PBK modeling for metals. Examples with lead, uranium, and chromium

Abstract

Physiologically-based models for metals differ in several key respects from models for organic compounds. Although sequestration by binding to specific metal-binding proteins in liver, kidney, and red cell may be important, neither the magnitude and pattern of metabolism nor potential accumulation in fat is a component of models of metal kinetics. In addition, the long residence times of bone-seeking elements require that bone turnover and metabolism be incorporated into physiologically-based models for these elements. Three mechanisms (rapid exchange at bone/blood interfaces, trapping or incorporation with forming bone and loss with resorbing bone, and slow exchange throughout the total bone volume) are potentially important in the overall interchange of bone-seeking elements between blood and bone. Three examples are given of applications of physiologically-based kinetic models for the bone-seeking elements lead, chromium, and uranium to assist in answering practical questions relating to bioavailability, distribution, and data interpretation.