Toxicokinetics of bisphenol A in female DA/Han rats after a single i.v. and oral administration

Bisphenol A [BPA; 2,2-bis-(4-hydroxyphenyl)propane] is a monomer used in th e manufacture of resins with a wide range of applications, e.g. plastic coa tings in the food packaging industry. BPA has been shown to have a weak oes trogenic activity in vitro and in vivo. Despite its low oestrogenic potency there is concern that, as a consequence of slow clearance, BPA might reach biologically significant levels in humans and animals exposed to environme ntal levels. To address this concern, we assessed the kinetic behaviour of BPA in female DA/ Han rats. Groups of female rats received 10 mg BPA/kg bod y weight intravenously or 10 or 100 mg BPA/kg body weight orally (by gavage ). Blood samples were collected at different time-points and plasma was pre pared. Free BPA in the samples was isolated by fluid-fluid extraction. BPA was measured by GC-MS which allowed the reliable determination of BPA conce ntrations as low as approximately 10 ng/ml plasma. immediately after i.v. a dministration, the BPA plasma concentration was in the range of about 15 mu g/ml and decreased rapidly within the first hour (to 700 ng/ml). The levels declined further (100 ng/ml at 2 h), and after 24 h the analytical detecti on limit was reached. BPA was detected in plasma as early as 10 min after S avage administration, indicating rapid initial uptake from the gastrointest inal tract. Absorption of BPA was variable. In animals receiving 10 mg/kg, maximal plasma levels were reached after 1.5 h (31 ng/ mi) and 6 h (40 ng/m l). In animals receiving 100 mg/kg, plasma levels reached maxima around 30 min (150 ng/ mi) and 3 h (134 ng/ml) after administration. After 48 h BPA w as at or below the detection limit in both dose groups. Fluctuations in the BPA plasma concentrations over time point to the possibility of enterohepa tic recirculation and protracted absorption from the gastrointestinal tract . Using the area under the concentration-time curves (AUCs), low bioavailab ilities of 16.4% and 5.6% were calculated fur the 10 and 100 mg/kg dose gro ups, respectively. The toxicokinetic properties of BPA in DA/Han rats are i n agreement with the hypothesis of a rapid first-pass elimination by the li ver and efficient metabolic clearance of low oral doses. Only excessive dos es may lead to bioaccumulation if detoxification pathways are saturated.