How NovaMechanics developed an integrated in silico approach combining aerosol dynamics, lung deposition, and PBPK modelling for nanomaterial occupational exposure assessment — from airborne concentration to organ-level dose. Bridging Exposure to Internal Dose Assessing the health risk of occupational nanomaterial exposure requires connecting airborne concentrations to internal organ doses. This demands integration of three distinct modelling domains: aerosol dynamics in workplace air, particle deposition in the respiratory tract, and pharmacokinetic distribution throughout the body. No single tool addressed this full chain for engineered nanomaterials. Multi-Box Aerosol Model Developed a two-zone (near field/far field) aerosol dynamics model accounting for coagulation, gravitational deposition, and ventilation. Predicts time-dependent airborne NM concentrations at the worker breathing zone during manufacturing operations. ICRP Lung Deposition Model Implemented ICRP-based deposition equations computing regional lung deposition fractions in head airways (HA), tracheobronchial (TB), and alveolar (AL) regions based on particle aerodynamic diameter and breathing parameters. PBPK Biodistribution Model Built a physiologically-based pharmacokinetic model with 10+ organ compartments including liver, spleen, kidneys, heart, brain, lungs, GI tract, and bone. Includes phagocytizing cell dynamics for NM-specific clearance mechanisms. Model Chain Integration Connected the three models into a seamless chain: aerosol model outputs feed lung deposition inputs, which in turn drive PBPK simulations. This enables end-to-end prediction from workplace emission to organ-level NM concentrations. TiO2 Validation and MPPD Comparison Validated the integrated framework using TiO2 nanomaterials (22 nm) in an occupational exposure scenario. Compared lung deposition predictions against the MPPD gold-standard model, demonstrating strong agreement across respiratory regions.
