The importance of a validated standard methodology to define in vitro toxicity of nano-TiO2.

Several in vitro studies on the potential toxicity of nano-TiO(2) have been published and recent reviews have summarised them. Most of these reports concluded that physicochemical properties of nanoparticles are fundamental to their toxicological effects. No published review has compared in vitro tests with similar test strategies in terms of exposure duration and measured endpoints and for this reason we have attempted to assess the degree of homogeneity among in vitro tests and to assess if they afford reliable data to support risk assessment. The responses in different in vitro tests appeared to be unrelated to primary particle size. The biologically effective concentrations in different tests can be seen to differ by as many as two orders of magnitude and such differences could be explained either by different sensitivities of cell lines to nanoparticles or by effect of the test media. Our review indicates that even when the in vitro tests measure the same biomarkers with the same exposure duration and known primary particle sizes, it is insufficient merely to use such data for risk assessment. In the future, validated standard methods should include a limited number of cell lines and an obligatory selection of biomarkers. For routine purposes, it is important that assays can be easily conducted, false negatives and false positives are excluded and unbiased interpretation of results is provided. Papers published to date provide an understanding of the mode on nano-TiO(2) action but are not suitable for assessment and management of risk.