Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

In vitro

The genetic toxicity of the substance was assessed at concentrations of 4000 µg/plate using S. typhimurium TA100, TA1535, TA98, TA1537, TA1538 and E. coliWP2 uvr A strains. All bacterial strains showed negative responses with and without metabolic activation. In an old Ames test, performed with less strains, this result was confirmed.

The potential of the substance to induce structural chromosome aberrations in cultured mammalian somatic cells has been investigated according to OECD 473 and GLP. Chinese hamster lung fibroblasts cells were treated for 6 hr (with and without S9-mix) and for 24 hr (without S9-mix) with the substance at doses ranging from 7.34 to 940 µg/mL (=0.01 M). Precipitation was observed (at the end of the treatment period) at dose levels of 330 µg/mL and above. The number of cells with chromosome aberrations found in the solvent and positive control cultures was within the laboratory historical control data range. Without S9 mix, the frequencies of cells with structural aberrations at 280 and 330 µg/mL were 11.5 and 13%, respectively and with S9 mix, the frequencies of cells with structural aberrations at 280; 330 and 380 µg/mL were 16.0; 23.5 and 38.5%, respectively. As the frequency is more than 10% and increases in a dose-related manner, it is concluded that the substance is clastogenic in Chinese hamster lung fibroblasts.

In accordance with REACH column 2, Annex VIII and IX, no further in vitro studies have been performed, as the chromosome aberration study is positive. Therefore, in vivo testing has been performed.

In vivo

In an in vivo micronucleus study performed according to OECD test guideline 474, XDI was administered orally twice up to 1000 mg/kg bw/day to rats. The frequency of the micronuclei did not increase by administering the test substance to rats. The positive control showed a significant increase compared to the negative control, it was confirmed that the test was valid. The exposure of substance to bone marrow cells could not be proved as the IE% did not show significant differences in substance treated compared to negative control. However, doses were set based on dead animals found after 4 days of administration in 14-d repeated dose toxicity study, and toxic symptoms indicative of systemic exposure were observed in this study. The potential to induce micronuclei could be evaluated adequately in this study. Therefore, it was concluded that XDI had no potential to induce the micronuclei under the present test conditions.


Justification for selection of genetic toxicity endpoint
In accordance with Practical Guide 14, there is no need to select a study.

Short description of key information:
Two Ames tests, one chromosome aberration study in vitro and an in vivo micronucleus study have been performed with XDI. Key studies were performed according to OECD test guidelines and GLP principles. The in vivo micronucleus test did not show a positive effect on genotoxicity.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data, XDI does not have to be classified according to the CLP Regulation (EC) No. 1272/2008 for mutagenicity.