Titanium

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
No substantial accumulation of titanium was observed in tissues following oral administration of titanium dioxide.
Short description of key information on absorption rate: 
Titanium dioxide is not able to penetrate human skin, thus an absorption rate of 0% is suggested.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

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 is considered justified.

In a toxicokinetic study rats were exposed with diets reinforced with different forms of titanium dioxide at approx. 200 ppm (equivalent to ca. 30 mg/kg bw) for 7 days. The main route of excretion was via the faeces accounting for means of 39 – 63% daily dose. For each collection interval (0 - 24, 24 – 48, 48 – 72 hours) there was no statistical evidence to suggest differences in patterns of excretion between different forms of titanium dioxide. The results suggest that there is no substantial accumulation of titanium in tissues following administration of diets with different forms of titanium dioxide.

In vitro bioaccessibility data on titanium released from titanium dioxide were determined when exposed to synthetic biological media of varying pH and composition. Only a small fraction of titanium was released/dissolved from the titanium dioxide powder during exposure to any of the media matrices of varying acidity and composition. A trend with somewhat higher release rates with increasing acidity and exposure period was evident. The test results suggest that there is no substantial accumulation of titanium in tissues following administration of diets with different forms of titanium dioxide.

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

Discussion on absorption rate:

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 is considered justified.

The absorption of titanium dioxide through porcine skin has been measured in an in vitro percutaneous study. Under the present testing conditions the total dermal absorption is estimated to 0 %, for the two tested titanium dioxide samples, retention in the skin was estimated to be 0.1-0.5%. Therefore, based on this study a value of 0% for dermal absorption is suggested. This value is supported by various supportive data in which the retention of titanium dioxide from sunscreen formulations in human skin has been investigated. It has been shown that titanium dioxide is retained in the outmost layers of the stratum corneum.

Furthermore, titanium dioxide was tested in various percutaneous absorption tests which have been reviewed by the Scientific Committee on cosmetic products and non-food products (SCCNFP/0005/98, 2000) and which concluded “extensive tests for percutaneous absorption, mostly in vitro, indicate that absorption does not occur, either with coated or uncoated material; one experiment found some evidence that a little of the material could be found in the openings of the follicles. [...] The toxicological profile of this material does not give rise to concern in human use, since the substance is not absorbed through the skin. In view, also, of the lack of percutaneous absorption, a calculation of the margin of safety has not been carried out.”