A Human Physiologically-based Bio-kinetic Model for Cadmium

Abstract

A physiologically-based bio-kinetic (PBBK) model, capable of simulating the absorption, distribution, and elimination of cadmium in humans has been developed. The formulation of this model was based on human data cleaned from literature. The liver, kidney, lung, artery, vein, stomach, small intestine and remainder of the body (other tissues not modelled explicitly) were modelled as compartments. While transfer rate coefficients were used to describe the kinetics of cadmium in the gastrointestinal track, the model used blood flow rates and partition coefficients rather than the traditional transfer rate coefficients to describe the distribution and accumulation of the chemical into critical organs such as liver, kidney and remainder of the body. A perfusion rate-limited kinetics model was assumed for these critical organs, where each of these tissues was regarded as a well-stirred compartment, without any concentration gradient within the compartment. The partition coefficients for critical organs modelled, along with transfer rate coefficients describing oral ingestion and inhalation were estimated by fitting the simulated concentration of cadmium in the liver, kidney and urine to observed concentrations found in literature. The model was capable of simulating, to a good degree of success, the results of empirical observations and other simulations found in literature. Simulations by the model also indicate that the partition coefficient of cadmium for the kidney, liver and other critical organs was higher in smokers.