In this contribution, we show the suitability of a 3D airway model, when coupled with a nebulizer system, for simulating workplace exposure to nanoparticles. As a proof of concept, workplace exposure to silica nanoparticles was experimentally measured in an occupational facility where nanoparticles are produced weekly, and compared with the official limit value for bulk silica materials. These values of potential exposure were simulated in a 3D airway model by nebulizing low doses (from 0.90 to 55 µg/cm2) of silica nanoparticles over a prolonged period (12 weeks of repeated exposure, 5 days per week). Overall, the results suggest the efficiency of the defense mechanisms of the respiratory system and the clearance of the breathed silica nanoparticles by the mucociliary apparatus in accordance with the recent in vivo data. This in vitro platform shows that the doses tested may correlate with the occupational exposure limit values. Such relationship could provide regulatory-oriented data useful for risk classification of nanomaterials.