Scientific Publications by FDA Staff

Toxicol Sci 2015 Dec;148(2):341-54

Impact of low dose oral exposure to bisphenol A (BPA) on juvenile and adult rat exploratory and anxiety behavior: a CLARITY-BPA consortium study.

Rebuli ME, Camacho L, Adonay ME, Reif DM, Aylor D, Patisaul HB

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 (NOAEL) 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 microg/kg body weight (bw)/day) on behaviors related to anxiety and exploratory activity was assessed in juvenile (pre-pubertal) and adult NCTR Sprague-Dawley rats of both sexes. Ethinyl estradiol (EE; 0.5 microg/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 EE-exposed groups were identified for some endpoints. Limitations of the present study are discussed and include sub-optimal 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.