Titanium

Endpoint summary

Description of key information

Acute toxicity, oral:
LD50 > 5000mg/kg bw
Acute toxicity, dermal:
Conduct of an acute dermal toxicity study is unjustified as 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).
Acute toxicity, 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 the modified Heubach method, as reported under section particle size distribution (granulometry). Based on the results of the MPPD model only about 0.01 % or less of inhaled material is predicted to be deposited in the pulmonary region (PU), whereas 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) (cf. Annex VIII section 8.5 Column 2 of regulation (EC) 1907/2006).

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 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 the modified Heubach method, as reported under section particle size distribution (granulometry). Based on the results of the MPPD model only about 0.01 % or less of inhaled material is predicted to be deposited in the pulmonary region (PU), whereas 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) (cf. Annex VIII section 8.5 Column 2 of regulation (EC) 1907/2006).

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 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).

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.

 

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.

 

Acute inhalation toxicity

The references Hall, G.T.(1979) and McDonald, P.(1989) are considered as the key studies for acute inhalation toxicity and will be used for classification. Rats were whole body exposed towards titanium dioxide dust for 4 hours at 4.99 and 6.82 mg/L, 3.43 and 5.09 mg/L air. During the conduct of the study no mortalities occurred.

LC50 inhalation, rat > 6.82 mg/L air

The classification criteria acc. to regulation (EC) 1272/2008 as acutely toxic are not met since the ATE for dusts and mists is above 5.0mg/L, hence no classification required.

 

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

The classification criteria acc. to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, inhalation dust/mist/fume 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, inhalation dust/mist/fume for a Category 1 classification of 1.0 mg/L/4h and at the guidance value, inhalation dust/mist/fume for a Category 2 classification of 5.0 mg/L/4h. Therefore, no classification is required. Finally, any category 3 classification should primarily be based on human data. However, such classification is also not warranted, since observations on respiratory irritation in test animals (mainly rats) only were only observed at artificially high inhalation exposure levels which are without relevance to current workplace conditions. It can be safely assumed that standard occupational hygiene measures provide a sufficient level of worker protection.