Conclusion

Several dose metrics have been tried to describe the relationship between particle dose and lung overload associated-effects. Particle mass is the most widely used dose metric for inhalation studies because of its practical convenience, but it has been shown to be less suitable to describe the relationship with lung overload effects. Dose metrics which have been proposed as being suitable are primarily the particle volume and the particle surface. Albeit that multiple studies have been published supporting the adequacy of these dose metrics, no one universal dose metric has been identified thus far, and it is unlikely that any metric will be singled out because the best metric might depend heavily on the investigated substance and the type of effect investigated.

Other particle characteristics have been shown to play a significant role in the way the respiratory system responds to particle exposure. The particle density is directly linked to the volumetric overload concept, and the way it is determined is a critical parameter. The particle size is directly related to the surface-based dose metric. The particle shape has been demonstrated to have a significant impact on the particle's aerodynamic behaviour and on how lung cells interact with particles. Also differences in surface reactivity of chemically similar particles can result in different biological effects.

The successful inclusion of studies on nanomaterials in both the models relying on the volume-based dose metric and the surface-based dose metric have demonstrated the relevance and applicability of the concept of lung overload also for nano-particles.

The parameters determining the dosimetry of inhaled particles both in laboratory animals and humans are well understood, and models allowing the estimation of the deposited dose have been developed and validated. When using these models, it is of critical importance that the methodologies used to obtain the input parameters are well developed and understood.