Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

The substance was not mutagenic in the Salmonella typhimurium (Ames assay), in a gene mutation assay in Chinese hamster ovary (CHO) AS52/XPRT cells (gpt locus), nor in a mammalian gene mutation assay at the TK-locus of L5178Y cells. 

The substance was tested in a Drosophila sex-linked recessive lethal (SLRL) test. The study was included in the US EPA Report of the Gene-Tox Program, where the substance could not be classified as positive or negative because of inadequate sample size. The results were considered ambiguous. 

The substance was negative in one in vivo mouse micronucleus assay, but positive in another recent in vivo mouse micronucleus study following OECD guideline 474. In the negative test, concentrations up to 500000 ppm were evaluated. In the positive test, no significant effects were observed during exposure up to 30000 ppm in both sexes, while at 300000 ppm a statistically significant test substance-related increase in the frequency of MN-RETs was observed in male mice only, and at the 72-hour time point only.

There are several reliable genetic toxicity tests available for the substance. Reliable in vivo results indicated that the substance did not produce mutations even during high exposure concentrations considered to be upper boundaries of the maximal recommended exposure concentrations for acute and chronic inhalation studies. In an in vivo mouse micronucleus test, no significant effects were observed during exposure up to 30000 ppm in both sexes while at 300000 ppm, a statistically significant test substance related increase in the frequency of MN-RETs was observed in male mice only, and at the 72-hour time point only.


Endpoint Conclusion:

Justification for classification or non-classification

There are several genetic toxicity tests available for the substance. The substance did not produce mutations in bacterial or mammalian cells when tested in cell culture. In vivo results indicated that the substance did not produce mutations even during high exposure concentrations considered to be upper boundaries of the maximal recommended exposure concentrations for acute and chronic inhalation studies. In an in vivo mouse micronucleus test, no significant effects were observed during exposure up to 500000 ppm. In another in vivo mouse micronucleus test, no significant effects were observed during exposure up to 30000 ppm in both sexes, while at 300000 ppm, a statistically significant test substance related increase in the frequency of MN-RETs was observed in male mice only and at the 72-hour time point only. Based on consideration of the entire genetic database and according to the fact that this dose-level is considerably above upper boundaries of the maximal recommended exposure concentrations for acute and chronic inhalation studies, the substance does not need to be classified for mutagenicity according the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.