title: Succimer and the urinary excretion of essential elements in a primate model of childhood lead exposure.
abstract: Succimer is considered to be a safe and effective treatment for lead (Pb) poisoning, since it reduces body Pb levels without an apparent diuresis of other essential elements. However, while existing clinical data indicate that succimer does not significantly increase the excretion of non-target elements, those studies have also reported a wide range of outcomes. Therefore, we investigated whether succimer treatment measurably increased the urinary excretion of essential elements in a primate model of childhood Pb exposure. Infant rhesus monkeys (Macaca mulatta) were exposed to Pb from birth through one year of age, and presented blood Pb levels of approximately 40-50 microg/dL at the start of treatment. Subsequently, they were treated with succimer (30 mg/kg/day x 5 days followed by 20 mg/kg/day x 14 days, n = 15) or vehicle (n = 14) for 19 days. Complete urine samples were collected over the first 5 days of treatment, and were analyzed for levels of calcium (Ca), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), magnesium (Mg), manganese (Mn), nickel (Ni), and zinc (Zn), using trace metal-clean techniques and magnetic sector-ICP-MS. Succimer treatment significantly (p < 0.05) reduced blood Pb levels when compared to the vehicle group over the treatment period, and concomitantly produced a significant >4-fold increase in urinary Pb excretion. Succimer treatment also significantly (p < 0.05, multivariate ANOVA) increased the urinary excretion of essential elements, but only when the cumulative total excretion over treatment days 1-5 for all elements were considered. None of these relative increases reached statistical significance for any particular element x day, although increases in Zn (day 3) excretion were only marginally non-significant (0.1 > p > 0.05). Multivariate analyses of a subset of elements (Cu, Fe, Mn, Zn) similarly indicated no significant effect of succimer treatment overall, although the urinary excretion of Mn was significantly increased on day 3 of treatment. Collectively, these data indicate that succimer does contribute to an increase in the urinary excretion of essential elements, although not significantly for any single element considered here. This may be important in Pb-exposed children, who can possess reduced trace element reserves due to nutritional deficiencies.
authors.affiliation: Department of Environmental Toxicology, University of California, Santa Cruz 95064, USA. dsmith@biology.ucsc.edu
authors.forename: D R
authors.initials: DR
authors.lastname: Smith
authors.forename: C
authors.initials: C
authors.lastname: Calacsan
authors.forename: D
authors.initials: D
authors.lastname: Woolard
authors.forename: M
authors.initials: M
authors.lastname: Luck
authors.forename: J
authors.initials: J
authors.lastname: Cremin
authors.forename: N K
authors.initials: NK
authors.lastname: Laughlin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D007854:Lead / Q000097:blood; D007855:Lead Poisoning / Q000188:drug therapy / Q000652:urine*; D008253:Macaca mulatta; D008297:Male; D004113:Succimer / Q000627:therapeutic use*; D014131:Trace Elements / Q000652:urine*
chemical_list: D014131:Trace Elements; D007854:Lead; D004113:Succimer