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Key value for chemical safety assessment

Additional information

The results of the Salmonella-Escherichia coli/mammalian-microsome reverse mutation assay indicate that the test article did not cause a positive increase in the number of revertants per plate of any of the tester strains with or without metabolic activation (tested up to limit concentration (with S9-mix) or cytotoxic levels(without S9-mix))

5-(Sodiosulfo)isophthalic Acid was tested in he mouse lymphoma L5178Y test systemup to concentrations of 2682 μg/ml (~ 0.01 M) in the absence and presence of S9-mix. The incubation time was 3 hours. 5-(Sodiosulfo)isophthalic Acid was tested up to cytotoxic levels of 61 and 57% in the absence and presence of S9-mix, respectively.5-(Sodiosulfo)isophthalic Acid did not induce a significant increase in the mutation frequency in the absence and presence of S9-mix after 3 hours treatment.

In an in vitro micronucleus assay, 5-(Sodiosulfo)isophthalic Acid was tested up to 2400 and 2682 (0.01 M) μg/ml for a 3 hours exposure time with a 27 hours harvest time in the absence and presence of S9-fraction, respectively. Appropriate toxicity was reached at this dose level. At the 3 hours exposure time both in the absence and presence of S9-mix, 5-(Sodiosulfo)isophthalic Acid induced a statistically significant increase in the number of binucleated cells with micronuclei. In addition, in the presence of S9-mix, in one of the duplicate cultures, the number of mononucleated cells with micronuclei was also statistically significant increased. These results indicate that 5-(Sodiosulfo)isophthalic Acid is positive in the in vitro micronucleus study and might be considered an aneugenic or clastogenic compound.

As a follow-up for the positive in vitro data, a bone marrow micronucleus assay was performed according to OECD/ EC guidelines and GLP principles. 5-(Sodiosulfo)isophthalic Acid was injected at 250, 125 and 62.5 mg/ kg bw at t=0 and t=42 hours in male mice. Bone marrow was sampled 48 hours after the first dosing. No biological relevant increase in the mean frequency of micronucleated polychromatic erythrocytes was observed in the bone marrow of animals treated with 5-(Sodiosulfo)isophthalic Acid compared to the vehicle treated animals. At 250 mg/kg bw 5-(Sodiosulfo)isophthalic Acid, a slight decrease in the ratio of polychromatic to normochromatic erythrocytes was observed indicating a toxic effect on erythropoiesis at 250 mg/kg. Positive and negative controls were valid, formulation analysis showed accurate exposure. Based on these results, it is concluded that 5-(Sodiosulfo)isophthalic Acid is not clastogenic or aneugenic in vivo.

Taken together, it is concluded that there are no indications that 5-(Sodiosulfo)isophthalic Acid has genotoxic properties.

Justification for selection of genetic toxicity endpoint
No single study selected, conclusion based on weight-of-evidence.

Short description of key information:
Three in vitro studies are present: a reverse mutation test using bacteria performed according to EU method B.13/14, an in vitro micronucleus test performed according to OECD 487, and a mammalian cell gene mutation test performed according to OECD 476 (all Klimisch 1). Both the reverse mutation test and the cell gene mutation test were negative, the in vitro micronucleus assay had a positive result. As a follow-up of this test, an in vivo micronucleus assay was performed (OECD 474, Klimisch 1), which also gave a negative result.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data, 5-(Sodiosulfo)isophthalic Acid is not classified for genotoxicity according to CLP Regulation (EC) No. 1272/2008.