Mechanistic computational framework for human half-lives of 931 organic chemicals

Abstract This study presents a mechanistic computational modeling framework to estimate chemical dissipation half-lives in the human body. The physiologically based kinetic matrix was developed to simulate organ-specific and whole-body half-lives for 931 chemicals across four exposure routes, incorporating age- and gender-specific physiological parameters. A supplementary database containing human physiological data, physicochemical parameters, and simulation codes is provided for users to perform customized analyses. Model predictions show that whole-body half-lives are longest in infancy and old age and shortest in young adulthood, reflecting developmental patterns of liver and kidney function. Gender differences reverse around age six due to differing maturation trajectories. While physiological parameters mainly determine whole-body half-life, organ-specific results reveal consistently long half-lives in fat and short half-lives in the liver under oral exposure. Predicted and reported values align well, though overestimation can occur. The computational framework can be further refined with improved physiological and chemical-specific data.