Development of a Physiologically Based Toxicokinetic Model for Human Exposure Risk Assessment of Methylene Diphenyl Diisocyanate(Mdi); [توسعه یک مدل توکسیکوکینتیکی مبتنی بر شواهد فیزیولوژیکی جهت ارزیابی ریسک مواجهه انسان با متیلن دیفنیل دیایزوسیانات )Mdi )] Publisher



Mozaffari S¹ ; Bayatian M² ; Hsieh NH³ ; Khadem M¹ ; Garmaroudi AA¹ ; Ashrafi K⁴ ; Shahtaheri SJ^{1, 5}
Source: Iran Occupational Health Published:2023

Abstract

Background and aims: Introduction: This study aims to develop a physiologically based toxicokinetic (PBTK) model for human systemic exposure assessment of methylene diisocyanate (MDI) and prediction of its urinary metabolites, given the lack of a developed model. Methods: A PBTK model was constructed with parameter uncertainty and variability to assess potential exposure to MDI. The model was calibrated using Bayesian analysis via the Markov chain Monte Carlo approach. Exposure reconstruction or reverse dosimetry was performed as an occupational exposure risk assessment through time-kinetic urinary elimination of methylenedianiline (MDA), the biomarker of MDI, in those exposed to unknown exposure scenarios. Results: The amount of MDA excretion peaked approximately 15 hours after the start of exposure. Simulation results of reverse dosimetry for both exposed persons to the unknown concentration of MDI revealed experienced more systemic exposure than NOAEL (NOAEL = 0.2 ug/l). The exposure concentration (±SD) was 1.58 (±0.856) and 1.005 (±0.705) ug/l for person A and B, respectively. Comparison of predicted results with experimental data shows the model can estimate kinetic elimination closely to experimental data (R2 = 0.9). Conclusion: The developed model can estimate the internal dose of body tissues and understand the risk of occupational exposures by comparing the simulation of biological monitoring with acceptable limit values and determining the potential of external exposure. © 2023 Iran University of Medical Sciences. All rights reserved.