Studies on repeated dose toxicity need not to be conducted as target chemical titanium oxychloride is an unstable intermediate resulting from the hydrolysis of parent compound titanium tetrachloride. Repeated dose toxicity studies on the final hydrolysis product titanium dioxide reveal that the substance needs not to be classified for repeated dose toxicity. Concerning the other final hydrolysis product hydrochloric acid, its corrosiveness is not of relevance in this case, as the target substance titanium oxychloride already is being classified as corrosive as well.
According to column 2 of the table given in REACH Annex VIII and IX, as a general rule no studies on repeated dose toxicity need to be conducted if the substance is highly unstable and if the final reaction products are well researched. This is deemed to be the case as target chemical titanium oxychloride is an unstable intermediate resulting from the hydrolysis of parent compound titanium tetrachloride. Repeated dose toxicity studies on the final hydrolysis product titanium dioxide reveal that the substance needs not to be classified for repeated dose toxicity. Concerning the other final hydrolysis product hydrochloric acid, its corrosiveness is not of relevance in this case, as the target substance titanium oxychloride already is being classified as corrosive as well.
No classification of the unstable intermediate compound titanium oxychloride as to its repeated dose toxicity properties.
Concerning classification of the final hydrolysis product titanium dioxide, see the following discussion:
According to regulation (EC) 1272/2008, a classification for specific target organ toxicity – repeated exposure shall be taken into account only when reliable evidence associating repeated exposure to the substance with a consistent and identifiable toxic effect demonstrates support for the classification. These adverse health effects include consistent and identifiable toxic effects in humans, or, in experimental animals, toxicologically significant changes which have affected the function or morphology of a tissue/organ, or have produced serious changes to the biochemistry or haematology of the organism and these changes are relevant for human health.
The following observations have been made in experimental animals and in human epidemiological studies (inhalation route):
(i) No systemic toxicity was shown to result from chronic inhalation exposure in rats to high concentrations of pigment grade titanium dioxide
(ii) Particle overload is observed for insoluble particles such as titanium dioxide (Levy, 1995), whereby the rat is the most sensitive species studied, and species-specific differences are demonstrated in various mechanistic animal studies (Oberdörster, 1996). It has been demonstrated with reasonable certainty that lung overload conditions are not relevant for human health and, therefore, results based on these data do not justify classification.
(iii) It has also been clearly demonstrated through epidemiological studies of titanium dioxide -exposed workers that there is no causal link between titanium dioxide exposure and the risk of non-malignant respiratory disease in humans
For the reasons presented above, no classification for specific target organ toxicant (STOT) – repeated exposure, inhalation is required.