By now, bisphenol A (BPA) has become a ‘household name’; many consumers are aware of this compound and various products where it is found. BPA is used in a wide range of goods including food and beverage containers, medical and sports equipment, other plastic products, thermal papers, and cosmetics, among others (Geens et al., 2012). Reference populations from around the world have shown that exposures to this compound are widespread in all age groups, indicating that leaching from consumer products is occurring (Vandenberg, 2011).

BPA is widely acknowledged to be an endocrine disrupting chemical (EDC), broadly defined as compounds that interfere with one or more hormone actions (Zoeller et al., 2012). In vitro and in vivo studies have shown that BPA can bind to and activate nuclear estrogen receptors (ER) α and β, membrane ERs, the G-coupled protein receptor GPER, thyroid hormone receptor, androgen receptor, and estrogen-related receptor (ERR)γ (Vandenberg et al., 2009). Thus, studies that examine the effects of BPA solely from the perspective of nuclear ER signaling are too limited to appropriately evaluate this promiscuous compound.

Hundreds of studies published to date have demonstrated that low doses of BPA, e.g., doses below the toxicological NOAEL of 50 mg/kg body weight/day, alter a range of endpoints in laboratory animals following controlled exposures (Richter et al., 2007; Vandenberg et al., 2013b). In fact, many of these studies have shown effects of BPA at doses below the US Environmental Protection Agency (EPA)’s reference dose of 50 μg/kg body weight/day. Many different groups of scientific experts have concluded that BPA can disrupt development of multiple organs in the body including those found in the male and female reproductive tracts, the prostate gland, the mammary gland, tissues and organs involved in metabolism, and the brain; that BPA alters neurobehaviors; and that BPA can sensitize tissues like the mammary and prostate glands to hormonal and carcinogen challenges (Richter et al., 2007; Diamanti-Kandarakis et al., 2009; Vandenberg et al., 2013b; Peretz et al., 2014; Gore et al., 2015; Seachrist et al., 2016).

The picture from human studies is equally concerning: more than 100 epidemiology studies suggest associations between BPA exposures and a range of conditions and diseases, including metabolic syndrome, infertility, and severity of asthma (Rochester, 2013). Building a case for causal relationships between BPA and human disease will take significant time and resources, especially because exposures are so ubiquitous. Decade-long longitudinal studies that adequately measure developmental exposures are needed to recapitulate what has been experimentally tested (and observed) in laboratory animals.

Considering the strength of the evidence linking BPA to harmful health outcomes, why is there so much controversy surrounding it? A widely circulated answer is that studies have not always replicated others’ adverse findings, with some reports refuting adverse results entirely while others produce disparate or nonidentical findings. Another contributing influence is a lack of consensus on what constitutes “adverse”; with some claiming that overt signs of toxicity must be identified whereas others consider developmental disruptions, interruption of measures of homeostasis, or other endpoints that are predictors of disease as qualifiers (Woodruff et al., 2008). However, one factor that cannot be ignored is the role of ‘manufactured doubt’, a concept that was originally invented by representatives from the tobacco industry to generate scientific debate about issues that were relatively well settled solely for the purpose of shaping public opinion and delaying regulatory action (Michaels, 2006). In the case of tobacco, the industry argued that the science that linked smoking to lung cancer was ‘unsettled’ and that ‘consensus’ had not been reached, long after their own scientists knew the true extent of the causal relationship between smoking and cancer (among other outcomes). It has been suggested that the chemical industry, as well as trade manufacturing groups, has used similar tactics to keep harmful EDCs, including BPA, on the market, long after scientific inquiry has identified their potential to cause harm (Bergman et al., 2015; Oreskes et al., 2015).

Another element that has contributed to the controversy surrounding BPA is the general lack of regulatory action against this chemical by agencies in the USA (e.g., the US EPA and US Food and Drug Administration, FDA) or Europe (e.g., the European Food Safety Authority, EFSA). Why have these agencies failed to act, in spite of hundreds of studies showing that BPA can induce adverse and/or disruptive outcomes in exposed laboratory animals? Unfortunately, the vast majority of studies on BPA conducted to date have been ignored by these regulatory agencies because of requirements that studies meet particular criteria for the results to be considered in risk assessments.