Impact of Low-Dose Oral Exposure to Bisphenol A (BPA) on Juvenile and Adult Rat Exploratory and Anxiety Behavior: A CLARITY-BPA Consortium Study
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
BPA crosses the blood-brain barrier in the CNS.
“This confirms that BPA could pass across the BBB,17”
From Bisphenol A Impairs Synaptic Plasticity by Both Pre‐ and Postsynaptic Mechanisms (2017) · cites this paper as [17]
The paper’s Abstract discusses possible effects of BPA exposure on brain development, and the Discussion mentions potential brain-related mechanisms, but neither passage addresses whether BPA crosses the blood-brain barrier. Searches for “blood-brain barrier,” “BBB,” and entry into the CNS found no passage establishing that point. Page numbers were not available in our copy. (LLM, conf=0.70)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Bisphenol A and human health: A review of the literature
Rochester, J. R. (2013) · Reproductive Toxicology · doi:10.1016/j.reprotox.2013.08.008 · Cited by 2,018 · see citing works
Exposure of the U.S. Population to Bisphenol A and 4- <i>tertiary</i> -Octylphenol: 2003–2004
Calafat, A. M., Ye, X., Wong, L.-Y., Reidy, J. A., & Needham, L. L. (2008) · Environmental Health Perspectives · doi:10.1289/ehp.10753 · Cited by 1,743 · see citing works
Russo, S. J., Murrough, J. W., Han, M.-H., Charney, D. S., & Nestler, E. J. (2012) · Nature Neuroscience · doi:10.1038/nn.3234 · Cited by 1,206 · see citing works
Sex differences in circadian timing systems: implications for disease
Bailey, M., & Silver, R. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2013.11.003 · Cited by 348 · see citing works
Prenatal Bisphenol A Exposure and Child Behavior in an Inner-City Cohort
Perera, F., Vishnevetsky, J., Herbstman, J. B., Calafat, A. M., Xiong, W., Rauh, V., & Wang, S. (2012) · Environmental Health Perspectives · doi:10.1289/ehp.1104492 · Cited by 332 · see citing works
The role of bisphenol A in shaping the brain, epigenome and behavior
Wolstenholme, J. T., Rissman, E. F., & Connelly, J. J. (2011) · Hormones and Behavior · doi:10.1016/j.yhbeh.2010.10.001 · Cited by 309 · see citing works
Tian, Y., Baek, J., Lee, S., & Jang, C. (2010) · Synapse · doi:10.1002/syn.20746 · Cited by 197 · see citing works
Gestational Exposure to Low Dose Bisphenol A Alters Social Behavior in Juvenile Mice
Wolstenholme, J. T., Taylor, J. A., Shetty, S. R. J., Edwards, M., Connelly, J. J., & Rissman, E. F. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025448 · Cited by 168 · see citing works
Transgenerational effects of prenatal bisphenol A on social recognition
Wolstenholme, J. T., Goldsby, J. A., & Rissman, E. F. (2013) · Hormones and Behavior · doi:10.1016/j.yhbeh.2013.09.007 · Cited by 157 · see citing works
Cao, J., Rebuli, M. E., Rogers, J., Todd, K. L., Leyrer, S. M., Ferguson, S. A., & Patisaul, H. B. (2013) · Toxicological Sciences · doi:10.1093/toxsci/kft035 · Cited by 141 · see citing works
Self-citationAdewale, H. B., Todd, K. L., Mickens, J. A., & Patisaul, H. B. (2011) · NeuroToxicology · doi:10.1016/j.neuro.2010.07.008 · Cited by 86 · see citing works
Self-citationFerguson, S. A., Law, C. D., & Abshire, J. S. (2011) · Toxicological Sciences · doi:10.1093/toxsci/kfr201 · Cited by 54 · see citing works
Patisaul, H. B., Blum, A., Luskin, J. R., & Wilson, M. E. (2005) · Behavioral Neuroscience · doi:10.1037/0735-7044.119.2.587 · Cited by 35 · see citing works
Self-citationFerguson, S. A., Law, C. D., & Kissling, G. E. (2014) · Toxicological Sciences · doi:10.1093/toxsci/kfu077 · Cited by 32 · see citing works
Flagged first, then by citations
Research works printed but not linked: 9
- Bailey, K. R., and Crawley, J. N. (2009). Anxiety-related behaviors in mice. In Methods of Behavior Analysis in Neuroscience, 2nd ed. (J. J. Buccafusco, Ed.). CRC Press, Boca Raton, FL.
- Gould, T. D., Kovacsics, D. T., and C. E. (2010). The open field test. In Mood and Anxiety Related Phenotypes in Mice (Todd D. Gould, Ed.). Humana Press, New York City, NY.
- Hogg, S. (1996). A review of the validity and variability of the ele- vated plus-maze as an animal model of anxiety. Pharmacol. Biochem. Behav. 54, 21-30.
- Jasarevic, E., Sieli, P. T., Twellman, E. E., Welsh, T. H., Jr., Schachtman, T. R., Roberts, R. M., Geary, D. C., and Rosenfeld, C. S. (2011). Disruption of adult expression of sexually se- lected traits by developmental exposure to bisphenol A. Proc. Natl. Acad. Sci. U S A 108, 11715-11720.
- Kinch, C. D., Ibhazehiebo, K., Jeong, J. H., Habibi, H. R., and Kurrasch, D. M. (2015). Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypotha- lamic neurogenesis in embryonic zebrafish. Proc. Natl. Acad. Sci. U S A 112, 1475-1480.
- Kundakovic, M., Gudsnuk, K., Franks, B., Madrid, J., Miller, R. L., Perera, F. P., and Champagne, F. A. (2013). Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure. Proc. Natl. Acad. Sci. U S A 110, 9956-9961.
- Leranth, C., Hajszan, T., Szigeti-Buck, K., Bober, J., and MacLusky, N. J. (2008a). Bisphenol A prevents the synaptogenic response to estradiol in hippocampus and prefrontal cortex of ovariec- tomized nonhuman primates. Proc. Natl. Acad. Sci. U S A 105, 14187-14191.
- Thigpen, J. E., Setchell, K. D., Padilla-Banks, E., Haseman, J. K., Saunders, H. E., Caviness, G. F., Kissling, G. E., Grant, M. G., and Forsythe, D. B. (2007). Variations in phytoestrogen con- tent between different mill dates of the same diet produces significant differences in the time of vaginal opening in CD-1 mice and F344 rats but not in CD Sprague-Dawley rats. Environ. Health. Perspect. 115, 1717-1726.
- Yeo, M., Berglund, K., Hanna, M., Guo, J. U., Kittur, J., Torres, M. D., Abramowitz, J., Busciglio, J., Gao, Y., Birnbaumer, L., et al. (2013). Bisphenol A delays the perinatal chloride shift in cor- tical neurons by epigenetic effects on the Kcc2 promoter. Proc. Natl. Acad. Sci. U S A 110, 4315-4320.
Cited by
Sorted by citations
Bisphenol A Impairs Synaptic Plasticity by Both Pre‐ and Postsynaptic Mechanisms
Hu, F., Li, T., Gong, H., Chen, Z., Jin, Y., Xu, G., & Wang, M. (2017) · Advanced Science · doi:10.1002/advs.201600493 · Cited by 87 · see citing works
Arambula, S. E., Belcher, S. M., Planchart, A., Turner, S. D., & Patisaul, H. B. (2016) · Endocrinology · doi:10.1210/en.2016-1339 · Cited by 87 · see citing works
Self-citation
- Authors
- Rebuli, M. E., Camacho, L., Adonay, M. E., Reif, D. M., Aylor, D. L., & Patisaul, H. B.
- Affiliations
- North Carolina State University (US)
- National Center for Toxicological Research (US)
- Venue
- Toxicological Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-07-23
- Volume
- 148
- Issue
- 2
- Pages
- 341-354
- ISSN
- 1096-0929 (ISSN-L)
- 1096-6080
- PMC
- PMC4683367
- OpenAlex
- W2176635843
- Cited by
- 64
- References
- 14
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 5 · 2022: 3 · 2021: 6 · 2020: 7 · 2019: 9 · 2018: 11 · 2017: 10 · 2016: 8 · 2015: 2
- FWCI
- 6.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Toxicological Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (#AES12013, U011ES020929)
- U.S. Public Health Service (AES12013)
- National Institute of Environmental Health Sciences (P42ES005948, U011ES020929, AES12013, R01ES019604, R01ES19604)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- bisphenol A, endocrine disruptors, perinatal exposure, developmental neurotoxicity, anxiety-like behavior, exploratory behavior, young rats, adult rats, sex differences, ethinyl estradiol, low-dose exposure, elevated plus maze, open field
- MeSH terms
- Bisphenol A Compounds, Age Factors, Animals, Anxiety, Behavior, Animal, Benzhydryl Compounds, Dose-Response Relationship, Drug, Exploratory Behavior, Female, Gestational Age, Lactation, Male, Motor Activity, Phenols, Pregnancy, Prenatal Exposure Delayed Effects, Sex Factors, Rats, Sprague-Dawley, Risk Assessment, Maternal Exposure, Neurotoxicity Syndromes, Endocrine Disruptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
