Titanium

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Titanium is a transition-metal and is subject at its surface to passivation by the formation of a passive and protective oxide (i. e. titanium dioxide) coating that effectively protects it from further reaction. In particular for titanium metal and granules, the oxide layer will form a quantitatively continuous layer to envelop the entire particle irrespective of product form. The reaction kinetics have been investigated and reported in various references (Uhlig, 1979; Schmets et al. 1953; Andreeva, 1964; Burleigh, 1989; El Din et al., 1988), indicating that the oxide layer is formed immediately after the interaction of the clean surface with the air atmosphere. Any melt processing of titanium metal has to be conducted under an inert atmosphere or vacuum to protect the metal from instant oxidation. Similarly the use of solid titanium at elevated temperatures is restricted due to its propensity for rapid oxidation.

 

Furthermore, transformation/dissolution testing according to “OECD 29 Environmental Health and Safety Publications, Series on testing and assessment, Guidance document on transformation/ dissolution of metals and metal compounds in Aqueous media” has shown that titanium metal compared to titanium dioxide has a similar release rate of titanium ions (please refer to the respective entry under the endpoint water solubility).

 

In view of this, it may be assumed that human exposure towards titanium metal is secondary to that of titanium dioxide.

Thus, unlimited read-across for sensitising properties is considered justified.

Titanium dioxide has been tested in two different systems for sensitising properties. Both study types show a negative response, thus titanium dioxide does not require classification as sensitiser.

References

H.H. Uhlig (1979) Passivity in Metals and Alloys, Corrosion Science, Vol. 19, pp. 777-791

 J. Schmets and M. Pourbaix (1953) Equilibrium Potential-pH Diagram for the System Ti-H2O, Corrosion of Titanium, Technical Report RT. 4, CEBELCOR, pp. 167-179

 V.V. Andreeva (1964) Behavior and Nature of Thin Oxide Films on Some Metals in Gaseous Media and in Electrolyte Solutions, Corrosion, Vol. 20, No. 2, pp. 35-47

 T.D. Burleigh (1989) Anodic Photocurrents and Corrosion Currents on Passive and Active-Passive Metals, Corrosion, Vol. 45, No. 6, pp.464-472

 A.M. Shams El Din and A.A. Hammoud (1988) Oxide Film Formation and Thickening on Titanium in Water", Thin Solid Films, Vol. 167, No. 1, pp. 269-280

Migrated from Short description of key information:
Titanium dioxide has been tested in two different systems for sensitising properties. Both study types show a negative response, thus titanium dioxide does not require classification as sensitiser.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

There are two reliable animal studies, performed according to OECD guidelines 406 and 429 and according to GLP, both showing that titanium dioxide has no sensitising properties.

Migrated from Short description of key information:
Titanium dioxide does not show respiratory sensitising properties in animal studies or in exposure related observations in humans.

Justification for classification or non-classification

Sensitisation

The references Hoban, D.(2006) and Moore, G.E.(1994), are considered as the key studies on skin sensitisation and will be used for classification. The overall sensitisation results are as follows:

Hoban, D.(2006) – Local lymph node assay (LLNA) in mice

SIs of less than 3.0 were observed at all test concentrations of titanium dioxide (5, 25, 50, 100%). Therefore, an EC3 value (the estimated concentration required to induce a threshold positive response, i.e., SI = 3) for the test substance under the conditions of the study was not calculable.

Moore, G.E.(1994) – Buehler method in guinea pigs

The incidence of sensitisation after the challenge application was 0/20. Thus, the classification criteria acc. to regulation (EC) 1272/2008 as skin sensitizer are not met since 0% of the test animals responded.

 

Respiratory sensitisation

There is no evidence on specific respiratory hypersensitivity in humans following repeated inhalation exposure with titanium dioxide. Furthermore, none of the repeated dose toxicity studies via inhalation reports respiratory hypersensitivity in the test animals. Thus, the classification criteria acc. to regulation (EC) 1272/2008 as respiratory sensitiser are not met.