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Additional information

MDEA was evaluated for mutagenicity at concentrations of 0.1, 0.3, 1, 3, 5, and 10 mg/plate in the Salmonella/microsome reverse gene mutation test (similar to OECD 471, no GLP). The strains tested were S. typhimurium TA98, TA100, TA1535, TA1537 and TA1538. Cytotoxicity was observed from 3 mg/plate onwards in absence of S9 mix, and at 10 mg/plate in presence of S9 mix. No mutagenic activity was observed in any of the 5 strains tested in the absence or the presence of S9 activation, either by evidence of a dose-response relationship or a doubling of the mean number of colonies over the vehicle control value. MDEA was therefore considered not mutagenic under the conditions of this in vitro mutagenicity test (Leung & Ballantyne, 1997).

In another Ames test (also similar the OECD 471), MDEA was tested in S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 (with and without metabolic activation) using concentrations of 33, 100, 333, 1000, 2000, 3333 and 10000 µg/plate (Zeiger et al, 1987). No mutagenic effects were observed. Cytotoxicity was observed from 3333 µg/plate.

 

In a CHO/HGPRT forward gene mutation test (similar to OECD 476, no GLP), MDEA treatment (0.1, 0.3, 0.6, 1.0, 1.5, 2.0, 33.0 mg/ml) did not produce a reproducible dose-related increase in the number of mutants over the range of concentrations tested either with or without an S9 metabolic activation system. Cytotoxicity was not observed. MDEA was not considered to be mutagenic in this in vitro gene mutation test (Leung & Ballantyne, 1997).

In a SCE test (similar to OECD 479, no GLP), statistically significant increases in the mean number of SCEs were observed in one culture at 0.3 mg/ml MDEA, and in duplicate cultures at 0.6 and 1.0 mg/ml MDEA in the absence of S9 metabolic activation. These increases were small, being less than 1.5-fold those of untreated controls, and they were not dose-related. In the presence of S9 metabolic activation, MDEA failed to produce any statistically significant increase in SCEs in comparison to concurrent controls. There were no increases in the numbers of first division cells which suggests that the dose ranges used were appropriate. Therefore, MDEA was not considered to induce reciprocal chromatid exchanges under the condition of this in vitro test (Leung & Ballantyne, 1997).

In the mouse micronucleus test (similar to OECD 474, no GLP), mice were dosed by a single intraperitoneal injection and observed for mortality for 72 h. Three dose levels of 175, 350, and 560 mg/kg bw (about 25, 50 and 80% of the LD50) were selected for the micronucleus test. There were no major gender differences in mortality responses. The LD50 (combined sexes) for MDEA was about 696 mg/kg bw. Selection of the top test dose was based on the lethality response rather than on bone marrow suppression. There were no significant differences in the polychromatic erythrocyte to normochromatic erythrocyte ratios at any dosages. Furthermore, no significant increases in the incidence of micronucleated polychromatic erythrocyte were observed at any sampling time. Therefore, MDEA was not considered to be an inducer of micronuclei under the conditions of this in vivo test (Leung & Ballantyne, 1997).


Short description of key information:
MDEA was evaluated for potential genotoxic activity using the Salmonella/microsome reverse gene mutation test (similar to OECD 471, no GLP), the CHO/HGPRT forward gene mutation test (similar to OECD 476, no GLP), a sister chromatid exchange test in cultured CHO cells (similar to OECD 479, no GLP), and an in vivo peripheral blood micronucleus test in Swiss-Webster mice (similar to OECD 474, no GLP). MDEA did not produce any significant or dose-related increases in the frequencies of gene mutations, chromosome aberrations, sister chromatid exchanges or micronuclei. These results indicate that MDEA is not genotoxic in the tests conducted.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data, the substance does not need to be classified for genotoxicity according to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.