Nanomaterial characteristics resulting in increased lung deposition (in alveoli), impaired clearance rate, and the induction of pulmonary inflammation. The figure shows the physico-chemical characteristics of nanoparticles that result in 1) Increased lung deposition in the alveoli (left panel): Nanoparticles with a primary/agglomerate size of <100 nm, or an agglomerate size between 100 nm and 1 μm with a high density, will deposit efficiently in the alveolar region. Non-hygroscopic nanoparticles will not grow in size by water uptake, resulting in a higher chance to reach the alveoli. 2) Impaired clearance rate (middle panel): Particles/agglomerates of <100 nm are less efficiently phagocytised, nano-fibres and –platelets are less efficiently cleared compared to spheres, chemical composition influences clearance rate, charged nanoparticles attract proteins and reduce their clearance, and none or slowly dissolving nanoparticles are less efficiently cleared compared to fast dissolving nanoparticles. 3) The induction of pulmonary inflammation (right panel): After deposition of nanoparticles in the alveoli, the shown characteristics all influence the induction of pulmonary inflammation. Cationic particles are easily taken up by cells, fast dissolving nanoparticles can release toxic ions, and nanoparticles with a high surface reactivity can damage the lungs.