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Administrative data

Key value for chemical safety assessment

Additional information

A sufficient number of good quality and valid in vitro and in vivo studies covering the required endpoints of bacterial and mammalian mutagenicity as well as mammalian clastogenicity are available to assess the genotoxicity potential of C12-C18 TMAC.

In vitro

An OECD 471 study was conducted to determine the mutagenic potential of C12-C18 TMAC. The test substance was examined for mutagenic activity in four strains TA 100, TA 1535, TA 1537 and TA 98 of Salmonella typhimurium using pour-plate assays. The studies were performed in the absence and in the presence of S9-mix. Doses for studies ranged from 1 to 100 µg/plate.No increase in reversion to prototrophy was obtained with any of the bacterial strain at any dose level 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, C12-C18 TMAC is not mutagenic in the presence and absence of exogenous metabolic activation (May K, 1989).

An OECD 476 study was conducted to evaluate the potential of C12-C18 TMAC 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 dose 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 dose-related increase in the mutant frequency at any dose level, either with or without metabolic activation. Adequate levels of toxicity were achieved in all exposure groups. Under the test conditions, C12-C18 TMAC did not show mutagenic activity in mouse lymphoma assay (Nolan, 2002).

An OECD 473 study was conducted to determine the clastogenic potential of C12-C18 TMAC in cultured human lymphocytes. After a dose range finding test, two independent tests have been performed in cultured peripheral human lymphocytes in the presence and absence of a metabolic activation system. With S9-mix cells were exposed for 24 hours. The test substance produced 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 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

An OECD 474 study was conducted to assess the potential of C12-C18 TMAC to cause chromosomal damage (clastogenicity) in an in vivo mouse bone marrow micronucleus test. The test substance was suspended in 1% methyl cellulose and was administered as an oral dose of 468 mg/kg bw to male and female mice based on the results of a dose range finding assay. Following dosing, the animals were examined regularly and any clinical signs of reaction to the test substance were recorded. Five males and five females were sacrificed 24, 48 and 72 hours after dosing. The number of polychromatic erythrocytes containing micronuclei was not increased. The ratio of polychromatic erythrocytes to total erythrocytes in both male and female animals remained unaffected by the treatment with test substance. Under the test conditions, C12-C18 TMAC was not mutagenic in the mouse micronucleus test (Allen et al.,1983).

Justification for selection of genetic toxicity endpoint
No one study was selected, since all the four studies (three in vitro studies and one in vivo study) were negative.

Short description of key information:
Based on the available data from in vitro and in vivo genetic toxicity assays, C12-C18 TMAC is not considered to have genotoxicity potential.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

C12-C18 TMAC was negative in in vitro and in vivo genotoxicity assays. Therefore no classification is required according to EC criteria (67/548/EEC) and according to CLP criteria (EC 1272/2008).