Titanium

Endpoint summary

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 genetic toxicity is considered justified.

In vitro genetic toxicity tests

It is concluded that titanium dioxide did not induce micronuclei in cultured human peripheral blood lymphocytes following treatments in the absence and presence of an Aroclor induced rat liver metabolic activation system (S-9). Concentrations were tested and analysed up to and in excess of the solubility limit in culture medium.

It is concluded that titanium dioxide did not induce mutation at the tk locus of L5178Y mouse lymphoma cells when tested under the conditions employed in this study up to 500µg/mL. These conditions included treatments up to precipitating concentrations in two independent experiments, in the absence and presence of a rat liver metabolic activation system (S-9). Furthermore titanium dioxide did not induce chromosome aberrations in chinese hamster ovary cells (CHO) when tested under the conditions employed in this study up to 2500µg/mL. These conditions included treatments up to precipitating concentrations in two independent experiments, in the absence and presence of a rat liver metabolic activation system (S-9).

In vivo genetic toxicity tests

It has been shown that titanium dioxide does not induce micronuclei or chromosome aberration in the bone marrow of male B6C3F1 mice following a single intraperitoneal injection of 1500 and 2500 mg titanium dioxide /kg bw respectively.

It can therefore be concluded thattitanium dioxidedoes not cause genetic toxicity in vitro and in vivo.

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

Short description of key information:
Titanium dioxide has been tested in bacterial reverse mutation assays, in vitro gene mutation and clastogenicity tests as well as in vivo. All tests show a negative response, thus titanium dioxide does not require classification for mutagenic properties.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Genetic toxicity, in vivo

The reference Shelby, M.D. (1995) is considered as the key study for in vivo genetic toxicity and will be used for classification. The overall results are as follows:

Titanium dioxide did not show a significant or dose-dependent increase in chromosome aberrations in the bone marrow of male mice via i.p. injection up to the maximum dose of 2500mg/kg bw 17 and 36 hours after dosing.

Titanium dioxide did not show a significant or dose-dependent increase in micronucleated cells in the bone marrow of male mice via i.p. injection up to the maximum dose of 1500mg/kg bw 24 hours after dosing.

 

Genetic toxicity, in vitro

None of the in vitro genotoxicity studies rated as reliable showed any effect in bacterial reverse mutation assays, in mammalian cell gene mutation tests (TK assay) or in mammalian cell chromosome aberration tests, thus supporting the negative findings in the in vivo tests as cited above. The classification criteria acc. to regulation (EC) 1272/2008 as germ cell mutagen are also not met.