substance was performed in accordance with OECD Guideline 471 and in compliance with GLP (Andres, 2014). In two independent experiments, the Salmonella typhimurium strains TA 97a, TA 98, TA 100, TA 102 and TA 1535 were exposed to the test substance suspended in ethanol using either the preincubation or the plate incorporation method. In a non-GLP pre-test, the solubility of the test item in water, dimethyl sulfoxide or ethanol was tested. The best result for a suspension was observed in ethanol. As the test substance was tested as suspension, precipitates were observed on all plates in all tested concentrations. In the first experiment (plate incorporation), test concentrations of 50, 150, 500, 1500 and 5000 µg/plate were used with and without metabolic activation. In the second experiment (preincubation method), test concentrations of 78, 156, 313, 625, 1250, 2500 and 5000 µg/plate were used with and without metabolic activation. No increase in the mean number of revertants per plate was observed in any of the test strains compared to the control. No signs of toxicity towards bacteria were noted after exposure of the test strains with any of the test concentrations in both experiments. The most values of the spontaneous revertants of the solvent control ethanol were outside the range of the historical data but were within the range of the literature data. All positive control values were found to be within the respective historical control ranges. Under the conditions of this experiment, the test substance did not show mutagenicity in the selected S. typhimurium strains in the presence and absence of metabolic activation.

 

Chromosome aberrations

The clastogenic activity of the test substance was investigated in an in vitro mammalian chromosome aberration test in cultured peripheral human lymphocytes performed according to OECD Guideline 473 and GLP (Verbaan, 2015). The test substance was soluble in tetrahydrofuran at concentrations of 0.34 mg/mL and below but formed a suspension at concentrations of 1.08 mg/mL and above. Precipitation of the test item occurred at a concentration of 17 µg/mL in the culture medium. In a first experiment, the test substance was tested up to 17 µg/mL for a short-term 3 h exposure period with and without metabolic activation (S9 mix). In a second experiment, the test substance was tested up to 175 µg/mL for a 24 and 48 h continuous exposure period with a 24 and 48 h fixation time without metabolic activation. Appropriate toxicity was reached at this dose level. The number of cells with chromosome aberrations found in the solvent control cultures was within the laboratory historical control data range. Positive control chemicals, mitomycin C and cyclophosphamide, both produced a statistically significant increase in the incidence of cells with chromosome aberrations, indicating that the test conditions were adequate and that the metabolic activation system (S9 mix) functioned properly. The test substance did not induce a statistically significant and biologically relevant increase in the number of cells with chromosome aberrations. No effects of the test substance on the number of polyploid cells and cells with endoreduplicated chromosomes were observed both in the absence and presence of S9 mix. Thus the test substance was considered not-clastogenic under the conditions of this test.


Justification for selection of genetic toxicity endpoint
No study was selected, since all available in vitro genetic toxicity studies were negative

Short description of key information:
In vitro:
Ames test (OECD 471): negative with S. typhimurium TA 97a, TA 98, TA 100, TA 102 and TA 1535, with and without metabolic activation
Chromosome aberration test (OECD 473): negative in cultured peripheral human lymphocytes with and without metabolic activation

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data, there is no indication that the substance induces genetic toxicity. Nevertheless, no final decision on classification for genetic toxicity according to Regulation (EC) 1272/2008 or Directive 67/548/EEC can be made, as no information on mutagenicity in mammalian cells/in vivo is available.