Provocative chelation with DMSA and EDTA: evidence for differential access to lead storage sites

OBJECTIVES--To validate a provocative chelation test with 2,3-dimercaptosuccinic acid (DMSA) by direct comparison with the standard ethylene diamine tetraacetic acid (EDTA) test in the same subjects; and to compare and contrast the predictors of lead excretion after DMSA with those after EDTA. A metal chelating agent given orally, DMSA may mobilise and enhance the excretion of lead from the storage sites in the body that are most directly relevant to the health effects of lead. A provocative chelation test with DMSA could thus have wide potential application in clinical care and epidemiological studies. METHODS--34 male lead workers in the Republic of Korea were given a single oral dose of 10 mg/kg DMSA, urine was collected over the next eight to 24 hours, and urine volume and urinary lead concentration determined at 0, 2, 4, 6, 8, and 24 hours. Either two weeks before or two weeks after the dose of DMSA 17 of these workers also received 1 g intravenous EDTA followed by an eight hour urine collection with fractionation at 0, 2, 4, 6, and 8 hours. RESULTS--Urinary lead concentration peaked at two hours after DMSA and four hours after EDTA. Lead excretion after DMSA was less than after EDTA, and cumulative excretion after DMSA plateaued at six to eight hours. The two hour and four hour cumulative lead excretions after DMSA were highly correlated with the eight hour total (r = 0.76 and 0.95). In multiple linear regression analyses, blood lead was found to be an important predictor of EDTA-chelatable lead, whereas urinary aminolevulinic acid (ALAU) was associated with DMSA-chelatable lead. Notably, lead excretion after DMSA was greatly increased if EDTA was given first. An earlier dose of EDTA also modified the relation between ALAU and DMSA-chelatable lead in that workers who received EDTA before DMSA showed a much steeper dose-response relation between these two measures. CONCLUSIONS--The predictors of lead excretion after DMSA and EDTA are different and an earlier dose of EDTA may increase lead excretion after a subsequent dose of DMSA. The results suggest that two hour or four hour cumulative lead excretion after DMSA may provide an estimate of lead in storage sites that are most directly relevant to the health effects of lead.