Single-dose toxicokinetics of aluminum in the rat.
The toxicokinetics of aluminum (Al) in male Wistar rats was studied after single intragastric (IG) doses of 1000 and 12,000 micrograms Al/kg and intravenous (IV) doses of 10, 100, 1000, and 12,000 micrograms Al/kg. Serial blood samples, daily samples of urine and feces as well as brain, liver, kidney, spleen, quadriceps muscle, and femur samples were collected. Al was measured by atomic absorption spectrometry. Al blood profiles after IV doses were adequately described by a two-compartment open model. Al toxicokinetics was dose dependent and appeared to plateau at 12,000 micrograms/kg. At IV doses between 10 and 1000 micrograms/kg the terminal half-life of elimination from whole blood (t1/2 beta) increased from 29.9 +/- 7.8 to 209.3 +/- 32.6 min, and the total body clearance (CL) decreased from 2.45 +/- 0.64 to 0.28 +/- 0.03 ml min-1 kg-1. Following an IV bolus of 10 and 100 micrograms/kg the administered Al was recovered completely from urine (94.4% +/- 9.9% and 98.5% +/- 3.2%). Twenty-nine days after the IV dose of 1000 micrograms/kg daily renal excretion decreased to baseline values while only 55.1% +/- 8.0% of the dose was excreted. Nineteen days after the single IV dose of 1000 micrograms/kg Al accumulated in liver (28.1 +/- 7.7 versus 1.7 +/- 0.5 micrograms/g of control rats) and spleen (72.5 +/- 21.1 versus < 0.4 microgram/g). After the single 1000 micrograms/kg IG dose no absorption of Al was detectable. The IG dose of 12,000 micrograms/kg resulted in a maximum blood Al level of 47.9 +/- 12.4 micrograms/l after 50 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Wilhelm
M
M
Institute of Toxicology, Heinrich-Heine-Universität Düsseldorf, Federal Republic of Germany.
Zhang
X J
XJ
Hafner
D
D
Ohnesorge
F K
FK
D000535:Aluminum / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D000818:Animals; D001682:Biological Availability; D004333:Drug Administration Routes; D005753:Gastric Mucosa / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000535:Aluminum