Pharmacokinetic disposition and tissue distribution of bisphenol A in ratsafter intravenous administration

This study examined the dose-linearity pharmacokinetics of bisphenol A, a U .S. Environmental Protection Agency ( EPA) classified endocrine disruptor, in rats following iv administration. Upon iv injection of 0.2, 0.5, 1, or 2 mg/kg, serum levels of bisphenol A declined biexponentially, with mean ini tial distribution and elimination half-life ranges of 4-8.2 min and 38.6-62 .2 min, respectively. There were no significant alterations in the systemic clearance rate ( mean range 90.1-123.6 ml/min/kg) and the steady-state vol ume of distribution ( mean range 4.6-6.0 L/kg) as a function of the adminis tered dose. In addition, the area under the serum concentration-time curve linearly rose as the dose was increased. In a second study, bisphenol A was given by simultaneous iv bolus injection plus infusion to steady state, an d levels were measured in serum and various organs. When expressed in conce ntration terms ( e.g., amount accumulated per gram organ weight), bisphenol A was found predominantly in the lung, followed by kidneys, thyroid, stoma ch, heart, spleen, testes, liver, and brain. Ratios of the organ to serum b isphenol A concentrations exceeded unity for all the organs examined ( rati o range 2.0-5.8) except for brain ( ratio 0.75). Given the high systemic cl earance and short elimination half-life, bisphenol A is unlikely to accumul ate significantly in the rat.