Titanium

Carcinogenicity

Description of key information

The available data in rats and mice clearly suggest that ingested titanium dioxide is neither toxic nor carcinogenic to both species. Based on the histopathological examination in a 103 week feeding study, titanium dioxide was considered to be neither toxic nor carcinogenic to rats and mice. Thus, the highest dietary concentration of 50000 ppm titanium dioxide is representing the NOAEL which corresponds to a dose of 3500 mg titanium dioxide/kg bw/d for rats.

Justification for classification or non-classification

Based on the weight of evidence from the available long-term toxicity/carcinogenicity studies in rodents and the relevant information on the toxicokinetic behaviour in rats, it is concluded that titanium does not present a carcinogenicity hazard via oral application. There is evidence from the animal chronic toxicity/carcinogenicity studies in rats and mice that the intake of high amounts of titanium dioxide was not associated with adverse effects.

For the reasons presented above, no classification for carcinogenicity is required.

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 acute toxicity is considered justified.

The available data in rats and mice clearly suggest that ingested titanium dioxide is neither toxic nor carcinogenic to both species. Based on the histopathological examination in a 103 week feeding study, titanium dioxide was considered to be neither toxic nor carcinogenic to rats and mice. Thus, the highest dietary concentration of 50000 ppm titanium dioxide is representing the NOAEL which corresponds to a dose of 3500 mg titanium dioxide/kg bw/d for rats. 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