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Salmonella test in vitro (AmesTest):

EDDHMA-Fe was tested for the ability to induce mutagenic effect in histidine-requiring strains of Salmonella. The results of the three tests revealed no increased incidence of mutants by the test item with and without metabolic activation. Therefore, it was concluded that the test compound did not show mutagenic activity in S. typhimurium. Although no E Coli WP2 strain or TA 102 strain have been tested, strains that should be used to also detect certain oxidising mutagens, cross-linking agents and hydrazines, it is not expected that EDDHMA-Fe would be an oxidising mutagen, nor a cross-linking agent, and it is not a hydrazine.

In-vitro Mammalian Chromosome Abberation Test

A statistically significant increase in the number of cells with chromosome aberrations was only seen at high and cytotoxic concentrations, and only in the absence of metabolic activation. Dose-response relationships were not observed, and the increases were much lower than those obtained using positive controls. Therefore, these increases, although statistically significant, were considered of low, if any, toxicological relevance.

In vivo Micronucleus test in mice

Following oral treatment with the test article at a level of 5000 mg/kg bw, the ratio between PCEs and NCEs was not affected as compared to the corresponding negative controls thus indicating no cytotoxic effects. In comparison to the corresponding negative controls there was no statistically significant enhancement in the frequency of the detected micronuclei at any preparation interval after application of the test article. An appropriate reference mutagen was used as positive control which showed a distinct increase of induced micronucleus frequency. A supporting study in mice, using intraperitoneal injection at 2000 mg/kg bw, neither induced micronuclei. In conclusion, the test article did not induce micronuclei as determined by the micronucleus test with bone marrow cells of the mouse.

Three other in vitro studies (Ames test, MLA and CAT) with the structurally related substance EDDHA-Fe also did not show genotoxic activity.

Conclusion: EDDHMA-Fe provoked no mutagenic activity, when tested for gene mutation in bacteria and chromosome aberration in mammalian cells in vitro. In addition, it did not induce micronuclei as determined by the micronucleus test with bone marrow of the mouse. Therefore, it is concluded that the test item is devoid of mutagenic activity.


Short description of key information:
EDDHMA-Fe was examined in two different in vitro genetic toxicity studies (three Ames tests and one Chromosome Aberration Test), all with and without metabolic activation. The test item did not induce gene mutations in the Ames test. EDDHMA-Fe tested up to cytotoxic concentrations did show an increase in the number of cells with chromosome aberrations only at high and cytotoxic concentrations, and only in the absence of metabolic activation. Finally the test substance showed no mutagenic effect in two in vivo Micronucleus test in the mouse (following oral & intraperitoneal adiministration). Overall, EDDHMA-Fe was considered non genotoxic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on results of two different in vitro genetic toxicity studies, and two in vivo mutagenicity tests, EDDHMA-Fe was not classified and labelled as genotoxic according to Regulation 1272/2008/EC (CLP).

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