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Distribution of bisphenol A in the neuroendocrine organs of female rats

Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Laurel, USA, csk{at}cfsan.fda.gov

PP Sapienza

Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Laurel, USA

IA Ross

Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Laurel, USA

W Johnson

Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Laurel, USA

HMD Luu

Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Rockville, USA

JC Hutter

Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Rockville, USA

The distribution of ¹⁴C-bisphenol A (BPA) in plasma and neuroendocrine organs was determined in Fischer 344 female rats following three oral doses (0.1, 10 or 100 mg/kg). Plasma and tissue maximum concentrations (C_max) were reached within 15-30 min of dosing. Plasma areas-under-the-curve (AUC) ranged from 0.06 to 53.9 mg-h/mL. The AUCs of the pituitary gland and uterus/gonads were 16-21% higher than that of plasma. The AUCs of hypothalamus and the rest of the brain were 43.7% and 77% of the plasma AUCs, respectively. In the brain tissue, the exposure increased linearly with the oral dose, as the dose was increased from 0.1 to 10 and 100 mg/kg; the exposure in the brain relative to the plasma increased by factors of 1, 1.19 and 1.24. This indicates that the brain barrier systems do not limit the access of the lipophilic BPA to the brain. The increases of the uterus/gonads relative to the plasma were 1, 1.07 and 1.04. Tissue partitioning was also examined in vitro by the uptake of ¹⁴C-BPA. The BPA tissue/blood partition coefficients were as follows: heart, 7.5; liver, 6.1; kidney, 6.4; fat, 3.6; muscle, 2.6; breast, 3.6; ovaries, 9.1; uterus, 5.9; stomach, 5.1; and small intestine, 6.7. The tissue/cerebrospinal fluid partition coefficients were as follows: pituitary gland, 12.8; brain stem, 6.1; cerebellum, 6.4; hippocampus, 7.1; hypothalamus, 6.1; frontal cortex, 4.9; and caudate nucleus, 6.8.

Key Words: bisphenol A • neuroendocrine organs • pharmacokinetics

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