title: Developmental treatment with bisphenol A causes few alterations on measures of postweaning activity and learning.
abstract: Widespread bisphenol A (BPA) exposure necessitates increased knowledge of its potential effects for better risk assessment and regulatory guidance. Here, female Sprague-Dawley rats, reared in low exogenous estrogen environments and bred at adulthood, were gavaged on gestational days 6-21 with vehicle (VEH), 2.5 or 25.0 μg/kg/day BPA, or 5.0 or 10.0 μg/kg/day ethinyl estradiol (EE₂). Offspring were orally treated on postnatal days (PNDs) 1-21 with the same dose their dam received. A naïve control group (NC) was not gavaged. Post-weaning, one offspring/sex/litter (n=11-12/sex/group) was assessed for the typical behaviors measured in developmental neurotoxicology studies. At PND 29, novelty preference was unaffected by treatment; however, relative to the VEH group, males and females of both EE₂ groups were more active. VEH males appeared somewhat hypoactive in open field assessments at PNDs 40-42 and, as a result, males of the BPA and EE₂ groups were significantly more active. Latency to locate the Barnes maze escape box at PNDs 47-50 was increased in males and females of the 5.0 μg/kg/day EE₂ group. Relative to other male groups, VEH males exhibited an increased startle response on the first trial block at PND 54 and thus, males of both BPA groups and the 10.0 μg/kg/day EE₂ group exhibited a significantly decreased startle response. PNDs 43-44 motor coordination and PNDs 75-79 water maze performance were unaffected by treatment. These results indicate few consistent or dose-related effects resulting from developmental treatment with BPA at these doses. Few of these behaviors, however, were sexually dimorphic which may prove more sensitive.
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA. Sherry.Ferguson@fda.hhs.gov
authors.forename: Sherry A
authors.initials: SA
authors.lastname: Ferguson
authors.forename: C Delbert
authors.initials: CD
authors.lastname: Law
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Abshire
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects*; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects; D014886:Weaning; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D004997:Ethinyl Estradiol; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds