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Additional information

There are four valid in-vitro tests available for the assessment of genetic toxicity potential of tripropenyl succinic anhydride .

In a mammalian cell gene mutation study, the registered substance was tested for its genetic toxicity at the mouse lymphoma thymidine kinase locus using the cell line L5178Y. The experiments were performed with and without metabolic activation. No precipitation of the test item was noted. Growth inhibition was observed with and without metabolic activation. No biologically relevant increase of the mutant frequency was observed. No dose-response relationship was observed. The colony sizing in the experiments also showed no clastogenic effects under the test conditions.

In a mammalian chromosome aberration test, the genetic toxicity potential was investigated using Chinese hamster V79 cells. Precipitation of the test item was observed at concentrations of 3 mM and above. In experiments with metabolic activation, less toxicity of the test item was found compared to the ones without metabolic activation. No biologically relevant increase of the aberration rates was noted with and without metabolic activation. The aberration rates of all dose groups evaluated were within the historical control data of the negative control. No biologically relevant increase in the frequencies of polyploid cels was found with and without metabolic activation compare to the controls.

In a mammalian cell gene mutation study, the genetic toxicity potential was investigated at the HPRT locus using CHO cells. The experiments were performed up to the concentration of 0.5 mg/mL with and without metabolic activation. At 0.5 mg/ml or higher precipitations were found. No increase of the mutation was found compared to vehicle control.

The genetic toxicity potential of tripropenyl succinic anhydride was investigated in a reverse gene mutation assay in bacteria. Strains TA98, TA100, TA1535, TA1537 and TA102 of S. typhimurium were exposed to the test item in the presence and absence of mammalian metabolic activation. The substance was tested up to the limit concentration of 5000 µg/plate or up to cytotoxic concentrations in the tester strains used. The positive controls induced the appropriate responses in the corresponding strains.There was no evidence of induced mutant colonies over background. It can be concluded that the test item did not cause gene mutations by base pair changes or frameshifts in the genome of the tester strains used. Therefore, Tripropenyl succinic anhydride is considered to be non-mutagenic in this bacterial reverse mutation assay.

Overall, it can be concluded from the data available that no mutagenicity and genotoxicity are caused by tripropenyl succinic anhydride and therefore classification for this end point is not warranted.

Further there is one more in-vitro genotoxicity test that is considered as not applicable for the genotoxicity assessment of the registration substance.

In a mammalian cell gene mutation study, the genetic toxicity potential was investigated at the HPRT locus using V79 cells of the Chinese Hamster. The experiments were performed with and without metabolic activation.The mutagenic potential of the test substance was assesses as “equivocal” without metabolic activation and as “not mutagenic” with metabolic activation.The study is of limited value for toxicological evaluation.The observed fluctuation of the mutation rates, despite of the continuously changing cytotoxicity, makes it difficult to accept that the results are related to the inherent property of the test substance.

So far following properties are known about the test substance:

-         The test substance may undergo spontaneous hydrolysis resulting into formation of acids (Half-life in the range 1 -2 hours). The pH value in the medium at the beginning of the cell treatment is not applicable for the cell-treatment condition of up to 20 hours incubation.

-         The test substance was not clastogenic in the chromosome aberration test, not mutagenic in Ames test, not mutagenic in Mouse Lymphoma Assay and not mutagenic in recently performed HPRT test (BIO-GT, 2016)

Therefore, the study is not relevant for the mutagenic assessment of the test substance.



Short description of key information:
In vitro studies:
Mammalian cell gene mutation test (TK locus; OECD 476): negative;
Chromosome aberration test (OECD 473): negative;
Mammalian cell gene mutation test (HPRT locus, OECD 476): negative;
Ames test (OECD 471): negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data, tripropenyl succinic anhydride is considered to be not genotoxic and therefore classification for this end point is not warranted according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).