Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

In vitro

 

A guideline study was conducted to determine the mutagenic potential ofC12-14 ADMAES(95% active ingredient). The test substance was examined for mutagenic activity in five strains of Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102, using the plate incorporation and pre-incubation methods. The studies were performed in the absence and presence of metabolic activation (S9-mix). The concentrations ranged from 1.23 to 100µg/plate in first experiment and 0.41 to 200µg/plate in second experiment.No increase in reversion to prototrophy was obtained with any of the bacterial strain at any concentration either in the presence or absence of S9-mix. Further, inhibition of growth, observed as thinning of the background lawn of non-revertant cells, occurred in all strains following exposure to the test substance at ≥100 µg/plate. Under the test conditions, the test substance was not considered to be mutagenic in the presence and absence of exogenous metabolic activation (Haddouk H, 2003).

An OECD 476 study was conducted to evaluate the potential of the read-across substance C12-18 TMAC (active ingredient 35%) to induce mutations at the TK (thymidine kinase) locus in L5178Y mouse lymphoma cells. After a preliminary toxicity test, 0.625, 1.25, 2.5, 5, 10 and 20 µg/L was selected for the first experiment. The experiment was repeated to confirm the results of the first experiment. Three hour exposures were used both with and without S9-mix while for the second experiment, the exposure time was increased to 24 hours. For the second experiment, the concentration range was 2.5 to 30 µg/L with S9-mix and 0.313 to 5 µg/L without S9-mix. The test substance did not induce a statistically significant or concentration-related increase in the mutant frequency at any concentration level, either with or without metabolic activation. Adequate levels of toxicity were achieved in all exposure groups. Under the test conditions, C12-18 TMAC did not show mutagenic activity in mouse lymphoma assay (Nolan, 2002).

An OECD 473 study was conducted to determine the clastogenic potential of the read-across substance C12-18 TMAC (active ingredient 33%) in cultured human lymphocytes. After a concentration range finding test, two independent tests were performed in cultured peripheral human lymphocytes in the presence and absence of a metabolic activation system (S9-mix). With S9-mix cells were exposed for 24 hours. The test substance produced a reduction in mitotic activity (i.e., approximately 48%) at 10 µg/L in the absence of S9-mix and at 10 (i.e., 20%) and 50 (i.e., 37%) µg/L in the presence of S9-mix. Further, consideration of mean aberrant cell frequencies showed no real increases in culture tested with the test substance, when compared to control. Statistical analysis confirmed these observations. However, there was an apparent increase in the number of polyploid cells, compared to concurrent control values in all tested cultures, although a marked effect was seen only in activated cultures exposed to 50 µg/mL the author concluded that the test substance is not clastogenic in human lymphocytes under the experimental conditions (Richardson, 1989).

In vivo

 

Data waiving applied since C12-14 ADMAES and the read-across substance C12-18 TMAC were negative in in vitro assays (i.e., bacterial and mammalian mutagenicity assays as well as mammalian chromosome aberration assay). Therefore an in vivo mutagenicity test is not required.


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

Short description of key information:
C12-14 ADMAES was non-mutagenic to S. typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and the read-across substance C12-18 TMAC did not induce mutations or chromosome aberrations in mammalian cells. Based on these data C12-18 TMAC, C12-14 ADMAES is not considered to have any genotoxic potential.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available negative data from in vitro assays onC12-14 ADMAES and the read-across substance C12 -18 TMAC, classification for genotoxicity according to Directive 67/548/EEC and Regulation EC 1272/2008 is not required.