Bisphenol-A BPA and the Great Divide

A Review of Controversies in the Endocrine Disruptors Field

Bisphenol-A and the Great Divide: A Review of Controversies in the Field of Endocrine Disruption
The data collected thus far in the field of environmental toxicology are sufficiently robust to raise concerns about the potentially deleterious impact of endocrine-disrupting chemicals on human development.

In 1991, a group of 21 scientists gathered at the Wingspread Conference Center to discuss evidence of developmental alterations observed in wildlife populations after chemical exposures. There, the term “endocrine disruptor” was agreed upon to describe a class of chemicals including those that act as agonists and antagonists of the estrogen receptors (ERs), androgen receptor, thyroid hormone receptor, and others. This definition has since evolved, and the field has grown to encompass hundreds of chemicals. Despite significant advances in the study of endocrine disruptors, several controversies have sprung up and continue, including the debate over the existence of nonmonotonic dose response curves, the mechanisms of low-dose effects, and the importance of considering critical periods of exposure in experimental design. One chemical found ubiquitously in our environment, bisphenol-A (BPA), has received a tremendous amount of attention from research scientists, government panels, and the popular press.

In their review, The Endocrine Society has covered the above-mentioned controversies plus six additional issues that have divided scientists in the field of BPA research, namely:

  1. mechanisms of BPA action
  2. levels of human exposure
  3. routes of human exposure
  4. pharmacokinetic models of BPA metabolism
  5. effects of BPA on exposed animals
  6. links between BPA and cancer

Understanding these topics is essential for educating the public and medical professionals about potential risks associated with developmental exposure to BPA and other endocrine disruptors, the design of rigorously researched programs using both epidemiological and animal studies, and ultimately the development of a sound public health policy.

Mice Study shows gestational Exposure to BPA leads to behavioral Changes for four Generations

Gestational exposure to bisphenol a produces transgenerational changes in behaviors and gene expression

BPA Exposure Effects May Last for GenerationsBisphenol-A BPADES and similar compounds are known as endocrine-disrupting chemicals, which are substances in the environment that interfere with the proper functioning of hormones.


Bisphenol A (BPA) is a plasticizer and an endocrine-disrupting chemical. It is present in a variety of products used daily including food containers, paper, and dental sealants and is now widely detected in human urine and blood. Exposure to BPA during development may affect brain organization and behavior, perhaps as a consequence of its actions as a steroid hormone agonist/antagonist and/or an epigenetic modifier. Here we show that BPA produces transgenerational alterations in genes and behavior. Female mice received phytoestrogen-free chow with or without BPA before mating and throughout gestation. Plasma levels of BPA in supplemented dams were in a range similar to those measured in humans. Juveniles in the first generation exposed to BPA in utero displayed fewer social interactions as compared with control mice, whereas in later generations (F(2) and F(4)), the effect of BPA was to increase these social interactions. Brains from embryos (embryonic d 18.5) exposed to BPA had lower gene transcript levels for several estrogen receptors, oxytocin, and vasopressin as compared with controls; decreased vasopressin mRNA persisted into the F(4) generation, at which time oxytocin was also reduced but only in males. Thus, exposure to a low dose of BPA, only during gestation, has immediate and long-lasting, transgenerational effects on mRNA in brain and social behaviors. Heritable effects of an endocrine-disrupting chemical have implications for complex neurological diseases and highlight the importance of considering gene-environment interactions in the etiology of complex disease.

Sources and more information
  • Gestational exposure to bisphenol a produces transgenerational changes in behaviors and gene expression, Endocrinology. 2012 Aug;153(8):3828-38. doi: 10.1210/en.2012-1195. PMID: 22707478 Epub 2012 Jun 15. Full text.
  • BPA Exposure Effects May Last for Generations, Endocrine Society, press-release-archives/2012.

Endocrine-Disrupting Chemicals Identification Protocols are inadequate

Endocrine-Disrupting Chemicals and Public Health Protection: A Statement of Principles from The Endocrine Society

Endocrinology: EDCs Endocrine-Disrupting Chemicals Identification Protocols are inadequate says The Endocrine SocietyDiethylstilbestrol DES is the first synthetic estrogen and the first chemical known to act as an endocrine disruptor.

In a Statement of Principles unveiled today, The Endocrine Society proposes a streamlined definition for endocrine-disrupting chemicals (EDCs) and offers recommendations that will strengthen the ability of current screening programs to identify EDCs.

Read Experts Say Protocols for Identifying Endocrine-Disrupting Chemicals Inadequate.


An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action. The potential for deleterious effects of EDC must be considered relative to the regulation of hormone synthesis, secretion, and actions and the variability in regulation of these events across the life cycle. The developmental age at which EDC exposures occur is a critical consideration in understanding their effects. Because endocrine systems exhibit tissue-, cell-, and receptor-specific actions during the life cycle, EDC can produce complex, mosaic effects. This complexity causes difficulty when a static approach to toxicity through endocrine mechanisms driven by rigid guidelines is used to identify EDC and manage risk to human and wildlife populations. We propose that principles taken from fundamental endocrinology be employed to identify EDC and manage their risk to exposed populations. We emphasize the importance of developmental stage and, in particular, the realization that exposure to a presumptive “safe” dose of chemical may impact a life stage when there is normally no endogenous hormone exposure, thereby underscoring the potential for very low-dose EDC exposures to have potent and irreversible effects. Finally, with regard to the current program designed to detect putative EDC, namely, the Endocrine Disruptor Screening Program, we offer recommendations for strengthening this program through the incorporation of basic endocrine principles to promote further understanding of complex EDC effects, especially due to developmental exposures.

Read Endocrine-Disrupting Chemicals and Public Health Protection: A Statement of Principles from The Endocrine Society, Endocrinology. doi: 10.1210/en.2012-1422, 2012 Sep; 153(9): 4097–4110.