title: Estrogen-like disruptive effects of dietary exposure to bisphenol A or 17α-ethinyl estradiol in CD1 mice.
abstract: Bisphenol A (BPA) is an endocrine disrupting chemical that is ubiquitous in wild and built environments. Due to variability in study design, the disruptive effects of BPA have proven difficult to experimentally replicate. This study was designed to assess the disruptive actions of dietary BPA exposure, while carefully controlling for known confounders. Parental CD1 mice were acclimated to defined diet containing BPA (0.03, 0.3, 3, 30, or 300 ppm) or 17α-ethinyl estradiol (EE; 0.0001, 0.001, and 0.01 ppm) and bred to produce progeny (F1) that were maintained through adulthood on the same diet as the parents. In F1 females, uterine weights were increased in all EE and the 30-ppm BPA-exposure groups, demonstrating model sensitivity and estrogen-like actions of BPA. In BPA-exposed females, no treatment-related differences were observed in parental reproductive function, or in the timing of puberty and metabolic function in female offspring. In F1 males, modest changes in body weight, adiposity and glucose tolerance, consistent with improved metabolic function, were observed. Associated with increased prolactin and increased circulating testosterone levels, balanopreputial separation was accelerated by 0.03 and 3.0 ppm BPA and anogenital distance at postnatal day 21 was increased in males by 0.03 ppm BPA. Sperm counts were also increased with 3.0 ppm BPA exposures. Overall, BPA was found to have modest, sex specific endocrine disruptive effects on a variety of end points below the established no observed adverse effect level. The dose response characteristics for many of the effects were nonmonotonic and not predictable from high-dose extrapolations.
authors.affiliation: Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Kendig
authors.forename: Dana R
authors.initials: DR
authors.lastname: Buesing
authors.forename: Susie M
authors.initials: SM
authors.lastname: Christie
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Cookman
authors.forename: Robin B
authors.initials: RB
authors.lastname: Gear
authors.forename: Eric R
authors.initials: ER
authors.lastname: Hugo
authors.forename: Susan N
authors.initials: SN
authors.lastname: Kasper
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Kendziorski
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Ungi
authors.forename: Karin
authors.initials: K
authors.lastname: Williams
authors.forename: Scott M
authors.initials: SM
authors.lastname: Belcher
mesh_terms: D000821:Animal Feed; D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D004967:Estrogens / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000633:toxicity*; D005260:Female; D005951:Glucose Tolerance Test; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008815:Mice, Inbred Strains; D019055:No-Observed-Adverse-Effect Level; D009765:Obesity / Q000139:chemically induced; D009929:Organ Size / Q000187:drug effects; D018812:Paternal Exposure; D010636:Phenols / Q000633:toxicity*; D012098:Reproduction / Q000187:drug effects; D012737:Sex Factors; D012741:Sexual Maturation / Q000187:drug effects; D013076:Sperm Count; D013094:Spermatozoa / Q000187:drug effects; D014599:Uterus / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D004967:Estrogens; D004997:Ethinyl Estradiol; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds