In a new article published online on April 20, 2014 in the peer-reviewed journal Toxicological Sciences, researchers from North Carolina State University report low dose effects of bisphenol A (BPA) on rat brains (Rebuli et al. 2014). Meghan Rebuli and colleagues examined brain tissue from the recent FDA low dose BPA study (previously reported by FPF) for differences between male and female brains due to exposure to the plastics chemical. Interestingly, significant differences were observed between the different dosing groups, whereby the lowest doses showed an effect which was not observed at the highest doses. In particular, the expression of estrogen receptors alpha and beta was measured in different brain regions which are known to be sexually dimorphic. The study’s samples were provided by FDA, stemming from a 90 day study to assess the toxicity of bisphenol A at various dose levels, including the so called low dose range relevant to human exposures (2.5 to 2700 µg/kg bw/d). Sprague-Dawley rats were treated orally by gavage starting during gestation until giving birth. Previous publications from the same study had reported no effects at the low dose range (Delclos et al. 2014), but had also shown that the negative control group was exposed to the same level of BPA as the lowest exposure group (2.5 µg/kg bw/d) due to contamination of the feed and additional unknown sources (Churchwell et al. 2014). This has been criticized by several scientists as flaw in the study’s design (previously reported by FPF).

The recent publication is noteworthy because statistically significant effects were observed between the contaminated negative control and the lowest exposure group; thereby, expression of both estrogen receptors in female brain regions mimicked levels observed in unexposed control males and differed significantly from levels seen in control females. However, it is unclear whether FDA will consider the observed changes in brain protein levels as adverse effects warranting regulatory consequences. The observed differences likely affect brain development and lead to behavioral changes, including more aggressive female behavior, later in life, and such behavioral effects will be the subject of further research.


Rebuli, M. et al. (2014). “Investigation of the Effects of Subchronic Low Dose Oral Exposure to Bisphenol A (BPA) and Ethinyl Estradiol (EE) on Estrogen Receptor Expression in the Juvenile and Adult Female Rat Hypothalamus.Toxicological Sciences (published online 20 April 2014).

Delclos, et al. (2014). “Toxicity Evaluation of Bisphenol A Administered by Gavage to Sprague Dawley Rats From Gestation Day 6 Through Postnatal Day 90.Toxicological Sciences 139 (1):174-197.

Churchwell et al. (2014).”Comparison of Life-Stage-Dependent Internal Dosimetry for Bisphenol A, Ethinyl Estradiol, a Reference Estrogen, and Endogenous Estradiol to Test an Estrogenic Mode of Action in Sprague Dawley Rats.Toxicological Sciences 139 (1):4-20.

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Bienkowski, B. (2014) New BPA experiments find no low dose effects, FDA says. Environmental Health News, February 13, 2014