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In vitro gene mutation study in bacteria:

Fatty acids, C18 unsaturated, reaction product with ammonia-ethanolamine reaction by-products(AAI-AEA) was tested in theSalmonella typhimuriumreverse mutation assay with five histidine-requiring strains of Salmonella typhimurium (TA1535, TA1537, TA 1538, TA98, TA100 and TA102). The test was performed in two independent experiments in the presence and absence of S9-mix (rat liver S9-mix induced with Aroclor 1254). The study followed OECD and EU protocols and was performed following GLP principles.

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.

With this test it is not possible to identify certain oxidising mutagens, cross-linking agents and hydrazines. Such substances may be detected by E.coli WP2 strains or S. typhimurium TA102 which have an AT base pair at the primary reversion site instead of GC base pairs in the strains tested in this study.

 

In vitro cytogenicity study in mammalian cells:

It was concluded that the test substance showed no clastogenic potential and was not capable of inducing chromosomal aberrations when tested using CHO cells grown in vitro in a study performed similar to OECD473.

AAI-AEA was studied for its effect on the number of chromosome aberrations in using Chinese hamster ovary (CHO) cells in vitro in the presence and absence of a metabolic activation system (rat liver S9-mix induced with Aroclor 1254) in two independent experiments in the presence or absence of S9 -mix. The study followed OECD and EU protocols and was performed following GLP principles.

Clear signs of cytotoxicity were in evidence at a dose of 50 µg/ml of test substance in both the presence and absence of S9 mix. Precipitation occurred at a concentration of 500 µg/ml.

There was no evidence of chromosomal aberration induction when cell cultures were exposed to the test substance in a concentration range of 1.6 – 100 µg/ml in either the presence or absence of S9 -mix. Concurrent positive controls demonstrated the sensitivity of the test system towards clastogenic agents and the metabolic activity of the S9 -mix. There was also no indication of aneuploidy or polyploidy induction at any of the exposure levels tested.

 

In vitro mutagenicity study in mammalian cells:

AAI-AEA 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 (rat liver S9- mix induced by a combination of phenobarbital and ß-naphthoflavone). 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, AAI-AEA 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, AAI-AEA is concluded to be not mutagenic in the TK mutation test.

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

Short description of key information:
Fatty acids, C18 unsaturated, reaction product with ammonia-ethanolamine reaction by-products (AAI-AEA) was not mutagenic in a bacterial mutagenicity study (Ames test), induced no chromosomal aberrations in a study in CHO cells, and was not mutagenic in a mammalian mutagenicity study in mouse lymphoma cells.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

For each endpoint bacterial mutagenicity, mammalian mutagenicity and mammalian clastogenicity a recent guideline and GLP compliant study is available.

Fatty acids, C18 unsaturated, reaction product with ammonia-ethanolamine reaction by-products(AAI-AEA) was not mutagenic in a bacterial mutagenicity study (Ames test), induced no chromosomal aberrations in a study in CHO cells, and was not mutagenic in a mammalian mutagenicity study in mouse lymphoma cells.

Also other AAI substances that have been tested similarly, have shown the same results.

It can therefore be concluded that AAI-DETA is not genotoxic, and therefore need not be classified.

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