title: The effects of CaNa(2)EDTA on brain lead mobilization in rodents determined using a stable lead isotope tracer.
abstract: Studies have demonstrated the efficacy of CaNa(2)EDTA for reducing lead (Pb) levels in blood and soft tissues, including brain. However, a concern remains that a single dose of CaNa(2)EDTA may cause a significant increase in brain Pb levels due to a redistribution of endogenous Pb. Here we utilized a rodent model of Pb exposure in combination with a sensitive stable Pb isotope tracer methodology to assess the effects of CaNa(2)EDTA chelation treatment on the redistribution of Pb in brain, blood, kidney, and bone tissues. Thirty-two adult female albino rats (n = 6-7 animals/group) were exposed to 100 microg Pb/mL in drinking water for 4 weeks. Stable (204)Pb tracer was administered via i.p. injection over 2 days prior to chelation. CaNa(2)EDTA was administered i.p. at a dose of 150 mg/kg/day for 1 to 5 days. Statistical differences were evaluated with univariate ANOVA. Under the Pb exposure and chelation treatment regimens utilized here, there was no evidence of a measurable redistribution of endogenous Pb (as total Pb or labile (204)Pb tracer) into the brain after a single CaNa(2)EDTA dose. Further, CaNa(2)EDTA was not efficacious in measurably reducing brain or bone Pb levels, although brain levels of labile (204)Pb tracer were significantly reduced after 5 days of chelation. CaNa(2)EDTA treatment was effective in significantly reducing both blood and kidney Pb levels. Overall, these data substantiate the efficacy of CaNa(2)EDTA for reducing soft tissue Pb levels, but not total brain Pb, and they do not support concern for a transient increase in brain Pb levels with treatment.
authors.affiliation: Environmental Toxicology, University of California, Santa Cruz, California, 95064, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Seaton
authors.forename: J
authors.initials: J
authors.lastname: Lasman
authors.forename: D R
authors.initials: DR
authors.lastname: Smith
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology*; D004492:Edetic Acid / Q000494:pharmacology*; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007854:Lead / Q000097:blood / Q000378:metabolism*; D007856:Lead Radioisotopes / Q000097:blood / Q000378:metabolism; D051381:Rats
chemical_list: D002614:Chelating Agents; D007856:Lead Radioisotopes; D007854:Lead; D004492:Edetic Acid