Succimer chelation does not produce lasting reductions of blood lead levels in a rodent model of retained lead fragments

Environ Toxicol Pharmacol. 2023 Nov:104:104283. doi: 10.1016/j.etap.2023.104283. Epub 2023 Sep 27.

Abstract

Retained lead fragments from nonfatal firearm injuries pose a risk of lead poisoning. While chelation is well-established as a lead poisoning treatment, it remains unclear whether chelation mobilizes lead from embedded lead fragments. Here, we tested whether 1) DMSA/succimer or CaNa2EDTA increases mobilization of lead from fragments in vitro, and 2) succimer is efficacious in chelating fragment lead in vivo, using stable lead isotope tracer methods in a rodent model of embedded fragments. DMSA was > 10-times more effective than CaNa2EDTA in mobilizing fragment lead in vitro. In the rodent model, succimer chelation on day 1 produced the greatest blood lead reductions, and fragment lead was not mobilized into blood. However, with continued chelation and over 3-weeks post-chelation, blood lead levels rebounded with mobilization of lead from the fragments. These findings suggest prolonged chelation will increase fragment lead mobilization post-chelation, supporting the need for long-term surveillance in patients with retained fragments.

Keywords: CaNa(2)EDTA; Chelation; Lead exposure; Retained fragments; Succimer.

MeSH terms

  • Animals
  • Chelating Agents / pharmacology
  • Chelating Agents / therapeutic use
  • Edetic Acid / pharmacology
  • Edetic Acid / therapeutic use
  • Firearms*
  • Humans
  • Lead / toxicity
  • Lead Poisoning* / drug therapy
  • Lead Poisoning* / metabolism
  • Rodentia
  • Succimer
  • Wounds, Gunshot*

Substances

  • Succimer
  • Lead
  • Edetic Acid
  • Chelating Agents