Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

The test item l-Glutamic acid, N-coco acyl derivs., monosodium salts (CAS No. 68187-32-6) was tested for mutagenicity with the strains TA 100, TA 1535, TA 1537 and TA 98 of Salmonella typhimurium according to OECD Guideline 471. The mutagenicity studies were conducted in the absence and in the presence of a metabolizing system derived from rat liver homogenate. A dose range of 6 different doses from 4 microgram/plate to 5000 microgram/plate was used. Control plates without mutagen showed that the number of spontaneous revertant colonies was similiar to that described in the literature. All the positive control compounds gave the expected increase in the number of revertant colonies. Toxicity: The test compound proved to be toxic to the dilution of the bacterial strain TA 100 in the absence of a metabolizing system at the dose of 5000 microgram/plate only in the cytotoxic experiment. 5000 microgram/plate was chosen as top dose level for the mutagenicity study. Mutagenicity: In the absence of the metabolic activation system the test compound did not show a dose dependent increase in the number of revertants in any of the bacterial strains. Also in the presence of a metabolic activation system, treatment of the cells with the test item did not result in relevant increases in the number of revertant colonies. Summarizing, it can be stated that the test item is not mutagenic in these bacterial test systems neither with nor without exogenous metabolic activation at the dose levels investigated.

L-Glutamic acid, N-coco acylderivs., disodium salts (CAS 68187-30 -4) was assessed for its potential to induce gene mutations at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in Chinese hamster ovary (CHO) cells in vitro following OECD guideline 476 (glp conform). Three independent experiments were carried out, with and without the addition of liver S9 mix from phenobarbital- and β- naphthoflavone induced rats (exogenous metabolic activation). In an initial range-finding cytotoxicity test(s) the experimental doses of the main experiments were determined. The vehicle controls gave mutant frequencies within the range expected for the CHO cell line. Both positive control substances, EMS and DMBA, led to the expected increase in the frequencies of forward mutations. In this study, in the 1st Experiment in the absence and presence of metabolic activation and in the 2nd Experiment in the presence of metabolic activation the highest concentrations tested for gene mutations were clearly cytotoxic. However, in the 2nd Experiment in the absence of metabolic activation no cytotoxicity was observed up to the highest applied concentration. Therefore, a 3rd Experiment was performed which showed clearly reduced colony numbers at least at the highest concentrations. Based on the results of the present study, the test substance did not cause any relevant increase in the mutant frequencies either without S9 mix or after the addition of a metabolizing system in three independent experiments. Thus, under the experimental conditions of this study, the test substance L-Glutamic acid, N-coco acyl derivs., disodium salts is not mutagenic in the HPRT locus assay under in vitro conditions in CHO cells in the absence and presence of metabolic activation.

The L-Glutamic acid, N-cocoacyl glutaminic acid, sodium salts (CAS 68187 -30 -4) was also investigated for clastogenic activity or for the induction of chromosome aberrations accoring to OECD guideline 487 under GLP conditions. Two indpendant experiments were performed. Cytotoxicity indicated by clearly reduced proliferation index, cell numbers or low quality of the slides was observed in the absence of S9 mix at 700 µg/mL (1st Experiment) and at 800 µg/mL (2nd and 3rd Experiment). In the presence of S9 mix cytotoxic effects were obtained from 800 µg/mL onward only in the 2nd Experiment. In the 1st Experiment a single statistically significant increase in the number of micronucleated cells was observed at 700 µg/mL after 4 hours exposure in the absence of metabolic activation. However, this finding was neither confirmed in the repeat experiment under similar conditions (3rd Experiment) nor in any additional experimental part under modified test conditions (24 hours exposure in the absence of metabolic activation or 4 hours exposure in the presence of metabolic activation). The finding has to be considered as artifactual due to strong cytotoxicity in this test group (RICC 41.4%). Thus, under the experimental conditions described, the test substance is considered not to be a chromosome-damaging (clastogenic) substance or to induce numerical chromosomal aberrations (aneugenic activity) under in vitro conditions in V79 cells.

The studies were conducted with structurally similar substances, namely l-Glutamic acid, N-coco acyl derivs., monosodium salts(CAS No. 68187-32-6) and L-Glutamic acid, N-coco acylderivs., disodium salts (CAS 68187-30 -4). Solubility, bioavailability and toxicity of the surrogates are not expected to differ from the registered substance as the target substance is the major component, and the central member of an homologous series of components, of the source substances, possessing identical functional groups and extremely similar structures. It is reasonable to expect that the toxicological properties of the target and source substances will not be markedly different. On this basis, experimental data on the source substances are expected to be directly applicable to the target substance, and can be used to adequately predict its properties. Further details are provided in the filed "attached document"

Justification for selection of genetic toxicity endpoint

None of the genotoxicity tests revealed a positive result.

Short description of key information:

It can be concluded that the test substance  l-Glutamic acid, N-coco acyl derivs., monosodium salts (CAS No. 68187-32-6) is not mutagenic to the strains TA 100, TA 1535, TA 1537 and TA 98 of Salmonella typhimurium neither in the absence nor in the presence of an exogenous metabolizing system. The substance N-cocoacyl glutaminic acid, sodium salts (CAS 68187 -30 -4) tested in CHO cells where no mutagenic activity was detected in the HPRT locus with and without metabolic activation in vitro. The test material N-cocoacyl glutaminic acid, sodium salts (CAS 68187 -30 -4) also exhibited no clastogenic or aneugenic activity in an in vitro micronucleus test in V79 cells in the absence or presence of metabolic activation.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

No classification and labelling is required according to Regulation No (EC) 1272/2008 (CLP) or Directive 67/548/EEC (DSD) criteria.