Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate

Endpoint summary

Additional information

Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6,will betested for genetic toxicity in three in vitro tests. Both the two available tests showed no biological relevant evidence on genetic toxicity. This is also supported by the preliminary results from the third test which is being finalized at this moment.

The bacterial reverse mutation assay (Ames test), reliability rating 1, showed that the substance did not cause any substantial increase in revertant colony numbers of any of the five tested strains at any dose level, either in the presence or absence of metabolic activation (S-9 mix). No evidence of mutagenic potential was seen in this study.

 

In the in vitro test on micronucleus assay in human lymphocytes, reliability rating 1,Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6,was not clastogenic or aneugenic, in presence of metabolic activation by S9 mix or after long time exposure without metabolica activation by S9 mix.The increased incidence of formation of micronuclei in one of the middle doses after the shortest exposure time of 3 hours without S9 metabolic activation is not considered to have any biological relevance since the lower and higher doses were negative. It is therefore not considered to be required from a legal, scientific or animal welfare point of view to perform anyin vivomicronucleus test.

The third genetic toxicity study, the mouse lymphoma assay, is being finalized at the moment. This study is performed according to OECD Guideline 476 and GLP. The preliminary results indicates thatSodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6,do not induce mutations in the mouse lymphoma thymidine kinase locus (TK+/-), but the dossier will be updated as soon as the test report is available.

Based on the available data, it can be concluded that Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6, would not be expected to have any genotoxic hazard to human health.

Justification for selection of genetic toxicity endpoint

No specific study has been selected as the conclusion that the substance is not genotoxic/mutagenic is based on the two negative studies available, the Ames test and the in vitro micronucleus assay in human lymphocytes, and the preliminary results from the in vitro Mouse Lymphoma study which is being finalized at this moment.

Short description of key information:

Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6, has been tested in three in-vitro genotoxicty studies.

The first study available on Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6, is the bacterial reverse mutation assay (Ames test) compliant to OECD Guideline 471 and performed under GLP. The reliability rating of the test is 1 and no evidence of mutagenic potential was reported in this study.

The second available study on genetic toxicity is the in vitro micronucleus assay in human lymphocytes, (OECD Guideline 487), which is GLP compliant and has reliability rating 1. No biological relevant evidence of clastogenic or aneugenic effects was seen in this study.

No indications on clastogenic or aneugenic effects were seen in the presence of S9-mix up to the highest tested concentration of 5000 μg/ml, or in absence of S9-mix after prolonged exposure period up to a dose level of 2000 μg/ml. After the shortest duration of exposure, 3 hours, and in absence of S9 mix one of the middle dose groups showed significantly increased number of micronulclei in human lymphocytes. The concentrations below and above, up to 5000 µg/ml did not show any increased number of micronucleated cells. The biological relevance of this increase is questionable and the overall test result is considered to be negative.

The third genetic toxicity study on Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6, is the mouse lymphoma assay according to OECD Guideline 476. This study is performed under GLP and is being finalized right now. The preliminary results from this study show that Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-ß-alaninate is not mutagenic in the mouse lymphoma L5178Y test system with or without S9 mix. This was tested in concentrations up to 5000 µg/ml, or to a cytotoxicity level of 81%. The dossier will be updated as soon as the test report is available.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the lack of biological relevant findings in the two available in-vitro tests for genotoxicity, Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6, does not require classification as a mutagen according to Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008.