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Key value for chemical safety assessment

Additional information

In vitro

- Gene mutation in bacteria

The bacterial gene mutation assay (Ames test) was conducted in compliance with OECD guideline 471 and under GLP conditions (Sokolowski, 2010). The assay was performed in two independent experiments both performed in the absence and in the presence of liver microsomal activation system (S9 mix). In the first experiment (pre-experiment), the direct plate incorporation procedure was conducted with the Salmonella typhimurium strains TA 98, TA 100, TA 1535 and TA 1537 and the Escherichia coli strain WP2 uvrA at concentrations ranging from 3 to 5000 µg/plate for a period of 48 h. In the second experiment, concentrations ranging from 33 to 5000 µg/plate were analysed using the same strains, but with modification of the study design (with pre-incubation period of 60 min). No signs of cytotoxicity, evident as a reduction in the number of revertants, were observed in both experiments. Precipitation of the test substance occurred at doses ≥ 2500 µg/plate, but did not influence data evaluation. The number of revertants was not increased at any concentrations tested. The positive and negative controls included showed the expected results in each experiment. Under the experimental conditions reported, the test substance did not induce mutations in the bacterial mutation assay in the absence and presence of metabolic activation in the selected strains of S. typhimurium (TA 98, TA 100, TA 1535 and TA 1537) and E. coli WP2 uvrA.

- Chromosome aberrations

The test substance Y-15866 was assayed in an in vitro mammalian chromosome aberration test conducted in accordance with GLP and similar to OECD guideline 473 (Hall, 2010). In two independent experiments, V79 Chinese hamster cells were treated with the test substance at concentrations up to 6950 µg/mL, with and without metabolic activation system (S9 mix). In the first experiment, continuous treatment with the test substance for 4 h followed by a 14 h-recovery period was performed. Since no clear cytotoxicity indicated by reduced mitotic indices or reduced cell numbers was observed up to the highest concentration, 6950 µg/mL was chosen as top treatment concentration in Experiment II. In this experiment, cells were analogously treated with the test substance in the presence of S9 (4 h + 14 h recovery period). In the absence of S9, cells were continuously treated for a period of 18 h without recovery period. Since no dose-response relationship was observed for cytotoxic effects in both experiments, concentrations used for evaluation of chromosome aberrations were selected based on the highest non-cytotoxic concentration tested. Thus, concentrations chosen for chromosome analysis ranged from 156.3 to 6950 µg/mL in Experiment I and 39.1 to 6950 µg/mL in Experiment II. In both experiments, no biologically relevant increase in the number of cells carrying structural chromosome aberrations was observed after treatment with the test substance in the absence and presence of S9 mix. The positive control substances yielded the expected results. Under the conditions of this chromosome aberration assay, it was concluded that Y-15866 did not show clastogenic activity in V79 Chinese hamster cells.


Short description of key information:
Negative Ames tests with S. typhimurium TA 98, TA 100, TA 1535 and TA 1537 and E. coli WP2 uvrA, with and without metabolic activation.
Negative results in a mammalian cell gene mutation test using V79 Chinese hamster lung fibroblast cells, with and without metabolic activation.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data on genetic toxicity of Y-15866 are conclusive but not sufficient for classification according to the CLP (1272/2008/EC) and DSD (67/548/EEC) criteria.