BIOAVAILABILITY AND MAMMARY EXCRETION OF BISPHENOL A IN SPRAGUE-DAWLEY RATS

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Abstract
This study reports the absolute oral bioavailability and mammary excretion of bisphenol A in rats. The oral bioavailability was determined after administration of relatively low iv (0.1 mg/kg) and oral (10 mg/kg) doses of bisphenol A to rats. After iv injection, serum levels of bisphenol A declined biexponentially, with the mean initial distribution and ter- minal elimination half-lives being 6.1 ± 1.3 min and 52.5 ± 2.4 min, respectively. The systemic clearance (Cls) and the steady-state volume of distribution (Vss) averaged 107.9 ± 28.7 ml/min/kg and 5.6 ± 2.4 L/kg, respectively. Upon oral administration, the maximum serum concentration (Cmax) and the time to reach the maximum concentra- tion (Tmax) were 14.7 ± 10.9 ng/ml and 0.2 ± 0.2 h, respectively. The apparent terminal elimination half-life of bisphenol A (21.3 ± 7.4 h) after oral administration was signifi- cantly longer than that after iv injection, indicating the flip-flop of the absorption and elimination rates. The absolute oral bioavailability of bisphenol A was low (5.3 ± 2.1%). To determine the extent of mammary excretion, bisphenol A was given by simultaneous iv bolus injection plus infusion to steady state at low, medium, and high doses. The steady-state serum levels of bisphenol A were linearly increased with higher dosing rates. The systemic clearance (mean range, 119.2-154.1 ml/min/kg) remained unaltered over the dosing rate studied. The levels of bisphenol A in milk exceeded those in serum, with the steady-state milk to serum concentration ratio being 2.4-2.7.

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