Reconstruction of exposure to methylene diphenyl-4,4′-diisocyanate (MDI) aerosol using computational fluid dynamics, physiologically based toxicokinetics and statistical modeling

Abstract

Objectives

This study employed computational fluid dynamics (CFD), physiologically based toxicokinetics (PBTK), and statistical modeling to reconstruct exposure to methylene diphenyl-4,4'-diisocyanate (MDI) aerosol. By utilizing a validated CFD model, human respiratory deposition of MDI aerosol in different workload conditions was investigated, while a PBTK model was calibrated using experimental rat data. Biomonitoring data and Markov Chain Monte Carlo (MCMC) simulation were utilized for exposure assessment.

Results

Deposition fraction of MDI in the respiratory tract at the light, moderate, and heavy activity were 0.038, 0.079, and 0.153, respectively. Converged MCMC results as the posterior means and prior values were obtained for several PBTK model parameters. In our study, we calibrated a rat model to investigate the transport, absorption, and elimination of 4,4′-MDI via inhalation exposure. The calibration process successfully captured experimental data in the lungs, liver, blood, and kidneys, allowing for a reasonable representation of MDI distribution within the rat model. Our calibrated model also represents MDI dynamics in the bloodstream, facilitating the assessment of bioavailability. For human exposure, we validated the model for recent and long-term MDI exposure using data from relevant studies.

Conclusion

Our computational models provide reasonable insights into MDI exposure, contributing to informed risk assessment and the development of effective exposure reduction strategies.

Keywords:

• PBTK model
• CFD model
• risk assessment
• exposure assessment
• isocyanates
• Bayesian analysis

Acknowledgments

The authors thank the HPC Center of Tarbiat Modares University to provide High-Performance Computing for CFD modeling in this work.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, [SJSh], upon reasonable request.

Notes

1 Root Mean square error

Additional information

Funding

The research was funded by the Tehran University of Medical Sciences and Health Services (Project number: 50578-99-3-99), ethical code of IR.TUMS.SPH.REC.1399.221 (2020-5-10).