Thursday, October 17, 2013

Strongest Evidence Yet Between BPA and Thyroid Cancer

Hypomethylation Of Cdk5 Protein Offers Possible Causal Link Between BPA and Medullary Thyroid Cancer

SUMMARY: Over-expression of Cdk5 protein causes medullary thyroid carcinoma in rats. BPA causes hypomethylation (over-expression) of Cdk5-related genes. Could BPA exposure cause epigenetic changes that promote medullary thyroid carcinoma?

By Lewis Perdue
Copyright 2013, All rights reserved

Bisphenol A (BPA) has been suspected in many studies(1-5) of disrupting thyroid hormones.

In addition, BPA exposure in pregnant mice has been shown to induce epigenetic changes in offspring(6).

Various mechanisms have been proposed including hypomethlyation in early development, specifically, "CpG methylation also was decreased at another metastable locus, the CDK5 activator-binding protein (Cabp IAP)(7) .

This previous work with BPA as a thyroid endocrine distruptor may offer significant insight into the origins of medullary thyroid carcinoma (MTC) when viewed in light of a recent accidental discovery in Texas..


According to a study published Oct 14 in Cancer Cell(8) research at The University of Texas Southwestern's Department of Psychiatry were investigating the origins of dementia and created a transgenic mouse that over-expressed the Cdk5 protein they felt could be connected with myloid plaques.

The study, run by Dr. James Bibb, Associate Professor of Psychiatry and Neurology and Neurotherapeutics, quickly found that the mice had all developed medullary thyroid carcinoma.

Monday, October 14, 2013

Does Fungicide Treatment on Grape Vines Lead to Thyroid Cancer in Humans?

One major concern regarding the use of fungicides in grape growing and other agricultural areas is the environmental and human health impacts of the use of synthetic fungicides.  Studies have found significant health impacts related to the use of conazole fungicides, including thyroid tumors and other cancers.  It is thought that these fungicides are related to higher incidences of cancerous tumors as a result of their endocrine disruption properties.  In fact, endocrine disrupting compounds have been demonstrated in many studies to cause significant health problems in both wildlife and humans, including but not limited to reproductive health issues, neurological problems, and cancer.

Are synthetic fungicides harmful for wildlife or human health based on their endocrine-disrupting properties?

If these fungicides are harmful, who is at risk?  The workers in the vineyard?  Or perhaps the people drinking the wine made from fungicide-treated grapes?

The Academic Wino highlights a recent study on this topic, and answers some of these questions and more.  Please follow this link to read more on this fascinating study.

Wednesday, October 9, 2013

Eastman Ekes Out Equivocal Lawsuit Win, Judge Says Verdict Not Necessarily Based On Trial Evidence

Eastman Chemical company has been denied all damage claims against two small start-up companies it accused of a laundry list of violations including deceptive advertising. Eastman did win a symbolic victory from a Texas jury, but the presiding judge expressed his views that the jury verdict was not necessarily based on the evidence presented and that he could easily have returned a different verdict.

When George Bittner (University of Texas neurobiology professor) decided to go into the business of testing and marketing "safe" plastics there was no indication that he'd wind up dodging a million-dollar, howitzer-sized bullet lobbed at him by a $9 billion chemical company who didn't like being his target.

And Eastman Chemicals, who sued Bittner's companies -- CertiChem and PlastiPure -- probably didn't think it would have to eat almost $4 million in legal fees to gain a mostly phyrric victory for what they claimed was Bittner's bad science and over-the-top marketing.

But life's full of surprises and that's what they both got at the hands of a Texas jury of average citizens who were asked to try and make sense out of rules, lab tests and science that even the best of scientists cannot agree upon.

Indeed, while Eastman Chemical touts its court victory as proof that its star plastic -- Tritan -- is safe, the verdict was so equivocal that the federal trial judge stated on the record that given his choice, he might well have found against Eastman, and that the jury verdict was not necessarily supported by the evidence presented at the trial:

"The jury ultimately sided with Eastman, but was by no means required to do so based on the record at trial ...."

The battle shaped up as on between two market competitors: Eastman Chemical, New York Stock Exchange company with $9 billion in revenues, versus a couple of small-sister company start-ups.

When the battles heated up in 2008 over concerns and bans over BPA (Plastic-bottle scare is a boon for some) Eastman began promoting its Tritan product as the "safe" alternative. This, despite mounting evidence, that BPA is one of hundreds of endocrine disruptors -- most of which have not been tested.

Eastman did not like having the tables turned on it by Bittner and his upstart companies who conducted a National Institutes of Health-funded study indicating that Eastman's Tritan plastic was one of several in a study done by Bittner and coauthors they said leached a class of endocrine disruptors (EDCs) that -- like BPA -- exhibit estrogenic activity (Most Plastic Products Release Estrogenic Chemicals: A Potential Health Problem That Can Be Solved).

Thus began a legal battle -- not over the paper itself -- but over what Eastman termed "false advertising" claims made in CertiChem and PlastiPure promotional material.

After a long, bitter, tangled trial filled with secret testimony and sealed documents, a federal jury in Texas District Court held the opinion that CertiChem and PlastiPure went over the promotional line when -- according to Eastman's court filings -- Bittner's companies used their study data in an attempt to sell their plastics and testing services.

Sam Sparks, the gruff, no-nonsense District Court trial judge on the other hand, seemed skeptical of the jury's decision and denied Eastman's request for $3,458,859.40  million in lawyer's billings and $318,745.73 in expenses.

Monday, October 7, 2013

Could Resveratrol in Red Wine Give Us a Clue Into the Mechanism of Action Behind Endocrine Disruptors?

The compound most commonly studied in terms of examining the health benefits of red wine is resveratrol.  Structurally, resveratrol is very similar to estrogen diethylstilbestrol (DES), a synthetic estrogen that is notorious for being given to pregnant women from the 1940s to the 1970s resulting in significant birth defects, with many of the children continuing to have significant health problems throughout the remainder of their lives.  Like DES, resveratrol has been shown to interact with estrogen receptors (ER), though more so with ERα than ERβ.  Unlike DES, resveratrol and its derivatives seem to have a positive effect on health, whereas DES has quite the opposite effect.

Studies have shown that the health benefits of resveratrol and its derivative may be a result of their interactions with estrogen receptors, however, what is unclear is exactly which form or forms of the metabolized compound is most important, or even the relative importance of all of the metabolites together.  A recent study by a group of collaborating scientists from the University of Parma, the University of Glasgow, and the University of Milan examined the interactions of resveratrol and its derivatives in the presence of human estrogen receptors; in hopes to gain further understanding of how exactly resveratrol in its various forms interacts on a chemical level in humans.

"If resveratrol is so structurally similar to DES, a harmful synthetic endocrine disruptor that is linked to a plethora of birth defects and health problems, how could it have such an opposite effect?”

"Could learning about the estrogenic activity of resveratrol help us understand the mechanisms of these more harmful synthetic endocrine disruptors?  Additionally, could understanding the estrogen activity and mechanisms of resveratrol help us develop a sort of “antidote” to harmful endocrine disruptors?" 

Read more on The Academic Wino here....

Saturday, October 5, 2013

Are Your Receipts Trying to Kill You?

We’ve mentioned several times already on this blog about bisphenol A (BPA) and how this endocrine disrupting chemical is present in all sorts of plastics from water bottles, baby bottles, and dental sealants.  What may not be inherently obvious is where else BPA can be found in everyday products.  One example is with thermal printing paper:  were you aware that thermal printing paper contains BPA and once touched could possibly transfer onto your fingers?

Who Uses Thermal Paper?

Thermal paper is found in many places, though most commonly it is found in the receipt paper at a store, or the paper used in certain recorders in various laboratories.  Could employees working the cash register or even the customer handling the receipt to file away in their records be exposed to BPA through the thermal paper?  Could researchers working with recorders be exposed to BPA when handling the paper to analyze their results?

What exactly IS thermal paper?

I already mentioned that thermal paper is the paper that’s used often in cash registers as well as recorders in the laboratory.  Breaking it down even further, imagine a piece of thermal cash register paper.  On the side to be printed, there is a layer of printing ink covering the entire surface.  The color used to print contains a leuco dye, which is a chemical that can exist in two forms: a colored form and a colorless form.  When it comes time to print, the thermal head of the printer causes the leuco dye and other chemicals on the surface to melt and react with one another, which results in the dye taking on its dark colored form.  These chemicals, in combination with the heating and melting process, result in chemical products including the endocrine disruptor, BPA.

Could the BPA on the thermal paper transfer to our skin?

This is certainly an interesting question, and one that has not been studied too often.  Those few studies in animals examining absorption of BPA by the skin found that BPA can be absorbed by the udders of cows, as well as through pig skin.  What about humans?  Is handling this thermal paper on our receipts a cause for concern?  Can the BPA on this paper be absorbed through our skin as it has been shown to occur in cows and pigs?

Preliminary Findings

Friday, October 4, 2013

Endocrine Disruptors and Behavior: BPA Exposure in utero Disrupts Sexual Differentiation and Associated Behaviors in Rats

You all have the image of someone you know or you’ve seen on TV in the past when you hear the term “a man’s man”.  Big, tough, pillars of masculinity wound tightly around a body of bulging muscles and brawn.  How, or better yet, when does this masculinization actually occur?  Is it something that is learned?  Or is there a chemical game of football that goes on in the body that seals the deal?  It’s probably a little of both, but without certain chemical processes happening at particular stages of development, the line in the sand between male and female behavior gets a little blurred.

In rats, testicular androgen is believed to be in charge of masculinization and feminization, which occurs sometime between days 18 and 27 after conception and involves the conversion of androgen to estrogen by the enzyme brain aromatase.  Timing of this conversion process, as well as other chemical dances involved, is critical to establish sexual differentiated behavior.  In other words, the timing of certain sex-related hormone conversion is very important in establishing “typical male behaviors” and “typical female behaviors”, respectively.

Blurred Lines

As you can imagine, something that needs to occur in such a specific time frame can be very sensitive to bumps in the road.  What happens if this process of androgen-estrogen conversion does not occur at the proper time or does not occur in the proper amounts?  When this happens, you get a sort of fuzzy distinction between male and female behaviors, with the de-masculinization of males or de-feminization of females.  Since this process is completed by hormonal balances, anything that can disrupt this balance can potentially interfere with the distinction in behaviors between the male and females sexes.

Endocrine disruptors, for example Bisphenol A (BPA), a commonly used chemical in plastic coating of food cans, baby bottles, lining of trash cans, and dental sealants, act in similar manners and interact with the same receptors of which androgens, estrogens, and other hormones also interact and function.  That being said, could these endocrine disrupting chemicals cause problems with sexual differentiation and sex-related behaviors in those living things that are exposed to them?

Endocrine Disruptors and Behavior

Nearly all studies to date related to endocrine disruptors effects on sexual behavior has been done in rodents, or at least species other than humans.  However, since studies in rodents can often be comparable to those in humans, it is certainly a good starting point for asking more specific questions humans.  In rats, BPA exposure has been linked to increased anxiety levels, changes in “typical” behaviors for the individual sexes, as well as changes in spatial learning.  In a few studies, when pregnant rats were given BPA during their pregnancy and also during the lactation period after pregnancy, changes in some sex-specific behaviors were observed at doses as low as 1ppm.

One of the few studies with humans focused on diethylstilbestrol (DES), a synthetic estrogen-like compound that at one time (between the 1940s and 1970s) had been given to women with the thought that it would protect them against problems in pregnancy.  In fact, DES had quite the opposite effect, causing major complications and birth defects in those children born from women who were given the drug.  In regards to behavior, one study found that children of those women given DES during pregnancy had increased rates of various psychiatric complications or diseases, including depression and anxiety.

Thursday, October 3, 2013

BPA and In Vitro Fertilization: Making Things Hard For People Already Struggling to Conceive

There is a whole host of research out there examining the effects of Bisphenol A (BPA) on reproduction both in vitro (a.k.a. in the lab) and in vivo in various species of animal.  Though one can often translates the effects of in vitro studies and in vivo studies on animals to how things might happen in humans, however, this is not always the case.  Therefore, there is a need to provide evidence in the human body prior to making sweeping judgments on the results based on effects seen in other animals or in the test tube.

In the mouse model, studies have shown that exposure to BPA at doses known to be present in the environment increases oocyte aneuploidy, which may result in miscarriage or severe birth defects.  Further studies elaborate on the mechanism behind this error in chromosome distribution in egg cells showing that BPA contributes to increased aneuploidy by disrupting meiotic spindle formation, as well as centrosome behavior and chromosome alignment and subsequent division.  Adding to the list of negative reproductive effects in animal models, BPA has been shown to inhibit the production of the natural hormone, estradiol, as well as negatively impacting fertility in general.

What about human studies?

Preliminary studies looking at the effects of BPA in humans, specifically in the area of in vitro fertilization (IVF), have shown that there may be significant negative relationships between BPA levels in urine and decreases estradiol and numbers of eggs retrieved at the finale of the IVF retrieval process.  There have been very few studies directly examining the effects of BPA on women undergoing the IVF process, in particular the associations between BPA and early reproductive outcomes, oocyte quality, and early embryonic growth (i.e. cleavage) rates.

Just last year, a group at Massachusetts General Hospital in Boston, MA,  a teaching hospital affiliated with Harvard University, set out to determine how BPA influenced the IVF process, in particular effects on the quality of the egg and developing embryo, as well as fertilization rates and cleavage rate of the developing blastocyst. 

Battle of the Sexes: Men Found to Have Higher Levels of BPA in Their Blood Than Women

There are many studies examining the levels of Bisphenol A (BPA) and other endocrine disruptors present in the environment, and a large number of studies investigating the mechanisms or pathways these chemicals may take to wreak havoc on living things. 

BPA and several other endocrine disruptors have been linked to a whole host of health problems, including but not limited to cancer, low testosterone and low sperm motility, miscarriages, and birth defects.

How much do I really have in my body?

Sure, that’s all fine and dandy if you can tell me just how a certain amount of BPA can affect my health, but really, is BPA even present in these amounts in my body?  Or are the amounts required to elicit these hazardous consequences much too large to have any meaning biologically?

In 2002, a team of researchers in Japan set out to answer a few simple, yet highly important questions: 1) How much BPA is present in human blood; 2) Are there any differences in BPA levels between men and women?; and 3) What are the relationships between BPA and sex hormones present in our bodies?

Guinea Pigs

Well, not ACTUAL guinea pigs, but real human beings…a group of 14 healthy women, a group of 16 women with diagnosed polycystic ovary syndrome (PCOS), and a group of 11 healthy men were recruited to give blood serum samples for this study. 

What they found…

What this team of researchers found was that serum BPA levels were significantly higher in healthy men than in healthy women.  Serum BPA levels in these healthy men were 1.49 +/- 0.11 ng/mL, while serum BPA levels in healthy women were 0.64 +/- 0.10 ng/mL (CONVERT TO PPM…..).  Also, they found that serum BPA levels significantly correlated with both free testosterone levels and total testosterone levels.  Interestingly, serum BPA levels were not significantly correlated with any other sex-related hormone, including luteinizing hormone, follicle stimulating hormone, prolactin, and estradiol.  Finally, these levels found in both men and women were HIGHER than the levels reported to cause problems

Why do the men have it all?

Why did the men in this study have a significantly higher level of the chemical in their blood than women?  Well, this study didn’t explicitly study the “why” side of things; however, a few possibilities come to mind.

Wednesday, October 2, 2013

Does BPA Exposure Cause Miscarriages?

BPA, along with many other man-made chemicals, has become quite prevalent in our environment, and have been shown to possess estrogen-like characteristics which have led to significant health problems for humans and wildlife alike.  BPA, along with other similar endocrine disruptors, can be found in many different products, including the plastic in your water bottle, to the thermal paper for your printer, and even in your dental sealants.  As you can imagine, something so potentially damaging and yet so prevalent in our environment is great cause for concern.

BPA can interrupt or otherwise harm many different hormone-dependent systems in the human body, one of which is the reproductive system.  Other endocrine disruptors, such as dioxin and DDT, have been implicated as linked to some cancers, endometriosis, small birth weights, and pre-term births.  Since these are endocrine disruptors that are known to cause problems in the reproductive system, the next question becomes whether or not these man-made chemicals are somehow associated with miscarriage early on in pregnancy. 

How common are miscarriages?

Somewhere between 10 and 25% of all pregnancies will likely result in spontaneous abortions, i.e. miscarriages.  Between 40 and 70% of these miscarriages are associated with chromosome abnormalities, in particular aneuploidy (having too few or too many chromosomes).
Previous studies have shown that BPA exposure during oogenesis or spermatogenesis results in increased incidences of aneuploidy, so naturally, the most obvious question would be: is BPA associated with miscarriages? 

BPA à Aneuploidy; Aneuploidy à Miscarriage; BPA --?--> Miscarriage?

BPA has been found to be present in the urine of at least 90% of Americans.  In Japan, about 350,000 tons of BPA per year is produced for various plastic-based products.  Thus, as in the US, BPA is very common in Japan as well as other parts of the world, and where a group of researchers set out to determine if BPA is at any way associated with miscarriages in the population.

45 women with a history of 3 to 11 miscarriages were examined during this study, with 32 healthy non-pregnant and no history of infertility or miscarriage used as controls.  Serum BPA levels were measured for all women in the study, in addition to several antibodies, immune response cells, progesterone, and prolactin.

What did they find?

Results of the study found that BPA is highly associated with the history of miscarriage in Japanese women, particularly with those women that were ANA-positive (a.k.a. they have antinuclear antibodies present in their blood, which may or may not be a red flag for an immune response and has also been linked to recurrent miscarriages). 

While this was not a study to get at the question of HOW BPA can cause miscarriage, however it does provide evidence that BPA exposure is associated with recurrent miscarriage and deserves further research.

Why are these pregnancies aborted?  Does BPA increase aneuploidy in eggs or sperm?  Does BPA interfere with early embryonic development in another manner?  More research will certainly give us the answer, and as luck would have it, that research has been done!  Stay tuned….

Source: Sugiura-Ogasawara, M., Ozaki, Y., Sonta, S., Makino, T., and Suzumori, K. 2005. Exposure to bisphenol A is associated with recurrentmiscarriageHuman Reproduction 20(8):2325-2329.