Age and dose dependency of the pharmacokinetics and metabolism of bisphenol A in neonatal sprague-dawley rats following oral administration. 2004

J Y Domoradzki, and C M Thornton, and L H Pottenger, and S C Hansen, and T L Card, and D A Markham, and M D Dryzga, and R N Shiotsuka, and J M Waechter
Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan 48674, USA.

Previous studies demonstrated the rapid clearance of bisphenol A (BPA) from blood following oral administration to adult rats with the principal metabolite being BPA-monoglucuronide (BPA-glucuronide). Since the ontogeny of glucuronyl transferases (GT) differs with age, the pharmacokinetics of BPA were studied in neonatal animals. (14)C-BPA was administered via gavage at 1 or 10 mg/kg body weight to rats at postnatal day (pnd) 4, pnd 7, pnd 21, or to 11 week old adult rats (10 mg/kg dose only). Blood (neonates and adults) and selected tissues (neonates) were collected at 0.25, 0.75, 1.5, 3, 6, 12, 18, and 24 h postdosing. BPA and BPA-glucuronide in the plasma were quantified by high-performance liquid chromatography; radioactivity in the plasma and tissues was quantified by liquid scintillation spectrometry. The data indicate that neonatal rats at all three ages metabolized BPA to BPA-glucuronide, although an age dependency in the number and concentration of plasma metabolites was observed, consistent with the ontogeny of GT. BPA-glucuronide and BPA concentrations in the plasma were greater in neonates than in adults, except at 24 h postdosing, suggesting an immaturity in the development of hepatic excretory function in neonatal rats. Nevertheless, the half-lives for the elimination of BPA-glucuronide in plasma were more rapid in neonatal animals than in adults, likely due to reduced microflora beta-glucuronidase activity and an absence of enterohepatic recirculation. A dose dependency in the metabolism and pharmacokinetics of BPA administered to neonates was also observed with nearly complete metabolism of BPA to BPA-glucuronide (94-100% of the plasma radioactivity) at a dose of 1 mg/kg. This was in contrast to finding up to 13 different plasma metabolites observed at the 10 mg/kg dose. These data indicate that, from early in neonatal life through pnd 21, there is sufficient GT activity in rats to efficiently metabolize BPA to its nonestrogenic metabolite at low doses.

UI MeSH Term Description Entries
D008297 Male Males
D010636 Phenols Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.
D010969 Plastics Polymeric materials (usually organic) of large molecular weight which can be shaped by flow. Plastic usually refers to the final product with fillers, plasticizers, pigments, and stabilizers included (versus the resin, the homogeneous polymeric starting material). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Plastic
D011076 Polycarboxylate Cement Water-soluble low-molecular-weight polymers of acrylic or methacrylic acid that form solid, insoluble products when mixed with specially prepared ZnO powder. The resulting cement adheres to dental enamel and is also used as a luting agent. Zinc Polycarboxylate Cement,Cement, Polycarboxylate,Cement, Zinc Polycarboxylate,Polycarboxylate Cement, Zinc
D002250 Carbon Radioisotopes Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes. Radioisotopes, Carbon
D002642 Chick Embryo The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching. Embryo, Chick,Chick Embryos,Embryos, Chick
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004968 Estrogens, Non-Steroidal Non-steroidal compounds with estrogenic activity. Estrogens, Nonsteroidal,Estrogens, Non Steroidal,Non-Steroidal Estrogens,Nonsteroidal Estrogens
D005260 Female Females
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations

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