Comparison of lifestage-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
The Churchwell study provides extensive data to assess the biological plausibility of results observed in the Delclos et al study. While the Delclos study evaluated the potential for BPA to cause health effects over a wide range of BPA doses and two doses of EE2 (ethinyl estradiol, a known potent estrogen), it did not generally test whether observed health effects seen in the Delclos study from either BPA or EE2 were a direct result of estrogenicity or not. To address this, the Churchwell study provides extensive data to assess the biological plausibility of effects observed in the Delclos study and, as importantly, effects that are not observed (in particular, the lack of effects observed at low doses). In other words, the Churchwell study allows the Delclos results, in their entirety at low and high doses, to be more reliably interpreted.
Specifically, the Churchwell study monitors the level of free BPA (internal dose) and metabolized BPA (conjugated BPA, known to be non-estrogenic) in blood at the various doses tested. This data can be directly compared to health effects observed, and not observed, in the Delclos study.
In the Delclos study, no low dose effects were found for BPA in the wide range of health endpoints examined. Overall, the results of the Churchwell study provide powerful evidence to support the validity of this finding. By assessing the estrogenicity from BPA, EE2 and endogenous estradiol (E2), the Churchwell study confirms the results of the Delclos study that only the highest BPA doses provided sufficient estrogenicity to be comparable to endogenous E2 or the two EE2 doses. Conversely, at the low doses, the estrogenicity provided by BPA would be far below what is already present from E2, and thus should have low potential to cause estrogenic health effects at low doses.