title: Comparison of serum bisphenol A concentrations in mice exposed to bisphenol A through the diet versus oral bolus exposure.
abstract: BACKGROUND
  Bisphenol A (BPA) is a widely produced endocrine-disrupting chemical. Diet is a primary route of exposure, but internal exposure (serum concentrations) in animals and humans has been measured only after single oral bolus administration.
  
  
  OBJECTIVE
  We compared serum concentrations of BPA over a 24-hr period after oral bolus administration or ad libitum feeding in mice and assessed for buildup with dietary exposure.
  
  
  METHODS
  Adult female mice were administered [dimethyl-d6]-BPA (BPA-d6) as a single oral bolus (20 mg/kg body weight) or fed a diet containing 100 mg BPA-d6/kg feed weight ad libitum for 1 week. Serum concentrations were analyzed using isotope dilution liquid chromatography coupled with electrospray tandem mass spectrometry and compared between exposure groups over the first 23 hr and after 7 days of dietary exposure.
  
  
  RESULTS
  Maximum concentration (Cmax) for BPA-d6 during the first 24 hr was reached at 1 hr and 6 hr for oral bolus and diet groups, respectively. Relative BPA-d6 bioavailability (unconjugated BPA-d6) was higher in diet-exposed mice than in the bolus group despite a relative lower absorption, a phenomenon consistent with an inhibitory effect of food on first-pass hepatic metabolism. In mice with ongoing dietary exposure, unconjugated BPA-d6 was higher on day 7 than on day 1.
  
  
  CONCLUSIONS
  This is the first report of serum BPA concentrations in an animal model exposed to this chemical via the diet. Although bolus administration of BPA-d6 led to peak concentrations within 1 hr, Cmax for diet-exposed mice was delayed for several hours. However, bolus administration underestimates bioavailable serum BPA concentrations in animals-and presumably humans-than would result from dietary exposure. Exposure via diet is a more natural continuous exposure route than oral bolus exposure and is thus a better predictor of BPA concentrations in chronically exposed animals and humans.
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri 65211, USA.
authors.forename: Paizlee T
authors.initials: PT
authors.lastname: Sieli
authors.forename: Eldin
authors.initials: E
authors.lastname: Jašarevic
authors.forename: Denise A
authors.initials: DA
authors.lastname: Warzak
authors.forename: Jiude
authors.initials: J
authors.lastname: Mao
authors.forename: Mark R
authors.initials: MR
authors.lastname: Ellersieck
authors.forename: Chunyang
authors.initials: C
authors.lastname: Liao
authors.forename: Kurunthachalam
authors.initials: K
authors.lastname: Kannan
authors.forename: Séverine H
authors.initials: SH
authors.lastname: Collet
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Toutain
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Vom Saal
authors.forename: Cheryl S
authors.initials: CS
authors.lastname: Rosenfeld
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds; D001682:Biological Availability; D002853:Chromatography, Liquid / Q000662:veterinary; D004032:Diet / Q000662:veterinary; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010636:Phenols / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000662:veterinary; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds