Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Bacterial mutagenicity

No data were available for the registered substance, but read across data were available from category members:

- A key study for acute bacterial reverse mutation was available with test item CAS No. 90268-36-3 (Butanedioic acid, sulfo-, 1-C12-18-alkyl esters, disodium salts) containing > 95% active ingredient in 5 Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 in two independent experiments, each carried out without and with metabolic activation (Flügge, 2013c). The first experiment was carried out as a plate incorporation test and the second as a preincubation test. The test item was completely dissolved in aqua ad iniectabilia. A correction factor of 1.05 was used to correct for the purity of the test item. In a preliminary cytotoxicity test without metabolic activation in test strain TA 100 employing a plate incorporation test, ten concentrations of 0.316 up to 5000 µg test item/plate were tested. Cytotoxicity was noted at concentrations of 316 µg/plate and higher. Hence, 316 µg test item/plate were chosen as top concentration for the main study in the plate incorporation test and in the preincubation test. Six concentrations of 1.0, 3.16, 10.0, 31.6, 100 and 316 µg test item/plate were employed in the plate incorporation test and in the preincubation test, each carried out without and with metabolic activation. No increase in revertant colony numbers as compared with control counts was observed for test item, tested up to a cytotoxic concentration of 316 µg/plate, in any of the 5 test strains in two independent experiments without and with metabolic activation, respectively (plate incorporation and preincubation test). Under the present test conditions the test item tested up to a cytotoxic concentration of 316 µg/plate, caused no mutagenic effect in the Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 neither in the plate incorporation test nor in the preincubation test each carried out without and with metabolic activation.

- A support study was available for category member CAS No. 37294-49-8 (Disodium C-isodecyl sulphonatosuccinate) containing 37% active ingredient tested in Salmonella typhimurium strains TA98, TAl 00, TA1535 and TA1537 at concentrations of 5000, 3330, 1000, 333, 100, 33.3, 10.0, 3.33, and 1.00 µg per plate both in the presence and absence of S9 mix (Mecchi, 2005a). The results of the Reverse Mutation Screening Assay indicate that under the conditions of this study, the test item did not cause a positive increase in the number of revertants per plate with any of the tester strains in either the presence or absence of S9 mix.

In conclusion, negative results were obtained for mammalian mutagenicity in a key study with read across substance CAS No. 90268-36-3 tested in V79 cells with genetic marker HPRT.

 

Mammalian mutagenicity

No data were available for the registered substance, but read across data were available from category member CAS No. 90268-36-3 (Butanedioic acid, sulfo-, 1-C12-18-alkyl esters, disodium salts), for which a key study was conducted with test item containing >=95% active ingredient in cultured mammalian cells (V79, genetic marker HPRT) both in the presence (4 hours) and absence (4 and 24 hours) of metabolic activation (Flügge, 2013d). Cytotoxicity in form of decreased plating efficiency was noted starting at concentrations of 39.06 or 156.3 µg test item/mL without and with metabolic activation (24-h or 4-h exposure), respectively. Hence, concentrations of 2.44, 4.88, 9.77, 19.53 or 39.06 and 9.77, 19.53, 39.06, 78.13 or 156.3 µg test item/mL were selected for the main experiments without and with metabolic activation, respectively. In the main study cytotoxicity in form of decreased plating efficiency (PE1) and (PE2) was noted in the first and second experiments at the top concentrations 39.06 or 156.3 µg/mL in the absence and presence of metabolic activation, respectively. Both in the experiments with and without metabolic activation, the mutation frequencies of treated cell cultures within the normal range of the vehicle controls. The positive controls caused a pronounced increase in the mutation frequencies, indicating the validity of this test system. Under the present test conditions, the test item tested up to cytotoxic concentrations in the experiments without and with metabolic activation, was negative in the HPRT-V79 mammalian cell mutagenicity test under conditions where positive controls exerted potent mutagenic effects.

In conclusion, negative results were obtained for mammalian mutagenicity in a key study with the read across substance CAS No. 90268-36-3 tested in V79 cells with genetic marker HPRT.

 

Chromosome aberration

No data were available for the registered substance, but read across data were available from category member CAS No. 90268-36-3 ( Butanedioic acid, sulfo-, 1-C12-18-alkyl esters, disodium salts), for which a key study was conducted with test item containing >=95% active ingredient in an in vitro micronucleus test using human peripheral lymphocytes both in the presence and absence of metabolic activation by a rat liver post-mitochondrial fraction (key study; Flügge, 2013e). The test was carried out employing 2 exposure times without S9 mix: 4 and 20 hours, and 1 exposure time with S9 mix: 4 hours. The test item was completely dissolved in aqua ad iniectabilia. A correction factor of 1.05 was used to correct for the purity of the test item. Aqua ad iniectabilia served as the vehicle control. In the preliminary experiment , cytotoxicity was noted starting at a concentration of 156.3 µg test item/mL. Hence, 156.3 µg/mL were employed as the top concentration for the mutagenicity tests without and with metabolic activation. In the main study cytotoxicity was noted at the top concentration of 156.3 µg/mL in the experiments without and with metabolic activation. Both in the experiments with and without metabolic activation, the mutation frequencies of treated cell cultures were within the normal range of the vehicle controls. In the same test, Mitomycin C and cyclophosphamide induced significant chromosomal damage and colchicine induced significant damage to the cell division apparatus, respectively. Under the present test conditions, the test item tested up to a cytotoxic concentration of 156.3 µg/mL medium, in the absence and in the presence of metabolic activation employing two exposure times (without S9) and one exposure time (with S9) revealed no indications of chromosomal damage in the in vitro micronucleus test.

In conclusion,negative results were obtained for chromosome aberration in a key study with read across substance CAS No. 90268-36-3 tested in an in vitro Micronucleus test in human peripheral lymphocytes.

 

Conclusion

Standard information requirements according to REACH Guidance Part 3 R7a were fulfilled for genotoxicity testing, including bacterial and mammalian mutagenicity and chromosomal aberration. Based on the available results, there were no indications of mutagenicity or genotoxicity, and no further testing is needed. The substance can be considered to have no mutagenic or genotoxic potential.


Justification for selection of genetic toxicity endpoint
Although the bacterial gene mutation study was selected, the mammalian gene mutation and chromosomal aberration tests are equivalent endpoints.

Short description of key information:
No data were available for registered substance, but key read across data from CAS No. 90268-36-3 (Butanedioic acid, sulfo-, 1-C12-18-alkyl esters, disodium salts) were available for bacterial and mammalian mutagenicity and chromosomal aberration. In a key Ames test no increase in mutations were observed in different Salmonella typhimurium strains with and without metabolic activation up to cytotoxic concentrations of 316 µg/plate.In a key mammalian gene mutation test in HPRT cells, the test item did not induce mutations up to cytotoxic concentrations of 39.06 or 156.3 µg test item/mL in the absence and presence of metabolic activation, respectively. In a key in vitro Micronucleus study in human peripheral lymphocytes, the test item did not induce chromosomal damage up to a cytotoxic concentration of 156.3 µg/mL in the absence and in the presence of metabolic activation employing two exposure times.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

As there was no indication for genotoxic potential, classification for genotoxicity is not warranted according to the EC Directive (No.93/21/EEC) and CLP (No. 1272/2008 of 16 December 2008).