Radioactivity In Fetal Tissues Research Articles

Disposition of bisphenol A in pregnant mice and fetuses after a single and repeated oral administration

The risk assessment of bisphenol A (BPA) on the development of offspring of humans is an important issue. There have been some reports on the fate of BPA in rodents, but information on the BPA level in fetal organs essential for the extrapolation to humans is inadequate. In the present study, we investigated the distribution pattern of 14C-BPA-derived radioactivity in fetal tissues following administration of 10 mg/kg 14C-BPA to the pregnant mice. The radioactivity was rapidly transferred through placenta and distributed to all fetal organs including reproductive organs and brains in a similar level. The concentration declined slowly compared with dams. Analysis of metabolites in fetuses showed that a fraction of BPA was unexpectedly large compared to the maternal blood. There was no clear effect of the fetal position in a uterus to influence the radioactivity concentration in whole fetuses. The dose dependence of pharmacokinetics should be recognized to extrapolate the pharmacokinetic result from animal experiments at high doses to humans at low doses. Similar experiments were conducted with an addition of two doses, 1 and 100 mg/kg, respectively. The pharmacokinetics seemed to be linear between 1 and 10 mg/kg, although at 100 mg/kg BPA was absorbed slowly and the radioactivity concentrations in fetuses were much higher than expected based on the linear dose dependence. Repeated doses were administered to pregnant mice since humans are exposed to BPA chronically. Radioactivity level in most of the fetal tissues on repeated administration was higher than single administration.

Metabolic Fate of Losartan, a New Angiotensin II Receptor Antagonist. (3). Transfer into Fetus and Milk in Rats.

The transfer of losartan into the fetus and milk was investigated after single oral administration of 14C-losartan at a dose of 10 mg/kg to pregnant and lactating rats, respectively.1. At 1, 8 and 24 hr after administration of 14C-losartan to 13-day pregnant rats, the whole-body autoradiography showed that no radioactivity was distributed to the fetus. Very low levels of radioactivity were detected in the fetus at 8 and 24 hr following administration to 18-day pregnant rats.2. The maternal tissues of 18-day pregnant rats had the highest levels of radioactivity at 1 hr after administration and thereafter, the radioactivity declined with time, whereas the radioactivity in fetal tissues reached its peak between 1 and 8 hr after dosing and remained virtually unchanged from 8 to 24 hr. At 24 hr after administration, the radioactivity levels in the fetal blood, liver and kidney, and in the whole fetus were higher than that in the maternal plasma. At 8 or 24 hr after dosing, the radioactivity in the fetus accounted for 0.01% of the administered dose, indicating a slow transfer of the radioactivity into the fetal tissues.3. Following oral administration of 14C-losartan to lactating rats on the 11th day after delivery, the radioactivity in the milk peaked at 8 hr after administration, indicating that the transfer of radioactivity into the milk is very slow. From 8 to 48 hr, the radioactivity in the milk declined similarly to that in plasma with a terminal t1/2 of approximately 16 hr. At 48 hr after dosing, the radioactivity level in the milk corresponded to 45% of the plasma concentration.

Disposition of rhIGF-I. (2). Transfer of 125I-rhIGF-I into fetus and milk in pregnant or lactating rats.

The transfer of 125I-rhIGF-I to the fetus or into the milk after a single subcutaneous administration was investigated in pregnant rats on 12th and 18th day of gestation and in lactating rats. The level of radioactivity in the fetus on the 18th day of gestation was higher than that on the 12th day of gestation, but was at least six times lower than that in maternal plasma. The level of radioactivity in fetal tissues disappeared parallelling the maternal plasma except that in thyroid gland, which might be due to free 125I. Most of radioactive substances of high molecular weight, which were found in the milk of lactating rats, might be on endogenous proteins which had in corporated a free iodine, otherwise the permeability of rhIGF-I into milk was thought to be low.

Comparative distribution, pharmacokinetics and placental permeabilities of all-trans-retinoic acid, 13-cis-retinoic acid, all-trans-4-oxo-retinoic acid, retinyl acetate and 9-cis-retinal in hamsters

Pregnant hamsters were given a single oral dose (35 mumol/kg) of all-trans-retinoic acid, 13-cis-retinoic acid, all-trans-4-oxo-retinoic acid, 9-cis-retinal or all-trans-retinyl acetate during the early primitive streak stage of development. The radioactivity associated with the acidic retinoids was distributed to all tissues sampled (including placenta and fetus), with the largest accumulation in the liver and the least accumulation in fat. Radioactivity from 9-cis-retinal or retinyl acetate concentrated in the liver and lung. The all-trans-retinoic acid was oxidized in vivo to all-trans-4-oxo-retinoic acid and isomerized to 13-cis-retinoic acid: 13-cis-retinoic acid was oxidized to 13-cis-4-oxo-retinoic acid and isomerized to all-trans-retinoic acid. No parent 9-cis-retinal or retinyl acetate could be detected in maternal plasma. Plasma concentrations of the parent acidic retinoids reached their maxima within 60 min and then followed exponential decay. Of all the retinoids examined here, 13-cis-retinoic acid showed the largest area under the plasma curve, the slowest clearance and the longest elimination t1/2. Total plasma radioactivity, consisting of unidentified metabolites, remained elevated at 4 days after dosing. Maternal peak circulating concentrations of the parent retinoids, total radioactivity, plasma pharmacokinetic parameters or the total concentrations of residual radioactivity in fetal tissues could not be correlated with the differential teratogenic potencies of these retinoids.