Kinetic analysis of lead metabolism in healthy humans.

Abstract

A B S T R A C T The steady state kinetics of lead metabolism were studied in five healthy men with stable isotope tracers. Subjects lived in a metabolic unit and ate constant low lead diets. Their intake was supplemented each day with 79-204 /Ag of enriched lead-204 as nitrate which was ingested with meals for 1-124 days. The concentration and isotopic composition of lead was determined serially in blood, urine, feces, and diet and less commonly in hair, nails, sweat, bone, and alimentary tract secretions by isotopic dilution, mass spectrometric analysis. The data suggest a three-compartmental model for lead metabolism. The first compartment encompasses blood and is 1.5-2.2 times larger than the blood mass. It contains approximately 1.7-2.0 mg of lead and has a mean life of 35 days. This pool is in direct communication with ingested lead, urinary lead, and pools two and three. The second compartment is largely composed of soft tissue, contains about 0.3-0.9 mg of lead, and has a mean life of approximately 40 days. This pool gives rise to lead in hair, nails, sweat, and salivary, gastric, pancreatic, and biliary secretions. Pool three resides primarily in the skeleton, contains the vast quantity of body lead, and has a very slow mean life. Bones appear to differ in their rates of lead turnover. Within the relatively small changes in blood lead observed in the present study, the transfer coefficients between the pools remained constant.

Indices of potential lead hazard.

“…On a comparative basis, Rabinowitz et al (33) point out that their results in humans differ from those reported for the rat and hamster. When rats and hamsters inhaled radioactive lead, lead accumulated in the erythrocytes only to about half the extent, there was more found in the kidneys, and clearance from the blood was more rapid (60).…”

“…However, its diagnostic value at the borderline of hazardous conditions is quite limited. It has been found that PbB is more a measure of very recent exposure (30)(31)(32)(33) than of total body burden, and most lead in the body is within the hard and soft tissues (33)(34)(35)(36). Below are some of the best data for "normal" concentrations of PbB.…”

“…Rabinowitz et al (33) studied lead under dynamic conditions at physiologic concentrations in five healthy men with the stable isotope, 204Pb. The data obtained could be explained on the basis of a three-compartment model, though it is more likely that there are many compartments (pools).…”

“…Analyses of the lead in different bones and in different parts of the same bones (34,35) and the metabolic, compartmental studies of Rabinowitz et al (33,90) show that bone is heterogeneous with regard to the uptake and metabolism of lead. There are both rather mobile and relatively stable compartments.…”

Bone lead (Pb) content at the tibia is associated with thinner distal tibia cortices and lower volumetric bone density in postmenopausal women

“…Plasma transfer of lead into bone, through partition exchange, results in the replacement of calcium within hydroxyapatite crystals by lead [9]. A three-compartment model of human lead metabolism and exchange developed by Rabinowitz et al illustrates the mean lifetime exposure of lead within soft tissue, blood, and bone [10]. Over time, bone serves as the largest volume for lead distribution with a total burden as high as 90-95% by adulthood [11].…”