Succimer and the urinary excretion of essential elements in a primate model of childhood lead exposure

Succimer is considered to be a safe and effective treatment for lead (Pb) p oisoning, since it reduces body Pb levels without an apparent diuresis of o ther essential elements. However, while existing clinical data indicate tha t succimer does not significantly increase the excretion of non-target elem ents, those studies have also reported a wide range of outcomes. Therefore, we investigated whether succimer treatment measurably increased the urinar y excretion of essential elements in a primate model of childhood Pb exposu re. Infant rhesus monkeys (Macaca mulatta) were exposed to Pb from birth th rough one year of age, and presented blood Pb levels of approximate to 40-5 0 mu g/dL at the start of treatment. Subsequently, they were treated with s uccimer (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), manganes e (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 peri od, and concomitantly produced a significant >4-fold increase in urinary Pb excretion. Succimer treatment also significantly (p < 0.05, multivariate A NOVA) increased the urinary excretion of essential elements, but only when the cumulative total excretion over treatment days 1-5 for all elements wer e considered. None of these relative increases reached statistical signific ance for any particular element x day, although increases in Zn (day 3) exc retion were only marginally non-significant (0.1 > p > 0.05). Multivariate analyses of a subset of elements (Cu, Fe, Mn, Zn) similarly indicated no si gnificant effect of succimer treatment overall, although the urinary excret ion of Mn was significantly increased on day 3 of treatment. Collectively, these data indicate that succimer does contribute to an increase in the uri nary excretion of essential elements, although not significantly for any si ngle element considered here. This may be important in Pb-exposed children, who can possess reduced trace element reserves due to nutritional deficien cies.