Didocosyl sebacate

Endpoint summary

Additional information

Genetic toxicity (mutagenicity) in bacteria in vitro

A reliable bacterial gene mutation study (Ames test) performed according to OECD TG 471 and in compliance with GLP with Didocosyl sebacate (CAS 42233-75-0) is available (Thompson, P.W., 2012). The strains Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100 and E.coli WP2 uvr A were tested according to the plate incorporation procedure in the absence and presence of a metabolic activation system (phenobarbitone/β-naphthoflavone-induced rat liver S9-mix). Two independent experiments were conducted in three repetitions at each concentration from 50 to 5000 µg/plate (experiment I and II).Cytotoxicity was evaluated in a pre-experiment with the tester strains TA 100 and E. coli WP2 uvr A prior to the main gene mutation study. No significant increase in the number of revertants was observed in any of the tester strains with and without metabolic activation. No cytotoxicity was observed at any of the tested concentrations. Appropriate solvent (tetrahydrofuran) and positive controls were included and gave the expected results. Precipitation of the test material was noted at concentrations ≥ 500 µg/plate. Based on the results of the study the test material was considered to be not mutagenic to bacteria under the conditions of the test.

 

Genetic toxicity (cytogenicity) in mammalian cells in vitro

An in vitro chromosome aberration test in human lymphocytes was performed with Didocosyl sebacate (CAS 42233-75-0) according to OECD TG 473 and in compliance with GLP (Morris, A., 2013a). Human peripheral lymphocytes were cultured and treated with the test material or vehicle (tetrahydrofuran) in the absence or presence of a metabolic activation system (phenobarbitone/β-naphthoflavone-induced rat liver S9-mix) in duplicates at concentrations of 2.5, 5, 10, 20, 40 and 80 µg/mL for 4 or 24 hours (without S9-mix) and 4 hours (experiment I/II with 2%/1% S9-mix) in two independent experiments. Fixation and staining of the cells were performed 24 hours after start of exposure with the test material. Cytotoxicity was assessed by determination of the mitotic index. Appropriate solvent and positive controls were included in the test and gave the expected results. The test substance did not cause a statistically significant, dose-related increase in chromosome aberrations under the tested conditions.Cytotoxicity was recorded at 80 µg/mL with (2% S9-mix) and without metabolic activation (experiment I). Precipitation of the test item was observed in the first experiment at the end of exposure period at concentrations ≥5 µg/mL in the 4 h exposure/24 h fixation group (without S9-mix), and at ≥10 µg/mL in the 4 h exposure/24 h fixation group (with 2% S9-mix). Moreover, precipitation of the test item was recorded in the second experiment at a concentration of 20 µg/mL in the 24 h exposure/24 h fixation group (without S9-mix) and 4 h exposure/24 h fixation (with 1% S9-mix) group. Based on the results of the study the test material is considered not to be clastogenic in this chromosome aberration test in vitro.

Genetic toxicity in vivo

A reliable mammalian bone marrow chromosome aberration test performed according to OECD TG 475 and in compliance with GLP with Didocosyl sebacate (CAS 42233-75-0) is available (Morris, A., 2013b). Seven male Wistar rats per dose were administered nominal doses of 500, 1000 or 2000 mg/kg bw of the test substance or vehicle alone via single intraperitoneal application. Cells were freshly isolated from the bone marrow, swollen, fixed and stained and analyzed for chromosomal aberrations 24 and 48 hours post-application. Appropriate negative (arachis oil) and positive controls (25 mg/kg bw cyclophosphamide) were included in the study and showed the expected result. No cytotoxicity was observed at any of the tested concentrations. The test item did not induce any statistical significant or dose-related increase in the incidence of cells with chromosome aberrations when the dose groups were compared to the vehicle control group. The test item did not induce a significant increase in the numbers of polyploid cells in any of the treatment groups. Based on the results of the study the test material was considered to be non-clastogenic to rat bone marrow cells in vivo.

Justification for selection of genetic toxicity endpoint
No study was selected, since all available in vitro and in vivo genetic toxicity studies were negative.

Short description of key information:
In vitro gene mutation:
Bacterial reverse mutation assay (Ames test / OECD 471): negative
In vitro chromosome aberration test in human lymphocytes (CA / OECD 473): negative

In vivo gene mutation:
In vivo chromosome aberration test in rat bone marrow (CA / OECD 475): negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data on genetic toxicity of the registered substance do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.