A human physiologically-based bio-kinetic model for uranium

Uranium is a naturally occurring element that humans are continuously exposed to at low levels due to its pervasive presence in the environment. However, elevated exposure can pose significant health risks. Daily exposure occurs through inhaling contaminated air, ingesting uranium-contaminated food or water, and dermal contact. Once absorbed, uranium enters the bloodstream and is distributed to various organs. Traditional pharmacokinetic models, employing a compartmental approach, have been widely used to study the distribution and toxicity of absorbed uranium. This study developed a physiologically based biokinetic (PBBK) model using Python programming to simulate the absorption, distribution, metabolism, and elimination (ADME) of uranium in humans. Unlike traditional models, this approach utilizes organ-specific blood flow rates and partition coefficients for better physiological realism. The model incorporates 17 compartments, including 15 critical organs and 2 dummy compartments. Permeability rate-limited kinetics were applied to bone compartments (cortical and trabecular), while perfusion rate-limited kinetics were assumed for soft tissues such as the liver, kidneys, and gut. Simulations of fractional uranium retention in infants, children (ages 5, 10, and 15), and adults following intravenous injection show reasonable agreement with previous studies using compartmental models, particularly in predicting skeletal retention, which increases with age due to bone mineralization. For chronic oral ingestion scenarios, the model reliably reproduces observed uranium retention patterns, demonstrating its robustness across different exposure routes.