Titanium tetrabutanolate

Endpoint summary

Additional information

In vitro mutagenic activity of titanium tetrabutanolate has been evaluated in one study with bacterial cells and in two studies with mammalian cells. These studies are performed according to the current guidelines in accordance with GLP, and evaluated to be reliable without restrictions. Thus, it is justified to select all three studies as key studies.

Mutagenicity in bacterial test systems

A bacterial mutagenicity study by Verspeek-Rip C. M (2012) 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, and TA1537) and Escherichia coli (WP2uvrA) with and without metabolic activation. Titanium tetrabutanolate was tested for its ability to induce mutations at the concentration of 3, 10, 33, 100, 333, 1 000, 3 330 and 5 000 µg/plate. The test substance did not induce mutations under conditions of this study.

Cytogenicity in mammalian cells

The potential of titanium tetrabutanolate to induce chromosome aberration was assessed in cultured peripheral human lymphocytes by Verbaan I. A. J (2013). This study is considered reliable without restrictions as the study was performed in compliance with GLP according to OECD guideline 473. Titanium tetrabutanolate was tested with and without metabolic activation in doses up to 1 000 µg/ml. The compound was not clastogenic in human lymphocyte assay either in the presence or absence of metabolic activation, i. e., it did not increase the number of polyploid cells and cells with endoreduplicated chromosomes in the cells.

Mutagenicity in mammalian cells

The potential gene mutagenic activity of titanium tetrabutanolate has been evaluated in L5178Y mouse lymphoma cells by Verspeek-Rip, C.M. (2013). The test method was comparable to OECD guideline 476 and the test was conducted in compliance with GLP. The test substance was tested in two independent experiments with modifications in the duration of treatment time and in the concentration of the metabolic activation system (S9-mix). Titanium tetrabutanolate was not mutagenic, both in the presence and absence of S9-mix.

The results from genotoxicity assays of titanium tetrabutanolate are universally negative. In addition, neither of the decomposition products (n-butanol and TiO2) of the target substance has classification entries for genotoxicity.

Justification for selection of genetic toxicity endpoint
Conclusion based on the following assays: Bacterial reverse mutation assay (Ames test); Mammalian cell gene mutation assay, In vitro mammalian chromosome aberration test.

Short description of key information:
Gene mutation (reverse mutation assay/Ames test): negative in all tested bacterial strains with and without metabolic activation (equivalent to OECD TG 471).
Chromosome aberration study in mammalian cells: negative, with and without metabolic activation (OECD 473).
Gene mutation study in mammalian cells: negative, with and without metabolic activation (OECD 476).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the results of in vitro bacterial gene mutation study, in vitro mammalian chromosomal aberration and gene mutation studies the substance has no potential to cause mutagenicity and genotoxicity. No classification is required according to the criteria of CLP regulation 1272/2008 and the EU directive 67/548/EEC.