Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, dioleates

Endpoint summary

Additional information

Cross-reading between from Oleyl-diamine dioleate to Tallow-diamine dioleate is acceptable on the basis of identical chemical structures. The only differences between the two substances are related to the alkyl-chains linked to the diamine. Contrary to oleyl do tallow-alkyl chains also contain some C16-chains next to the C18-alkyl chains. The toxicological relevance of this difference is expected to be negligible. The higher level of unsaturation in oleyl-alkyl chains compared to tallow-alkyl chains can be considered a worst case representation with respect to possible toxicity when compared to tallow-alkyl chains, related to a probably marginal higher solubility. Due to this very great similarity between these two substances, results obtained from Oleyl-diamine dioleate are fully applicable for the evaluation of Tallow-diamine dioleate as well.

 

Oleyl-diamine dioleate was tested in the bacterial reverse mutation test according to OECD 471 and in compliance to GLP. The test item was then tested in two independent experiments, with and without a metabolic activation system, from a liver microsomal fraction of Aroclor 1254 induced rats. Both experiments were performed according to the direct plate incorporation method except for the second test with S9-mix, which was performed according to the preincubation method (60 minutes, 37°C). Five strains ofSalmonella typhimurium,TA1535, TA1537, TA98, TA100 and TA 102 were exposed to five dose-levels of the test item in triplicate.

A moderate to marked toxicity was generally observed at dose-levels from 31.3 μg/plate to 125 µg/plate without S9 and from 125 μg/plate to 500 µg/plate in the presence of S9-mix. The number of revertants for the vehicle and positive controls was as specified in the acceptance criteria.

The test item did not induce any noteworthy increase in the number of revertants, both with and without S9 mix, in any of the five strains.

 

A second older study also evaluated Oleyl-diamine dioleate in the bacterial reverse mutation according to OECD 471. In this study the evaluation was performed onS. typhimuriumstrains TA1535, TA1537, TA1538, TA98, and TA100, in two independent experiments, with and without a S9-mix from Aroclor 1254 induced rat liver microsomes. Both experiments were performed according to the direct plate incorporation method. Each strain was exposed to five dose-levels 5000, 1500, 500, 150, and 50 µg/plate of the test item, and a solvent control, with three plates/dose-level.

Oleyl diamine, dioleate was found to be slightly toxic towards the tester strains at the highest dose level. No substantial increases in revertant colony numbers of any of the five tester strains were observed, either in the presence or absence of metabolic activation (S-9 mix).

 

Oleyl-diamine dioleate was recently assessed for its potential to induce gene mutations at the thymidine kinase (TK) locus in L5178Y mouse lymphoma cells according to OECD 476 guidelines and in compliance to GLP. The test was performed in two independent experiments in the absence and presence of S9-mix (rat liver S9-mix induced by a combination of phenobarbital and ß-naphthoflavone). Oleyl diamine, dioleate precipitated in the exposure medium at a test substance concentration of 100 μg/ml. Oleyl-diamine dioleate was tested beyond the limit of the solubility to obtain adequate cytotoxicity data.

In the first experiment, Oleyl-diamine dioleate was tested up to concentrations of 4 and 45 μg/ml for 3 hours with and without S9-mix. Oleyl diamine, dioleate was tested up to cytotoxic levels of 18 and 19% in the absence and presence of S9-mix, respectively.

In the second experiment, Oleyl-diamine dioleate was tested up to concentrations of 3.5 and 50 μg/ml, in the absence and presence of S9-mix. The incubation times were 24 hours and 3 hours for incubations in the absence and presence of S9-mix, respectively. Oleyl-diamine dioleate was tested up to cytotoxic levels of 3 and 17% in the absence and presence of S9-mix, respectively.

The positive and negative controls showed acceptable response.

In both experiments, Oleyl-diamine dioleate did not induce a significant increase in the mutation frequency with or without S9-mix.

 

Oleyl-diamine dioleate was further evaluated forpossible clastogenicity and aneugenicityin anin vitromicronucleus assay in cultured peripheral human lymphocytes (with independent repeat) in the presence and absence of a metabolic activation system. The study was performed according to OECD 487 and in compliance to GLP. The results of the positive and negative controls indicate that the conditions of the test were adequate.

Oleyl diamine, dioleate did not induce a statistically significant or biologically relevant increase in the number of mono- and binucleated cells with micronuclei in the absence and presence of S9-mix, in either of the two independently repeated experiments.

Justification for selection of genetic toxicity endpoint
For each endpoint bacterial mutagenicity, mammalian mutagenicity and mammalian clastogenicity a GLP compliant study is available by read-across from Oleyl-diamine dioleate.

Short description of key information:
For each endpoint bacterial mutagenicity, mammalian mutagenicity and mammalian clastogenicity a GLP compliant study is available from testing with Oleyl-diamine dioleate. None of the studies indicate a potential concern for genotoxicity.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

For each endpoint bacterial mutagenicity, mammalian mutagenicity and mammalian clastogenicity a GLP compliant study is available from read-across from Oleyl-diamine dioleate. None of the studies indicate a potential concern for genotoxicity.