Easier to implement than experiments on animals, research "in vitro" uses cell cultures (lungs, liver, etc.) to study the mechanism of interaction with cells with nanoparticles or with biological molecules. But, it seems necessary to use adapted cellular models, capable of internalizing nanomaterials and appropriate to simulate human conditions of exposure. The cellular model must be representative of the target organ: primo-exposed organs or organs exposed after translocation. Human cell use is thus preferred [M. Honma et al., Environmental and Molecular Mutagenesis 52 (2011) 373-384].

The culture experimental conditions may also be changed and improved. Some recent studies have been evaluated kinetic and toxic effects via most appropriate cellular models (as an example the co-culture system) [D. Napierska et al., Toxicology Letters 211 (2012) 98-104] and the cultured lung cells at the air-liquid interface [P. Mertes et al., Journal of Aerosol Medicine and Pulmonary Drug Delivery 26 (2013) 228-235].

Nanomaterial interaction with the experimental system (affinity for proteins, growth drivers,…) must be take into account whatever the implemented test system.