Effects of diethyldithiocarbamate on the toxicokinetics of cadmium chloride in mice.
Diethyldithiocarbamate (DDC) efficiently alleviates the acute toxicity of injected cadmium chloride, but enhances the acute toxicity of orally administered cadmium chloride. Further, DDC induces extensive changes in organ distribution of cadmium, and mobilizes aged cadmium depots. The present study investigates effects of DDC on the toxicokinetics of cadmium at lower doses of cadmium than those used in previous studies. During single exposure to subtoxic oral doses of cadmium chloride DDC enhanced intestinal cadmium absorption, both after intraperitoneal and oral administration of DDC. In such acute exposure experiments orally administered DDC only slightly changed the relative organ distribution of absorbed cadmium, while intraperitoneal administration of DDC induced extensive changes in organ preference of absorbed cadmium. The relative hepatic and testicular deposition was reduced, while the relative deposition in heart, spleen, lungs, brain and carcass was increased. Bi-weekly intraperitoneal injections of DDC enhanced the rate of elimination of aged cadmium depots and changed the organ distribution of retained cadmium, compared to the control group. Chronic exposure to DDC in the feed and cadmium chloride in the drinking water did however not result in increased whole-body retention, and the organ distribution in the DDC-exposed group was similar to that in the control group. This result could be due to both increased rate of absorption and increased published extensive changes in the toxicokinetics of cadmium induced by DDC are mainly due to the high cadmium doses employed and the intraperitoneal administration of DDC. At lower doses and more realistic administration routes for cadmium and DDC, the effect of DDC is less. However, still DDC does not seem to have any potential as an antidote for cadmium or for mobilization of cadmium depots in humans.
Andersen
O
O
Department of Environmental Medicine, Odense University, Denmark.
Nielsen
J B
JB
D000284:Administration, Oral; D000818:Animals; D001822:Body Burden; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002104:Cadmium / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D019256:Cadmium Chloride; D004050:Ditiocarb / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007408:Intestinal Absorption / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013270:Stomach / Q000187:drug effects; D014915:Whole-Body Counting
D002104:Cadmium; D004050:Ditiocarb; D019256:Cadmium Chloride