Registration Dossier

Administrative data

Description of key information

No reliable results are available for acute toxicity of synthetic rutile. Therefore, read-across is proposed to available data on TiO2.
Acute toxicity, oral:
LD50 > 5000mg/kg bw
Acute toxicity, inhalation:
LC50 > 6.82mg/L (MMAD=1.55 µm, GSD=1.70 µm)
Acute toxicity, dermal:
Conduct of an acute dermal toxicity study is unjustified as inhalation of the substance is considered as major route of exposure and physicochemical properties and dermal absorption data of the substance do not suggest a significant rate of absorption through the skin (cf. Annex VIII section 8.5 Column 2 of regulation (EC) 1907/2006).

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 repeated dose oral 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).

The conduct of an acute inhalation toxicity study is unjustified as inhalation of the substance is considered negligible, based on the outcome of the dustiness testing according to method EN 15051/ DIN 33897-2, as reported under section particle size distribution (granulometry). The results demonstrate that synthetic rutile has a limited ability to be inhaled by humans: 0.025 % of airborne material is estimated to be inhalable, whereas about 0.002 % or less of inhaled material is predicted to be deposited in the pulmonary region (PU), i.e. respirable fraction. The material deposited in the tracheobronchial (TB) and the extrathoracic region (Head) may be assumed to be cleared to the GI tract (i.e., by mucociliary escalation and subsequent swallowing).

Several animal studies on acute oral exposure are available, conducted according to OECD guidelines 401, 420, 425 or according to state of the art methodology at that time. They indicate that oral LD50 is in excess of 25000 mg/kg bw in rats. However, the study selected as key study reports a LD50 > 5000mg/kg bw in rats which will be used further for the human health hazard assessment.

There are no reliable reports whatsoever on acute dermal toxicity in the public domain. However, the conduct of an acute dermal toxicity study is unjustified as ingestion of the substance is considered as major route of exposure and physico-chemical properties and dermal absorption data of the substance do not suggest a significant rate of absorption through the skin (cf. Annex VIII section 8.5 Column 2 of regulation (EC) 1907/2006).

Justification for classification or non-classification

Acute oral toxicity

The reference Finlay, C. (2006) is considered as the key study for acute oral toxicity and will be used for classification. Rats were dosed at 175, 550, 1750 and 5000 mg/kg orally via gavage. During the conduct of the study no mortalities occurred, no biologically important body weight loss occurred after dosing, and no gross lesions were present in the rats at necropsy.

LD50 oral, rat > 5,000 mg/kg bw

The classification criteria acc. to regulation (EC) 1272/2008 as acutely toxic are not met since the ATE is above 2000mg/kg body-weight, hence no classification required.

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

 

Specific target organ toxicant (STOT) – single exposure: oral

The classification criteria acc. to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, oral for a Category 1 classification of 300 mg/kg bw and at the guidance value, oral for a Category 2 classification of 2000 mg/kg bw. No classification required.

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

Acute inhalation toxicity and Specific target organ toxicant (STOT) – single exposure: inhalation

The conduct of an acute inhalation toxicity study is unjustified as inhalation of the substance is considered negligible, based on the outcome of the dustiness testing according to method EN 15051/ DIN 33897-2, as reported under section particle size distribution (granulometry). The results demonstrate that synthetic rutile has a limited ability to be inhaled by humans: 0.025 % of airborne material is estimated to be inhalable, whereas about 0.002 % or less of inhaled material is predicted to be deposited in the pulmonary region (PU), i.e. respirable fraction. The material deposited in the tracheobronchial (TB) and the extrathoracic region (Head) may be assumed to be cleared to the GI tract (i.e., by mucociliary escalation and subsequent swallowing).

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