Registration Dossier

Administrative data

Description of key information

No reliable results are available for irritation / corrosion of synthetic rutile. Therefore, read-across is proposed to available data on TiO2. Titanium dioxide has been tested in three in vivo skin irritation and one eye irritation study. All tests show a negative response, thus titanium dioxide does not require classification either  as skin or as eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

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 data in skin and eye irritation 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).

Three in vivo key studies on the dermal irritation of titanium dioxide were identified which were conducted according or equivalent to OECD guideline 404. One study reported a mean erythema score of 0.7, 0.5, 0.17 at time point 1, 24, 48h respectively after exposure. All further studies report no irritation whatsoever. Based on the outcome of these studies titanium dioxide is considered as not irritating to the skin. The supportive information undermine this interpretation since in none of the reliable studies, titanium dioxide was identified as irritating to the skin.

In a recent (2006) very well-conducted and reported acute eye irritation/corrosion test with highly pure titanium dioxide, performed according to OECD guideline 405 and in compliance with GLP regulations, the only observation was conjunctival redness (grade 1) observed in 2 animals at 1 hour after installation and grade 2 in 1 animal at 1 hour after instillation, respectively. This effect was fully reversible. There were no corneal lesions, the iris was not affected by instillation of the item, and there were no systemic intolerance reactions.

Justification for classification or non-classification

Skin irritation

References Finlay, C. (2006), Finlay, C. (2003), Filliben, T.A. (1994) are considered as the key studies for skin irritation and will be used for classification. It is considered that these conclusions can be read across to Synthetic Rutile. The overall irritation results are as follows:

Finlay, C. (2006):

erythema, 0-72h after application: mean score=0.0

oedema, 0-72h after application: mean score=0.0

Finlay, C.(2003)

erythema, 0-48h after application: mean score=0.0

oedema, 0-48h after application: mean score=0.0

Filliben, T.A.(1994)

erythema, 1h after application: mean score=0.7 fully reversible

erythema, 24h after application: mean score=0.5 fully reversible

erythema, 48 and 72h after application: mean score=0.17 fully reversible

oedema, 0-72h after application: mean score=0.0

The classification criteria acc. to regulation (EC) 1272/2008 as irritating to skin are not met since the mean erythema score after 24h was 0.5, hence no classification required.

 

Eye irritation

Reference Finlay, C. (2006) is considered as the key study for eye irritation and will be used for classification. It is considered that these conclusions can be read across to Synthetic Rutile. The overall irritation results are as follows:

conjunctival redness, 1h after application: mean score=1.3

conjunctival redness, 24h after application: mean score=0.3

conjunctival redness, 48 and 72h after application: mean score=0.0

The classification criteria acc. to regulation (EC) 1272/2008 as irritating to eyes are not met since the mean score after 24h was 0.3, hence no classification required.

Respiratory irritation

The classification as respiratory irritant is covered under the endpoint specific target organ toxicity- single exposure and repeated exposure. Please refer to the endpoint summaries on acute toxicity (endpoint 7.2) and repeated dose toxicity (endpoint 7.5) for further information.