N-(3-aminopropyl)-N- (C12-18 even numbered) alkyl-propane-1,3-diamine

Endpoint summary

Additional information

Cocodipropylenetriamine was tested in the Salmonella typhimurium reverse mutation assay with four histidine-requiring strains of Salmonella typhimurium (TA1535, TA1537, TA98 and TA100) and in the Escherichia coli reverse mutation assay with a tryptophan-requiring strain of Escherichia coli (WP2uvrA). The test was performed in two independent experiments in the presence and absence of S9-mix (rat liver S9-mix induced by a combination of Phenobarbital and ß-naphthoflavone). The study followed the most recent OECD and EU protocols and was performed under GLP.

There was no significant or dose-related increase in the number of revertant colonies in any of the applied strains, both with and without S9-mix. This was confirmed in an independently repeated experiment.

It is concluded that Cocodipropylenetriamine is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.

 

Cocdipropylenetriamine was studied for its effect on the number of chromosome aberrations in cultured peripheral human lymphocytes in the presence and absence of a metabolic activation system (phenobarbital and ß-naphthoflavone induced rat liver S9-mix), in two independent experiments. The study was performed under GLP and according to the most recent OECD and EU guidelines.

Cocodipropylenetriamine did not induce a statistically significant or biologically relevant increase in the number of cells with chromosome aberrations in the absence and presence of S9-mix, in either of the two independently repeated experiments.

It was noted that Coco dipropylene triamine increased the number of polyploid cells both in the absence and presence of S9-mix in the first cytogenetic assay and in the presence of S9-mix in the second cytogenetic assay. Polyploidy alone does not indicate aneugenic potential and can simply indicate cell cycle perturbation; it is also commonly associated with increasing cytotoxicity.

There were no effects of Cocodipropylenetriamine on the number of cells with endoreduplicated chromosomes both in the absence and presence of S9-mix, in either of the two independently repeated experiments. Therefore, it is concluded that Cocodipropylenetriamine is not clastogenic in human lymphocytes.

 

Cocodipropylenetriamine was evaluated for its possible induction of forward mutations at the thymidine-kinase locus (TK-locus) in L5178Y mouse lymphoma cells. The test was performed in two independent experiments in the absence and presence of S9-mix. The study was performed under GLP and according to the most recent OECD and EU guidelines.

In both the presence and absence of S9-mix, Cocodipropylenetriamine did not induce a significant increase in the mutation frequency in the first experiments. This result was confirmed in a repeat experiment with modifications in the duration of treatment time (without S9-mix) or S9 concentration (with S9-mix). Therefore, Cocodipropylenetriamine is not mutagenic in the TK mutation test.

 

Additionally, polyamines do not react with DNA or react to protein (indicated by OECD Toolbox profiling).

Justification for selection of genetic toxicity endpoint
For each in vitro endpoint, bacterial mutagenicity, mammalian mutagenicity and mammalian clastogenicity, a GLP compliant study is available.

Short description of key information:
Cocodipropylenetriamine was not mutagenic in a bacterial mutagenicity study (Ames test), induced no chromosomal aberrations in a study in human lymphocytes, and was not mutagenic in a mammalian mutagenicity study in mouse lymphoma cells. All studies were performed under GLP according to current guidelines.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the results of the in vitro genetic toxicity studies, the substance does not need to be classified for genotoxicity according to EU CLP Regulation (EC) No. 1272/2008.