Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Ames test:

B508 was tested in the bacterial reverse mutation assay with Salmonella typhimurium TA 1535, TA 1537, TA 100, TA 98 and E. coli WP2uvrA using a pre-incubation method with and without S9-mix. No toxicity was observed up to and including the top dose of 5000 µg/plate. Precipitation was observed at 1250µg/plate and higher.The numbers of revertant colonies in the test substance treatment groups were less than two times compared with that in each negative control in all test strains with and without S9-mix. It is concluded that B508 is not mutagenic under the conditions of this test.

Chromosome aberration test:

A chromosome aberration study with B508 was performed according to OECD 473 guideline and GLP principles, in cultured Chinese hamster lung fibroblasts (CHL/IU cells) with and without S9-mix including a confirmation experiment. Appropriate toxicity was reached at the dose levels selected for scoring. The frequencies of cells with numerical aberrations showed less than 5% at all doses in the short-term treatment with and without S9 -mix and the 24 -hour continuous treatment. The frequencies of cells with structural aberration showed less than 5% at all doses of the test substance in the short-term treatment without S9 and 24 hours continuous treatment without S9. The frequencies of cells with structural aberration was 6.0% at 640 µg/mL in the short-term treatment time with S9 and induction of structural aberration by the test substance was suspected. However, the frequencies of cells with structural aberration showed less than 5% at all doses of the test substance tested in the confirmation experiment under the same conditions. Therefore, it was concluded that B508 is not clastogenic in cultured Chinese hamster lung fibroblasts (CHL/IU cells).

The results of the negative and positive controls were within the historical data range.

Mouse lymphoma assay:

An in vitro mammalian cell gene mutation test with B508 was performed according to OECD 476 guideline and GLP principles, in cultured L5178Y mouse lymphoma cells with and without S9-mix in two independent experiments.

In the first experiment, B508 was tested up to the cytotoxic level of 70% in the absence of S9-mix. No toxicity was observed at the highest dose level tested in the presence of S9-mix. In the second experiment, B508 was tested up to cytotoxic levels of 81 and 30% in the absence and presence of S9-mix, respectively. In the presence of S9 -mix B508 was tested including a precipitating concentration.

In the absence of S9-mix, B508 did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in a repeat experiment with modifications in the duration of treatment time.

In the presence of S9-mix, B508 did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in an independent experiment with modifications in the composition of the S9 concentration for metabolic activation. Positive and negative control data showed valid results.

In conclusion, B508 is not mutagenic in the mouse lymphoma L5178Y test system under the experimental conditions described in this report.


Justification for selection of genetic toxicity endpoint
One Ames test, one chromosome aberration test and mouse lymphoma test are available.

Short description of key information:
B508 was tested in the Salmonella typhimurium reverse mutation assay with TA 1535, TA 1537, TA 100, TA 98 and WP2uvrA according to OECD Guideline 471 and GLP principles.
A chromosome aberration study with B508 was performed according to OECD 473 guideline and GLP principles, in cultured Chinese hamster lung fibroblasts (CHL/IU cells) in a chromosomal aberration test and a confirmation experiment.
An in vitro mammalian cell gene mutation test with B508 was performed according to OECD 476 guideline and GLP principles, in cultured L5178Y mouse lymphoma cells.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available studies, it can be concluded that B508 is not considered mutagenic/clastogenic according to EC regulation 1272/2008.