Weight of epidemiological evidence for titanium dioxide risk assessment: current state and further needs.

We address here the importance of epidemiological evidence in risk assessment and decision-making in Europe. To illustrate this, titanium dioxide (TiO <sub>2</sub> ) was used as a model compound. TiO <sub>2</sub> is widely used as an odorless white pigment and opacifying agent. A recent systematic review assessing the weight of evidence on the relationship between exposure to TiO <sub>2</sub> (all forms) and cancer in humans questions the assumptions that TiO <sub>2</sub> is an inert material of low toxicity. Based on this new data, France submitted a proposal to classify TiO <sub>2</sub> as a possible human carcinogen under the European regulation. The European Chemicals Agency Risk assessment committee concluded that TiO <sub>2</sub> (all forms) warrants a classification as a suspected human carcinogen via inhalation (Category-2) under the CLP regulation (for Classification, Labeling and Packaging of chemicals). No considerations was given to TiO <sub>2</sub> particle size, which may affect human health effects. Consequently, further epidemiological studies are needed to assess possible associations between different physical-chemical characteristics of TiO <sub>2</sub> exposures and their impact on human health. This would allow strengthening the evidence on which to build the most appropriate regulation and to guaranty safe use given any exposure route of any TiO <sub>2</sub> particle shape or size