Fetal toxicity of cadmium chloride: the pharmacokinetics in the pregnant Wistar rat.
The pharmacokinetics of a single subcutaneous injection of 40 mumol/kg CdCl2 in pregnant rats on day 18 were studied during an 18-hour time period. Previous studies demonstrated that this dose of CdCl2 induced fetal death, placental necrosis, and a reduction of uteroplacental blood flow without maternal lethality; direct fetal injections of CdCl2 indicated that the site of toxic action was not in the fetus. Cadmium was rapidly absorbed from the intrascapular subcutaneous depot with the highest blood levels occurring within 5 minutes of injection. The release from the depot appeared to be multiphasic with both rapid and slow absorption components observed in the blood. Uptake of cadmium was greatest in the liver, followed by the placenta, kidney, and pancreas. The best fit to the data was obtained by assuming the existence of two pools of cadmium in the organs: one freely exchangeable with the blood and the other nonexchangeable. Deviations from model predictions were observed for the placenta and adrenals; these deviations are consistent with the concomitant diminished blood flow to these organs. Cadmium uptake by the fetus was also investigated, and the results support the hypothesis that the placenta is relatively impermeable to the toxicant. It is concluded that the rapid and extensive accumulation of cadmium by the placenta may play a role in the development of early placental cellular damage and the eventual induction of fetal death through uteroplacental dysfunction.
Department of Obstetrics and Gynecology, University of Rochester, School of Medicine and Dentistry, New York 14642.
A A
AA
Levin
R W
RW
Kilpper
R K
RK
Miller
D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics* / Q000633:toxicity; D019256:Cadmium Chloride; D005260:Female; D005333:Fetus / Q000187:drug effects*; D008433:Mathematics; D009336:Necrosis; D010920:Placenta / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D014018:Tissue Distribution
D002104:Cadmium; D019256:Cadmium Chloride