Effects of tetraethylthiuram disulfide on the toxicokinetics of cadmium in mice.
This study examines the effects of tetraethylthiuram disulfide (TTD; disulfiram, Antabuse) on the toxicokinetics in mice of 109Cd-labelled cadmium chloride, as determined by whole-body and organ gamma-counting. At the highest single dose of orally administered CdCl2, i.e. 70 mumol/kg, orally administered TTD enhanced the inhibitory effect of CdCl2 on intestinal motility and increased the fractional whole-body retention of the dose of cadmium chloride, indicating enhanced intestinal cadmium absorption. Also, TTD induced extensive changes in organ distribution of absorbed cadmium; the relative hepatic and testicular deposition was reduced, while the relative deposition in heart, spleen, lungs, brain and carcass was increased. In a prolonged exposure experiment where CdCl2 was added to the drinking water and TTD to the feed, TTD increased the intestinal absorption of cadmium by more than four-fold as compared to the controls. Further, decreased deposition was seen in the carcass and increased deposition in intestines and liver. In a third experiment, oral doses of TTD given twice weekly had no influence on the rate of excretion of aged cadmium depots, and also the organ distribution was unchanged. Thus, the effect of TTD on cadmium metabolism seems to be exerted only during intestinal absorption and the distribution phase immediately thereafter.
Andersen
O
O
Department of Environmental Medicine, Odense University, Denmark.
Grandjean
P
P
D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics* / Q000633:toxicity; D004221:Disulfiram / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007408:Intestinal Absorption / Q000187:drug effects; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D014018:Tissue Distribution / Q000187:drug effects
D002104:Cadmium; D004221:Disulfiram