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Published on: February 23, 2020
Inhalation toxicity assessment of imidazolium ionic liquids by a physiology-based high-throughput lung-burden
Wanjun Zhang1, Yizhe Wu2, Jiayin Sun3
1Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan 250001, China; Department of Occupational and Environmental Health, School of Public Health, Qingdao University, Qingdao 266071, China; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, University of Chinese Academy of Sciences, Beijing 100190, China.
A new computational model predicts lung chemical burden to assess inhalation toxicity of diverse organic compounds, including ionic liquids. This approach aids in identifying chemicals with higher pulmonary toxicity potential for safer design.
Area of Science:
- Toxicology
- Computational Chemistry
- Pharmacokinetics
Background:
- Assessing inhalation toxicity of diverse organic chemicals, like imidazolium-based ionic liquids (ILs), is challenging.
- Lung-selective retention is a key factor driving potential pulmonary hazards.
Purpose of the Study:
- To develop a computational framework for simulating time-resolved lung burden after intratracheal instillation.
- To evaluate the framework's ability to predict pulmonary retention and its association with toxicity.
Main Methods:
- Developed a physiology-based computational framework (burden-based pulmonary tissue kinetics, BB-PTK).
- Incorporated passive diffusion, electro-migration, pH-pKa ionization, and lipid-water partitioning.
- Validated model predictions against experimental data for four compounds and analyzed literature data for 22 chemicals.
Main Results:
- BB-PTK showed reasonable concordance between simulated and observed pulmonary burden trajectories.
- Compounds linked to pulmonary toxicity had significantly longer lung half-lives (22.00 h vs. 3.32 h).
- Predicted 7-day integrated lung burden correlated with acute lung injury scores, suggesting utility for toxicity screening.
Conclusions:
- The BB-PTK framework offers a scalable, mechanistically interpretable strategy for high-throughput screening of inhalation hazards.
- Identified lipophilicity, pKa, and charge state as key determinants of cumulative lung exposure.
- Provides a basis for safer-by-design prioritization of ionic liquids and related organic chemicals.
