Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure.

Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA 02111, United States
Reproductive Toxicology (Impact Factor: 2.77). 01/2007; 24(2):131-8. DOI: 10.1016/j.reprotox.2007.07.005
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Available from: Scott M Belcher, Jul 17, 2015
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    • "Recent research suggests that BPA can stimulate responses via ERs associated with the cell membrane at very low (ppb) concentrations equivalent in potency to E2 (Quesada et al. 2002, Vom Saal et al. 2007, Wozniak et al. 2005, Zsarnovszky et al. 2005); however, a biologically-plausible explanation for effects that appear at low doses is currently lacking (Chapin et al. 2008). In addition, a definition of " low dose " in relation to BPA exposure is inconsistent. "
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    ABSTRACT: Chemicals with estrogenic activity are derived from many different natural and synthetic processes and products, including endogenous production (e.g., estradiol, conjugated estrogens), drugs (e.g., ethinyl estradiol, conjugated estrogens), plants used as foods (phytoestrogens such as genistein, daidzein, S-equol), and man-made chemicals (xenoestrogens such as bisphenol A). Human exposure to low doses of endogenous estrogens, estrogenic drugs, phytoestrogens, and xenoestrogens has the potential to improve health or disrupt normal endocrine activity, as well as impact the diverse systems with which estrogens interact, including the cardiovascular system, and lipid and carbohydrate metabolism. Mechanisms of action and diversity of adverse and non-adverse effects following human exposure to low doses of estrogen active chemicals (EACs, defined as chemicals which interact with an estrogen receptor [ER]) are poorly understood. This review summarizes our current understanding of the pharmacological action with a focus on pharmacokinetics (PK) and toxicokinetics (TK) of several representative EACs in both physiological and pathological processes. The goal of this review is to assess the current state-of-the-science on: (i) the potential for EACs to interfere with endocrine activity, (ii) factors which contribute to endocrine-related clinical outcomes, and (iii) existing knowledge gaps. While classical PK approaches (compartmental or non-compartmental) can be used to characterize absorption, distribution, metabolism, and elimination of EACs, many of the detailed pharmacological characteristics necessary to understand benefit-risk balance have not yet been clarified. Pharmacological complexities mirror the complexity of determining whether and under what conditions exposure to estrogens in drugs, foods or to xenoestrogenic chemicals are beneficial or harmful to human health.
    Critical Reviews in Toxicology 08/2014; 44(8). DOI:10.3109/10408444.2014.930813
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    • "Several recent experimental results support the findings from earlier studies that suggested BPA exposure affects the resumption of meiosis in the peri ovulatory oocyte (reviewed by vom Saal et al. 2007) (see Supplemental Material, Table S1). Chao et al. (2012) reported that neonatal exposure to low-dose BPA inhibited germinal vesicle breakdown (GVBD) in CD-1 F 1 hybrid female mice, confirming the previous work of Hunt et al. (2003). "
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    ABSTRACT: Background: In 2007, an expert panel reviewed associations between bisphenol A (BPA) exposure and reproductive health outcomes. Since then, new studies have been conducted on the impact of BPA on reproduction. Objective: In this review, we summarize data obtained since 2007, focusing on a) findings from human and animal studies, b) the effects of BPA on a variety of reproductive end points, and c) mechanisms of BPA action. Methods: We reviewed the literature published from 2007 to 2013 using a PubMed search based on keywords related to BPA and male and female reproduction. Discussion: Because BPA has been reported to affect the onset of meiosis in both animal and in vitro models, interfere with germ cell nest breakdown in animal models, accelerate follicle transition in several animal species, alter steroidogenesis in multiple animal models and women, and reduce oocyte quality in animal models and women undergoing in vitro fertilization (IVF), we consider it an ovarian toxicant. In addition, strong evidence suggests that BPA is a uterine toxicant because it impaired uterine endometrial proliferation, decreased uterine receptivity, and increased implantation failure in animal models. BPA exposure may be associated with adverse birth outcomes, hyperandrogenism, sexual dysfunction, and impaired implantation in humans, but additional studies are required to confirm these associations. Studies also suggest that BPA may be a testicular toxicant in animal models, but the data in humans are equivocal. Finally, insufficient evidence exists regarding effects of BPA on the oviduct, the placenta, and pubertal development. Conclusion: Based on reports that BPA impacts female reproduction and has the potential to affect male reproductive systems in humans and animals, we conclude that BPA is a reproductive toxicant. Citation: Peretz J, Vrooman L, Ricke WA, Hunt PA, Ehrlich S, Hauser R, Padmanabhan V, Taylor HS, Swan SH, VandeVoort CA, Flaws JA. 2014. Bisphenol A and reproductive health: update of experimental and human evidence, 2007–2013. Environ Health Perspect 122:775–786;
    Environmental Health Perspectives 06/2014; 122(8). DOI:10.1289/ehp.1307728
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    • "Importantly, for both treatment protocols, the dose used resulted in serum unconjugated dBPA in rhesus monkeys within the median concentrations (range, 0.3–4.4 ng/mL, or 1–19.4 nM) reported in humans [3] [12]. "
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    ABSTRACT: We measured serum dBPA in non-pregnant and pregnant female rhesus monkeys, fetuses and amniotic fluid. dBPA was administered by a daily oral bolus or sc implantation of Silastic capsules; both resulted in daily average serum unconjugated dBPA concentrations of <1 ng/ml. We observed lower serum concentrations of unconjugated dBPA in pregnant females relative to pre-pregnancy values, and generally lower concentrations in fetal serum than in maternal serum. Differences in pharmacokinetics of dBPA were evident between pre-pregnancy, early and late pregnancy, likely reflecting changes in maternal, fetal and placental physiology. The serum ratio of conjugated to unconjugated dBPA after continuous sc release of dBPA was similar to values reported in human biomonitoring studies and markedly lower than with oral administration, suggesting oral bolus exposure is not an appropriate human exposure model. We report elsewhere that there were numerous adverse effects on fetuses exposed to very low serum dBPA in these studies.
    Reproductive Toxicology 06/2014; 45. DOI:10.1016/j.reprotox.2014.01.007
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