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Key value for chemical safety assessment

Additional information

There are no data available for the genetic toxicity of CAS 12004488-68-5. In order to fulfil the standard information requirements, a read-across from structurally related substances was conducted.

The mutagenic potential of the structural analogue substance CAS#4192-55-9 was tested in a Salmonella typhimurium reverse mutation assay according to OECD Guideline 471 and GLP. The following strains were used: TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2. Tester strains were incubated with test material concentrations of 33, 100, 333, 1000, 2500 and 5000 µg/plate with and without the addition of a metabolic activation system. Two independent experiments were performed with triplicates each. No toxicity of the test substance was observed.

No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment at any dose level, neither in the presence nor absence of metabolic activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance. 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 article did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used. Therefore, test item is considered to be non-mutagenic in this Salmonella typhimurium and Escherichia coli reverse mutation assay.

 

An in vitro mammalian chromosome aberration test was performed with the structural analogue substance CAS#16470-24-9 in V79 cells of the Chinese hamster according to OECD Guideline 473 and GLP. Duplicate cultures of V79 cells were evaluated for chromosome aberrations in the presence and absence of metabolic activation (rat liver S9-mix). In the first experiment in the absence of S9 mix the test article did not increase the frequency of cells with aberrations at any fixation interval. At fixation interval 7 h, in one test group (1.0 mg/mL) the statistical analysis revealed a significant result. This effect was due to the randomly extremely low control rate. As the aberration rate of the test group is near to the control range of this study and within our historical control data the statistical result is not regarded as biologically relevant. In the presence of S9 mix, at fixation interval 7 h the aberration rate was distinctly increased after treatment with 5.0 mg/mL as compared to the corresponding solvent control. This result could not be confirmed. In addition, the metaphase quality was relatively poor so that an accurate scoring was partially inhibited. Similar observations were made on the slides treated with lower dose levels on which not enough scorable cells could be found. A second experiment was performed to clarify the effects observed in the first experiment. In this experiment II, there was no incidence of an increased aberration rate after treatment with 5.0 mg/mL. On both slides enough scorable cells with good spreading quality could be scored. Therefore, the finding observed in experiment I is not regarded as biologically relevant. At fixation intervals 18 and 28 the aberration rates were not biologically relevantly increased as compared to the solvent controls. In the occurrence of polyploid metaphases evaluation no relevant deviation from the control data was found after treatment with the test article. In conclusion, it can be stated that in the described study and under the experimental conditions reported, the test article did not induce structural chromosome aberrations in the V79 Chinese hamster cell line.

 

A mammalian mutagenicity test according to OECD 476 (HPRT) was performed on CAS 68971-49-3, the analogous dihydroxyethyl hexasulphonated sodium salt. For the experiments test in V79 hamster fibroblasts substance concentrations of 0.15, 0.5, 1.5 and 5 mg/mL were used. Experiments were performed with and without metabolic activation using the supernatant of rat liver and a mixture of cofactors. A preliminary cytotoxicity test (3-hour treatment) was performed at first. The test substance was assayed at a maximum concentration of 5 mg/mL. Nearly no toxicity occurred in any concentration. In the first experiment (3 hour treatment) with the test substance each of the four concentrations was tested in replicate. Increased numbers of mutants were observed in some concentrations without dose response dependence. No such increase was observed in experiments with metabolic activation. The same concentrations were used in a second experiment with a treatment time of 24 hours. The second experiment gives no evidence of the mutagenicity of test substance. Therefore, the test substance is non-mutagenic for V79 cells with or without metabolic activation.


Justification for selection of genetic toxicity endpoint
Hazard assessment is conducted by means of read-across based on an analogue approach. No study was selected since all available in vitro genetic toxicity studies were negative. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Short description of key information:
Negative results in several Salmonella typhimurium strains , with and without metabolic activation (OECD 471, GLP, analogue approach).
Negative results in mammalian chromosomal aberration test (OECD 473, GLP, analogue approach).
Negative results in mammalian cell gene mutation tests (OECD 476, GLP, analogue approach).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on read-across from structurally similar substances, the available data on genetic toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.