D-Glucitol, 1-deoxy-1-(methylamino)-, N-[C8-16 (even numbered) and C18 unsaturated acyl] derivs.

Endpoint summary

Additional information

Glucamide CC was tested for potential point mutation in a guideline conform bacterial reverse mutation assay (Ames test) according to OECD TG 471 in theSalmonella typhimuriumstrains TA98, TA100, TA1535, TA1537 and TA102 in two independent experiments. There were no mutagenic responses in any of the tester strains up to test concentrations of 5000 µg per plate, neither with nor without metabolic activation (S9-mix from induced rat liver). Therefore the registration substance is considered to be non-mutagenic in this bacterial reverse mutation assay. This study is selected as key study.

Glucamide CC was tested for potential gene mutation in a guideline conform mammalian cell gene mutation assay (HPRT locus) according to OECD TG 476 in V79 cells of the Chinese hamster. Using independent experiments, no biologically relevant increase of mutants was found after treatment with the test item, neither with nor without metabolic activation. No dose-response relationship was observed. Therefore, the registration substance is considered to be non-mutagenic in the HPRT locus using V79 cells of the Chinese hamster. This study is selected as key study.

Likewise, Glucamide CC was also not mutagenic when tested in an oral (gavage) in vivo micronucleus assay in mice up to the limit dose of 2000 mg/kg body weight. Therefore, the registration substance is considered to be non-mutagenic in the micronucleus test in mice. This study is selected as key study.

In conclusion, Glucamide CC is not mutagenic in the bacterial reverse mutation assay, the mammalian (HPRT) mutation test in V97 cells and in the in vivo micronucleus test in mice.

The negative findings reported with Glucamide CC are consistent with findings of no mutagenicity for the structural and biological analogue Glucamide 24. The read-across compound (Glucamide 24, Test material SS0001.01, 45% active) was negative for mutagenic activity when evaluated in the in vitro mammalian mutation assay (mouse lymphoma assay) and in the in vivo chromosomal aberration assay (structural and numerical aberrations) in rats. In the mouse lymphoma assay, doses selected for cloning in the initial assay under non-activated conditions were 2.3 microgram/mL to 36 microgram/mL(total growth (TG) indices were 16 to 93% of controls) and activated cultures selected were 2.3 microgram/mL to 50 microgram/mL (TG indices of 18 to 107% of controls). The confirmatory study examined doses of 2.3microgram/mL to 32 microgram/mL (TG indices of 10 to 106%) and 13microgram/mL to 45 microgram/mL (TG indices of 12 to 109%), under non-activated and activated conditions, respectively. In either assay, none of the cultures increased the mutant frequency by the limit of two times the solvent controls nor was a dose response observed. In thein vivocytogenicity study, Sprague-Dawley rats were orally (gavage) exposed to 180, 600, or 1800 mg a.i./kg bw for males and 210, 700, or 2100 mg a.i./kg body weight for females (bone marrow was examined 8 and 12 hours post dosing). Both studies employed appropriate negative and positive controls demonstrating the validity of the test system. 

Justification for selection of genetic toxicity endpoint
There are several key studies available, covering bacterial point mutation testing, testing for gen mutations in mammalian cells as well as chromosome mutations in vivo. All studies are guideline conform tests according to GLP. No derivations and/or confounders have been observed. Klimisch rating 1 is representing reliability without restrictions. The information is valid and meet data requirements with regard to classification and labelling.

Short description of key information:
The registration substance was not mutagenic in a guideline conform Salmonella typhimurium reverse mutation assay (Ames test) using five tester strains with and without metabolic activation (S9-mix from induced rat liver). Likewise, the submission substance was also not mutagenic in a guideline compliant mammalian cell gene (HPRT) mutation assay in V79 Chinese hamster cells and did not induce chromosome aberrations (micronuclei) or clastogenic effects in a guideline conform micronucleus test in vivo. Absence of mutagenic / genotoxic properties is supported by data from the structural and biological close analogue Glucamide 24.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on all availabe data, the registered substance is not consiered to be mutagenic. Accordingly, classification & labelling does not apply.