Integrated IATA: From Indoor Air to Whole-Body Biodistribution

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.

Environmental Science: Nano • 2022
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The Challenge

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.

3 Models
Aerosol + lung deposition + PBPK integrated
10+
Organ compartments in PBPK model
22 nm
TiO2 NMs as reference case study

Our Methodology

A seamless multi-stage pipeline bridging workplace air to organ-level exposure

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.

Results at a Glance

3-in-1
Model Integration
Aerosol → lung → PBPK seamless chain
10+
Organ Compartments
Liver, spleen, kidneys, heart, brain, lungs
22 nm TiO2
Reference Case
Validated occupational exposure scenario
Near/Far Field
Aerosol Zones
Two-zone workplace concentration model
MPPD Validated
Gold Standard
Lung deposition comparison confirmed
3 Web Tools
Cloud Deployed
Each model accessible independently

Related Publication

Peer-Reviewed Paper

Towards an in silico integrated approach for testing and assessment of nanomaterials: from predicted indoor air concentrations to lung dose and biodistribution

Tsiros P., Cheimarios N., Tsoumanis A., Jensen A.C.Ø., Melagraki G., Lynch I., Sarimveis H., Afantitis A. — Environmental Science: Nano, 2022, 9(4):1282–1297 — DOI: 10.1039/D1EN00956G