Fig. 3

Compatibility of the different dose metrics between in vivo and in vitro approaches. In order to compare in vitro and in vivo conditions it is important to use common dose metrics. The doses are often expressed as concentrations, including mass/volume of liquid in vitro in submerged conditions and mass/volume of air in vivo in inhalation studies. However, these metrics cannot be used within the different in vivo (inhalation or instillation) and in vitro (ALI or submerged) methodologies. Moreover, using concentrations in mass/volume does not take into account the real contact between the NMs and the cells or tissues. Thus it does not seem appropriate to use such dose metrics for in vivo-in vitro comparisons; more particularly for poorly soluble NMs as their toxicity is attributable to their surface reactivity. In vivo, the total mass of NMs administered per lungs, animal or mass is often used as dose metric. This dose metric takes into account the deposition in the overall organ, but cannot be used in vitro. Nevertheless, common dose metrics can be used by normalizing the mass deposited on cells in vitro or into the lungs in vivo by the surface of the tissues or by the number of cells. Doses expressed in mass can also be normalized NM surface areas, that has been shown to be the most effective dose metric for acute NM toxicity in the lung