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

Abstract

Hydrogen cyanide (HCN) is volatile and highly toxic with acute and chronic effects on humans. Gaseous HCN enters the atmosphere from natural processes or industrial activities, which lead to human exposure. Effective intervention in cases of HCN inhalation requires an efficient diagnostic tool. The existing physiologically based pharmacokinetic (PBPK) model for HCN cannot clearly simulate continuous HCN inhalation or predict HCN levels in inhaled air. The current study presents a PBPK model for continuous inhalation of HCN, called Human Continuous Cyanide Inhalation Predictor (HCCIP). Since existing data on pharmacokinetics of HCN inhalation are limited, HCCIP utilizes extensive data from the current authors' PBPK model on cyanide ingestion. The structure of HCCIP comprises the lungs, kidneys, liver, and slowly perfused tissue. In both the human body and in exhaled air, HCCIP features the ability to predict concentration-time courses of cyanide. Moreover, HCCIP can predict HCN concentration in inhaled air from known blood cyanide levels. After completion, the results of HCCIP were validated against preexisting published datasets. The simulation results agreed with these datasets, validating the model. The HCCIP model is an effective tool for assessing risk from continuous HCN inhalation, and HCCIP extends the capabilities of air dispersion modeling, such as AERMOD or CALPUFF, to assess HCN risk from specific release sources.