title: Pharmacokinetics of bisphenol A in serum and adipose tissue following intravenous administration to adult female CD-1 mice.
abstract: Bisphenol A (BPA) is an important industrial chemical used as the monomer for polycarbonate plastic and in epoxy resins for use in food can liners. Worldwide biomonitoring studies consistently find high prevalence of BPA conjugates in urine consistent with pervasive exposure at levels typically below 1 μg/kg bw/day. The current study used LC/MS/MS to measure serum pharmacokinetics of unconjugated (active) and conjugated (inactive) BPA in adult female CD-1 mice following intravenous (IV) injection, which produces higher serum levels by circumventing the processes of absorption from the GI tract and presystemic metabolism that occur after oral administration. Deuterated BPA (100 μg/kg bw) was used to avoid interference by background contamination from trace amounts of native BPA. Additionally, the pharmacokinetics of unconjugated BPA were determined in adipose tissue, a proposed site of action and "depot" for BPA. After IV injection, unconjugated BPA rapidly distributed out of the circulation (t(1/2)=0.2 h) and terminal elimination also proceeded rapidly (t(1/2)=0.8 h). Consistent with the degree of aqueous solubility, lipid/water solubility ratio, and partitioning from blood into adipose tissue in vivo, the levels of unconjugated BPA in mouse adipose tissue rapidly reached a maximal level (0.25 h) that did not exceed the serum maximum at the initial sampling time (0.08 h). Terminal elimination of unconjugated BPA from adipose tissue (t(1/2)=7.0 h) was similar to that for conjugated BPA in serum (t(1/2)=6.6 h) and <0.01% of the administered dose remained in adipose tissue after 24 h. These plasma and tissue kinetics are consistent with rapid equilibria and underscore the non-persistent nature of BPA, particularly when compared with slowly metabolized lipophilic organic pollutants like halogenated dibenzodioxins.
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA. daniel.doerge@fda.hhs.gov
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Doerge
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Twaddle
authors.forename: Michelle
authors.initials: M
authors.lastname: Vanlandingham
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Fisher
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D002853:Chromatography, Liquid; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D051379:Mice; D010636:Phenols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds