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

Abstract

Bisphenol A (BPA) is a weak xenestrogen (ADI = 50 microg 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 microg kg(-1)), and i.v. injected at 100 and 500 microg kg(-1). 14C-BPA (500 microg 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 microg 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.

Environmental levels of oestrogenic and antiandrogenic compounds feminize digit ratios in male rats and their unexposed male progeny

“…Our study is also different from previous studies in the continuous exposure of the pups to BPA or mixtures during the lactation period. Digit ratios were found to be fixed exclusively by prenatal exposure, whereas AGD was modulated by the compounds both during gestation and postnatal exposure of the pups (the transmission to pups to the three compounds tested via milk has been demonstrated; ( [47,48], J. P. Cravedi 2005, unpublished data). In summary, digit ratios and AGDs in experimental studies involving continuous exposure to endocrine disruptors are different markers that may be jointly assessed for the detection of associations with other phenotypic changes.…”

Effects of bisphenol A on growth and nitrogen nutrition of roots of soybean seedlings

“…Crain et al [7] reported that BPA at the environmentally relevant concentration of 21 mg/L or less can disrupt the endocrine system of many living organisms. Suzuki and Hattori [13] demonstrated that BPA can cause a decrease in the calcium level and calcitonin secretion in plasma of goldfish, suppressing the activities of tartrate-resistant acid phosphatase and alkaline phosphatase b. Kurebayashi et al [14] found trace disposition of BPA in adult, pregnant, and neonatal rats. Domoradzki et al [15] reported the pharmacokinetics and metabolism of BPA at three different stages of pregnancy in Sprague-Dawley rats.…”

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“…Kurebayashi et al (2005) also reported that a small amount of radioactivity is transferred to the rat foetus, but only during late pregnancy (not before GD 18). No distinction could be made between free-or conjugated BPA, due to the low levels observed.…”

“…Considering that the BPA concentration in water in polycarbonate bottles was indicated to be as low as 0.33 ± 0.15 μg/L, this finding seems to be not fully consistent and limits the value of the described results. Kurebayashi et al (2005; cited in the 2006 EFSA opinion) reported the recovery of BPAderived radioactivity in neonatal tissues (mostly located in the intestinal content) from two pups 24 and 48 hr after oral administration of 14 C-BPA (500 μg/kg b.w.) to a single lactating rat on PND 11 (Kurebayashi et al, 2005).…”

“…Kurebayashi et al (2005; cited in the 2006 EFSA opinion) reported the recovery of BPAderived radioactivity in neonatal tissues (mostly located in the intestinal content) from two pups 24 and 48 hr after oral administration of 14 C-BPA (500 μg/kg b.w.) to a single lactating rat on PND 11 (Kurebayashi et al, 2005). The results also indicate a transfer of BPA via milk during lactation, with a peak concentration in milk 8 h after treatment of 3 lactating dams (4.46 ng/ml).…”