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Additional information

The mutagenic potential of TS-2863/SP-334 (2 –(2 -hexyl-decyloxy)-benzamide) was assessed in three in vitro tests.

A bacterial reverse mutation assay (Ames test) was performed using TS-2863, according to OECD 471 (Verspeek-Rijp, 1998). The plate incorporation method was applied using S. typhimurium strain TA 100 and E. coli WP2 uvr A at concentrations up to the limit value of 5000 µg/plate with and without metabolic activation; and S. typhimurium strains TA 1535, TA 1537 and TA 98 at concentrations up to the precipitation limit of 333 μg/plate,with and without metabolic activation.The test substance did not induce mutations in any of the S. typhimurium strains or in E. coli WP2 uvr A with or without metabolic activation. No cytotoxic effects were observed up to and including the limit value of 5000 μg/plate. Precipitation was noted from 333 µg/mL, with and without metabolic activation. The positive controls were shown to be valid.

In a mammalian cell gene mutation test performed according to OECD 476, Chinese hamster lung V79 cells were exposed to SP-334 (Bednáriková, 2011). In two independent experiments, V79 cells were exposed to concentrations from 62.5 -1000 µg/mL. The test substance did not cause an increase gene mutation levels, with or without metabolic activation. The upper dose range was limited by precipitation of the test substance in the culture medium from 1500 µg/mL in a range-finding study, while no precipitation was observed in the main experiments. There was no cytotoxicity up to and including the highest dose level of 1500 µg/mL and the positive controls induced significant increases in mutation frequency. In conclusion, SP-334 did not induce gene mutationsin vitroat the HPRT locus of V79 Chinese hamster lung cells when tested under the conditions of this study.

 

The potential of TS-2863 to induce chromosomal aberrations was tested in cultured human peripheral lymphocytes, according to OECD 473 (Bertens, 1998). Lymphocytes were exposed to the test substance at concentrations up to 33 µg/mL. Precipitation of the test substance was observed at the highest dose, limiting the dose range that could be tested. A short-term treatment (3 hours) was performed with a 24- and 48-hour harvest time, in the presence of metabolic activation. In addition, a 24-hour treatment with 24 hours harvest time without metabolic activation, and a 48-hour treatment with 48 hours harvest time with metabolic activation were performed. There were no increases in the number of chromosome aberrations at any dose level. No cytotoxic effects were observed and the positive controls induced a significant increase in the number of chromosomal aberrations.


Short description of key information:
In vitro:
Bacterial reverse mutation assay, Ames test (OECD 471): negative
Mammalian cell gene mutation test, Chinese hamster lung V79 cells (OECD 476): negative
Mammalian cytogenetic test, chromosome aberrations, cultured human peripheral lymphocytes (OECD 473): negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data on genetic toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.