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A dynamic simulation of bisphenol A dosimetry in neuroendocrine organs

Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Rockville, MD, USA, jch{at}cdrh.fda.gov

Hoan My Luu

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

Chung S Kim

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

Bisphenol A (BPA) is a known xenoestrogen with similar properties to 17b-estradiol. BPA and estrogen are hydrophobic compounds, and this affects the pharmacokinetics of both compounds in mammals. In a previous study we measured the distribution of BPA in female F344 rats exposed to oral doses of 0.1, 10 and 100 mg/kg. The results showed distribution to target neuroendocrine organs at all doses tested. Using these results, we developed a pharmacokinetic model to predict the dynamic uptake and excretion of BPA by various routes of exposure (po, iv, sc, ip). The model was able to simulate the entire time course (48 h) following various routes of exposure in rats over the dose ranges tested. The model indicated that the ultimate tissue uptake of BPA was established by the rapid initial transfer of free BPA into tissues. After free BPA enters the systemic circulation, metabolism and excretion reactions cause a relatively short duration and rapid decline. This period is followed by a slower long-term decline characteristic of BPA’s biphasic pharmacokinetics. Plasma protein and tissue binding reactions established the long-term half-life of BPA in the body. Route differences in tissue uptake were directly related to the competition between transfer and binding reactions during the absorption phase.

Key Words: bisphenol A • neuroendocrine organs • pharmacokinetic modelling

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