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Additional information

In vitro studies:

DEAE was not mutagenic in an Ames test (OECD471) tested up to 5000µg/plate in Salmonella typhimurium TA1535, TA1537, TA98, TA 100 and E.coli WP2 uvrA. A weak bacteriotoxic effect (slight decrease in the number of his+ revertants) was occasionally observed in the standard plate test depending on the strain and test conditions at a concentration of 5000 μg/plate. In the preincubation assay bacteriotoxicity (reduced his- or trp- background growth, slight decrease in the number of his+ or trp+ revertants) was observed depending on the strain and test conditions from about 2500 μg/plate onward (BASF SE 2015; Val.1)

DEAE was not mutagenic in a standard plate and pre-incubation Ames test with and without metabolic activation according to OECD guideline 471 (tested up to 5000 μg/plate in Salmonella typhimurium TA 1535, TA 1537, TA 98 and TA 100; metabolic activation: liver S-9 mix from Aroclor-induced male Sprague-Dawley rats). Cytotoxicity (reduction of the background lawn) was observed at TA 1537 with S-9 mix (standard plate test) and with TA 1535, TA 1537 and TA 98 without S-9 mix (preincubation test) at 5000 µg/plate (BASF AG 1989; Val. 1).

DEAE was also evaluated for mutagenicity in the Salmonella/microsome preincubation assay using a standard protocol approved by the National Toxicology Program. Doses of 33, 100, 333, 1000, 2500 and 3333 µg/plate were tested in four Salmonella typhimurium strains (TA98, TA100, TA1535, and TA1537) in the presence and absence of Aroclor-induced rat or hamster liver S9. These tests were negative and the highest ineffective dose level tested in all four Salmonella tester strains under all treatment conditions was 2500 µg/plate (Zeiger et al. 1988; Val. 2).

A third Ames-Test validated the previous results (Life Science 1991; Val. 2). No increases in reversion were obtained with any of the five bacterial strains (TA1535, TA1537, TA1538, TA98 and TA100) at the DEA levels tested, either in the presence or absence of S-9 mix. Inhibition of growth, observed slight thinning of the background lawn of non-revertant cells and reduction in revertant colony numbers, occurred in all strains following exposure to DEAE at 5000 µg per plate.

In addition to the Ames-Tests also the mutagenic activity at the HPGRT locus in a Chinese hamster V79 cell mutation system was observed according to the OECD guideline 476 (Life Science 1991; Val. 1). Cultures exposed to DEAE (1st expt.: 4.8, 24, 120, 600, 3000 µg/ml; 2nd expt.: 5.6, 28, 140, 700, 3500 µg/ml) showed no increases in 6 -TG resistant colony numbers and no significantly increased mutant frequencies compared to solvent controls. However, in both experiments at the end of the exposure time, changes in the cell morphology were observed.

 

The effects on DNA damage in E. coli strains WP2, WP67 and CM871 was observed in an assay according to EPA OTS 798.5500 (Bacterial DNA Damage or Repair Tests). Cells were treated with doses of 35, 110, 350, 1100 and 3500 µg/ml DEAE and did not produce lethal DNA damage under the conditions of test (Life Science 1991; Val. 1).

 

In vivo studies:

In a micronucleus assay with NMRI mice according to OECD TG 474, 5 male/female animals per group were orally administered single doses of 20, 100 and 500 mg/kg bw by gavage (Life Science 1991; Val. 1). There was no statistically significant or biologically relevant enhancement in the frequency of the detected micronuclei at any preparation interval after administration of the test item and with any dose level used. It could be stated that under the experimental conditions reported, DEAE was non-mutagenic in this micronucleus assay.


Short description of key information:
In vitro studies:
Ames-Test: negative (OECD 471);
HGPRT: negative (OECD 476);
DNA damage in E. coli: negative;

In vivo studies:
Mouse Micronucleus Test: negative (OECD 474)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Four valid Ames-tests, with or without metabolic activation through S9-Mix, a valid HGPRT test, a DNA damage test in E. coli and an in vivo mouse micronucleus assay failed to provide any evidence for a mutagenic or clastogenic effect of DEAE.

Thus, no classification for mutagenicity is needed according to the EU Directive 67/548/EEC and to EC/1272/2008 (CLP) Regulation.