BPA, BPA-free and why Internet titles can be misleading

A few years ago, when I still had both kids in preschool, I became painfully aware that plastic is made of oil. I know, I know, where had I been until then? Underground, I guess. All the bottles I'd used to feed milk and drinks to my kids were scratched and chewed and horrid. I screeched in panic, threw them all away and replaced everything with stainless steel. My kids hated the new bottles and refused to take them to school. Yeah, the joys of parenthood.

So, imagine my joy when BPA-free came around. Finally something my kids will love and that will not harm them. Except, my friend Cristina sent me the bad news a few days ago:

"Dozens of studies link the common plastic chemical bisphenol A (BPA) to all sorts of health problems, including breast and prostate cancers, heart trouble, type 2 diabetes, autism, liver tumors, asthma, infertility, and even obesity. With such a bad track record and hormone-disrupting tendencies, many companies, particularly plastic water bottle manufacturers, have switched to the BPA-free chemical called bisphenol S, or BPS. But a groundbreaking study from University of Calgary researchers suggests we need to diligently avoid both, thanks to newly discovered impacts on the brain [Source]."

Aware of the journalistic exaggerations that infest the Web, I logged onto the PNAS website and downloaded the original paper [1], titled: "Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish."

Kinch et al. [1] treated embryonic zebrafish (not humans!) with low doses of both BPA and BPS (the compound commonly used in BPA-free products). Apparently, both chemicals are so widespread that, quoting from the PNAS article,

"A recent examination of urine samples in the United States and Asia confirmed previous work showing that 93% of people had detectable levels of BPA but surprisingly showed that 81% had detectable levels of BPS, illustrating the wide-spread use of this poorly known bisphenol analog in consumer products [1]."

BPA molecules behave as receptor antagonists to sex steroid (estrogen or testosterone): what this means is that they bind to the sex steroid receptors, thus blocking the hormone effect. While the general dosage in plastic bottles may be really low to have any effect on adults, the question as to whether or not they are relevant during embryonic development is indeed well posed since that's the time when the hypothalamus is particularly vulnerable due to lack of blood-brain barrier.

The researchers treated the zebrafish embryos with a very low dose for BPA, 1,000-fold lower than the accepted human daily exposure, and then repeated the experiment with the same dosage for BS. They chose the same BPA dose measured in the Oldman River, which serves two major cities in Alberta, Canada. Their results show that BPA exposure in the zebrafish embryos induced hyperactivity and caused precocious neurogenesis in the hypothalamus. Unfortunately, BPS (the BPA-free alternative) wasn't any better, as it still altered brain development and behavior.

Two questions popped in my head. First, the researchers immersed the embryos in the contaminants, whereas human embryos are immersed in amniotic fluid, which is always filtered by the placenta, a filter between what circulates in the mother's blood stream and the child's. Given this, did Kinch et al. make a fair comparison? The researchers address the placenta issue, claiming that BPA concentration has been measured in the human placenta and that the dosage used in the experiment was 100-fold lower than circulating levels found in fetal serum.

The other question a critical reading of the paper should pose is: how good of a model is the zebrafish embryo for human embryonic development? Especially knowing that zebrafish embryos develop in a mere 72 hours and grow up to a couple of centimeter long, whereas the hypothalamus in the human embryo starts forming around week 8, when it's roughly 1.5 centimeters. It turns out, it is a good model when it comes to embryonic neurogenesis:

"Despite the large evolutionary distance between fish and mammals, the overall organization, basic structures, and functional capacities of major hypothalamic components are highly conserved between zebrafish and mammalian brains. [...] In contrast to mammals, zebrafish embryos develop externally and are transparent, and highly amenable to genetic manipulation, making them an ideal vertebrate model for in vivo studies of neural patterning and neuronal specification. As such, zebrafish models have been used extensively in recent years to study the roles played by key signaling pathways in controlling the development of hypothalamic neurons [2]."

Having addressed in a satisfactory way my two main concerns with the PNAS paper [1], I particularly like the two points the researchers make in the discussion section. The first one is that the way tolerable levels are determined is using a linear model, starting from the highest possible dose and gradually lowering until no effect is detected. Kinch et al. rightfully argue that dose-response relationships are hardly ever linear when it comes to endocrine-disrupting compounds like BPA and BPS.

Second, the researchers claim that the switch from BPA to BPS was done without adequate toxicology testing. What if it turns out that BPS is comparable to BPA in terms of damaging potential?

BPA and BPS aside, I wanted this post to also make a case for critical thinking. I'm seeing way too much junk on the Internet being passed for science when in fact it's just bad reporting/journalism (in genetics in particular!!). While the Internet article my friend sent me didn't make any incorrect statement, and it did discuss the actual study a few paragraphs into the article, still, the title, "Popular 'BPA-Free' Chemical Causes Brain Damage, Study Finds" had me frowning because it lacks to mention two fundamental points: 1) the study was conducted on zebrafish (not on humans!) and 2) the supposed brain damage was on the zebrafish embryos (not on humans, and not on children or adults).

In fact, let me open a quick parenthesis and cite some numbers a friend of mine posted on Facebook: a paper on some break-through research on Alzheimer's published by the Journal of Clinical Investigation titled "Prostaglandin signaling suppresses beneficial microglial function in Alzheimer’s disease..." got shared 116 times. Stanford posted the story under the title "Blocking receptor in brain’s immune cells counters Alzheimer’s in mice, study finds" and got shared almost 10,000 times. The Telegraph titled its piece "Has Stanford University found a cure for Alzheimer's disease?" and got almost 50,000 shares. But at the very top of the sharing contest came Rod D. Martin  (over 130,000 shares) with the title "Happy New Year! Stanford May Have Just Cured Alzheimer’s" .

Bottom line 1: yeah, you can get very popular when you blow up science.
Bottom line 2: if you want to draw some useful conclusions from any pseudo-sceintifc news, go back to the source before getting too excited and/or too alarmed.

The zebrafish experiment indicates that compounds containing BPA and BPS could potentially harm the fetus and as a safety precaution it recommends pregnant women to steer away from plastic bottles, but it doesn't present any evidence on the effects on children or (non-pregnant) adults. It does not conclude that BPA and/or BPS exposure has the same effect in humans, but it does pose a foundation for further studies as it raises a flag that there may be a risk associated to these chemicals. The way to further validate this hypothesis would be to measure BPA and BPS levels in the urine of pregnant women and then follow the babies' neurological development for a few years to see if the women with higher levels had problematic children compared to the women with lower levels.

Of course, it's still a good idea to avoid plastic and use it only when other alternatives aren't handy. Plastic use has certainly increased exponentially in the past few decades and it's a good idea to reduce its use anyways, since it could not only be potentially harmful for our bodies, but it's also definitely bad for the environment. As in all things, cautiousness (whether it's used to avoid plastic or to avoid Internet content) is the best measure for a happy living.

 [1] Kinch, C., Ibhazehiebo, K., Jeong, J., Habibi, H., & Kurrasch, D. (2015). Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1417731112

 [2] Machluf, Y., Gutnick, A., & Levkowitz, G. (2011). Development of the zebrafish hypothalamus Annals of the New York Academy of Sciences, 1220 (1), 93-105 DOI: 10.1111/j.1749-6632.2010.05945.x