Extensive metabolism and route-dependent pharmacokinetics of bisphenol A (BPA) in neonatal mice following oral or subcutaneous administration.
Orally administered bisphenol A (BPA) undergoes efficient first-pass metabolism to produce the inactive conjugates BPA-glucuronide (BPA-G) and BPA-sulfate (BPA-S). This study was conducted to evaluate the pharmacokinetics of BPA, BPA-G and BPA-S in neonatal mice following the administration of a single oral or subcutaneous (SC) dose. This study consisted of 3 phases: (1) mass-balance phase in which effective dose delivery procedures for oral or SC administration of (3)H-BPA to postnatal day three (PND3) mice were developed; (2) pharmacokinetic phase during which systemic exposure to total (3)H-BPA-derived radioactivity in female PND3 mice was established; and (3) metabolite profiling phase in which 50 female PND3 pups received either a single oral or SC dose of (3)H-BPA. Blood was collected from 5 pups/route/time-point at various times post-dosing, the blood plasma samples were pooled by group, and time-point and samples were profiled by HPLC with fraction collection. Fractions were analyzed for total radioactivity and data used to reconstruct radiochromatograms and to integrate individual peaks. The identity of the BPA, BPA-G, and BPA-S peaks was confirmed using authentic standards and LC-MS/MS analysis. The result of this study revealed that female PND3 mice have the capacity to metabolize BPA to BPA-G, BPA-S and other metabolites after both routes of administration. Systemic exposure to free BPA is route-dependent as the plasma concentrations were lower following oral administration compared to SC injection.
WIL Research, Ashland, OH 44805, USA. Electronic address: dragomir_ivanov.draganov@roche.com.
Dragomir I
DI
Draganov
The Dow Chemical Co., Midland, MI 48674, USA. Electronic address: DAMarkam@dow.com.
Dan A
DA
Markham
Bayer Healthcare AG, Wuppertal D-42096, Germany. Electronic address: dieter.beyer@bayer.com.
Dieter
D
Beyer
The Dow Chemical Co., Midland, MI 48674, USA. Electronic address: john.waechter@cardno.com.
John M
JM
Waechter
SABIC Innovative Plastics, Pittsfield, MA 01201, USA. Electronic address: Stephen.Dimond@sabic-ip.com.
Stephen S
SS
Dimond
The Dow Chemical Co., Midland, MI 48674, USA. Electronic address: RABudinsky@dow.com.
Robert A
RA
Budinsky
Bayer Material Science, Pittsburgh, PA 15205, USA.
Ronald N
RN
Shiotsuka
Bayer Material Science, Pittsburgh, PA 15205, USA. Electronic address: stephanie.snyder@bayer.com.
Stephanie A
SA
Snyder
Toxicology Regulatory Services, Inc., Charlottesville, VA 22911, USA. Electronic address: kehman@rti.org.
Kimberly D
KD
Ehman
American Chemistry Council, Washington, D.C. 20002, USA. Electronic address: Steve_Hentges@americanchemistry.com.
Steven G
SG
Hentges
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005260:Female; D020719:Glucuronides / Q000493:pharmacokinetics; D007279:Injections, Subcutaneous; D055432:Metabolomics / Q000379:methods; D051379:Mice; D010636:Phenols / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D013431:Sulfates / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D020719:Glucuronides; D010636:Phenols; D013431:Sulfates; C512161:bisphenol A glucuronide; D000098826:Bisphenol A Compounds; C006780:bisphenol A
Bisphenol A; CAS No. 80-05-7; Mice; Neonates; Pharmacokinetics; Route-dependent