Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

A bacterial mutagenicity study by Bowen, R. (2010) is considered reliable without restrictions as the study was performed in compliance with GLP according to OECD guideline 471. This study was conducted by using five strains of Salmonella typhimurium bacteria (TA98, TA100, TA1535, TA1537 and TA102) with and without metabolic activation. Titanium tetraisopropanolate, was tested for its ability to induce mutations at the concentration of 171.8, 343.4, 686.9, 1374, 2748 and 5495 micrograms/plate. Test substance did not induce mutations under conditions of this study.

The additional bacterial mutagenicity studies conducted for titanium tetraisopropanolate (Koops, A. 1977) and for the main hydrolyzing degradation product, isopropyl alcohol, did not indicate any evidence of mutagenicity (Shimizu, H. et al. 1985).

Weight of evidence from the above bacterial tests and the in vivo tests (Kapp, R.W. 1993, Barilyak, I. and Kozachuk, S. 1988) conducted for the most relevant decomposition product isopropyl alcohol, were used to evaluate the further in vitro testing needs of this substance. The potential of IPA to induce chromosome aberration was assessed in vivo mouse micronucleus study by Kapp, R.W. et al. 1993. No increased incidence of micronuclei was observed in bone marrow polychromatic erythrocytes (PCE) harvested at 24, 48, or 72 hr post-dosing of the test substance. Under the experimental conditions of this test, IPA is concluded to be not mutagenic.There is no in vitro mammalian gene mutation and chromosome aberration testing available for this substance. However, as there is reliable in vivo chromosome aberration test available for the most relevant decomposition product of this substance, these in vitro tests were considered scientifically unjustified.

Since titanium tetraisopropanolate is hydrolytically unstable intrinsic properties are related to the hydrolysis products of this substance. The hydrolysis is rapid (<3min) when the substance comes in contact with water or moisture (key study on hydrolysis. Scholz, T. 2010). After hydrolysis no significant reaction products other than isopropyl alcohol and hydrated titanium dioxide exist. There is enough evidence that these degradation products are not genotoxic. In addition, neither of these decomposition products has harmonized classification entries for genotoxicity.

Based on weight of evidence approach there is enough reliable information to conclude that this substance is not mutagenic, and no classification is required according to the criteria of CLP Regulation 1272/2008 and the EU directive 67/548/EEC.


Justification for selection of genetic toxicity endpoint
No study was selected, since all studies were negative. One in vitro study and one in vivo study are for the degradation product (IPA) since the substance is highly reactive.

Short description of key information:
In vitro:
Gene mutation study in bacteria
Gene mutation (reverse mutation assay/Ames test): negative in all tested bacterial strains with and without metabolic activation (equivalent to OECD TG 471)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The intrinsic properties of titanium tetraisopropanolate are related to the main degradation product; isopropyl alcohol (IPA). Based on the weight of evidence approach on the in vitro bacterial tests of the substance and in vivo tests of IPA there is no need for classification of the substance for mutagenic effects in accordance with the criteria of CLP Regulation 1272/2008 and the EU directive 67/548/EEC.