Articles

Phthalates and BPA: Of Mice and Men

Is your soup poisoning you? In a recent study  subjects who ate canned vegetable soup had markedly increased levels of BPA in their urine compared to those who ate freshly prepared soup. We are constantly bombarded with alarmist warnings about the dangerous chemicals in the products we use. Especially BPA (Bisphenol A) and phthalates. Beware plastic bottles! Beware rubber ducks! And now, beware canned soup!   BPA and phthalates are classified as endocrine disruptors. They have been discussed before on SBM here and here.  BPA has been accused of causing everything from obesity to prostate cancer. Phthalates have been accused of causing everything from breast cancer to reduced anogenital distance in baby boys (the significance of this is unknown: there is not even any standard for what the normal distance is).

In the book Slow Death by Rubber Duck

Using a variety of test methods, the authors determined individual “body burdens,” or the toxic chemical load we carry. The innocuous rubber duck, for example, offers a poison soup of phthalates that “permeate the environment and humans.” From other products and food we also have a collection of chemicals shorthanded as PFCs, PFOAs, PSOSs, and PCBs. None of them are good, and they are everywhere…

Is this science or irresponsible fear-mongering? What does the best evidence tell us? Should we be afraid of our canned soup and rubber ducks?

Phthalates and BPA are ubiquitous and unavoidable. They are widely used in the manufacture of plastics, medical devices, and many consumer products. How dangerous are these and other common chemicals in our environment? Does it mean anything to have a high level of a chemical in our urine if the chemical is rapidly eliminated from the body and didn’t cause any harm while it was there? When does intelligent concern become irrational fear?

The canned soup study was reported in a “Research Letter” rather than as a typical peer-reviewed journal article. It was single-blind and its sole purpose was to measure “total BPA and conjugated species” in the urine. It did not even attempt to investigate whether there was any effect on the subjects’ health. The researchers themselves noted that the elevation of urinary BPA was transient and that further research is needed. They found the highest levels ever reported outside of occupational exposure, which raises questions. If levels this high are confirmed in other studies, that still doesn’t tell us whether such transient levels have any clinical significance.

I won’t attempt to cover the vast body of research on endocrine disruptors; but for those who are interested, Wikipedia provides useful compilations of studies on the health effects of phthalates and BPA. To summarize: research by chemical companies has generally shown no risk; studies elsewhere have raised many concerns, but results are inconsistent and inconclusive and often based on animal experiments with no confirmation in humans. The World Health Organization (WHO) and government agencies in various countries have concluded that current use is not risky, but a few groups have disagreed. Canada banned BPA in baby bottles as a precautionary measure.

What Do the Measurements Mean?

Measurement of these chemicals in urine is problematic. Nearly all the BPA found in the urine is in the form of metabolites. Trace levels of BPA found in some samples may be due to degradation of metabolites back to BPA after collection. It makes a difference which metabolite is chosen. One-time measurement is not likely to reflect overall exposure. Excretion varies by time of day and other confounding factors. These compounds are rapidly excreted from the body and may not stay around long enough to cause any problems. BPA is rapidly and completely metabolized into glucuronide, which is not estrogenic and is rapidly excreted in the urine. Even premature infants can metabolize it at the low levels involved. Rodents have a different metabolism. They excrete BPA through bile into the gut where it can be reabsorbed and has a longer half-life. Studies using IV administration are inapplicable to oral consumption.

Reassuring Reviews

Kamrin reviewed and analyzed all the available data in his 2009 article “Phthalate Risks, Phthalate Regulation, and Public Health: A Review.”  He concluded that “the risks are low, even lower than originally thought, and that there is no convincing evidence of adverse effects on humans… [so] phthalate regulations that have been enacted are unlikely to lead to any marked improvement in public health.”

He says, “Early high-dose studies in animals suggested that phthalates might induce liver cancer in humans, but careful consideration of the mechanism of action, peroxisome proliferation, led to the conclusion that animal studies are not relevant for humans.” Animal studies can alert us to possible problems in humans, but they can also create false alarms. For instance, aspirin causes congenital defects in mice, but it has no such effects in humans.

Do combined exposures to multiple phthalates increase risk? He argues that they probably don’t, because individual exposures are so small that the total doesn’t approach effect levels, there is no evidence of additive effects in humans, and not all phthalates affect the body in the same way.

Epidemiological evidence is inconsistent and not persuasive. Adults and neonates who have been exposed to high levels of the phthalate DEHP from medical procedures do not exhibit the adverse effects seen in animals.The lowest levels at which adverse effects occur in sensitive animals are much higher than the doses to which humans are exposed.

There is further reassurance in a 2010 article by Witorsch and Thomas. They reviewed endocrine disruptors in personal care products and concluded “although select constituents exhibit interactions with the endocrine system in the laboratory, the evidence linking personal care products to endocrine disruptive effects in humans is for the most part lacking.”

Should We Be Worried?

We were once blissfully unaware of the trace amounts of all these things in our bodies. Our improving technology enables us to measure them and worry about them. My interpretation of the evidence on endocrine disruptors like phthalates and BPA is that the risks are still theoretical and unproven, that drastic measures are not warranted without more evidence, and that we need to keep an open mind and evaluate any new evidence as it comes along. As we do that, we need to keep a couple of things in mind:

  • We are not mice. Concerns from animal experiments can’t be automatically extrapolated to humans. Human studies are required.
  • We can’t protect ourselves from every conceivable risk. Trying to eliminate one risk often results in other, unforeseen ones. Banning BPA and phthalates would result in substituting other compounds that are more costly, may not work as well, and have not been as well tested for safety. BPA-free products are marketed for what they are not, not for what they are.

Conclusion

In my opinion, current evidence might be sufficient to justify banning phthalates and BPA for mice, but not for men. I’m not going stop eating canned food, and I’m not about to throw my rubber ducky away. I’m with Ernie.

Posted in: Politics and Regulation, Public Health

Leave a Comment (16) ↓

16 thoughts on “Phthalates and BPA: Of Mice and Men

  1. Janet Camp says:

    Thanks. This is one that I used to worry about, especially after reading the book, “Our Stolen Future” by Theodora Kroeber–but that was long before I began reading blogs like this and being much more skeptical than I used to be.

    I will still make my own soup, though; I think it tastes better and it’s cheaper, but at least I can stop feeling guilty for giving the grandchildren those rubber duckies.

  2. @Harriet Hall, If you get a chance, I’d be interested to hear what you think of this study.

    http://www.ncbi.nlm.nih.gov/m/pubmed/22025598/?i=1&from=bpa%20girls

    It is concerned with GPA and behavior in children, which I know is not a major life or death issue, but still important to parents who have to live with the children. :)

  3. damn autocorrect, bpa, not GPA,

  4. DugganSC says:

    @micheleinmichigan
    Oh darn… and here I was hoping for a good scholarly article.

    I’ll admit that the reports on the stuff on our food have become a bit more alarming after reading the earlier treatise on how cancer prevention looks to be more important than cancer cures, but if this chemical shows no signs of harming us, I suppose that’s OK. Admittedly, they used to say that DDT, thalidomide, and cigarettes wouldn’t harm us either, but the science has gotten better.

  5. WilliamLawrenceUtridge says:

    First Big Pharma, now we’re shilling for Big Plastic and Big Duckie? Tsk, I’m disappointed. And want my cheque! All that arguing with pec and Th1Th2 and I don’t even get a free sample of something carcinogenic?!?!? I’m outraged.

    MIM, at least one confound I can see is money. Parents with more money may have more time to spend with their children and more money to spend on BPA-free products – thus lower BPA rates could be associated with better functioning. They would probably also be the same parents who are concerned about the effects of vaccination on autism rates. I’d have to see the full version to determine if they did some sort of stratification or control (and I probably wouldn’t be able to say whether they did a good job or not, I’m not a stats wonk). There could be a genuine effect and BPA may have an adverse impact on the neurodevelopment of girls – but that study is at best a starting point on speculation rather than a conclusion. Claiming this means people have to avoid BPA based on the results is an over-reach in my opinion.

    Anyone else ever heard Disco Duckie, Ernie’s version of Rubber Ducky redone for Saturday Night Fever? It’s awesome.

  6. passionlessDrone says:

    Hello friends –

    There does seem to be a large set of data implicating these types of chemicals with low birth weight; i.e.,

    Biomonitoring of bisphenol A concentrations in maternal and umbilical cord blood in regard to birth outcomes and adipokine expression: a birth cohort study in Taiwan.

    Elevated prenatal BPA exposure increased the risk of LBW, SGA, and adverse actions of adipokines in neonates, especially in male infants. These results provide further evidence that maternal exposure is correlated with adverse birth outcomes.

    In utero exposure to bisphenol-A and its effect on birth weight of offspring

    A dose-response relationship was observed with increased BPA exposure levels in pregnancy associated with greater magnitude of decrease of birth weight in offspring (P=0.003). Our findings provide the new epidemiologic evidence suggesting that in utero exposure to BPA during pregnancy may be associated with decreased birth weight in offspring.

    Phthalate levels and low birth weight: a nested case-control study of Chinese newborns.

    Newborns in China are ubiquitously exposed to phthalates; significantly higher phthalate levels were detected in LBW cases compared with controls. In utero DBP and DEHP exposures were associated with LBW in a dose-dependent manner. Prenatal phthalate exposure may be a risk factor for LBW.

    Note that none of these studies were in mice, and all were published since the ‘reassuring’ review by Kamrin. Here’s a funny side note, Michael Kamrin is an advisor to the ACSH, the organization that never met a chemical that it didn’t like, or an angle it couldn’t utilize to exhonerate reckless introduction of chemicals into our environment. What a crazy coincidence!

    In my arena, a dose relationship between low birth weight and autism was recently described:

    Lower birth weight indicates higher risk of autistic traits in discordant twin pairs

    Analyses of birth weight as a continuous risk factor showed a 13% reduction in risk of ASD for every 100 g increase in birth weight (n=78). Analysis of the effect of birth weight on ASD symptoms in the entire population (most of whom did not have ASD) showed a modest association. That is, for every 100 g increase in birth weight, a 2% decrease in severity of ASD indexed by scores on the Autism – Tics, attention-deficit hyperactivity disorder (AD/HD), and other Comorbidities (A-TAC) inventory would be expected in the sample as a whole.

    I was already making my own soup.

    - pD

  7. Ash says:

    There are certainly some studies showing potential effects from BPA, but there isn’t a lot of good information on what doses. The problem with the available literature is that on the one hand most of the chemical industry studies were using standardized methods that may not have captured the right endpoints. On the other hand, most of the studies cited by environmental groups were based on subcutaneous injection, which doesn’t properly account for the metabolism of BPA in the liver after it is ingested (so you can’t draw any conclusions about whether the specific dose used was really harmful). I believe FDA is funding some work right now that addresses these weaknesses so hopefully within the next few years we’ll start go get some more reliable data.

    I’ve looked at BPA a few times: http://ashartus.wordpress.com/2011/04/27/how-toxic-is-bpa/ and http://ashartus.wordpress.com/2010/09/07/relating-bpa-in-urine-to-exposure-doses/ for example.

  8. windriven says:

    PVC and their phthalate plasticizers are ubiquitous in medical products and polycarbonates (which contain bisphenol A) only slightly less so. Both phthalates and BPA are much larger issues in Europe (at least in the medical community) than in the US – at least for now.

    There are quite good non-phthalate alternatives to plasticize PVC. Without plasticizers PVC is hard – like PVC water pipes. To make PVC pliable, plasticizers are added. For many years DEHP was a common plasticizer in medical products. DEHP has now been replaced by di-isononyl phthalate (DINP). We use a plasticizer that is made from castor bean oil for the soft cushions of anesthesia face masks. Non-phthalate plasticizers tend to be rather more expensive than the phthalates they replace.

    In any event, fear and superstition win out over science and technology every time, so we’ve made the switch to phthalate-free, entirely for marketing reasons.

    BPA is a different problem. Polycarbonates (PC) are rigid thermoplastics that offer good strength and exceptional clarity. Bisphenol A is, to the best of my knowledge, irreplaceable in the production of polycarbonates. Some other engineering resins are available with similar properties but none have the broad acceptance of PC for use in medical products. One cannot simply switch resins for most medical products without going through a significant acceptance process.

    I suspect that pressure will continue on BPA and that its use in the medical industry will wane, albeit at a much slower pace than phthalate-plasticized PVC.

  9. nybgrus says:

    @michele & WLU:

    From the full article, 33% of the cohort was lost to follow up and:

    Dyads with complete follow-up data were more likely to be white, married, 25 to 34 years of age, more educated, and wealthier, compared with dyads with incomplete data (results not shown).

    It was also noted that:

    Gestational urinary BPA concentrations were lower among women who completed the follow-up assessments, compared with those who did not

    So it seems that there indeed could have been some confounding via selection bias.

    Also, the difference between boys and girls is interesting:

    The magnitude of these associations was greater among girls, compared with boys (P < .10)

    With boys essentially showing no effect whatsoever, but the p-value for the difference is rather high.

    Based on a recent neurophysiology lecture I went to, this disparate effect between the sexes is actually perfectly reasonable. However, the added confounder here is that the sex difference may exist with or without the BPA in play.

    Also:

    Notably, gestational BPA concentrations were associated with increases in BASC-2 hyperactivity scores among girls (β = 9.1 [95% confidence interval [CI]: 3.1–15]) but decreases among boys (β = −6.3 [95% CI: −12 to −0.6]).

    Essentially, these are very wide error bars. The 95% CI is very big, and in opposite directions between boys and girls. Once again this is neurophysiological reasonable… as well as a potential descriptor of something to do with sex difference independent of BPA exposure.

    They also go on to say that the post-natal BPA levels had no discernible effect.

    They also note that in emotional control and inhibition scores, after adjustment for confounders, gestational BPA seemed to have a positive effect (with a magnitute and sex distribution similar to that of the BASC-2 scores).

    Also of note:

    Adjustment for confounders shifted most point estimates for associations between gestational BPA exposure and BASC-2/BRIEF-P scores up, and in some cases through the null.

    In other words, they were looking at a lot of things and when they attempted to adjust for confounders (I say attempted because it is really hard to do and in many cases impossible to fully do so) they found at least some of the effect to disappear.

    The authors even state:

    Our results suggested that girls in this cohort were more sensitive to gestational BPA exposures than were boys. This pattern should be interpreted cautiously, given the imprecision of the observed associations among girls and the low statistical power for interactions between gender and BPA exposures.

    The bold refers to those wide error bars in the 95%CI I referred to above.

    They also did not perform any corrections for multiple comparisons, preferring instead to:

    [focus] on the patterns, magnitudes, and consistency of our results and compared those factors with findings from our previous studies and experimental studies with animal

    And of course the authors do realize that:

    The clinical relevance of these findings is unclear at this point.

    So overall, to me at least, it looks like there might be some small signal in a fair bit of noise. The signal is of unknown significance. And, although the researchers here seemed to genuinely do a decent job of it all, these sorts of metrics are difficult in 3 year olds and the confounders are tough to pick out. The study was only moderately sized and so the error bars are quite big (which the authors also realize).

    In sum, it seems that indeed this might be a good starting point for some speculation, but nothing much beyond that. The reality is that just about anything can have some sort of effect on developing brains (and other organs). As Dr. Hall pointed out, will removing BPA change that effect in a positive way? Is the effect long lasting? Is it clinically significant? There don’t seem to be answers for those questions – at least not in this study.

  10. Always Curious says:

    BPA has fascinated me for a few years now. The FDA & EPA have very different approaches and concerns. The EPA’s research is what really got me interested in the problem and probably really the governmental source for . However, the FDA report I read (2008?) seemed to immediately gloss over the EPA’s food related angle–epigenetic modifications and synergistic effects with soy. The FDA, to their credit, continue to fund research, but they said straight up that their interest primarily was that it didn’t cause discernible death & dismemberment in the consumer or easily detectable death & dismemberment in the second generation [only variable under consideration being total quantity of BPA ingested].

    The EPA, however, has a wider area to be concerned with than the FDA: they may need to be considering what BPA ultimately does in the environment after we flush it all down the drain & what happens to the people actually working with it in a pure form.

    Also from my angle, I’d be interested in seeing a human BPA study that controlled the starting BMI and diet of pregnant women. These variables could possibly change the final health of the newborn–both physically & mentally. Alas, the expense & followup required would likely make it small & underpowered. Certainly there is a lot more to do to define the safety parameters of BPA, but it’s not going to keep me up all night anymore. And it’s likely the best alternatives are even less well understood.

    Thanks for the article!

  11. Scott says:

    They also did not perform any corrections for multiple comparisons, preferring instead to:

    This point is really, really important. In fact, it automatically relegates it to the “purely hypothesis-generating” bin for anything except a drastic effect (not the case here). Especially since we’re not talking about 3 or 4 comparisons, but dozens. I accordingly disagree with the statement that “the clinical significance of these findings is unclear.” I’d say it’s quite clear that there is no clinical significance at this time.

  12. Ray Greek MD says:

    Thanks for the nice summary!

  13. Angora Rabbit says:

    Speaking as an NIEHS-funded developmental toxicologist who doesn’t give a hoot if BPA is toxic or not, I do view with caution whenever a study is sponsored by ACSH. They definitely have an agenda and are not unbiased.

    Regarding BPA I’ve not followed this one closely and I’m going to read the article tonight. However, I do want to comment on this: “These compounds are rapidly excreted from the body and may not stay around long enough to cause any problems. BPA is rapidly and completely metabolized into glucuronide, which is not estrogenic and is rapidly excreted in the urine. Even premature infants can metabolize it at the low levels involved.”

    I would be very cautious extrapolating from this to the conclusion that prenatal exposure is safe. Unlike moms and premies, the conceptus excretes urinary toxicants (and yes, they do “pee” once the kidneys are developed) into the amniotic fluid. Metabolite clearance from amniotic fluid is much slower than from the blood. Thus the conceptus has a longer duration exposure than the mother. The amniotic fluid is also swallowed, and ultimately is concentrated into the meconium, and we know from NHANES that there are measurable levels of BPA and metabolites present. And of course, this is when gonadal structures are being developed and are a critical period for the effects of endocrine disrupters.

    Just wearing my developmental toxicologist hat – the fat lady ain’t done singing yet. :)

  14. rmgw says:

    “Rodents have a different metabolism”…. “We are not mice. Concerns from animal experiments can’t be automatically extrapolated to humans. Human studies are required.”……”Animal studies can alert us to possible problems in humans, but they can also create false alarms. For instance, aspirin causes congenital defects in mice, but it has no such effects in humans.”…….

    - and so it goes. It’s wonderful, being the dominant species.

  15. @dugganSC “Oh darn… and here I was hoping for a good scholarly article.”

    Oh…took me a minute, but this was a reference to my BPA, GPA typo, right? hehe, don’t look to me to be scholarly, I’m just a bumbling artist type.

    @WLU “Parents with more money may have more time to spend with their children and more money to spend on BPA-free products – thus lower BPA rates could be associated with better functioning. They would probably also be the same parents who are concerned about the effects of vaccination on autism rates. I’d have to see the full version to determine if they did some sort of stratification or control (and I probably wouldn’t be able to say whether they did a good job or not, I’m not a stats wonk). There could be a genuine effect and BPA may have an adverse impact on the neurodevelopment of girls – but that study is at best a starting point on speculation rather than a conclusion. Claiming this means people have to avoid BPA based on the results is an over-reach in my opinion.”

    Yes, this was one thing I was looking for in asking for comments, possible confounders. An income association in BPA exposure was not obvious to me. It seems to me the “more time to spend with children” could go either way in child behavior, but if the BPA levels are varying with income, then income could be a factor in child behaviors as well as being tied to other environmental exposures (lead, etc) that could skew things.

    I’m not sure who claimed people have to avoid BPA? Is that rhetorical or did I miss something.

    I guess my concern would be, if there is a question of whether or not prenatal exposure to BPA may cause behavior issues, as a consumer, why should I default to using food products containing BPA without considering whether BPA products offers me any clear advantages over non-BPA products?

    It is not like considering whether to vaccinate or not. A vaccine offers clear benefits without competitive products.

    Isn’t is supposed to be a risk/benefit analysis, not just a risk analysis? :)

    @nybgrus, thanks for the detailed looks at that paper. It may help me to take a second pass reading the paper with your comments in mind.

  16. Werdna says:

    @PD – It’s important not to confuse all causes LBW with specific cause of LBW.

Comments are closed.