Reaction product of Propanoic acid, 3-[[bis(2-methylpropoxy)phosphinothioyl]thio]-2-methyl- and tridecanamine, N-tridecyl-, branched and linear

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The tes article was negative in an GLP-compliant Ames test (OECD 471) and in a GLP-compliant chromosome aberration study (OECD 471)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

AMES TEST

This study was performed to investigate the potential of the test article dissolved in ethanol to induce gene mutations according to the plate incorporation test (experiment I) and the pre-incubation test (experiment II) using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100, and the Escherichia coli strain WP2 uvrA. The assay was performed with and without liver microsomal activation. Each concentration, including the controls, was tested in triplicate. The test item was tested at the following concentrations: Pre-experimet/Experiment I: 3; 10; 33; 100; 333; 1000; 2500; and 5000 μg/plate. Experiment II: 33; 100; 333; 1000; 2500; and 5000 μg/plate. The test item precipitated in the overlay agar in the test tubes at 2500 and 5000 μg/plate in experiment I. Precipitation of the test item in the overlay agar on the incubated agar plates was observed at 5000 μg/plate in experiment I. In experiment II no precipitation of the test item occurred up to the highest investigated dose. The undissolved particles had no influence on the data recording. The plates incubated with the test item showed normal background growth up to 5000 μg/plate with and without S9 mix in all strains used. No toxic effects, evident as a reduction in the number of revertants (below the indication factor of 0.5), occurred in the test groups with and without metabolic activation in both experiments. No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with the test article at any dose level, neither in the presence nor absence of metabolic activation (S9 mix). Appropriate reference mutagens were used as positive controls and showed a distinct increase of induced revertant colonies. In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used. Therefore, the test article is considered to be non-mutagenic in this Salmonella typhimurium and Escherichia coli reverse mutation assay.

CHROMOSOMAL ABERRATION

The test item dissolved in ethanol, was assessed for its potential to induce structural chromosome aberrations in V79 cells of the Chinese hamster in vitro in two independent experiments. In each experimental group two parallel cultures were analysed. Per culture 100 metaphases were evaluated for structural chromosomal aberrations, except for the positive control in Experiment II, in the absence of S9 mix after 28 hours continuous treatment, where only 50 metaphases were evaluated. The highest applied concentration in the pre-test for toxicity (5.2 μL/mL of the test item) was chosen with regard to the purity (97 %) of the test item and with respect to the current OECD Guideline 473. Dose selection of the cytogenetic experiment was performed considering the toxicity data in accordance with OECD Guideline 473. In Experiment I in the absence of S9 mix cytotoxicity was observed at the highest evaluated concentration. In Experiment II in the absence of S9 mix and in Experiment I and II in the presence of S9 mix concentrations showing clear cytotoxicity were not evaluable for cytogenetic damage. In both independent experiments, neither a statistically significant nor a biologically relevant increase in the number of cells carrying structural chromosomal aberrations was observed after treatment with the test item. No evidence of an increase in polyploid metaphases was noticed after treatment with the test item as compared to the control cultures. Appropriate mutagens were used as positive controls. They induced statistically significant increases in cells with structural chromosome aberrations. In conclusion, it can be stated that under the experimental conditions reported, the test item did not induce structural chromosomal aberrations in V79 cells in vitro. Therefore, the test item is considered to be non-clastogenic in this chromosome aberration test, when tested up to cytotoxic or the highest evaluable concentration.