Toxicokinetics and Metabolism

Archives of Toxicology

, Volume 79, Issue 5, pp 243-252

First online:

Disposition of low doses of 14C-bisphenol A in male, female, pregnant, fetal, and neonatal rats

  • Hideo KurebayashiAffiliated withDivision of Pharmacology, National Institute of Health Sciences Email author 
  • , Shin-Ichiro NagatsukaAffiliated withADME/TOX Research Institute, Daiichi Pure Chemicals Co. Ltd
  • , Hiroyuki NemotoAffiliated withADME/TOX Research Institute, Daiichi Pure Chemicals Co. Ltd
  • , Hideyo NoguchiAffiliated withADME/TOX Research Institute, Daiichi Pure Chemicals Co. Ltd
  • , Yasuo OhnoAffiliated withDivision of Pharmacology, National Institute of Health Sciences

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Bisphenol A (BPA) is a weak xenestrogen (ADI=50 μg kg−1, US EPA) which is mass-produced, with potential for human exposure. To study absorption, distribution, excretion, and metabolism of BPA, BPA labeled with carbon-14 was administered p.o. to male and female Fischer (F344) rats at relatively low doses (20, 100, and 500 μg kg−1), and i.v. injected at 100 and 500 μg kg−1. 14C-BPA (500 μg kg−1) was also administered orally to pregnant and lactating rats to examine the transfer of radioactivity to fetuses, neonatal rats, and milk. Radioluminographic determination using phosphor imaging plates was employed to achieve highly sensitive determination of radioactivity. Absorption ratios of radioactivity after three oral doses were high (35–82%); parent 14C-BPA in the circulating blood was quite low, however, suggesting considerable first-pass effect. After an oral dose of 100 μg kg−1 14C-BPA, the radioactivity was distributed and eliminated rapidly, but remained in the intestinal contents, liver, and kidney for 72 h. The major metabolite in the plasma and urine was BPA glucuronide, whereas most of the BPA was excreted with the feces as free BPA. A second peak in the time-course of plasma radioactivity suggested enterohepatic recirculation of BPA glucuronide. There was limited distribution of 14C-BPA to the fetus and neonate after oral administration to the dam. Significant radioactivity was not detected in fetuses on gestation days 12 and 15. On day 18, however, radioactivity was detected in the fetal intestine and urinary bladder 24 h after oral dosing of 14C-BPA to the pregnant rats. Part of radioactivity was transferred to neonatal rats from the milk of the treated lactating dam and remained in the intestine of the neonates after 24-h nursing by an untreated dam.


Bisphenol-A Distribution Pregnant rat Fetus Neonate