title: Impact of Low-Dose Oral Exposure to Bisphenol A (BPA) on Juvenile and Adult Rat Exploratory and Anxiety Behavior: A CLARITY-BPA Consortium Study.
abstract: Bisphenol A (BPA) is a high volume production chemical and has been identified as an endocrine disruptor, prompting concern that developmental exposure could impact brain development and behavior. Rodent and human studies suggest that early life BPA exposure may result in an anxious, hyperactive phenotype but results are conflicting and data from studies using multiple doses below the no-observed-adverse-effect level are limited. To address this, the present studies were conducted as part of the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) program. The impact of perinatal BPA exposure (2.5, 25, or 2500 µg/kg body weight (bw)/day) on behaviors related to anxiety and exploratory activity was assessed in juvenile (prepubertal) and adult NCTR Sprague-Dawley rats of both sexes. Ethinyl estradiol (0.5 µg/kg bw/day) was used as a reference estrogen. Exposure spanned gestation and lactation with dams gavaged from gestational day 6 until birth and then the offspring gavaged directly through weaning (n = 12/sex/group). Behavioral assessments included open field, elevated plus maze, and zero maze. Anticipated sex differences in behavior were statistically identified or suggested in most cases. No consistent effects of BPA were observed for any endpoint, in either sex, at either age compared to vehicle controls; however, significant differences between BPA-exposed and ethinyl estradiol-exposed groups were identified for some endpoints. Limitations of this study are discussed and include suboptimal statistical power and low concordance across behavioral tasks. These data do not indicate BPA-related effects on anxiety or exploratory activity in these developmentally exposed rats.
authors.affiliation: *Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695; Keck Center for Behavioral Biology, North Carolina State University, Raleigh, North Carolina 27695;
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Rebuli
authors.affiliation: National Center for Toxicological Research, Jefferson, Arkansas 72079; and.
authors.forename: Luísa
authors.initials: L
authors.lastname: Camacho
authors.affiliation: Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina 27695.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Adonay
authors.affiliation: *Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695; Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina 27695.
authors.forename: David M
authors.initials: DM
authors.lastname: Reif
authors.affiliation: *Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695; Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina 27695.
authors.forename: David L
authors.initials: DL
authors.lastname: Aylor
authors.affiliation: *Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695; Keck Center for Behavioral Biology, North Carolina State University, Raleigh, North Carolina 27695; hbpatisa@ncsu.edu.
authors.forename: Heather B
authors.initials: HB
authors.lastname: Patisaul
mesh_terms: D000367:Age Factors; D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D005106:Exploratory Behavior / Q000187:drug effects*; D005260:Female; D005865:Gestational Age; D007774:Lactation; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D009043:Motor Activity / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000523:psychology; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D012737:Sex Factors; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: BPA; CLARITY; EDC; anxiety; behavior; bisphenol A; brain; endocrine disruption; exploratory activity; plastic; sexually dimorphic