In recent years, there’s been a lot of media coverage and scientific interest in environmental toxicants such as bisphenol A (BPA) – including campaigns to eliminate BPA from plastics and other consumer products. What about BPA is so concerning and why is it important to regulate it? The answer lies in two important characteristics of BPA (and chemicals like it): 1) BPA can disrupt normal hormone function in the body and 2) BPA doesn’t follow the rules in terms of the Environmental Protection Agency (EPA)’s “safe exposure”levels  .
Fig. 1 BPA and estrogen have some similarities in chemical structure. The ring structures with a hydroxyl group (OH) that are circled in red are important for both chemicals to bind to estrogen receptors in the body.
Endocrine disrupting chemicals moonlight as hormones in the body
Studies investigating how BPA functions in the body have shown that it mimics the effects of estrogen, a female sex hormone . BPA’s chemical structure resembles that of estrogen, thus classifying BPA as an endocrine disrupting chemical (EDC) . EDCs disrupt the body’s natural hormone signaling by a number of different mechanisms (though I will only discuss a few):
Normal hormone function. Hormones are molecules that influence cellular function through binding to their specific “hormone receptors” – other proteins than can specifically bind with a hormone based (largely) on how the hormone is shaped (Fig. 2A) .
Hormone mimicking. However, EDCs that mimic hormone shape can interact with the hormone receptor, even when the actual hormone is not present. In a normal setting, without the hormone present, there would be no consequential (downstream) effects of stimulating the hormone receptor because it was not interacting with the hormone. However, when the EDC binds the receptor in place of the hormone, it will stimulate an effect despite a lack of hormone (Fig. 2B) .
Hormone blocking. Alternatively, the EDC may bind the hormone receptor in a way that doesn’t cause a direct response, but rather blocks further binding of the hormone with its receptor and decreases the efficacy of the hormone on that cell (Fig. 2C) .
Fig. 2 Some ways in which endocrine disrupting chemicals that mimic hormones can alter normal hormone function in cells. Adapted from the NIEHS website . Green rectangle = naturally-produced hormones; purple hexagon = naturally-occurring hormone receptors; pink rectangles & red triangles = hormone mimicking EDCs.
As an example, BPA can interact with the estrogen receptor to stimulate a response even without the presence of estrogen (as depicted in Fig. 2B), and has been linked to early onset puberty, which itself has been linked to a higher risk for certain cancers .
Our relationship status with BPA (and other EDCs) is “complicated”
So we know endocrine disruptors like BPA can change a cell’s function through altered hormone signaling. Our next concern should be “how much BPA can we be exposed to before we see those effects?” Hundreds of research studies have shown that the answer is “it’s complicated” . For many years, we have largely considered the effects of synthetic (and other) chemicals in light of the mantra “the dose makes the poison” – implying that a little of something isn’t nearly as harmful as a lot of that something. While this is sometimes true, we’re finding that it is not always the case.
In many studies, BPA behaves in a non-monotonic manner – meaning that a higher dose of BPA does not always prompt a stronger effect than lower doses . Figure 3 is a simplified comparison of monotonic and non-monotonic dose responses . In Fig. 3A, the response on the Y-axis (which is intentionally vague – it could be any cellular function) increases as dose increases (shown on the x-axis). This is an example of a monotonic response where the response increases or decreases in a consistent direction in relationship to the dose. However, Fig. 3B demonstrates an example of a non-monotonic dose response in which the median exposure level elicits a greater response than either the lowest or highest dose. Biological causes for non-monotonic dose responses can be incredibly complex – too little of a substance can cause particular biological pathways to activate or deactivate while too much of a substance can influence those same pathways differently, or completely different pathways (for more information, refer to ).
Fig. 3 Monotonic and non-monotonic dosage responses.
This is important because we are discovering that many endocrine disrupters demonstrate non-monotonic dose responses but are regulated by the EPA as if they have monotonic dose responses, wherein keeping exposure levels below a certain threshold would ensure safety. While having a single threshold is convenient and even appropriate for some synthetic chemicals, it’s probably not appropriate for EDCs  . For example, the EPA’s safety threshold for lead is 400 parts per million (ppm) of lead in soil in children’s play areas . However, if lead exhibited a non-monotonic dose response like BPA does, there could be little biological effect at both 100 ppm and 400 ppm but a significant effect at 250 ppm – and only very thorough research would determine the dynamics of exposure levels. Proper regulation of these chemicals will involve very particular dosage considerations for individual EDCs – not a “one size fits all” regulation for all EDCs.
Endocrine disruptors such as BPA are public health concerns due to their potential to interfere with hormone signaling in the body that may lead to abnormal development and/or disease. Many groups of scientists around the world are researching these chemicals, but the verdict is still out on precisely how to regulate safe exposure levels. Our goal is to learn more about the extent of EDCs’ biological effects in addition to developing proper exposure regulations to keep ourselves and the environment safe.
 “Endocrine-disrupting compounds: Chemicals that interfere with the body’s natural hormones.” 2013. Breast Cancer Fund. N.p.
 “Endocrine Disruptors.” 2016. National Institute of Environmental Health Sciences. N.p.
 Nah, W. H., M. J. Park, and M. C. Gye. 2011. “Effects of early prepubertal exposure to bisphenol A on the onset of puberty, ovarian weights, and estrous cycle in female mice.” Clinical and experimental reproductive medicine 38: 75-81.
 Vandenberg, L. N. 2014. “Non-monotonic dose responses in studies of endocrine disrupting chemicals: bisphenol a as a case study.” Dose-response 12: 250-276.
 Lagarde, F., C. Beausoleil, S. M. Belcher, L. P. Belzunces, C. Emond, M. Guerbet, and C. Rousselle. 2015. “Non-monotonic dose-response relationships and endocrine disruptors: a qualitative method of assessment.” Environ Health 14: 13.
 Environmental Protection Agency (US). 2001. “Lead; identification of dangerous levels of lead; final rule” [Internet]. Fed Regist 66: 1206-40.
More From Thats Life [Science]
- Got Lactase? Breaking Down the Enzyme
- Why Do I Shiver When It’s Cold?
- Crap you didn’t really need to know
- You Can't Observe A Lot Just By Watching
- What Do You Do When It's Too Hot to Move?
- 5 Fun Facts about Hormones
- Death stinks - literally
- Why the sea salt fad could be very bad
- Henry's Pockets: A Poem
- Biology Superpowers: X-Ray Vision
- How to Expand Your Senses by Reading a Blog Post
- What's up with bat echolocation?
- Seeing is Believing - How Can We Visualize Tiny Colorless Bacteria?
- Saving water is no longer a matter of how short our showers are · Water balance in a man-made world
- Double Digestion in Rabbits · Why Does Mopsy Eat Her Own Poop?
- Should I say sex or gender? Pt. 2
- Should I say sex or gender? Pt. 1
- How To Catch Hard-to-Catch Fish?
- Finding the Perfect Partner
- Is your gut trying to kill your resolve? · Mind over microbe
- Why Do Mothers Mother?
- GMO! The Places You'll Go!
- New-Fangled Paleontology · Really Old Fossils, Really Strong Predators, and Cool New Tech
- A Brief History of Evolutionary Thought, part III
- Saving face: transplanting our most distinctive features
- A Brief History of Evolutionary Thought, part II
- DNA as a solution for data storage · DNA - Nature’s Hard Drive
- A Crash Course in the Coolness of Mitochondria · Mitochondria: The Underrated Organelles
- A Pollinator’s Job Description and Why We Should All Care About Them · Pollination 101
- You May Say I’m Biased, But I’m Not the Only One
- The evolution of one of the greatest medical discoveries in history. · The Path of Least Resistance: Our Relationship with Antibiotics
- Mother Nature’s History Book · Estimating the Age of Life Long-Gone
- Proprioception as a vital sense · Know Your Limb-its
- Man’s Best Artificially-Selected Friend · Your Dog is a GMO Wolf
- Better Safe Than Sorry: The Pesticide Industry is Getting a Revamp
- Sometimes scientists have to get creative in order to effectively do science – especially on a budget. · The Bizarre Shopping List of a Determined Scientist
- Insects Get Sick Too: The Study of Insect Pathology
- Our teeny tiny friends and their huge potential · Employee of the Month - Hire a Microbe to Do Your Work
- A Brief History of Evolutionary Thought - Part I
- The Effects of Custom Build Paradise · Artificial Islands
- To B(PA) Or To Not B(PA): Regulating Endocrine Disruptors
- Bioluminescence truly looks like it is nothing short of sorcery, and although this naturally occurring phenomenon is well studied and explained, that does not take away from its beauty. · Fireflies of the Ocean: Lighting up the Dark with Science
- Part II - Cases of altruism in the animal kingdom · Charity cases in nature - when are animals more likely to be altruistic?
- Part I - Why true altruism is a rare behavior in the animal kingdom · Being selfish means staying alive
- Penguins and other strange things we study from space
- Pseudoreplication and the Art of Biological Statistics
- What is wrong with my tomatoes?...And other plant disease questions · Why did orange prices increase?
- How fecal microbiota transplants can improve lives and possibly save them · The Wonders of Fecal Transplants
- The scientific facts behind the safety and efficacy of childhood vaccines · Calling the Shots - Discussing Vaccines
- 3D Printing for Fun and Science
- What is wrong with my tomatoes?...And other plant disease questions · What is Phytopathology?
- Medical Mysteries Still Surrounding Zika Virus
- More ›