Assessment of bisphenol A exposure in Korean pregnant women by physiologically based pharmacokinetic modeling.
The objective of this study was to predict the exposure to bisphenol A (BPA) after oral intake in human blood and tissues using physiologically based pharmacokinetic (PBPK) modeling. A refined PBPK model was developed taking into account of glucuronidation, biliary excretion, and slow absorption of BPA in order to describe the second peak of BPA observed following oral intake. This developed model adequately described the second peak and BPA concentrations in blood and various tissues in rats after oral administration. A prospective validation study in rats additionally supported the proposed model. For extrapolation to humans, a daily oral BPA dose of 0.237 mg/70 kg/d or 0.0034 mg/kg/d was predicted to achieve an average steady-state blood concentration of 0.0055 ng/ml (median blood BPA concentration in Korean pregnant women). This dose was lower than the reference dose (RfD, 0.016 mg/kg/d) and the tolerable daily intake established by the European Commission (10 μg/kg/d). Data indicate that enterohepatic recirculation may be toxicologically important as this pathway may increase exposure and terminal half-life of BPA in humans.
College of Pharmacy, Catholic University of Daegu, Gyeongsan-si, Gyeongbuk, Korea.
Beom Soo
BS
Shin
Sang Wook
SW
Hwang
Jurgen B
JB
Bulitta
Jong Bong
JB
Lee
Seung Du
SD
Yang
Joong San
JS
Park
Min Chang
MC
Kwon
Do Jung
DJ
Kim
Hae-Seong
HS
Yoon
Sun Dong
SD
Yoo
D000284:Administration, Oral; D000328:Adult; D000818:Animals; D001559:Benzhydryl Compounds; D004781:Environmental Exposure; D004784:Environmental Monitoring / Q000379:methods*; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D018811:Maternal Exposure; D008954:Models, Biological; D010636:Phenols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D056910:Republic of Korea; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds