title: A review of pitfalls and progress in chelation treatment of metal poisonings.
abstract: Most acute and chronic human metal poisonings are due to oral or inhalation exposure. Almost 80% of published animal experiments on chelation in metal poisoning used single or repeated intraperitoneal, intramuscular or intravenous administration of metal and chelator, impeding extrapolation to clinical settings. Intramuscular administration of dimercaptopropanol (BAL) has until now been used in acute arsenic, lead, and mercury poisonings, but repeated BAL administration increased the brain uptake of As, Pb and Hg in experimental animals. Also, diethyl dithiocarbamate (DDC) has been used as antidote in acute experimental animal parenteral Cd poisoning, and both DDC and tetraethylthiuram disulfide (TTD, disulfiram, Antabuse) have been used in nickel allergic patients. However, even one dose of DDC given immediately after oral Cd or Ni increased their brain uptake considerably. The calcium salt of ethylenediamminetetraacetic acid (CaEDTA) but not dimercaptosuccinic acid (DMSA) increased the brain uptake of Pb. In oral Cd or Hg poisoning, early oral administration of DMSA or dimercaptopropane sulfonate (DMPS) increased survival and reduced intestinal metal uptake. Oral administration of Prussian Blue or resins with fixed chelating groups that are not absorbed offer chelation approaches for decorporation after oral exposure to various metals. Diethylenetriaminepentaacetic acid (DTPA) nebulizers for pulmonary chelation after inhalation exposure need further development. Also, combined chelation with more than one compound may offer extensive advances. Solid knowledge on the chemistry of metal chelates together with relevant animal experiments should guide development of chelation procedures to alleviate and not aggravate the clinical status of poisoned patients.
authors.affiliation: Roskilde University, Roskilde, Denmark, Denmark. Electronic address: oa@ruc.dk.
authors.forename: Ole
authors.initials: O
authors.lastname: Andersen
authors.affiliation: Innlandet Hospital Trust and Hedmark University College, Elverum, Norway, Norway.
authors.forename: Jan
authors.initials: J
authors.lastname: Aaseth
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000627:therapeutic use*; D000075322:Heavy Metal Poisoning; D006801:Humans; D011041:Poisoning / Q000188:drug therapy*
chemical_list: D002614:Chelating Agents
keywords: Acute; Chelation; Chronic; Decorporation; Efficacy; Local and systemic effects; Metal intoxication; Side effects