In vivo studies need to be performed using the most realistic mode of application, the nearest considered route of human exposure.The toxic effects resulting from a pulmonary exposure has been widely documented, in particular to contribute to a professional risk evaluation. But the animal exposure methods are moving towards more realistic systems than the classical intratracheal administration: aerosol production then exposition of the whole animal or “nose only” [O. Creutzenberg et al., Inhalation Toxicology 24 (2012) 821-830 / L. Geraets et al., Toxicological Sciences 127 (2012) 463-473].

To avoid non-specific toxic effects of materials due to administration of higher doses, it is better to focus on low dose chronic exposures [Q. Sun et al., Journal of Hazardous Materials 235-236 (2012) 47-53 / S. Seok et al., Journal of Applied Toxicology 33 (2013) 1089-1096]. For example, many studies have been observed, throughout single administration (pulmonar or intra cavitary) with doses exceeding the threshold of thelung overload, a cytotoxicity then an inflammation. Given much lower human exposure levels, the relevance of these effects is questionable.

Animal toxicology studies bring to light a more intense inflammatory response than with micron-sized particles. This inflammation may be accompanied by fibrosis reactions or granulomas more or less durable.

A large variability of effects is observed depending on the characteristics of nanoparticles (chemical nature, size, shape, surface condition, associated impurities such as catalysts). In some cases, the surface presented by all nanoparticles seems to be a parameter that is better correlated to the effects observed than the mass.