Developmental Treatment with Bisphenol A or Ethinyl Estradiol Causes Few Alterations on Early Preweaning Measures

Ferguson, Sherry A.; Law, Charles D.; Abshire, Jordan S.

doi:10.1093/toxsci/kfr201

Cited by 54Effects and risks of endocrine disrupting chemicalsSexual Differentiation and DisordersEstrogen and related hormone effects

Developmental Treatment with Bisphenol A or Ethinyl Estradiol Causes Few Alterations on Early Preweaning Measures

Ferguson, Sherry A., Law, Charles D., Abshire, Jordan S.·2011·Toxicological Sciences

DOI 10.1093/toxsci/kfr201

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Abstract

Because bisphenol A (BPA) exposure is nearly ubiquitous, increased knowledge of its potential effects on development will enable better risk assessment and regulatory guidance. Here, Sprague-Dawley rats were reared in low exogenous estrogen environments. After breeding at adulthood, dams were gavaged on gestational days (GDs) 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 the dam received. Relative to the VEH group, dams of both EE₂-treated groups weighed less throughout gestation and lactation. PND 1 absolute anogenital distance and anogenital index were unaltered by any treatment. Ages at fur development and eye and ear opening were unaffected by any treatment. Despite a significant treatment effect, no group was significantly different from VEH in PNDs 3-6 righting latencies; although males had shorter latencies and all latencies decreased with age. PNDs 8-11 slant board behavior was unaffected by any treatment; however, males had shorter turning latencies and latencies decreased with age. Preweaning body weights of BPA- and EE₂-treated groups as well as naive controls were less than VEH. No treatment affected PND 21 whole or regional brain weights or levels of estradiol, testosterone, corticosterone, T3, T4, luteinizing hormone, ghrelin, or leptin. These results add to the literature indicating that developmental BPA treatment at these doses has no effects on gestational or lactational body weight, offspring anogenital distance, preweaning behaviors or hormone levels, and whole and regional brain weights measured at weaning.

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Previously, the authors described few BPA effects on pre- and postweaning behaviors that are not generally thought to be sexually dimorphic.
“Previously, we described few BPA effects on pre-and postweaning behaviors that are not generally thought to be sexually dimorphic (Ferguson et al., 2012(Ferguson et al., , 2011)).”
From Developmental Treatment with Ethinyl Estradiol, but Not Bisphenol A, Causes Alterations in Sexually Dimorphic Behaviors in Male and Female Sprague Dawley Rats (2014) · cites this paper as Ferguson et al., 2011
The Discussion reports no BPA effects on the two preweaning behaviors tested, supporting the preweaning part of the claim. It says postweaning behavioral results would be reported separately, so this paper does not support the postweaning part. It also does not characterize the tested behaviors as generally non-sexually dimorphic; its results report a sex difference in slant-board performance. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Our previous descriptions of significant EE2, but few BPA, effects on pre- and postweaning behaviors add to the growing body of literature indicating lack of effect at these orally administered BPA doses.
“Our previous descriptions of significant EE 2 , but few BPA, effects on pre-and postweaning behaviors (Ferguson et al., 2011(Ferguson et al., , 2012) ) add to the growing body of literature indicating lack of effect at these orally administered BPA doses.”
From Developmental Treatment with Ethinyl Estradiol, but Not Bisphenol A, Causes Alterations in Sexually Dimorphic Behaviors in Male and Female Sprague Dawley Rats (2014) · cites this paper as Ferguson et al., 2011
The Discussion reports few effects of oral BPA at the tested doses, and the preweaning behavioral results show no significant BPA effects. But this paper does not show significant EE2 effects on preweaning behavior: the Righting reflex section reports no treatment group differed significantly from vehicle, and the Slant board behavior section reports no treatment effect. Postweaning behavioral results were reserved for a separate report. (LLM, conf=0.86)
Experimental — accuracy not yet measured
In mammals, pharmacological levels of EE2 exert important effects on reproductive physiology and behavior.
“In mammals, pharmacological levels of EE2 exert important effects on reproductive physiology and behavior [18, 31–34].”
From Developmental exposure to low levels of ethinylestradiol affects social play in juvenile male rats (2020) · cites this paper as [33]
The results on dam body weight and litter outcomes (pages not provided) show that EE2-treated rats had lower gestational body weights and, at the higher dose, lower pup birth weights. But the Righting reflex and Slant board behavior results report no significant differences from controls attributable to EE2. The paper therefore supports effects on some pregnancy-related measures in rats, not the broader claim of important effects on both reproductive physiology and behavior in mammals. (LLM, conf=0.83)
Experimental — accuracy not yet measured
The lack of significance for BPA treatment here is consistent with previous descriptions from the same cohort.
“Additionally, the lack of significance for BPA treatment here is consistent with our previous descriptions from the same cohort (Ferguson et al., 2011(Ferguson et al., , 2012)).”
From Developmental Treatment with Ethinyl Estradiol, but Not Bisphenol A, Causes Alterations in Sexually Dimorphic Behaviors in Male and Female Sprague Dawley Rats (2014) · cites this paper as Ferguson et al., 2011

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Advance Access publication August 3, 2011 Developmental Treatment with Bisphenol A or Ethinyl Estradiol Causes Few Alterations on Early Preweaning Measures
Ferguson, S. A., Law, C., & Abshire, J. S. (2011)
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Developmental treatment with bisphenol A causes few alterations on measures of postweaning activity and learning
Ferguson, S. A., Law, C. D., & Abshire, J. S. (2012) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2012.09.006 · Cited by 37 · see citing works
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Developmental Bisphenol A (BPA) or Ethinyl Estradiol Treatment at Relatively Low Doses Has No Effects on Early Preweaning Behaviors
Ferguson, S. A., Law, C., & Abshire, J. S. (2011) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2011.05.021
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Pubertal Development and Reproductive Functions of Crl:CD BR Sprague-Dawley Rats Exposed to Bisphenol A during Prenatal and Postnatal Development
Kwon, S. (2000) · Toxicological Sciences · doi:10.1093/toxsci/55.2.399 · Cited by 133 · see citing works
Developmental Treatment with Ethinyl Estradiol, but Not Bisphenol A, Causes Alterations in Sexually Dimorphic Behaviors in Male and Female Sprague Dawley Rats
Ferguson, S. A., Law, C. D., & Kissling, G. E. (2014) · Toxicological Sciences · doi:10.1093/toxsci/kfu077 · Cited by 32 · see citing works
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Authors: Ferguson, S. A., Law, C. D., & Abshire, J. S.
Affiliations: National Center for Toxicological Research (US)
ORCID: Ferguson, Sherry A.
Venue: Toxicological Sciences
Publisher: Oxford University Press (OUP)
Published: 2011-08-03
Volume: 124
Issue: 1
Pages: 149-160
ISSN: 1096-0929 (ISSN-L)
1096-6080
DOI: 10.1093/toxsci/kfr201
OpenAlex: W2116247529
Cited by: 54
References: 84
Citations by year: 2026: 1 · 2023: 3 · 2022: 1 · 2021: 7 · 2020: 7 · 2019: 7 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 5 · 2014: 7 · 2013: 8 · 2012: 2
FWCI: 3.93
Type: journal article
Language: en
Open access: closed
Locations: Toxicological Sciences (publishedVersion)
PubMed (publishedVersion)
Topics: Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords: bisphenol A, ethinyl estradiol, developmental toxicity, prenatal estrogen exposure, anogenital distance, brain weight, hormone levels
MeSH terms: Bisphenol A Compounds, Animals, Behavior, Animal, Benzhydryl Compounds, Body Weight, Brain, Dose-Response Relationship, Drug, Ethinyl Estradiol, Female, Genitalia, Gestational Age, Hormones, Male, Organ Size, Phenols, Pregnancy, Prenatal Exposure Delayed Effects, Weaning, Proportional Hazards Models, Rats, Sprague-Dawley, Rats, Reflex, Righting

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Developmental Treatment with Bisphenol A or Ethinyl Estradiol Causes Few Alterations on Early Preweaning Measures

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