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Key value for chemical safety assessment

Additional information

Mutagenicity:

11 -aminoundecanoic acid has been extensively tested for genotoxicity, both in vitro and in vivo.

In vitro studies:

Eight in vitro assays are reported for this endpoint. Among them, the publication Hatch et al. (1986) was considered unreliable because the test system used was unsuitable. 11 -aminoundecanoic acid did not show a genotoxic potential in reverse gene mutation assays in Salmonella typhimurium and Escherichia coli (Mortelmas et al., 1986; Weill, 1982, Toray, 1982), in a chromosome aberration test on CHO cells (Galloway et al., 1987) and in a gene mutations test on L5178 Y tk+/tk- cells (Mc Gregor et al., 1988). A slight increase in Sister Chromatid Exchanges (SCE) in CHO cells has been observed in the absence of metabolic activation (Galloway et al., 1987).

In vivo studies:

Four in vivo assays are reported for this endpoint. The publication of Shelby at al. (1993), describing results from a mouse bone marrow micronucleus assay, was chosen as key study. In that study, 11 -aminoundecanoic acid, administered intraperitoneally, induced negative results up to 500 mg/kg. In Yoon et al. (1985), the results from mutagenicity tests in Drosophila melanogaster using the sex-linked recessive lethal (SLRL) assay showed that 11 -aminoundecanoic acid was not mutagenic in this test system. In Mirsalis at al. (1989), an in vivo-in vitro hepatocyte DNA repair was performed. Results showed that 11 -aminoundecanoic acid did not induce UDS in rats hepatocytes following in vivo treatment. Yoon et al. (1985) and Mirsalis et al. (1989) were both selected as supporting study. In a DNA-binding study with labelled 11 -aminoundecanoic acid using male and female F-344 rats, liver, kidneys and urinary bladder have been examined both for association of radioactivity with DNA and for DNA alkylation (i.e., formation of altered radioactive nucleosides in DNA) (Bolt, 1987). There was minor incorporation of 11 -aminoundecanoic acid derived radioactivity into the physiological DNA nucleosides (in the liver higher than in kidneys, in males higher than in females). This could not be observed in DNA from the urinary bladder, but from this organ only low amounts of DNA were isolated due to the limited mass of tissue available. Upon chromatography (HPLC) of hydrolysates from DNA (isolated from livers and kidneys) no significant radioactive peaks were observed besides those of the physiological nucleosides; therefore, there was no indication of DNA alkylation by 11 -aminoundecanoic acid or a metabolite thereof, there was no indication of DNA alkylation by 11 -aminoundecanoic acid or a metabolite thereof. On this basis, this DNA-binding study was considered as being negative.

Conclusion:

All together in vitro and in vivo results provided evidence that 11 -aminoundecanoic acid has no potential mutagenic. The slight increase in SCE observed in vitro is overridden by the negative in vivo assays. Moreover, no DNA binding was observed in the target organs identified in the repeat-dose toxicity and carcinogenicity studies in rats. In conclusion, with few exceptions, as a large battery of additional in vitro and in vivo non-guideline studies confirmed the lack of genotoxic potential.


Short description of key information:
- in vitro Gene mutation (Bacterial reverse mutation assay/Ames test):
S. typhimurium TA 1535, TA 1537, TA 1538, TA 98, TA 100, up to 10 mg/plate: negative with and without metabolic activation (similar to OECD TG 471)
- in vitro Gene mutation (mammalian cell gene mutation assay):
L5178Y Mouse Lymphoma cells, up to 320 µg/ml: negative with and without metabolic activation (similar to OECD TG 476)
- in vitro DNA primary lesion (Sister Chromatid Exchange):
CHO cells, up to 1 mg/ml: negative with metabolic activation and slight increase without metabolic activation (similar to OECD TG 479)
- in vitro chromosome aberrations:
CHO cells, up to 1mg/ml: negative with and without metabolic activation (similar to OECD TG 473)
- in vivo mouse bone marrow micronucleus assay:
up to 500 mg/kg: negative (similar to OECD TG 474)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

No classification for mutagenicity has to be applied for 11 -aminoundecanoic acid according to EU Directive 67/584/EEC and EU regulation (EC) No 1272/2008 (CLP).