Therapeutic Approaches for Management of Lead Exposure from Embedded Lead Metal Fragments
Elevated blood lead levels from retained lead fragments is a significant but insufficiently recognized public health risk for which there are no well-accepted management guidelines. It is estimated that there are 67,000 non-fatal firearm injuries a year in the U.S., and 42,000 U.S. veterans with retained lead metal fragments from bullet or improvised explosive injuries. To investigate the efficacy of succimer chelation to manage elevated lead levels in patients with embedded lead fragments, an in vitro experiment was done to determine if meso-2,3-Dimercaptosuccinic acid (DMSA) or ethylenediaminetetraacetic acid calcium disodium salt (CaNa2EDTA) directly increase the release of lead from a solid lead pellet in an artificial extracellular fluid (aECF) cell-free system. Also, a rodent model of elevated lead levels from embedded lead pellets was established using stable lead isotope tracer methodologies to differentiate lead chelated from tissues or from embedded lead pellets. Results from the in vitro study show that DMSA and CaNa2EDTA significantly mobilized lead from a solid lead fragment in an aECF environment. The in vivo results show that 5 days of oral succimer chelation (Chemet, 50 mg/kg/day) significantly reduced blood and tissue lead, as expected, though blood and tissue lead levels rebounded within 1 week post-chelation to levels comparable to the vehicle group. During the initial (day 1) stage of chelation where the greatest blood lead reductions and increases in urine lead excretion occurred, there was no evidence of the pellet lead isotopic signature in the blood or urine, indicating that embedded pellet lead was not mobilized in the first day of chelation. However, lead from the embedded pellet environment was mobilized to the blood and urine with continued chelation (beyond day 1) and during the post-chelation blood lead rebound period. These findings indicate that prolonged succimer chelation in patients with elevated blood lead levels from embedded lead fragments may not produce lasting reductions in blood or tissue lead levels and may in fact increase mobilization of fragment lead into blood and tissues. Thus, the risks of succimer chelation in subjects with embedded lead fragments, which may represent an inexhaustible internal source of lead exposure, may outweigh the benefits of transiently reducing blood lead levels.