Physiologically based models for bone-seeking elements. IV. Kinetics of lead disposition in humans.

A model of lead disposition in humans has been developed. In addition to liver, kidney, other well-perfused and poorly perfused tissues, the model incorporates bone as an explicit compartment whose volume, composition, and metabolic activity are all age-dependent. The rates of all transfers of lead out of the blood are related to plasma lead. The relationship between plasma lead and blood lead is expressed as a capacity-limited binding associated with the erythrocyte. Interchanges of lead between plasma and bone are modeled as partially interactive events linked in series. Blood traversing the bone passes first through a surface region of rapid exchange before entering the metabolically active region of bone, where lead is incorporated with calcium into mineralizing bone and returned to the blood with resorbing bone. After leaving the larger vessels, plasma superfusate enters the canalicules that feed bulk bone, where lead diffuses radially outward into the total bone volume. Model simulations are compared with data from epidemiologic and experimental dietary and inhalation studies in adults.