Titanium tetrabutanolate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The weight of evidence approach is used to determine the sensitization hazard of titanium tetrabutanolate evaluating relevant data from the substance itself but also from the decomposition products and from the analogue category member. Read-across data from the decomposition products (n-butanol and titanium dioxide) is used for assessment, because the target substance is hydrolytically unstable having the half-life less than 5 minutes (Brekelmans, M. J. C., 2013).

The potential sensitization properties of titanium tetrabutanolate were tested in non-guideline primary sensitization test on guinea pigs. The test substance was administrated as 1 % solution (vol/vol) in a series of four sacral intradermal injections (10 animals). At the time of challenge 0.05 ml 5 % and 50 % test substance (vol/vol) was applied and lightly rubbed to the shaved intact shoulder skin. A control group of 10 previously unexposed guinea pigs received similar applications at the same time to provide a direct comparison of the challenge reactions. At challenge no sensitization response was observed in any dose level tested. Based on the study results test substance is considered as not a skin sensitizer.

Further evidence on the skin sensitization comes from titanium tetraisopropanolate, the analogue category member of the target substance. All titanates in this category behave similar way when in contact with water. Isopropyl alcohol is released from titanium tetraisopropanolate and n-butanol from titanium tetrabutanolate when the substances are in contact with water. Released alcohols have no harmonized classification entries as sensitizers. The category justification and the read-across justifications are presented in the Annexes of the CSR.

The local lymph node assay (LLNA) by Dreher (2010) was conducted for analogue category member in compliance with GLP conditions and according to EU method B.42. The test substance did not demonstrate any evidence of skin sensitivity.

n-Butanol, the degradation product of the target substance, is not likely to be a skin sensitizer since the substance have no classification as skin sensitizer according to EU regulation No. 1272/2008 (CLP).

Published information on titanium and TiO2 confirmed that there was no human evidence of skin sensitization, contact dermatitis or appreciable dermal absorption (Clayton & Clayton (eds.), 1981). There is also evidence of a lack of titanium compound toxicity to the skin demonstrated by its use in the therapy of skin disorders and as a biocompatible implant material (West & Wyzan, 1963 cited in WHO, 1982)

As a conclusion on skin sensitization, there is available enough information from the substance itself, from the analogue category member and from the degradation products to support the conclusion that titanium tetrabutanolate is not skin sensitizer.

Migrated from Short description of key information:
Primary sensitization study in guinea pigs: negative (conducted for the target substance)
LLNA study: negative (conducted for the analogue category member)

Justification for selection of skin sensitisation endpoint:
Conclusion based on the following assays: Primary sensitization study in guinea pigs conducted for the target substance and LLNA study conducted for the analogue category member.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Titanium tetrabutanolate is not classified for skin sensitization in accordance to the CLP Regulation No. 1272/2008 and EU Directive 67/548/EEC.