Objectives: Previous research suggests that binding of lead by δ-aminolevulinic acid dehydratase (ALAD) may vary by ALAD genotype. This hypothesis was tested by examining whether ALAD genotype modifies urinary lead excretion (DMSA chelatable lead) after oral administration of dimercaptosuccinic acid (DMSA). Methods: 57 South Korean lead battery manufacturing workers were given 5 mg/kg oral DMSA and urine was collected for four hours. Male workers were randomly selected from two ALAD genotype strata (ALAD 1-1, ALAD 1-2) from among all current workers in the two plants (n = 290). Subjects with ALAD 1-1 (n = 38) were frequency matched with subjects with ALAD 1-2 (n = 19) on duration of employment in the lead industry. Blood lead, zinc protoporphyrin, and plasma aminolevulinic acid concentrations, as well as ALAD genotype, duration of exposure, current tobacco use, and weight were examined as predictors or effect modifiers of levels of DMSA chelatable lead. Results: Blood lead concentrations ranged from 11 to 53 μg/dl, with a mean (SD) of 25.4 (10.2) μg/nl. After 5 mg/kg DMSA orally, the workers excreted a mean (SD) 85.4 (45.0) μg lead during a four hour urine collection (range 16.5-184.1 μg). After controlling for blood lead concentrations, duration of exposure, current tobacco use, and body weight, subjects with ALAD 1-2 excreted, on average, 24 μg less lead during the four hour urine collection than did subjects with ALAD 1-1 (P = 0.05). ALAD genotype seemed to modify the relation between plasma δ-aminolevulinic acid (ALA) and DMSA chelatable lead. Workers with ALAD 1-2 excreted more lead, after being given DMSA, with increasing plasma ALA than did workers with ALAD 1-1 (P value for interaction = 0.01). Conclusions: DMSA chelatable lead may partly reflect the stores of bioavailable iead, and the current data indicate that subjects with ALAD 1-2 have lower stores than those with ALAD 1-1. These data provide further evidence that the ALAD genotype modifies the toxicokinetics of lead - for example, by differential binding of current lead stores or by differences in long term retention and deposition of lead.
- chelating agents
- dimercaptosuccinic acid
- δ-aminolevulinic acid dehydratase genotype
ASJC Scopus subject areas
- Public Health, Environmental and Occupational Health