Effects of diethyldithiocarbamate and selected analogs on lead metabolism in mice.
Diethyldithiocarbamate (DDTC) and certain of its N,N-disubstituted analogs were evaluated for effectiveness in reducing organ concentrations and whole body burdens of lead (Pb) in mice which had received 0.06 mg of Pb(II) acetate along with 2.0 microCi of 210Pb 9 days earlier. CaNa2EDTA was used as a positive control for studies in which the compounds were administered ip, and meso-2,3-dimercaptosuccinic acid (DMSA) was used as a positive control for po studies. DDTC was more effective than EDTA in lowering the whole body Pb burdens after 5 ip injections, while N-methyl-N-dithiocarboxyglucamine (MDCG) was less active than EDTA. The other 4 analogs tested were inactive. When DDTC (1.5 mmoles/kg) was coadministered with EDTA (1.5 mmoles/kg), the reduction of total body Pb burdens was significantly greater than that attained with either compound alone at 3.0 mmoles/kg. DDTC was particularly effective in reducing hepatic and splenic Pb concentrations, but was less active than EDTA in lowering the Pb content of bone, kidneys, and brain. Excretion of Pb following ip treatment with EDTA, DDTC, or MDCG was predominantly by the fecal route. DDTC was significantly more effective than DMSA at an equimolar dose in reducing whole body Pb burdens when each was given po. However, po administration of DDTC caused a substantial increase in brain Pb levels.
D000818:Animals; D004050:Ditiocarb / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D007854:Lead / Q000378:metabolism*; D007855:Lead Poisoning / Q000188:drug therapy; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013012:Sorbitol / Q000031:analogs & derivatives*; D013113:Spin Labels; D013859:Thiocarbamates / Q000494:pharmacology*; D014018:Tissue Distribution
D013113:Spin Labels; D013859:Thiocarbamates; D007854:Lead; D013012:Sorbitol; C041262:N-methyl-D-glucamine dithiocarbamate; D004050:Ditiocarb; D004492:Edetic Acid