Single-dose toxicokinetics of aluminum in the rat

Abstract

The toxicokinetics of aluminum (Al) in male Wistar rats was studied after single intragastric (IG) doses of 1000 and 12000 μg Al/kg and intravenous (IV) doses of 10, 100, 1000, and 12000 μg 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 12000 μg/kg. At IV doses between 10 and 1000 μg/kg the terminal half-life of elimination from whole blood (t_1/2β) 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 μg/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 μg/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 μg/kg Al accumulated in liver (28.1±7.7 versus 1.7±0.5 μg/g of control rats) and spleen (72.5±21.1 versus <0.4 μg/g). After the single 1000 μg/kg IG dose no absorption of Al was detectable. The IG dose of 12000 μg/kg resulted in a maximum blood Al level of 47.9±12.4 μg/l after 50 min. The blood concentration time curve fitted a one-compartment open model with a half-life of absorption of 28.2±3.6 min and a t_1/2β of 81.2±20.2 min. Cumulative renal Al excretion was 0.18%±0.10% of the dose and oral bioavailability was 0.02%. Seventeen days after the 12000 μg/kg IG dose the Al content in femur samples was increased (2.7±1.3 versus 0.6±0.4 μg/g). In no case was fecal elimination of incorporated Al observed.