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Administrative data

Key value for chemical safety assessment

Additional information

Read across concept

Synthetic rutile consists primarily of a titanate phase (solid solution) most of which is titanium in an oxidised form. Upon ingestion, a low rate of dissolution in the GI tract is assumed, based on the experimental verified inertness of the material. Any material being released from Synthetic rutile under physiological conditions will be in the form of ionic titanium, which is similarly the case for titanium dioxide, thus read-across from genetic toxicity data on titanium dioxide is considered feasible without any restrictions.

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 synthetic rutile compared to titanium dioxide has a similar release rate of titanium ions (please refer to the respective entry under the endpoint water solubility).

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 that titanium dioxide does not cause genetic toxicity in vitro and in vivo.


Short description of key information:
No reliable results are available for genetic toxicity of synthetic rutile. Therefore, read-across is proposed to available data on TiO2.
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.

It is considered that these conclusions can be read across to Synthetic Rutile.

 

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.

It is considered that these conclusions can be read across to Synthetic Rutile.