LAUSR

Abstract Dynamic modeling of how particulate matter (PM) transport, deposit, and translocate from human respiratory systems to systemic regions subject to indoor and outdoor exposures are essential for case-specific lung dosimetry predictions and occupational health risk assessments. Because of the invasive nature and imaging resolution limitations of existing in vitro and in vivo methods, Computational Fluid-Particle Dynamics plus Physiologically Based Pharmacokinetic/Toxicokinetic (CFPD-PBPK/TK) models have been employed to predict the fate of the respirable aerosols for decades. This paper presents a guide on how to use the multiscale CFPD-PBPK/TK models to predict lung dosimetry and systemic translocations quantitatively with 3D subject-specific human respiratory systems. The tutorial aims to clarify possibly ambiguous concepts. The step-by-step modeling procedure should help researchers set up the CFPD-PBPK/TK model accurately, following the standard model validation and verification (VV (b) the significance of choosing the appropriate turbulence model to predict the laminar-to-turbulence pulmonary airflow regimes; and (c) the standard (V&V) procedures of submodels in the CFPD-PBPK/TK modeling framework. The tutorial also highlights the deficiencies of current CFPD-PBPK/TK models, clarifies the missing biomechanisms and aerosol dynamics in the respiratory systems that need to be considered to build the next-generation virtual human whole-lung models.