9-Octadecenedioic acid

Endpoint summary

Additional information

Genetic toxicity (mutagenicity) in bacteria in vitro

EC 802-122-7

The in vitro genetic toxicity of Octadec-9-enedioic acid was assessed in a bacterial reverse mutation assay (Ames test), performed according to OECD guideline 471 and under GLP conditions (Queffurus, 2015). S. typhimurium strains TA 1535, TA 1537, TA 1538, TA 98, TA 100 and TA 102 were exposed to concentrations in the range 50 - 5000 µg/plate, with and without metabolic activation. The plate incorporation method was applied in experiment 1 and 3, while the preincubation assay was applied in experiment 2. In experiment 2, cytotoxicity was observed in strain TA 100 from 1600 μg/plate and in TA 1537 at 5000 μg/plate; while in experiment 3, cytotoxicity was observed in strain TA 100 and TA 1535 at 5000 μg/plate. No precipitation was observed. The vehicle (DMSO) and positive controls were shown to be valid. During the first step of experiment 1 without metabolic activation, a ratio R higher than the double of the spontaneous rate of reversion was shown for strain TA 98 at 50 μg/plate and a ratio higher to the triple of the spontaneous rate of reversion was observed for strain TA 1535 at 50 μg/plate. As these results were not reproducible in experiment 2, experiment 3 was performed according to the same protocol as experiment 1. The results were not reproducible in experiment 3 either, and therefore are not considered to be valid. The test substance did not induce an increase in reversions in the S. typhimurium strains tested, with or without metabolic activation.

Genetic toxicity (cytogenicity) in mammalian cells in vitro

EC 802-122-7

The potential of Octadec-9-enedioic acid to induce chromosomal aberrations was assessed using human peripheral blood lymphocytes, in an in vitro mammalian cell micronucleus test performed according to OECD 487 and under GLP conditions (Dewaele, 2015). The lymphocytes were exposed to Octadec-9-enedioic acid in DMSO at concentrations up to 250 µg/mL, with and without metabolic activation (S9-mix). A 4-h treatment was performed with and without metabolic activation, using 62.5, 125 and 250 µg/mL concentration levels with a 28-h expression time. A 24-h treatment without metabolic activation was performed at concentrations of 125, 187.5 and 250 µg/mL with a 48-h expression time. Al l treatments were performed in duplicate and 2000 binucleated cells were evaluated per concentration. The vehicle and positive controls were show to be valid. In the genotoxicity assays with 4-h treatment, the highest concentration of 250 μg/mL induced very slight toxicity with percentages of cytostasis of 19.2 and 14.3%, without and with metabolic activation, respectively, corresponding to replication indexes of 80.8 and 85.7%, when compared with the respective solvent controls. In the genotoxicity assay with 24-h treatment, the highest concentration of 250 μg/mL induced a strong but acceptable cytotoxicity with a percentage of cytostasis of 50.5%, corresponding to a replication index of 49.5%, when compared with the solvent control. The test material did not induce a statistically significant increase in the frequency of cells with chromosome aberrations, measured as micronucleus frequency, with or without metabolic activation.

 

Overall conclusion for genetic toxicity

There are in vitro studies on genetic toxicity in bacterial cells and in mammalian cells. The results of the available studies were consistently negative. Based on the available data, Octadec-9-enedioic acid (EC 802-122-7), is not considered to be mutagenic.

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

Short description of key information:
Ames test (OECD 471): negative in S. typhimurium TA 1535, TA 1537, TA 100, TA 98 and TA 102, with and without metabolic activation
Chromosome aberration in mammalian cells (OECD 487): negative in human peripheral blood lymphocytes with and without metabolic activation

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data on genetic toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.