Redistribution and Increased Brain Uptake of Lead in Rats After Treatment with Diethyldithiocarbamate
Diethyldithiocarbamate (DDTC), a chelating agent, is an active metabolite of disulfiram (Antabus®) and is used in the rubber industry. The effect of DDTC on the tissue distribution of 203Pb was studied in rats. Two groups of rats were given an i.v. injection of 100 μCi 203Pb (28.6 nmol/kg b.wt.) as lead acetate. After 10 min one group received 2 mmol/kg b.wt. of DDTC as an i.p. injection. Rats were killed 4 and 72 h after injection of 203Pb and tissue concentration and excretion of 203Pb was determined by gamma counting. The brain concentration of 203Pb in DDTC-treated rats was nine times higher than in controls after 4 h and 14 times higher after 72 h. Treatment with DDTC also increased the lead concentration in fat about seven times at both survival intervals. On the other hand, uptake of 203Pb in bone was reduced by treatment with DDTC and at 4 h also kidney and blood had a lower concentration of 203Pb in DDTC-treated rats compared to controls. Kidney and femur of DDTC-treated rats had an increased 203Pb concentration at 72 h compared to 4 h. Most of the lead was excreted via feces; 28% of the dose in DDTC-treated rats and 16% in controls during the first 72 h after injection. The urinary excretion of 203Pb was higher in control rats (11% of the dose) than in DDTC-treated rats (6%). The results indicate that a lipid-soluble complex of lead and DDTC is formed, which is capable of penetrating the blood-brain barrier to a much higher extent than inorganic lead. The toxic effects of the lead-DDTC complex are not known, but one may expect that inorganic lead is released causing adverse effects in the central nervous system, when the lead-DDTC complex is further metabolized.
Key wordsLead Diethyldithiocarbamate Chelating agent Brain lead Tissue distribution
Unable to display preview. Download preview PDF.
- Aaseth J, Alexander J, Wannag A (1981) Effect of thiocarbamate derivatives on copper, zinc, and mercury distribution in rats and mice. Toxicology 48: 29–39Google Scholar
- Needleman HL (1980) Low level lead exposure. Raven, New YorkGoogle Scholar
- Rutter M (1980) Raised lead levels and impaired cognitive/behavioural functioning: A review of the evidence. Dev Med Child Neurol [Suppl 42] 22: 1–25Google Scholar
- Swinscow TDV (1978) Statistics at Square One. Published by the British Medical Association. Dawson & Goodall, The Mendip Press, BathGoogle Scholar