Human continuous hydrogen cyanide inhalation predictor with a physiologically based pharmacokinetic (PBPK) model

Area of Science:

• Toxicology
• Pharmacokinetics
• Environmental Health

Background:

• Hydrogen cyanide (HCN) is a highly toxic, volatile substance with significant human health risks from inhalation.
• Existing physiologically based pharmacokinetic (PBPK) models struggle to simulate continuous HCN inhalation and predict atmospheric concentrations.
• Effective diagnostic tools are crucial for managing HCN exposure incidents.

Purpose of the Study:

• To develop and validate a PBPK model, the Human Continuous Cyanide Inhalation Predictor (HCCIP), for simulating continuous HCN inhalation.
• To enable prediction of cyanide concentration-time courses in the human body and exhaled air.
• To enhance risk assessment capabilities for HCN exposure scenarios.

Main Methods:

• Developed the HCCIP model, incorporating lungs, kidneys, liver, and slowly perfused tissues.
• Utilized existing PBPK model data for cyanide ingestion due to limited HCN inhalation pharmacokinetic data.
• Validated HCCIP predictions against published datasets for cyanide concentration-time courses and inhaled air levels.

Main Results:

• The HCCIP model successfully predicts cyanide concentration-time courses in the human body and exhaled air.
• HCCIP accurately forecasts HCN concentration in inhaled air based on blood cyanide levels.
• Model validation against existing datasets confirmed the accuracy and reliability of HCCIP simulations.

Conclusions:

• The HCCIP model is an effective tool for assessing risks associated with continuous HCN inhalation.
• HCCIP enhances current air dispersion models (e.g., AERMOD, CALPUFF) for specific HCN release source risk assessment.
• This PBPK model provides a valuable advancement for managing and mitigating HCN exposure risks.