Titanium(4+) ethanolate

Endpoint summary

Additional information

Weight of evidence approach was used to evaluate the testing needs of this endpoint as there are no studies available from the titanium (4+) ethanolate. The substance hydrolyses rapidly (<5min) when it comes in contact with water or moisture (Brekelmans, M.C.J., 2013). After hydrolysis no significant reaction products other than ethanol and non-hazardous hydrated titanium dioxide (TiO2) exist.

Based on the rapid hydrolysis, the intrinsic properties are most likely related to these two decomposition products, ethanol being the most relevant decomposition product for CSA.

TiO₂is considered a non-mutagenic substance, although evidence of mutagenic activity of titanium or its compounds is scant. However, TiO₂ has been shown to be negative when tested using the rec-assay with Bacillus subtilis (Kada et al., 1980).

Multiple studies exist on the potential of ethanol to cause genotoxicity. In a reverse mutation assay in bacteria strains TA97, TA98, TA100, TA104 and TA1535 there was no evidence of ethanol induced mutation up to a concentration of 10 mg/plate with and without metabolic activation systems derived from two species (rat and hamster) used at two different concentrations (Zeiger, 1992).

Further evidence of non-genotoxicity of ethanol comes from the assays done with mammalian cells. In a cytogenicity assay (Lin, 1989), Chinese Hamster Ovary cells were exposed to ethanol at 4 -5% for a period of 3 hours following which there was no evidence of any clastogenicity. However, the study did not use metabolic activation and so cannot be considered definitive. In a mammalian cell mutation study using mouse lymphoma cells in the TK forward mutation assay, ethanol was found to be non mutagenic with and without metabolic activation at very high doses up to and including those that cause significant cytotoxicity (typically in the region 0.3 -0.5M (Wagenheim, 1988). 

The results from genotoxicity assays with ethanol are universally negative. In addition, neither of these decomposition products has harmonized classification entries for genotoxicity. Based on read-across from decomposition products of titanium (4 +) ethanolate there is enough evidence to conclude that titanium (4 +) ethanolate is not genotoxic.

Justification for selection of genetic toxicity endpoint
No studies available for the target substance which is highly reactive. All three studies, performed for the main decomposition product (ethanol), were negative. Thus, no study was selected.

Short description of key information:
In vitro:
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, no metabolic activation used.
Gene mutation study in mammalian cells: negative, with and without metabolic activation.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The intrinsic properties of titanium(4+) ethanolate are related to the main degradation product ethanol. Based on the weight of evidence approach on the ethanol read-across data of the in vitro tests 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.