Sodium dimethyl 5-sulphonatoisophthalate

Endpoint summary

Additional information

In vitro bacterial reverse mutation assay (Ames test)

 

Sodium dimethyl 5 -sulphonatoisophthalate (SIM-Ester) was tested in the Samonella typhimurium reverse mutation assay (BioReliance, 2004, OECD 471, GLP compliance) in Salmonella typhimurium (TA 1535, TA 1537, TA 98 and TA 100) and Escherichia coli (WP2 uvr A) in the absence and presence of Arochlor-induced rat liver S9. The plate incorporation method was used. Concurrent positive and solvent (water) controls were included. They revealed the expected results, indicating the suitability and sensitivity of the test system. All test concentrations were plated in triplicate. In the initial experiment, performed as toxicity-mutation test, the dose levels tested were 2.5, 7.5, 25, 75, 200, 600, 1800 and 5000 µg per plate. Since neither precipitate nor appreciable toxicity was observed 75, 200, 600, 1800 and 5000 µg/plate were tested in the confirmatory experiment. Again, neither precipitate nor toxicity was seen. In both experiments no positive mutagenic response was observed. The results of the Bacterial Reverse Mutation Assay indicate that, under the conditions of this study, the test item did not cause a positive mutagenic response in either the presence or absence of Aroclor-induced rat liver S9.

 

In vitro mammalian chromosome aberration test

 

In a chromosome aberration assay (Toxi-Coop Zrt (f), 2012, OECD 473, GLP compliance) Sodium dimethyl 5-sulphonatoisophthalate (SIM-Ester) was tested in concentrations of 625, 1250, 2500 and 5000 µg/mL in Chinese Hamster V79 cells. In the two independent experiments of the Chromosome Aberration Assay (Experiment A and B, both run in duplicate) at least 200 well-spread metaphase cells were analysed. Experiment A was performed with a 3/20 hour treatment/sampling time in the absence and presence of an induced rat liver S9 mix. Experiment B was run with a 20/20 hour and 20/28 hour treatment/sampling time in the absence of S9 and with a 3/28 hour treatment/sampling time in the presence of S9. In Experiments A and B, there were no biologically and/or statistically significant increases in the number of cells showing structural chromosome aberrations, either in the absence or in the presence of metabolic activation, as compared with concurrent solvent controls. No dose-response relationships were noted. The observed chromosome aberration rates were within the ranges of the historical control data. There were no biologically relevant increases in the rate of polyploid or endoreduplicated metaphases in either experiment in the presence or absence of metabolic activation. There was no precipitation of the test item at any dose level tested. No biologically relevant changes in pH or osmolality of the test system were noted at the dose levels tested. Cytotoxicity was observed in Experiment B at concentrations of 1250 μg/mL, 2500 μg/mL and 5000 μg/mL. Experiment A indicated no cytotoxicity. The validity of the test was shown using Ethyl methanesulphonate (0.4 or 1.0 μL/mL) and Cyclophosphamide (5.0 μg/mL) as concurrent positive controls, which induced biologically and statistically significant increases in the number of cells with chromosome aberration(s) over background. In conclusion, SIM Ester tested up to the maximum recommended concentration of 5000 μg/mL, both with and without mammalian metabolic activation system, did not induce structural chromosome aberrations in Chinese Hamster lung cells, and is thus considered as not clastogenic in this system.

 

In vitro mammalian cell gene mutation test

 

In a mammalian gene mutation test (Toxi-Coop Zrt. (g), 2012, OECD 476, GLP compliance) Sodium dimethyl 5-sulphonatoisophthalate (SIM-Ester) was dissolved in Ham's F12 medium in concentrations of 312.5, 625, 1250, 2500 and 5000 µg/mL. Two independent experiments (both run in duplicate) were performed. In Experiment 1, where the treatment period lasted for 5 hours, there were no biologically or statistically significant increases in mutation frequency at any concentration tested compared to the concurrent control, either in the absence or in the presence of metabolic activation.

In Experiment 2, the mutant frequency of the cells did not show biologically or statistically significant alterations compared to the concurrent control, when the test item was tested without S9 mix over a prolonged treatment period (20 hours) as well as in the presence of S9 mix over a five-hour treatment period.

The concurrent solvent and positive controls revealed the expected results, indicating the reliability and sensitivity of the test system.

In conclusion, SIM-Ester tested both without and with metabolic activation (S9 mix), did not induce increases in mutant frequency over the background (negative solvent control) in this in vitro test in Chinese Hamster ovary cells. Thus, SIM-Ester was not mutagenic under the conditions of this study.

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

Short description of key information:
Sodium dimethyl 5-sulphonatoisophthalate did not cause a positive mutagenic response in the Samonella typhimurium reverse mutation assay, did not induce structural chromosome aberrations in Chinese Hamster lung cells and was not mutagenic in the HPRT assay.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the results obtained in the in vitro genotoxicity tests, Sodium dimethyl 5-sulphonatoisophthalate

is considered to be non-genotoxic/mutagenic according to Directive 67/548/EEC and according to Regulation (EC) No 1272/2008.