Prediction of response of blood lead to airborne and dietary lead from volunteer experiments with lead isotopes

Abstract

To predict the response of blood lead to airborne and dietary lead requires knowledge of the rate of uptake of lead into the body from lung and gut, its subsequent partitioning between compartments, the stay time in those compartments, and its redistribution or excretion. Tracer studies with volunteers have shown no differences in systemic distribution of inorganic lead between tissues whether it is taken by inhalation, ingestion or injection. Lead is rapidly transferred from plasma to red cells, and there is slower movement thence into liver and other soft tissues, to bone, and to excreta. Work at Harwell and elsewhere with 203 Pb has shown that the initial rapid distribution leaves rather over half the assimilated lead attached to red cells. The result is remarkably consistent, and applies also to dogs and baboons. The renal clearance ( V u ) (ratio of U to C B , or daily urinary output expressed as mass of blood having the same lead content), and also the endogenous faecal clearance excretion rate ( V f ), have been measured on human subjects with 203 Pb. The results are consistent with V u , as measured with stable lead, with many results giving V u about 0.1 kg d -1 . However, there is evidence that V u increases when C B is elevated above the normal. This may explain the nonlinear relation between uptake of lead and the corresponding C B , which has been observed in humans exposed to environmental lead. V f is about half V u , and a similar result applies to calcium. The clearance rate V a of 203 Pb from blood to bone has been measured, and a variety of human and animal data in the literature has been reviewed to support this result. Combined with bone turnover rates (from data on 90 Sr), the postulated inputs to bone give estimates of skeletal burdens which agree with post-mortem results. The results are combined in a compartment model. The retention of lead aerosol in the lung, and uptake from the gut are then considered, with use made of radioactive tracer ( 203 Pb), stable isotopic tracer ( 204 Pb) and total lead measurements. Here there is great diversity of results. Particle size affects the fractional lung retention and the site of retention, which in turn affects the fractional uptake to blood. Presence or absence of food in the stomach when lead is ingested greatly affects the fractional gut uptake. Finally, a limited selection of results of volunteer exposures to stable lead in air or diet are reviewed. It is shown that the elevation in C B from the measured intakes, over weeks or years in some cases, can be explained by the results of the proposed metabolic model, provided reasonable assumptions are made about the input parameters.