Aluminum bioavailability and disposition in adult and immature rabbits

Prolonged aluminum (Al) exposure produces neurobehavioral and skeletal toxicity. To further characterize the risk from Al exposure, lactating rabbits were administered iv (40 or 80 mumol/kg), po (4 or 20 mmol/kg), and sc (400 mumol/kg) doses of Al lactate on Days 10, 15, and 20 of lactation. Baseline pretreatment Al concentration averaged 138 ng/ml in serum and 710 ng/ml in milk. Individual baseline values were subtracted from posttreatment samples, and pharmacokinetic analysis was performed on these residual values. The high and low doses did not produce statistically significant differences in systemic clearance, half-life, or the apparent volume of distribution. The amount of aluminum in milk 24 hr after injection was estimated to be 2.4% of the iv and 3.3% of the absorbed sc dose. Systemic bioavailability of Al after low- (0.7 +/- 0.5% means +/- SD) and high-dose po Al (1.9 +/- 1.7%) was not significantly different. Bioavailability of sc Al was 27 +/- 7%. Rabbits receiving daily sc Al injections (400 mumol/kg) for 28 consecutive days demonstrated nonlinear kinetics. Preinjection serum Al concentrations and the area under the curves associated with the 7th dose were considerably greater than with the 1st dose. Further increases were seen with the 28th dose. Seven days after the last Al injection, 12% of the total Al injected was still in the region of the injections, indicating prolonged absorption. The bioavailability and disposition of Al were determined in 17- to 24-day old suckling rabbit offspring after iv (40 mumol/kg) and po (4 mmol/kg in water or milk) doses of Al lactate. Baseline pretreatment serum Al concentration averaged 119 ng/ml. Mean systemic clearance was comparable in offspring and adults, although the apparent volume of distribution was greater in offspring producing a longer half-life in the offspring. The limited distribution of Al into milk and poor GI absorption of Al support the observation that there is little risk of Al toxicity in suckling offspring of Al exposed nursing females.