Use of Sequentially Administered Stable Lead Isotopes to Investigate Changes in Blood Lead during Pregnancy in a Nonhuman Primate (Macaca fascicularis)

Abstract

The effects of pregnancy on the flux of lead from maternal bone were investigated in five females from a unique colony of cynomolgus monkeys (Macaca fascicularis) which had been dosed orally with lead (approximately 1100–1300 μg Pb/kg body wt) throughout their lives (about 14 years). Through the use of stable lead isotopes²⁰⁴Pb,²⁰⁶Pb, and²⁰⁷Pb, it was possible to differentiate between the lead contributed to blood lead from the skeleton and the lead contributed from the current oral dose. Blood samples and bone biopsy samples taken before, during, and after pregnancy were analyzed for lead (total and stable isotope ratios) by thermal ionization mass spectrometry. Through the use of end-member unmixing equations, the contribution to blood of lead from maternal bone during pregnancy was estimated and compared to the contribution of lead from maternal bone before pregnancy. A 29 to 56% decrease in bone lead mobilization in the first trimester was followed by an increase in the second and third trimesters, up to 44% over baseline levels. In one monkey, the third-trimester increase did not reach baseline levels. In a single low-lead monkey, a similar decrease in the first trimester was followed by a 60% increase in the third trimester, indicating that a similar pattern of flux is seen over a wide range of lead concentrations. Analysis of maternal bone and fetal bone, brain, liver, and kidneys confirmed a substantial transplacental transfer of endogenous lead. Lead concentrations in fetal bone often exceeded maternal bone lead concentrations. From 7 to 39% of the lead in the fetal skeleton originated from the maternal skeleton.