Abstract
In order to assess the comparability of lead disposition in the cynomolgus monkey to that in the human, we determined the relationships among blood lead concentration, plasma lead concentration, and lead excretion in monkeys. Six adult (3–5 kg) female cynomolgus monkeys (Macaca fascicularis) without previous experimental lead exposure were given single intravenous injections of from 750 to 3300 μg lead as lead nitrate, labeled with210Pb, per kilogram body weight. Four additional monkeys, fasted overnight, were administered single oral doses of either 750 or 1500 μg lead as lead nitrate, labeled with210Pb, per kilogram for the assessment of fractional absorption. Blood and plasma lead concentrations (10 monkeys) and urinary and fecal excretion of lead (2 monkeys) were followed for up to 16 days after lead administration. Fractional absorption from an oral dose was 44% at the lower of the two doses and 22–28% at the higher dose. The relationship between plasma and blood lead concentrations was found to be similar to that in humans, with plasma lead concentration at most a few percent of total blood lead concentration at low concentrations. Partitioning of lead across the red cell membrane in the 2 monkeys given exceptionally high doses (3300 μg/kg) intravenously was distinctly lower than that in the 4 monkeys given lower intravenous doses. Urinary clearance of lead in these 2 monkeys was 19% of the estimated glomerular filtration rate, within the range of efficiencies reported for humans. Fecal clearance, however, was anomalous and appeared to be an artifact of the very high dose. Examination of published data for urinary and fecal lead excretion in three adult baboons showed that both functions in the baboons were quantitatively similar to those in humans. Urinary clearance in the baboons was 14–24% of the estimated glomerular filtration rate, and fecal clearance was 78–85% of the urinary clearance. We conclude that nonhuman and human primates are comparable with respect to the relationship of plasma lead concentration to blood lead concentration and the relative efficiency of lead excretion in urine and feces.
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