Stable isotopic tracers of lead mobilized by DMSA chelation in low lead-exposed rats

Abstract

The ability of DMSA to mobilize skeletal lead or effect a redistribution of endogenous lead to other target organs in low lead-exposed organisms is unclear. Discrepant results of past studies of DMSA and other lead chelators (e.g., CaNa2EDTA) may be due, in part, to experimental differences and difficulties in distinguishing mobilized skeletal lead from other endogenous or exogenous lead sources. Therefore, the influence of DMSA on the mobilization and redistribution of lead in skeletal and soft tissue compartments of low lead-exposed female Wistar (115-125 g) rats was investigated using ultraclean stable lead isotope tracer techniques. Rats that had been reared on a low lead-level diet (lead intake approximately 80 ng Pb/g body/day) were fed 206Pb-enriched drinking water (210 ng Pb/ml) for 1.5 days and then were chelated with a single ip injection of a 0.11 mmol/kg dose of DMSA. Blood, kidney, brain, tibia, urine and feces were collected 24 hr after chelation and analyzed for lead concentrations by graphite furnace atomic absorption spectrometry and for lead isotopic compositions by thermal ionization mass spectrometry. These analyses demonstrated that DMSA chelation significantly increased (15-fold) the diuresis of labile soft tissue lead, but not skeletal lead. DMSA also appeared to effect a redistribution and input of a comparable amount of lead to the skeleton and smaller relative amounts of lead to the soft tissues (blood, kidney) of the chelated animals. The clinical significance of these latter observations beyond the context of this preliminary study is not clear.