N-(carboxymethyl)-3-[(2Z)-docos-2-enoylamino]-N,N-dimethylpropan-1-aminium

Endpoint summary

Additional information

In vitro

Bacterial gene mutation:

One fully reliable study is available (Gen. tox in vitro_V1_2003_May) conducted according to OECD TG 471 and GLP (5 - 5000 µg/plate; two indipendent tests: pre-incubation and plate incorporation, both with and without liver microsomal activation). No toxic effects occurred with and without metabolic activation, except for E. coli at the highest dose. No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with DV6850 at any dose level, neither in the presence nor absence of metabolic activation (S9 mix).

Therefore, DV6850 is considered not to be mutagenic in this Salmonella typhimurium and Escherichia coli reverse mutation assay.

 

Mammalian gene mutation:

One fully reliable study is available (Gen.tox in vitro_V1_2003_Woll) conducted according to OECD TG 473 and GLP (mouse lymphoma assay, 6.25 – 5000 µg/mL, with and without liver microsomal activation 3 and 20 h of treatment).

Relevant toxic effects were observed at 90.6 µg/mL and above in the absence of metabolic activation (4 hour treatment). In the presence of metabolic activation, relevant toxic effects were observed at 362.5 µg/mL and above (4 hour treatment). The test item did not induce mutations in the thymidine kinase locus assay using the mouse lymphoma cell line L5178Y up to the highest tested concentrations.

Therefore, DV6850 is considered not to be mutagenic in this mouse lymphoma assay.

 

Mammalian chromosome aberration:

One fully reliable study is available (Gen.tox in vitro_V1_2003_Prit) conducted according to to OECD TG 473 and GLP (mouse lymphoma assay, 5.0 – 400 µg/mL, with and without liver microsomal activation, 4 and 24 h of treatment).

In both the absence and presence of S9 mix, DV6850 caused no statistically significant increase in the proportion of metaphase figures containing chromosomal aberrations, at any dose level, when compared with the solvent controls in either test after treatment with the test item up to cytotoxic concentrations (150 µg/mL, with and without activation). At this level, a statistically significant increase of polyploidy cells was observed in both tests (except for experiment 1 without activation where a trend was seen, but statistical significance was not reached). However, in this study, polyploidy was scored on a relatively low number of cells (500 per concentration), and scoring was performed in controls and high-concentration treated cells only, providing no information on concentration-response relationship. Furthermore, increases in polyploid cells were observed at a concentration inducing high levels of cytotoxicity (40 to 56% relative mitotic index), and the amplitude of the increase was inconsistent between 2 assays conducted under the same experimental conditions (with S9 mix, 3-hour exposure): 5 or 9/500 (assay 1) and 31 or 40/500 (assay 2). Therefore, the toxicological significance of these observations remained uncertain. These findings were considered irrelevant. DV6850 is considered not to be clastogenic in this in vitro mammalian chromosome aberration assay.

 

In vivo

No data available. Based on REGULATION (EC) No 1907/2006 as at July 2011 and the absence of positive results in the three above mentioned in vitro tests no additional testing for genetic toxicity in vivo is necessary.  

 

General: 

For each endpoint (bacterial gene mutation, mammalian gene mutation, & mammalian chromosome aberration) reliable, GLP compliant in vitro studies are available that all gave negative results. Only in the mammalian chromosome aberration assay signs for increased polyploidy were seen that nevertheless occurred at cytotoxic concentrations.

Therefore it can be concluded that DV6850 is neither clastogenic or aneugenic nor mutagenic.

Accordingly it can be concluded that DV6850 is not genotoxic.

Short description of key information:
- genetic toxicity in vitro: negative; 1 study positive (Sokolowski (2010) Genetic toxicity in bacteria), 1 study negative (Bohnenberger (2010) Genetic toxicity in vitro - Chromosome abberation)
- genetic toxicity in vivo: no data available

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Three in vitro genotoxicity tests are available. None of the tests showed relevant evidence of genotoxicity. The substance is therefore not regarded to have genotoxic effects and does not require classification for genetic toxicity.