Increased lead levels in brain after long-term treatment with lead and dithiocarbamate or thiuram derivatives in rats.
Lead concentrations in blood and brain were measured in rats exposed to lead via drinking water, 0.25% Pb (12 mM), and dithiocarbamate/thiuram derivatives administered by gavage singly or in combination for 6 weeks. Sodium salts of diethyldithiocarbamate (DEDTC) and dimethyldithiocarbamate (DMDTC) were given in doses of 0.2 mmol/kg and tetramethylthiuram disulfide (thiram) and tetraethylthiuram disulfide (disulfiram) in doses of 0.1 mmol/kg twice a week. In rats that received lead plus dithiocarbamate/thiuram derivatives lead concentrations in blood and brain were significantly increased; disulfiram being most effective in increasing lead levels, followed by thiram, DMDTC and DEDTC. In blood, lead levels were increased 3-fold and in brain almost 4-fold after treatment with lead plus disulfiram compared to treatment with lead alone. When rats were given DEDTC or thiram by gavage (0.1 mmol/kg/day 5 days a week for 2 weeks) after cessation of the lead treatment, there was no increase in blood lead levels but in thiram-treated rats brain lead concentration was increased 2.7-fold. In rats treated with DEDTC intraperitoneally after cessation of lead treatment, both blood and brain concentrations of lead were increased. This study suggests that combined exposure of lead and dithiocarbamate/thiuram derivatives causes a substantial increase in brain levels of lead which are not always reflected in increases of blood lead levels. This interaction effect ought to be taken into consideration when evaluating the health effects of environmental and occupational lead exposure.
Oskarsson
A
A
Lind
B
B
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004125:Dimethyldithiocarbamate / Q000494:pharmacology; D004221:Disulfiram / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology; D007854:Lead / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013859:Thiocarbamates / Q000494:pharmacology*; D013893:Thiram / Q000494:pharmacology*; D014018:Tissue Distribution / Q000187:drug effects
D004125:Dimethyldithiocarbamate; D013859:Thiocarbamates; D013893:Thiram; D007854:Lead; D004050:Ditiocarb; D004221:Disulfiram