Development of a physiologically based pharmacokinetic model for bisphenol A in pregnant mice.
Bisphenol A (BPA) is a weakly estrogenic monomer used to produce polymers for food contact and other applications, so there is potential for oral exposure of humans to trace amounts via ingestion. To date, no physiologically based pharmacokinetic (PBPK) model has been located for BPA in pregnant mice with or without fetuses. An estimate by a mathematical model is essential since information on humans is difficult to obtain experimentally. The PBPK model was constructed based on the pharmacokinetic data of our experiment following single oral administration of BPA to pregnant mice. The risk assessment of bisphenol A (BPA) on the development of human offspring is an important issue. There have been limited data on the exposure level of human fetuses to BPA (e.g. BPA concentration in cord blood) and no information is available on the pharmacokinetics of BPA in humans with or without fetuses. In the present study, we developed a physiologically based pharmacokinetic (PBPK) model describing the pharmacokinetics of BPA in a pregnant mouse with the prospect of future extrapolation to humans. The PBPK model was constructed based on the pharmacokinetic data of an experiment we executed on pregnant mice following single oral administration of BPA. The model could describe the rapid transfer of BPA through the placenta to the fetus and the slow disappearance from fetuses. The simulated time courses after three-time repeated oral administrations of BPA by the constructed model fitted well with the experimental data, and the simulation for the 10 times lower dose was also consistent with the experiment. This suggested that the PBPK model for BPA in pregnant mice was successfully verified and is highly promising for extrapolation to humans who are expected to be exposed more chronically to lower doses.
Kawamoto
Yuko
Y
Kyoto University, Graduate School of Engineering, Urban & Environmental Engineering, 4 Kyotodaigaku Katsura, Nishikyo, Kyoto, 615-8540, Japan.
Matsuyama
Wakoto
W
Wada
Masahiro
M
Hishikawa
Junko
J
Chan
Melissa Pui Ling
MP
Nakayama
Aki
A
Morisawa
Shinsuke
S
D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds; D003198:Computer Simulation; D004334:Drug Administration Schedule; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005312:Fetal Blood; D005333:Fetus / Q000378:metabolism; D006801:Humans; D008431:Maternal-Fetal Exchange; D051379:Mice; D008954:Models, Biological; D010636:Phenols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods*; D013045:Species Specificity; D014018:Tissue Distribution; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds