N,N'-dimethyldiphenylthiuram disulphide

Endpoint summary

Additional information

Genemutatuin test in bacteria

N,N'-Dimethyldiphenylthiuram disulphide (Vulkacit I) was investigated for point mutation using the Ames test according to OECD TG 471(pate incorporation and preincubation method) and the strains Salmonella typhimurium TA98, TA100, TA102, TA1535, TA1537. Doses up to 5000 µg/plate in the presence and absence of a metabolicactivation system (S9 -mix) were applied. Substance precipitation occurred at the dose of 500 µg/plate and above. Evidence of mutagenic activity of Vulkacit I was not seen . No biololgical ly relevant increase in the mutant count in comparison with the negatife controls was observed. Therefore , Vulkacit I was considered to be non-mutagenic withour and with S9 -mix (Herbold 2001)

Gene mutation test in mammalian cell system.

The study was performed to investigate the potential of N,N'-Dimethyldiphenylthiuram disulphide to induce gene mutations at the HPRT locus in V79 cells of the Chinese hamster according to OECD TG 476. The assay was performed in two independent experiments, using two parallel cultures each. The first main experiment was performed with and without liver microsomal activation and a treatment period of 4 hours. The second experiment was performed with a treatment time of 4 hours with and 24 hours without metabolic activation. The highest concentration (1000 µg/mL) applied to the pre-experiment was limited by the solubility properties of the test item in DMSO abd aquous medium. The dose-range of the main experiments was limited by cytotoxic effects.

No substantial and reproducible dose dependent increase of the mutation frequency was observed in both main experiments.

Appropriate reference mutagens, used as positive controls, induced a distinct increase in mutant colonies and thus, showed the sensitivity of the test system and the activity of the metabolic activation system.

In conclusion it can be stated that under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells. Therefore, N,N'-Dimethyldiphenylthiuram disulfide is considered to be non-mutagenic in this HPRT assay (Harlan 2012)

Chromosome aberration test (MNT in vitro).

N,N-dimethyldiphenylthiuram disulphide was examined for mutagenic activity in the micronucleus test in vitro according to OECD TG 487 in the presense and in th absence of a metabolic activation system. In the experiments without S9 mix, limiting cytotoxicity was reached at a concentration of 0.1 µg/mL (4 hours treatment) or 7.5 µg/mL (24 hours treatment). In the experiment with S9 mix (4 hours treatment), limiting cytotoxicity was observed at a concentration of 0.15 µg/mL.The micronucleus test showed no biologically relevant increase in the frequencies of micronucleus containing V79 cells treated with the test item in the absence (4 hours or 24 hours treatment) or in the presence of S9 mix.

Evaluation of the data does not indicate that N,N‘-dimethyldiphenylthiuram disulfide is a mutagen in the micronucleus test in vitro, when tested up to cytotoxic concentrations in the absence or presence of metabolic activation.(Sutter 2012)

Overall conclusion

Based on the available data there is no evidence that N,N'-dimethyldiphenylthiuram disulphide causes mutagenic effects.

Justification for selection of genetic toxicity endpoint
No study was selected since all three key studies were negative

Short description of key information:
N,N-Dimethyldiphenylthiuram disulphide was tested in Ames test and in HPRT test for gene mutation. and in the Micronucleus test-in-vitro for chromosome aberrations. There was no evidence that N,N'-Dimethyldiphenylthiuram disulphide causes mutagenic effects.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data no classification and labelling is required