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    Are You Exposed To BPA, And Does It Matter?
    By Steve Hentges | July 14th 2014 10:41 AM | 9 comments | Print | E-mail | Track Comments
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    Steven G. Hentges holds a Ph.D. in organic chemistry from Stanford University and a B.S. in chemistry from the University of Minnesota. He is the...

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    For quite a few years, one of the most popular chemicals for scientific inquiry has been bisphenol A (BPA).  Scientists around the world have been conducting a diverse array of studies aimed at understanding whether BPA poses a risk to human health. 

    Based on the weight of evidence from these many studies, the U.S. Food and Drug Administration (FDA) recently answered the question “Is BPA safe?” with a simple and unambiguous answer - “Yes.”

    By far, the majority of the studies conducted on BPA provide information on potential hazards, which are intrinsic properties of the chemical.  Since risk describes the probability that exposure to a hazard will cause harm, information is also needed on human exposure to BPA.

    Considering that BPA is a commonly usedchemical, primarilyas a raw material to make polycarbonate plastic and epoxy resins, it is not surprising to find that people are exposed to BPA.  Of critical importance, though, is the magnitude of exposure.  If there is no exposure, there can be no risk and, conversely, only when exposure is sufficiently high would risks potentially be present.

    An increasingly accepted way to assess human exposure is through biomonitoring studies, which measure the level of a chemical in biological samples such as urine or blood.  For BPA, analyzing urine is most appropriate since BPA is converted in the body to a biologically inactive metabolite and excreted in urine within hours of exposure.  Urine biomonitoring thus measures short-term exposure to BPA over the last day or so. 

    When applied to a representative group of people, urine biomonitoring can provide a reasonable measure of average exposure to BPA across a population.

    Recent U.S. and Canadian Data

    Two recently published large-scale urine biomonitoring studies provide up-to-date exposure data for the U.S. population (age 6 years and above) and Canadian pregnant women, respectively.  The U.S. data is from a long-standing program run by the Centers for Disease Control and Prevention (CDC) and known as the National Health and Nutrition Examination Survey (NHANES). 

    The most recent data, from samples collected in 2011-2012, is contained in the fifth set of biennial data over a 10-year period, which allows temporal exposure trends to be assessed.

    The Canadian data is from the Maternal-Infant Research on Environmental Chemicals (MIREC) study, which is sponsored by Health Canada and other Canadian government agencies.  The study provides exposure data for a large population ofwomenin the first trimester of pregnancy, with samples collected in the 2008-2011 timeframe.  The MIREC data is particularly valuable since pregnant women might generally be considered to be one of the most vulnerable subpopulations.

    The median and 95th percentile urinary BPA concentrations from both new studies are shown in the figure below.  Also shown for assessment of temporal trends are NHANES data from four earlier biennial studies in the 2003-2010 timeframe.

     

    A quick way to understand this type of data in a safety context is to compare the measured urinary concentration values with a Biomonitoring Equivalent (BE) value.  A BE is defined as “the concentration or range of concentrations of chemical in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guidance value such as a reference dose (RfD) or tolerable daily intake (TDI).”  Essentially a BE value is an estimated safe limit.

    Several years ago, Health Canada sponsored a project to calculate a BE value for BPA in urine.  Based on Health Canada’s TDI for BPA, the BE value was calculated as 1,000 micrograms/L, which is shown as a bar across the top of the figure.

    Casual inspection of the figure reveals that even 95th percentile urine concentrations of BPA are approximately 2 orders of magnitude below the BE value.  Typical human exposure, in the range of the median values, is hundreds of times below the BE value and Health Canada’s safe intake limit.  Although BE values are primarily useful as screening tools, the large margin of safety between the BE value and the recent biomonitoring data clearly indicates that the U.S.population and pregnant women in Canada are not at risk from real-lifeexposures to BPA. 

    Accordingly, in its announcement of the MIREC data, Health Canada stated “Based on the overall weight of evidence, Health Canada continues to conclude that dietary exposure to BPA through food packaging is not expected to pose a health risk to the general population, including newborns and young children.”

    A second interesting feature in the figure is the apparent downward trend in exposure to BPA from 2003-2004 to 2011-2012.  The trend might best be described as suggestive since the decrease in urine concentrations is small and we cannot be certain whether the decrease is due to subtle changes in the NHANES program (e.g., analytical methodology, participant selection, urine sampling) or is due to decreased exposure in the US population.

    Although biomonitoring data are a very useful measure of exposure levels, the data provide no information on sources of exposure, which makes it difficult to determine if the sources have changed over time.

    In spite of the clear statements of safety from government agencies such as FDA and Health Canada, it would nevertheless not be surprising if some limited deselection of BPA has taken place in certain markets.  In that case, it would be of particular interest to know what is being used to replace BPA. 

    That’s a fascinating subject, but one that will discussed another day in the near future.

    Comments

    Bonny Bonobo alias Brat
    For quite a few years, one of the most popular chemicals for scientific inquiry has been bisphenol A (BPA).  Scientists around the world have been conducting a diverse array of studies aimed at understanding whether BPA poses a risk to human health.  
    Based on the weight of evidence from these many studies, the U.S. Food and Drug Administration (FDA) recently answered the question “Is BPA safe?” with a simple and unambiguous answer - “Yes.”
    Well maybe someone should tell this to the people who have written the BPA wikipedia article? Steve, you have written other articles at Science20 about bisphenol-A in the past and I remember finding those articles quite reassuring and thinking that there was nothing much to worry about regarding BPA health effects but after reading this latest article I decided to have a quick read of the Wikipedia article and I am quite shocked at what I read there! Here are a few exerpts that I found very alarming, maybe you will be able to explain here why Wikipedia is making these outrageous claims :- 
    Fetal and early-childhood exposures A 2009 study found higher urinary concentrations in young children than in adults under typical exposure scenarios.[68][69] In adults, BPA is eliminated from the body through a detoxification process in the liver. In infants and children, this pathway is not fully developed so they have a decreased ability to clear BPA from their systems. Several recent studies of children have found levels that exceed the EPAs suggested safe limit figure.[50]
    Children may be more susceptible to BPA exposure than adults (see health effects).[citation needed] A 2010 study of people in Austria, Switzerland, and Germany has suggested polycarbonate (PC) baby bottles as the most prominent role of exposure for infants, and canned food for adults and teenagers.[74] In the United States, the growing concern over BPA exposure in infants in recent years has led the manufacturers of plastic baby bottles to stop using BPA in their bottles. However, babies may still be exposed if they are fed with old or hand-me-down bottles bought before the companies stopped using BPA.
    One often overlooked source of exposure occurs when a pregnant woman is exposed, thereby exposing the fetus. Animal studies have shown that BPA can be found in both the placenta and the amniotic fluid of pregnant mice.[75] A small US study in 2009, funded by the EWG, detected an average of 2.8 ng/mL BPA in the blood of 9 out of the 10 umbilical cords tested.[76] A study of 244 mothers indicated that exposure to BPA before birth could affect the behavior of girls' at age 3. Girls whose mother's urine contained high levels of BPA during pregnancy scored worse on tests of anxiety and hyperactivity. Although these girls still scored within a normal range, for every 10-fold increase in the BPA of the mother, the girls scored at least six points lower on the tests. Boys did not seem to be affected by their mother's BPA levels during pregnancy.[77] After the baby is born, maternal exposure can continue to affect the infant through transfer of BPA to the infant via breast milk.[78][79] 
    Breast cancer
    Further information: Risk factors of breast cancer § Bisphenol A
    Evidence from animal models is accumulating that perinatal exposure to BPA alters breast development and increases breast cancer risk.[130]
    A 2008 review stated that "evidence from animal models is accumulating that perinatal exposure to (...) low doses of (..) BPA, alters breast development and increases breast cancer risk".[130] Another 2008 review concluded that "animal experiments and epidemiological data strengthen the hypothesis that fetal exposure to xenoestrogens may be an underlying cause of the increased incidence of breast cancer observed over the last 50 years".[131]
    A 2009 in vitro study has concluded that BPA is able to induce neoplastic transformation in human breast epithelial cells.[132] Another 2009 study concluded that maternal oral exposure to low concentrations of BPA during lactation increases mammary carcinogenesis in a rodent model.[133]
    A 2010 rat study with the mammary glands of the offspring of pregnant rats treated orally with 0, 25 or 250 µg BPA/kg body weight has found that key proteins involved in signaling pathways such as cellular proliferation were regulated at the protein level by BPA.[134]
    A 2010 study found that BPA may reduce sensitivity to chemotherapy treatment of breast cancer cells.[135]
    Prostate development and cancer A 1997 study in mice has found that neonatal BPA exposure of 2 μg/kg increased adult prostate weight.[140] A 2005 study in mice has found that neonatal BPA exposure at 10 μg/kg disrupted the development of the fetal mouse prostate.[141] A 2006 study in rats has shown that neonatal bisphenol A exposure at 10 μg/kg levels increases prostate gland susceptibility to adult-onset precancerous lesions and hormonal carcinogenesis.[142]A 2007 in vitro study has found that BPA within the range of concentrations currently measured in human serum is associated with permanent increases in prostate size.[143] A 2009 study has found that newborn rats exposed to a low-dose of BPA (10 µg/kg) showed increased prostate cancer susceptibility when adults.[144]
    Reproductive system and sexual behavior A 2009 study had shown exposure to BPA in the workplace was associated with self-reported adult male sexual dysfunction.[145]
    A 2009 study on Chinese workers in BPA factories found that workers were four times more likely to report erectile dysfunction, reduced sexual desire and overall dissatisfaction with their sex life than workers with no heightened BPA exposure.[146] BPA workers were also seven times more likely to have ejaculation difficulties. They were also more likely to report reduced sexual function within one year of beginning employment at the factory, and the higher the exposure, the more likely they were to have sexual difficulties.[147] A 2010 study found that fetuses and young children exposed to BPA were at risk for secondary sexual developmental changes, brain and behavior changes and immune disorders.[148]
    A study released in 2013 demonstrated that BPA in weak concentrations is sufficient to have a negative effect on the human testicle. The researchers found that a concentration equal to 2 micrograms per litre of bisphenol A in the culture medium, a concentration equal to the average concentration generally found in the blood, urine and amniotic fluid of the population, was sufficient to produce the effects. The researchers stated that exposure of pregnant women to bisphenol A may be one of the causes of congenital masculinisation defects of the hypospadiaand cryptorchidism types, the frequency of which has doubled overall in the past 40 years. They also suggested that "it is also possible that bisphenol A contributes to a reduction in the production of sperm and the increase in the incidence of testicular cancer in adults that have been observed in recent decades."[149]
    Animal studies in 2009 found:
    • Mouse ovary anomalies from exposure as low as 1 µg/kg, concluded that BPA exposure causes long-term adverse reproductive and carcinogenic effects if exposure occurs during prenatal critical periods of differentiation.[153]
    • Neonatal exposure of mice as low as 50 µg/kg disrupts their ovarian development.[154][155]
    • Neonatal rat BPA exposition of as low as 50 µg/kg permanently alters the hypothalamic estrogen-dependent mechanisms that govern sexual behavior in the adult female rat.[156]
    • Prenatal exposure to BPA at levels of (10 μg/kg/day) affects behavioral sexual differentiation in male monkeys.[157]
    • In placental JEG3 cells in vitro BPA may reduce estrogen synthesis.[158]
    • A 2009 rodent study, funded by EPA and conducted by some of its scientists, concluded that, compared with ethinyl estradiol, low-dose exposures of bisphenol A (BPA) showed no effects on several reproductive functions and behavioral activities measured in female rats.[160] That study was criticized as flawed for using polycarbonate cages in the experiment (since polycarbonate contains BPA) and the claimed resistance of the rats to estradiol,[161] but that claim was contested by the authors and others.[162]
    • Another 2009 rodent study found that BPA exposure during pregnancy has a lasting effect on one of the genes that are responsible for uterine development and subsequent fertility in both mice and humans (HOXA10). The authors concluded, "We don't know what a safe level of BPA is, so pregnant women should avoid BPA exposure."[163]
    There is much more supposed evidence of BPA causing health problems in that Wikipedia Bisphenol-A article, too much more to copy and paste here. Can you please explain why they are misreporting so many adverse health effects of Bisphenol-A at Wikipedia? Is Wikipedia now losing any scientific credibility that it may have had in the past?
    My article about researchers identifying a potential blue green algae cause & L-Serine treatment for Lou Gehrig's ALS, MND, Parkinsons & Alzheimers is at http://www.science20.com/forums/medicine
    Hank
    Can you please explain why they are misreporting so many adverse health effects of Bisphenol-A at Wikipedia? Is Wikipedia now losing any scientific credibility that it may have had in the past?
    I can't answer for Steve but you are one of few who thinks they ever had credibility. When it comes to controversial topics, it can't be trusted. This entry was debated widely:



    This is what it looks like now:
    Steve_Hentges
    There's much that could be said about the pluses/minuses of Wikipedia (and I'm sure much of it has already been said by others), but whether it has any scientific credibility depends on whether you think of Wikipedia as a scientific publication. The Wikipedia article on BPA certainly compiles a wide range of scientific topics, but that doesn't make it a scientific publication and for sure not a good one.
    To a large extent the BPA article is an incomplete list of studies with brief comments on what individual studies reported. There's little or no analysis of what the studies mean collectively, or even any analysis of whether individual studies have any meaning at all. In the data-information-knowledge-wisdom hierarchy (and you can look that up in Wikipedia too), the BPA article is at best incomplete data. So maybe not so much a question of scientific credibility but whether the BPA article has any value or utility. Reading that study A says this, study B says that, and study C says something else, while ignoring studies D-Z and providing no analysis, isn't particularly useful.

    To increase the value or utility of the article requires far more analysis than Wikipedia provides and, to be fair, far more than Wikipedia is probably intended to provide. That analysis comes from weighing all of the relevant evidence, not just some of it as compiled by Wikipedia, and drawing conclusions based on the evidence. That's what government agencies do in the form of weight-of-evidence evaluations, or more recently as systematic reviews. When FDA answers the questions "Is BPA safe?" with the one-word answer "Yes," it's not based on a cursory Wikipedia style article. It's based on a detailed review and analysis of all relevant data, including the incomplete set of studies cited in the Wikipedia article along with much more. Similarly, the Health Canada quote that I provided refers to "the overall weight of evidence."

    I haven't and won't go through the Wikipedia article in detail as that wouldn't be worth the effort, but here's two quick example of Wikipedia's inadequacies that caught my eye in the first Wikipedia paragraph quoted by Helen (emphasis mine):
    In adults, BPA is eliminated from the body through a detoxification process in the liver. In infants and children, this pathway is not fully developed so they have a decreased ability to clear BPA from their systems. 
    At the same time, the Wikipedia article says this:
    Multiple pharmacokinetic studies in monkeys supported by preliminary results in humans, have now demonstrated, that newborn and young primates metabolize BPA at or very near the level of adult metabolism. [..] potential fetal exposure is significantly reduced by the mother's metabolic capabilities, and that the fetus can effectively metabolize BPA."[40]
    The first quote has no citation and is not supported by available data. The second provides a citation (which indirectly gets back to the supporting studies) and is based on the best available data. The inconsistency could not survive any rigorous analysis, had there been any.

    The second quote is this one:
    Several recent studies of children have found levels that exceed the EPAs suggested safe limit figure.[50]
    Although a citation is given, the cited paper does not at all support the statement made.

    So, is the Wikipedia article on BPA credible and useful. Not so much.







    Bonny Bonobo alias Brat
    Thanks for replying in such detail Steve, you raise some very valid points about the scientific validity of some of Wikipedia's articles which to be honest Hank and others have also raised these concerns here at Sceince20 before. I now have to admit that I have much less trust in the validity of the scienctific content than I had before and also that as you point out there's often 'llittle or no analysis of what the studies mean collectively, or even any analysis of whether individual studies have any meaning at all'. However, you go on to say :-
    To increase the value or utility of the article requires far more analysis than Wikipedia provides and, to be fair, far more than Wikipedia is probably intended to provide. That analysis comes from weighing all of the relevant evidence, not just some of it as compiled by Wikipedia, and drawing conclusions based on the evidence. That's what government agencies do in the form of weight-of-evidence evaluations, or more recently as systematic reviews. When FDA answers the questions "Is BPA safe?" with the one-word answer "Yes," it's not based on a cursory Wikipedia style article.
    I don't personally like to rely upon government agencies to make these black and white decisions about overall safety of everyday products for me, especially after having worked in and even been involved in taking over outsourced government agencies in the past and understanding that regardless of how many government policies and procedures were or are in place often the final decisions and verdicts on any subject can be influenced unfairly or unscientifically by individuals in positions of power and especially those with vested interests in the outcomes of those decisions. I also don't like black and white answers about commonly available products and accompanying causal factors that have the potential to impact different individuals with such a broad spectrum of possible effects. Even vaccines can be harmful to people with compromised immune systems for example, so it is not possible to say 'Are vaccines safe?' and answer 'Yes'. The answer is 'Yes they are safe for most people' and of course necessary for the benefit of society as a whole.

    So who can we rely upon to give these verdicts about the overall safety of everyday products? As far as I can see it is unbiased people with appropriate qualifications in that field, often but not always people with PHDs, which is why many articles at Science20 written by PHDs who are experts in the field, like yourself, are often a good source of information. However, who decides which PHDs  can write here and whether they are unbiased? The former is decided by Hank and the latter must be decided by the public reading the articles I suppose. At the end of the day it is our own responsibility to decide what information we read is unbiased and valid and what isn't and that means informed decisions can get very complicated and many of the general public probably do not have the time, patience or possibly even the aptitude to do this. 


    I am now uncertain as to whether I think that the BPA in many of the products that I and my family and friends come into contact with is safe. Five of my previously very healthy living women friends that I spent a lot of time with in my 20s have developed breast cancer in their 40s and 50's and i am trying to understand why? I respect your opinion that BPA is safe but I also was a bit overwhelmed by the many links to scientific articles that were claiming that it was not safe for some individuals, in particular developing foetuses, young children and people with developing, compromised or immature organs and that it could be potentially causing breast and prostate cancer, so I now intend to read all of the scientific links on the BPA Wikipedia article and also to search the academic databases. This will take a long time as I have many other commitments but eventually I hope that I will decide like you that BPA is safe for everyone. If you have any useful links to help me on that quest for knowledge I would be very grateful :)

    My article about researchers identifying a potential blue green algae cause & L-Serine treatment for Lou Gehrig's ALS, MND, Parkinsons & Alzheimers is at http://www.science20.com/forums/medicine
    Steve, Health and Welfare Canada reported in April 2013 that exposure levels of bisphenol A are lower than previously estimated ones, but to this day they maintain the ban of the compound in baby bottles as a precaution. They are also continuing investigations into the compound.

    http://www.healthycanadians.gc.ca/health-sante/environment-environnement/home-maison/bisphenol_a-eng.php


    Steve, you certainly use an appropriate tone in your outreach articles, but some do not. This featured science  2.0 article explores the dangers of the wrong tone and also discusses the bisphenol A controversy in a fairly balanced manner.
    http://www.science20.com/chemical_education/tone_can_spoil_good_science_news_article-107561

    BPA has a rather weak binding affinity to the estrogen receptor. The attention paid to it is due to its environmental pervasiveness. Other plastic extracts can have a much greater agonist effect, but that reality is buried in the public's love for chemicals with three letter acronyms.

    If you're concerned with BPA's endocrine disrupting effects, then be concerned about endocrine disruptors in general, not just one chemical.

    Nice to know the effects on men are ignored... Let's see a study of the effects of this horrible chemical on men, male fertility, etc. Why is it men simply aren't being given equal consideration when it comes to protecting our health?

    I would like to point out that BPA is only not of concern when implemented at current protocols -- that is, not in infant packaging at all. The NIH says that at current levels from analysis from NTP that there is "some concern" for effects on fetuses, infants, and children with regards to brain, prostate, and behavior. http://www.niehs.nih.gov/health/topics/agents/sya-bpa/

    I posted this above accidentally - apologies.