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Key value for chemical safety assessment

Additional information

A gene mutation test with prokaryotes, a gene mutation study with mammalian cells and a chromosome aberration test with mammalian cells on TAEE are available (all in vitro data), all performed in accordance with OECD guidelines and under GLP.

 

TAEE was tested in a GLP-compliant guideline bacterial mutation assay (reverse mutation assay, Method B13/14 of Directive 2004/73/EC) using Salmonella typhimurium tester strains TA98, TA100, TA1535, TA1537 and TA102 exposed via plate incorporation (one experiment) and liquid pre-incubation (one experiment with partial repeat) (Covance Laboratories Ltd, 2009e). Test concentrations up to 5000 µg/plate were used in the absence and in the presence of Aroclor 1254-induced rat S9 fraction. The test substance was not cytotoxic nor was there any consistent increase in the frequency of revertant colonies in any strain both with and without metabolic activation. The results indicate that TAEE is not mutagenic in this Ames test when tested up to the maximum concentration required in current test guidelines.

Mutagenic potential of TAEE in mammalian cells was assessed in a GLP compliant guideline MLA study (Method B17 of Directive 2004/73/EC) using L5178y TK+/- cells (Covance Laboratories Ltd, 2009f). Test concentrations of up to 1162 µg/ml were used in the main test both in the absence and in the presence of Aroclor 1254-induced rat S9 fraction, and the study was run using 2 independent repeats. No cytotoxicity was present at the maximum concentration used, equivalent to 10 mM. A statistically significant linear trend observed in the presence of S-9 in one experiment was not replicated in the independent repeat and increases in mutation frequency for all treated cultures were in any event below the global evaluation factor for the test. The vehicle and positive controls (-S9 methylmethanesulphonate; +S9 benzo(a)pyrene) gave acceptable responses in both experiments. The results indicate that the test substance is not mutagenic in L5178Y TK+/- cells in vitro in the absence or presence of Aroclor 1254-induced rat S9 fraction.

Clastogenic potential of TAEE was assessed in a GLP compliant guideline study (draft OECD guideline 487) using cultured human lymphocytes (Covance Laboratories Ltd, 2009g). Test concentrations in a range 500-1200 µg/ml were evaluated in the absence and in the presence of S9 fraction using a 3+21 hr treatment protocol, and concentrations of 5-200 µg/ml in the absence of S9 using a 24+0 hr protocol. Under these conditions, cytotoxicity of approx. 50-70% was present at the highest concentrations examined for each protocol. The frequencies of binucleate cells with micronuclei following treatment in the absence and presence of S9 were not significantly different from those observed in concurrent vehicle controls for all concentrations examined. The vehicle and positive controls (-S9 mitomycin C, vinblastine; +S9 cyclophosphamide) gave acceptable responses and all other aspects of the tests were valid. The results indicate that the test substance is not clastogenic in human lymphocytes in vitro in the absence or presence of Aroclor 1254-induced rat S9 fraction.


Short description of key information:
A gene mutation test with prokaryotes, a gene mutation study with mammalian cells and a chromosome aberration test with mammalian cells (all in vitro and performed in accordance with OECD guidelines and under GLP) were negative.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the negative results of the available in vitro studies and in accordance with Directive 67/548/EEC and EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification is not necessary for mutagenicity.