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The 2008-2009 Report of the President’s Cancer Panel: Mostly good, some bad, and a little ugly

Mark Crislip is always a hard act to follow, particularly when he’s firing on all cylinders, as he was last Friday. Although I can sometimes match him (and, on rare occasions, even surpass him) for amusing snark, this time around I’m going to remain mostly serious because that’s what the subject matter requires. I’ve said it before and I’ll say it again: I’m a bit of an odd bird in the world of cancer in that I’m both a surgeon and I run a lab. Sadly, there just aren’t very many surgeons doing basic and translational research these days, thanks to declining NIH funding, increasing clinical burden necessitated by declining reimbursements, and the increasing complexity of laboratory-based research. That’s not to say that there aren’t some surgeons out there doing excellent laboratory research, but sometimes I feel as though I’m part of an endangered species, particularly years like this when grants are running out and I need to renew my funding or secure new funding, the consequence of failure being the dissolution of my laboratory. It’s a tough world out there in biomedical research.

As tough as biomedical research is in cancer, to my mind far tougher is research trying to tease out the relationship between environmental exposures and cancer risk. If you want complicated, that’s complicated. For one thing, obtaining epidemiological data is incredibly labor- and cost-intensive, and rarely are the data clear cut. There’s always ambiguity, not to mention numerous confounding factors that conspire to exaggerate on the one hand or hide on the other hand correlations between environmental exposures and cancer. As a result, studies are often conflicting, and making sense of the morass of often contradictory studies can tax even the most skillful scientists and epidemiologists. Communicating the science and epidemiology linking environment and cancer to the public is even harder. What the lay person often sees is that one day a study is in the news telling him that X causes cancer and then a month later another study says that X doesn’t cause cancer. Is it any wonder that people are often confused over what is and is not dangerous? Add to this a distinct inability on the part of most people, even highly educated people, to weigh small risks against one another (an inability that has led to phenomena such as the anti-vaccine movement), and the task of trying to decide what is dangerous, what is not, how policy is formulated based on this science, and how to communicate the science and the policy derived from it to the public is truly Herculean.

The President’s Cancer Panel (PCP) marched straight into this fray last week by issuing its 2008-2009 Annual Report entitled Reducing Environmental Cancer Risk, What We Can Do Now. The Panel on Cancer was mandated under the National Cancer Act of 1971, the legislation passed as a result of President Richard Nixon’s declaration of “war on cancer,” and its function is to “monitor the development and execution of the activities of the National Cancer Program, and shall report directly to the President.” Previous reports have addressed subjects such as Promoting Healthy Lifestyles (2006-2007); Translating Research Into Cancer Care: Delivering on the Promise (2004-2005); Living Beyond Cancer: Finding a New Balance (2003-2004); and The Meaning of Race in Science–Considerations for Cancer Research (1997). Not surprisingly, this year’s report is more contentious than the average President’s Cancer Panel Report because few areas of cancer research are as controversial or impact as directly on public policy as the assessment of environmental risks of cancer and what to do about those risks.

The PCP report is very long (over 200 pages), although there is a lot of white space on each page, but for those of you who don’t feel inclined to read the whole thing, the executive summary does a good job of boiling down the vastness of the report into a more digestible chunk. It begins, as all such reports do, by pointing out the enormity of the cancer problem in the U.S.:

Despite overall decreases in incidence and mortality, cancer continues to shatter and steal the lives of Americans. Approximately 41 percent of Americans will be diagnosed with cancer at some point in their lives, and about 21 percent will die from cancer. The incidence of some cancers, including some most common among children, is increasing for unexplained reasons.

Public and governmental awareness of environmental influences on cancer risk and other health issues has increased substantially in recent years as scientific and health care communities, policy makers, and individuals strive to understand and ameliorate the causes and toll of human disease. A growing body of research documents myriad established and suspected environmental factors linked to genetic, immune, and endocrine dysfunction that can lead to cancer and other diseases.

Between September 2008 and January 2009, the President’s Cancer Panel (the Panel) convened four meetings to assess the state of environmental cancer research, policy, and programs addressing known and potential effects of environmental exposures on cancer. The Panel received testimony from 45 invited experts from academia, government, industry, the environmental and cancer advocacy communities, and the public.

In order to address the question of environmental influences on cancer, the Panel decided to address the following areas:

  1. Exposure to Contaminants from Industrial and Manufacturing Sources. These include a wide variety of manufactured chemicals and industrial by products used in the manufacture of mass-produced products. The report notes that numerous chemicals used in manufacturing remain on products as residues or are integral parts of the products themselves. It is also noted that new chemicals are being created continually.
  2. Exposure to Contaminants from Agricultural Sources. There are numerous chemical exposures due to chemicals used in agriculture, particularly pesticides, solvents, and fillers. Some of these leech into the soil and water and produce exposure this way.
  3. Environmental Exposures Related to Modern Lifestyles. These exposures include pollution from vehicles, chemicals used in pest control, and exposure to radio waves and electromagnetic fields from cell phone radiation and electrical power lines, respectively.
  4. Exposure to Hazards from Medical Sources. This source consists primarily of radiation from medical tests and the potential of contamination of the environment from discarded pharmaceuticals.
  5. Exposure to Contaminants and Other Hazards from Military Sources. There still remain a lot of areas around military bases. Nearly 900 Superfund sites are abandoned military facilities or facilities that produced materials for military use.
  6. Exposure to Environmental Hazards from Natural Sources. This class of exposure includes naturally occurring carcinogens such as radon, uranium, and arsenic.

Overall, the report is a comprehensive look at environmental exposures that could potentially contribute to various cancers and that we can do something about. In all my years in cancer research, I can’t recall ever seeing its like coming from such a mainstream source. The panel proposes several suggested approaches to this problem, including:

  1. The adoption of a new “precautionary, prevention-oriented approach” to replace our “current reactionary approaches in which human harm must be proven before action is taken to reduce or eliminate exposure.” As a part of this approach, it is recommended that the burden of proof of safety should be shifted to the manufacturer, rather than the current burden of proof being upon the government to prove harm.
  2. A thorough new assessment of workplace and other exposures to quantify risk.
  3. A more coordinated system for promulgating environmental contaminant policy and regulations driven by science and free of political and industry influence.
  4. Epidemiological and hazard assessment research in areas where the evidence is unclear.
  5. New research tools and endpoints to assess environmental exposure and risk, including high throughput models to assess multiple exposures simultaneously, methods for long term monitoring and quantification of electromagnetic energy sources, such as power lines and cell phones.
  6. Better policies regarding cancer risk due to radon.
  7. Actions to minimize exposure to medical radiation sources.
  8. Addressing the unequal burden to known and suspected carcinogens.
  9. Encouraging physicians to take better health histories of environmental exposures.
  10. “Green chemistry” initiatives.
  11. Measures to increase public awareness of risk due to environmental exposures.

As you can see, if the recommendations, some of the details of which are fleshed out (mostly) in the 200 page report, if adopted would require enormous policy changes. Of course, one thing that must be remembered about reports like this is that they are every bit as much political documents as they are scientific and medical documents. After all, they point out problems that very well could require new laws and/or new regulations in order to address. This report definitely falls into this category in a big way because, if adopted, its recommendations would demand action by the government. Indeed, the report itself blames weak laws, lax enforcement, and overlapping and conflicting regulatory authority, but, more strongly, it blames the attitude that industrial chemicals are safe unless strong evidence that they are not safe emerges.

But how strong is the science?

From my perspective, the report is a mixed bag, a mixture of the (mostly) good, a (little) bad, and (at least one) ugly thing. It’s also rather annoying that, of the over 400 references, most of them appear to be government reports and review articles, with very little primary literature cited. First the good, though. The report emphasizes quite strongly that what we know about the environmental contribution to cancer has lagged far behind our knowledge of other aspects of cancer. More importantly, one aspect of the environmental contribution to cancer that we often don’t consider strongly enough is that children tend to be more susceptible to environmental insults of many kinds, particularly carcinogenic insults:

An analysis by the National Academy of Sciences found that children are particularly vulnerable to environmental contaminants for several reasons. Due to their smaller size, children’s exposures to toxics are disproportionately large compared with adults. Because their metabolic pathways are immature (particularly during fetal development and in the first months after birth), they are slower to metabolize, detoxify, and excrete many environmental chemicals. As a result, toxins remain active in their bodies for a longer period of time than would be the case in adults. In addition, children have lower levels of some chemical-binding proteins, allowing more of a toxic agent to reach various organs, and their blood-brain barrier is more porous than that of adults, allowing greater chemical exposures to the developing brain. Children’s bodies also are less able to repair damage due to toxic exposures, and the complex processes that take place during the rapid growth and development of children’s nervous, respiratory, immune, reproductive, and other organ systems are easily disrupted.

Children have many more years of life ahead of them than do adults—more time in which to be exposed to environmental toxics and time to develop diseases (including cancer) with long latency periods initiated by early exposures.

Moreover, at the same time that mortality rates for childhood cancers have been plummeting dramatically, the incidence of childhood cancers has been steadily climbing, as shown by this graph “borrowed” from the report:

ChildhoodCancer

The reason for this increase is not known, but genetics is an unlikely cause for such a rapid increase. In addition, it is unlikely that better diagnosis due to the introduction of MRI and better CT scanning is likely to be the cause, because the increase is too steady. That leaves environmental factors as one suspect for a major cause. Certainly, this is worth examining, as it may provide the “greatest bang for the buck.” Such studies could even benefit adults in terms of cancer risk. For example, lately, our cancer institute has become very interested in environmental contributors to breast cancer. One thing that has become clear is that such exposures may have their greatest effect in childhood or, in particular, during puberty, which is when the mammary gland undergoes its most rapid growth and development. Indeed, although this increases susceptibility to carcinogens in children has long been appreciated, but the characterization of these differences, again, has lagged behind other areas of cancer research. This is especially relevant to the section on the risk of medical radiation, with recent studies suggesting the possibility of tens of thousands of excess cancers in the U.S. due to medical radiation from the increasingly common use of CT scans and studies suggesting that radiation from mammography may contribute to a small number of breast cancers.

Another good part of the report is its emphasis on the deficiencies in our current technology and tools for assessing the carcinogenic potential of various chemicals. Related to the report’s emphasis on how little we know about carcinogenesis in children, the report criticizes current animal models because they fail to capture the impacts of early exposures and miss the late effects of such exposures. Also problematic is that most animal studies use long-term, high-dose exposures that may have little relation to humans. Consequently, the report urges the development of alternatives to animal testing involving testing in human cells in vitro. I’m rather skeptical that this recommendation will produce much benefit very fast. After all, one reason we use animals is because, as imperfect as animal carcinogenesis studies are, the correlation between cell culture studies is even more unreliable than that of animal studies.

One recommendation of the report that intrigued me was its assessment of how science has generally focused on one compound at a time without considering how they may interact. This reminds me of how in the past we concentrated on one gene at a time as a causative agent for cancer (such as oncogenes); yet over the past ten years it has become increasingly clear that cancer is often driven by many genes, each of which individually plays a relatively small role. The Panel thus recommends the development of high throughput screens that can examine many chemicals at once and test for interactions, a recommendation that struck me as worthwhile, although I am having trouble envisioning what such a test would look like or how it would be validated. The problem, of course, is that, as more chemicals are tested, the possible combinations skyrocket exponentially.

One major part of the report deals with one specific environmental exposure, the thousand pound gorilla these days, namely BPA, which was discussed in the context of the report’s increasing emphasis on the precautionary principle. This part of the report, to me, was a little bit dicey in that the precautionary principle is very difficult to apply. I’ve discussed this matter before in the context of how preemptively removing mercury from vaccines helped fuel an anti-vaccine panic over the mercury in the thimerosal preservative that used to be in vaccines. The question of how much evidence is necessary to justify banning a compound doesn’t go away, and it still remains a profoundly political question. The report basically glosses over the question of where one should draw the line in implementing the principle, other than suggesting shifting it to more caution. It also dances around the question of how we would pay for this, given that the implementation of the recommendations in this report would require massive increases in the budgets of the relevant agencies — particularly since the report itself documents just how short-staffed and under-funded many of these agencies are.

One glaringly dubious part of the report compared to the rest is how it deals with the issue of cell phones and cancer. After emphasizing that there is no good evidence to support a link between cell phones and cancer and pointing out that the epidemiological evidence is in essence negative, the report proceeds as though a link between cell phone use and brain or head and neck tumors were biologically plausible. As I’ve described before, it’s not. Indeed, from a biological standpoint, a strong link between cell phone use and brain cancer (or any other cancer) is not very plausible at all; in fact, it’s highly implausible. Cell phones do not emit ionizing radiation; they emit electromagnetic radiation in the microwave spectrum whose energy is far too low to cause the DNA damage that leads to mutations that lead to cancer. While it is possible that perhaps heating effects might contribute somehow to cancer, most cell phones, at least ones manufactured in the last decade or so, are low power radio transmitters. It is also necessary to acknowledge the possibility that there might be an as yet undiscovered biological mechanism by which low power radio waves can cause cancer, perhaps epigenetic or other, but the evidence there is very weak to nonexistent as well. Basically, based on what we know about carcinogenesis, a postulated link between cell phones and cancer is highly implausible. It’s not homeopathy-level implausible, but it’s pretty implausible nonetheless. Consequently, in the absence of better basic science, I have a hard time managing to muster any enthusiasm about recommending more studies than the ones that are already going on.

That ugly bit aside, though, the President’s Cancer Panel report is in general cautious and makes sensible policy recommendations. It also makes a number of (mostly) sensible recommendations for individual citizens. In general, it is cautious and highlights a neglected aspect of cancer research.

That must be why the pro-industry group American Council on Science and Health (ACSH) is on the counterattack, for example:

Elizabeth M. Whelan, president of the American Council on Science and Health, whose views often coincide with industry’s, noted that despite the growing exposure to chemicals in the environment, “cancer death rates are going down. The so-called environmental trace levels of chemicals play no role whatsoever in the etiology of cancer.”

And:

“This so-called Presidential Cancer Panel, which consists of two physicians, has obviously been politically pressured by the activists running the EPA,” says ACSH’s Dr. Gilbert Ross. “When they mention babies being ‘pre-polluted’ and the alleged dangers of all of these chemicals, they not only sign their name to activist screeds, they neglect to mention that the dose makes the poison, and that finding traces of chemicals at levels of parts-per-billion does not imply a health hazard. And of course they do not address the potential health hazards of banning important chemicals from consumer products.”

Of course, the obvious retort to that is that the presence of chemicals at levels of parts-per-billion doesn’t imply that there’s isn’t problem, either, but that’s apparently what ACSH wants you to believe. There may be a problem; there may not. We’ll never know if we don’t study the issue. It is probably true that most trace contaminants are not health hazards, it’s also very likely true that some of them are, and if we don’t study the issue we will never know. But that’s ACSH’s M.O.: deny there is a problem; deny even the possibility that there might be a problem; criticize the tools used to study a problem even if they are the best we have, however imperfect. Sometimes ACSH even takes it to ridiculous extremes. In other words, other than tobacco, when it comes to the assessment of health risks to listen to ACSH is in essence to hear industry’s viewpoint, as Jon Stewart demonstrated so brilliantly last year. Any organization that can claim with a straight face that encouraging healthy eating is “elitist” is not one that I can take seriously.

A more reasonable criticism comes from the American Cancer Society’s Michael J. Thun, MD:

Issues highlighted in both reports include the accumulation of certain synthetic chemicals in humans and in the food chain; the large number of industrial chemicals that have not been adequately tested; the potentially greater susceptibility of children; the possibility that some chemicals or combinations of chemicals may have effects at low doses; and the potential risks from widely used medical imaging procedures that involve ionizing radiation.

Unfortunately, the perspective of the report is unbalanced by its implication that pollution is the major cause of cancer, and by its dismissal of cancer prevention efforts aimed at the major known causes of cancer (tobacco, obesity, alcohol, infections, hormones, sunlight) as “focused narrowly.”

This seems to be missing the point by more than a bit. The very point of the report was to focus on an aspect of cancer prevention that the Panel considered to have been historically underrepresented. This year, the President’s Cancer Panel report was designed to focus on one aspect of cancer, namely environmental influences on cancer. As such, of course it emphasized — shockingly — environmental influences on cancer. It’s also just plain wrong that the report “dismisses” cancer prevention efforts aimed at the stronger known exposures and risk factors for cancer; rather, it argues that we should be doing more to ameliorate cancer risk from environmental exposures, be it to chemicals or the excessive use of medical radiation in imaging tests.

Basically, I found the ACS’s objections to be rather puzzling, given that just last fall the ACS published a position paper, many parts of which sound eerily similar to the President’s Cancer Panel report. For example, these are the things that the ACS recommends:

The position statement on cancer prevention also says:

  • New strategies for toxicity testing, including the assessment of carcinogenicity, should be implemented that will more effectively and efficiently screen the large number of chemicals to which people are exposed. This very same recommendation is in the President’s Cancer Panel report.
  • Occupational and community exposures should meet regulatory standards, and research to identify and reduce carcinogenic hazards should be supported. Ditto.
  • The agencies that set and enforce environmental standards need to be appropriately funded and science-based to keep pace with scientific developments and to update their standards accordingly. This is more or less the same as what the President’s Cancer Panel recommends.
  • Although certain exposures are unavoidable, exposure to carcinogens should be minimized or eliminated whenever feasible. A little different emphasis, but basically the same idea as embodied in the President’s Cancer Panel report.
  • The public should be provided with information so that they can make informed choices. Absolutely the same as the President’s Cancer Panel report.
  • Communications should acknowledge and not trivialize public concerns, but at the same time should not exaggerate the potential magnitude or level of certainty of the potential risk.

The last point seems to be the only point where the ACS and the President’s Cancer Panel differ significantly, and I will admit that the President’s Cancer Panel report is a bit too certain in its tone when it comes to several issues. And, straight from the article:

The exposure levels to the general public are typically orders of magnitude lower than those experienced historically in occupational or other settings in which cancer risks have been demonstrated. The resulting cancer risks are generally so low that they cannot be measured directly. Nevertheless, there is reason to be concerned about low-level exposures to carcinogenic pollutants because of the multiplicity of substances, the involuntary nature of many exposures, and the potential that even low-level exposures contribute to the cancer burden when large numbers of people are exposed. Concerns about the toxic and carcinogenic potential of these exposures are amplified by broader public concerns regarding the effectiveness of hazard identification and the regulation of potentially toxic exposures in the United States and other economically developed countries, as well as high levels of exposures to known carcinogens that still occur in many developing countries.

All of this is very similar to what is in the President’s Cancer Panel report, the main difference being more of emphasis than anything else and a disagreement over whether environmental contributions to cancer other than the strong, well-characterized ones (like smoking) are underestimated or not. At the risk of falling prey to the fallacy of the Golden Mean, I rather suspect that the real risk is somewhere in between the position of the ACS and that of the President’s Cancer Council. The reason that I don’t think the Golden Mean fallacy will be a big deal here is because the positions of the two are actually pretty close, despite Dr. Thun’s objections. When the ACSH points to the ACS as “harshly criticizing” the report, even going so far as to entitle one post Praise be to Thun, it’s clearly exaggerating the extent of disagreement for its own purposes.

The President’s Cancer Panel report represents a document that is at the same time scientific, medical, and also highly political, and that needs to be remembered. It has also been heartening to epidemiologists and public health officials, some of whom have criticized the National Cancer Institute system for publicizing avoidable causes of cancer other than smoking to be “virtually non-existent.” This report, as flawed as parts of it are, represents a refreshing first step towards addressing that shortcoming. My only fear is that, if the results are not communicated well, we could have a series of environmental cancer scares on the basis of very little evidence, given the uncertainty inherent in many of these studies. However, if this is handled well, the result could be science-based health policies that minimize public exposure to known carcinogens and give people the information necessary to allow them to act for their own benefit.

Posted in: Cancer, Politics and Regulation, Public Health

Leave a Comment (29) ↓

29 thoughts on “The 2008-2009 Report of the President’s Cancer Panel: Mostly good, some bad, and a little ugly

  1. Very nice piece Dr Gorski. This is the kind off informative article that keeps bringing me back to SBM.

    One thought regarding “The question of how much evidence is necessary to justify banning a compound doesn’t go away, and it still remains a profoundly political question. The report basically glosses over the question of where one should draw the line in implementing the principle, other than suggesting shifting it to more caution.”

    This idea may have limited application (or be just wrong), but in the case of BPA in plastics there are other plastic compounds that are considered safer. When in doubt, could the line be drawn at how the potential product risk compares to other competing products?

    Just a thought.

  2. passionlessDrone says:

    Hi David Gorski –

    Great piece. Thank you.

    I’d be curious in your take on a piece that I heard on NPR a few years ago, but cannot re-find for the life of me, concerning a national initiative on studying the galaxy of chemicals we are now exposed to. If I remember correctly, the study had already burned through tens of millions of dollars, they were still trying to figure out which type of rodent to use in testing! It turns out there were big differences in things like how robustly different strains handled exposures to chemicals; if you chose a tough rat, you couldn’t be sure if your exposure threshold was meaningful, but if you chose a rat that was very succeptible, and never bred, you ran the risk of not generating any data at all.

    Very nicely done.

    - pD

  3. Zoe237 says:

    Thanks for this! Definite bookmark, and pass it along for sure.

  4. Zoe237 says:

    You know, I read a lot of newspapers, at home here and international ones, and it’s really annoying for every other day to see a press release about this or that causes or doesn’t cause cancer. Often, the study is presented as the issue being settled, and then a few months later a contradicting one comes out. Really frustrating for a layperson to sort through it all, and a lot of people don’t understand that one study does not consensus make. It also REALLY fuels mistrust in the system, not a good thing when it comes to vaccines.

  5. David Gorski says:

    Thanks, all.

    Of course, I’m just waiting for SD to show up and do his radical Libertarian schtick. If he’s reading, I know he won’t be able to resist. It’s like red meat to a dog.

    Countdown 5…4…3…2…1…

  6. Stroh says:

    For a moment I thought the title said “The 2008-2009 Report of the Presidents Candy panel”. A man can dream…

  7. “The 2008-2009 Report of the Presidents Candy panel”. A man can dream…”

    The report starts out “Who can take a sunrise? Sprinkle it with dew?” Before naming the new candy czar.

  8. cervantes says:

    I commented along similar lines though considerably more briefly. (BTW Dr. G, if you’re willing to make essentially the same post under your real world name as you do using your secret identity, do you really need the secret identity any more? Just askin’). My take:

    I expect most readers have seen news stories about the President’s Cancer Panel report. The headline is that the panel claims that environmental exposures — by implication at least, meaning mostly to human-produced chemicals — make a far more important contribution to the burden of cancer than has been recognized. This has long been what I must, sadly, call an article of faith among environmentalists, but the report actually does not come to that conclusion, nor does it present any direct evidence for it. This spin must come from a press release, is the only conclusion I can make. In fact, in the executive summary, they say this:

    ” At this time, we do not know how much environmental exposures influence cancer risk and related immune and endocrine dysfunction. Environmental contamination varies greatly by type and magnitude across the nation, and the lifetime effects of exposure to combinations of chemicals and other agents are largely unstudied. Similarly, the cancer impact of exposures during key “windows of vulnerability” such as the prenatal period, early life, and puberty are not well understood.”

    In other words, we don’t know, but maybe it’s worse than we think, so we ought to try to find out. That’s a less exciting headline, but it has the virtue of being accurate.

    Here’s some context. Environmental epidemiology is a notoriously difficult endeavor. First, it’s quite difficult to measure how much of any given agent people are exposed to. You can find people who live in a place where something or other is known to be in the air, for example, but they will all vary widely in how much time they spend at home, how much time they spend outdoors, how much they open the windows, etc. And living in that place also means that they likely have all sorts of other things in common that might be relevant to their cancer risk. We can try to measure and account for as many of those factors as we can think of, but we can’t be sure we haven’t missed the one that matters.

    What is worse, it might be that exposure to X only matters if also Y. For example, radon exposure was found to increase the lung cancer risk of uranium miners, but it turned out to mostly be a synergistic effect with tobacco smoking. The effect was difficult to detect in non-smokers. Since smoking and environmental tobacco smoke were — and still are — by far the most powerful environmental cause of cancer, overwhelming everything else, people in public health (public healthists?) found it hard to get as excited about other kinds of exposures. Also, a lot of much hyped suspected links, for example between environmental endocrine disrupters such as many pesticides and breast cancer, haven’t panned out.

    Another inconvenient truth is that we do know about other environmental cancer risks, but they don’t indict giant soulless corporations but rather your grandmother and your own sorry self. Smoked and grilled meat products and starchy fried foods contain carcinogens. Also, excessive alcohol consumption promotes cancer. And of course, so does getting a sunburn.

    Now, we do know that some products of incomplete combustion — ergo compounds found in motor vehicle exhaust and smokestack emissions — called polycyclic aromatic hydrocarbons, are carcinogenic. More complicated versions called dioxins are found as contaminants in pesticides as well as smokestack emissions (including, by the way, your fireplace chimney) and paper mill effluent. A lot of reactive hydrocarbon compounds probably can cause genetic damage, mess with hormones, and just cause inflammation and irritation which makes cells divide more than usual, which also may increase cancer risk. The problem is that all of these exposures mix and match and interact, and that it probably matters how old you are and how long it lasts and whether you are overweight or underweight or male or female and what your particular genetic endowment is and who the hell knows what else.

    Most chemicals approved for various uses, including as ingredients in food or food packaging, believe it or not, have not been adequately tested for safety. But that is also very hard to do. You can’t do experiments by feeding them to people. You can feed stuff to mice, despite PETA’s objections, but a) mice aren’t people and b) you can’t feasibly mimic human exposures. It’s just too expensive to give millions of mice a tiny bit of something for a long time. Instead you have to give a small number of mice a whole lot of it. That just ain’t the same thing; and mice don’t live nearly as long as people anyway so you can’t do twenty or thirty year follow up. And sorting out what people are exposed to from their natural history, and trying to relate that to their lifelong risk of cancer, is just really, really hard and can very easily lead you to wrong conclusions.

    So yeah, we need to keep studying these questions, and we probably need to do it bigger and better. But so far there are only a few specific things we can tell you. Don’t smoke. Don’t do shots every night. Don’t live near the highway. Maintain an appropriate body weight. Don’t work as a hot tar roofer or a paver — although somebody has to do it.

  9. TrevorButterworth says:

    A few points for those who may think BPA is the poster child for environmental estrogens/carcinogens and the precautionary principle.

    First, it is worth reading Richard Sharpe’s recent piece in Toxicological Sciences. on BPA Sharpe, who chairs the UK’s Endocrine Disruptor Expert Panel and is Principal Investigator for the Medical Research Council’s Human Reproductive Sciences Unit, is not in the risk “from environmental exposure to chemicals is poppycock” school of thought, so his explication of why politics has hijacked the research on BPA is essential reading for anyone who has been schooled by the American media on this issue.

    http://toxsci.oxfordjournals.org/cgi/content/full/114/1/1

    He also wrote an op-ed for the Independent which gives a less technical explanation of why, in his view, the recent EPA study (Ryan et al) “and other similarly detailed studies in rodents more or less close the door on the possibility that bisphenol A is an environmental chemical to be concerned about because of its ER-mediated estrogenic activity.”

    http://www.independent.co.uk/opinion/commentators/richard-sharpe-let-common-sense-guide-you-in-the-saga-of-bisphenol-a-1942935.html

    Among the key aspects of his argument is that in toxicology, one cannot accept single dose studies as being superior to studies that establish a dose response curve, and that subcutaneous injection of BPA is incorrect for establishing toxicity in humans. (The NIEHS, btw, adopted both of these criteria in establishing grant requirements for continued research on BPA with stimulus money).

    This is relevant to the claim that BPA is a carcinogen in the following, as noted by the toxicologist Calvin Willhite:

    “[A]ll of the observations of changes in the female rodent mammary gland associated with BPA exposure were made after subcutaneous injections (e.g., Biology of Reproduction, Volume 65, pages 1215-1223, 2001; Congenital Anomalies, Volume 41, pages 187-193, 2002; Endocrinology, Volume 148, pages 116-127, 2007; Reproductive Toxicology, Volume 18, pages 803-811, 2004).

    In contrast, the U.S. National Toxicology Program in 1982 [Carcinogenesis Bioassay of Bisphenol A (CAS No. 80-05-7) in F344 Rats and B6C3F1 Mice (Feed Study), Technical Report No. 215] concluded based on the results of lifetime BPA feeding studies that ‘there was no convincing evidence that bisphenol A was carcinogenic for F344 rats or B6C3F1 mice of either sex.’”

    He also noted that “since there was no indication whatsoever of preneoplastic or neoplasic changes in the mammary gland of the rats and mice after lifetime ingestion of very high BPA doses (to as much as 148 milligrams/kilogram per day in rats and 1,900 milligrams/kilogram per day in mice), the suggestion that somehow BPA injection studies in rodents are directly relevant to human health is without empirical support.”

    http://stats.org/stories/2009/science_suppressed_BPA_part_8_a_jun12_09.html

    For humans, average daily BPA intake (over the years 2005 to 2008) was 0.03 microgram per kilogram of body weight per day, with the highest exposure 0.233 micrograms per kilogram body weight per day (Volkel et al, Toxicology Letters Volume 179, pages 155-162).

    As a consequence of this research, The Susan G Komen for the Cure concluded, “at this time, there is no evidence to suggest a link between BPA and risk of breast cancer.”

    http://ww5.komen.org/ContentSimpleLeft.aspx?id=6442451903&ecid=emklmay10:5

    It appears, however, that neither Susan G. Komen, nor any toxicologist from the EPA or FDA or NTP was invited to discuss environmental factors in cancer exposure or, specifically, BPA, on the President’s Panel. However, the Breast Cancer Fund, Devra Davis, and Philip Landrigan were. All three have rather extreme views on this issue, which is fine; but it’s important to note, as a consequence, who wasn’t invited to testify (this may also explain the American Cancer Society’s testy response to the report).

    http://deainfo.nci.nih.gov/advisory/pcp/pcp0908/agenda.pdf

    As you noted, Dr. Gorski, the panel report is a political artifact. Given that my ongoing conversations with toxicologists in regulatory agencies here and in Europe reveal enormous frustration with the obsession over BPA (and the monetary cost) while vastly more important chemical risks go relatively unstudied (estradiol in drinking water, BPA-F, carcinogens and estrogens in botanicals) this politicization is a shame. Perhaps this kind of investigation would be better handled by the National Academies of Science.

    One final thing of possible interest – our survey of almost 1,000 members of the Society of Toxicology found that 69 percent did not support regulation through the precautionary principle.

    http://stats.org/stories/2009/are_chemicals_killing_us.html

  10. passionlessDrone says:

    Hi TrevorButtersworth –

    I am interested in your thoughts concerning what we do seem to observe in humans; the higher your BPA levels, the more likely it is that you will suffer from heart disease or diabetes.

    - pD

  11. passionlessDrone says:

    Hello friends -

    For anyone interested, try googling ‘bpa’ and ‘trevor butterworth’ and see what you’ll find. I’m not sure he is an objective observer.

    It turns out, he’s loved by the ACSH.

    http://www.acsh.org/factsfears/newsID.1346/news_detail.asp

    Trevor Butterworth wrote a detailed history for the non-profit Statistical Assessment Service (STATS) of the falling-out between toxicology and endocrinology experts and the anti-BPA activist faction led by Dr. Frederick vom Saal. The outcome, Butterworth writes, is that, “[t]he panic over the chemical bisphenol A (BPA) is not only unjustified, it has reached a point where the failure to accept basic, rational principles in scientific research is damaging toxicology itself, wasting taxpayers’ money, and undermining scientific progress.”

    “Butterworth cites as the beginning of the controversy a study published in the journal Toxicological Sciences, which showed that rats were not susceptible to the alleged estrogenic effects of BPA, known amongst the activists as ‘endocrine disruption,’” explains Dr. Ross. “Dr. vom Saal immediately attacked the study, of course, claiming that the species of rats used was inappropriate. Britain’s top reproductive endocrinology expert Dr. Richard Sharpe defended the study, and Dr. Earl Gray, the EPA’s Senior Reproductive Toxicologist, refuted all of Dr. vom Saal’s arguments point by point, so it was pretty well established that the study was valid and that the anti-BPA crowd simply refused to accept the results.”

    (my emphasis! hah!)

    Shame on you, Trevor Butterworth.

    - pD

  12. SF Mom and Scientist says:

    @passionlessDrone – “I am interested in your thoughts concerning what we do seem to observe in humans; the higher your BPA levels, the more likely it is that you will suffer from heart disease or diabetes.”

    This is certainly not my field of expertise. However, one thing I have read is that our largest exposure to BPA is through canned foods. Therefore, those with the highest levels of BPA would possibly also be those who eat the most canned foods, which have high levels of sodium, which would account for the high levels of heart disease. Also, I would imagine that people who eat most of their food out of cans don’t eat a very healthy diet in general, so that might account for the increased rate of diabetes.

    This obviously does not let BPA off the hook, but I thought it was an interesting point. Anyone with more knowledge on this subject out there?

  13. Prometheus says:

    My biggest concern with this report is that is raises the spectre of legislators, filled with concern, rushing off to “do something!”

    Too often, politicians read reports like this and “spring into action” without the slightest idea what to do or where to go. It is action without direction, energy without grace, a random shot with the hope that the target will be somewhere in the line of fire.

    Ready! Fire! Aim?

    The problem when regulations and laws are made before the science is clear, that we eventually end up with regulations that are behind (or, more often, lateral to) the science. And once you have a law and a bunch of regulations in place, you have a bureaucracy that is highly resistant to being told, “Ooops! We were wrong about that – never mind!”.

    Prometheus

  14. David Gorski says:

    The problem is, Prometheus, that the science is rarely that clear when it comes to environmental issues. There is always uncertainty–often a lot of uncertainty, at least more so than many other areas of science. Waiting for the science to be crystal clear is very often a prescription for doing nothing, which could potentially be every bit as harmful, if not more so, than ill-conceived rushes to “do something.” In a way, one could easily liken the environmental contribution to cancer to anthropogenic global warming in that the science behind AGW also has a fair degree of uncertainty. Demanding ever-higher levels of certainty there is a prescription for inaction.

    That being said, it is entirely reasonable to ask: Where should the balance be, and what level of uncertainty is low enough that regulation is desirable? These are both tough questions. The ACSH, for instance, makes it its specialty to play up the uncertainty, exaggerating it if necessary, in order to encourage inertia and inaction. In contrast, some activists exaggerate the certainty, in order to encourage action. Determining where the balance is is a tricky scientific question. Determining what level of risk and what uncertainty about that risk is low enough that regulation is desirable is an even trickier political question.

  15. Harriet Hall says:

    As I understand it, BPA itself is rapidly metabolized and when you read that someone’s BPA level was high, it isn’t the endocrine-disrupting chemical that’s being measured but an inactive metabolite.

  16. qetzal says:

    cervantes writes:

    The headline is that the panel claims that environmental exposures — by implication at least, meaning mostly to human-produced chemicals — make a far more important contribution to the burden of cancer than has been recognized. This has long been what I must, sadly, call an article of faith among environmentalists, but the report actually does not come to that conclusion, nor does it present any direct evidence for it. This spin must come from a press release, is the only conclusion I can make.

    Actually, the spin starts in the report itself. The cover letter from Leffall & Kripke to the president states:

    The Panel was particularly concerned to find that the true burden of environmentally induced cancer has been grossly underestimated.

    As you point out, the rest of the report is a bit more careful to acknowledge that we’re not really sure what fraction of cancers are due to environmental or occupational exposures. The authors should have been similary judicious in the cover letter. Overselling the science is always a bad idea.

  17. Zoe237 says:

    “The problem is, Prometheus, that the science is rarely that clear when it comes to environmental issues. There is always uncertainty. Waiting for the science to be crystal clear is a prescription for doing nothing, which could potentially be every bit as harmful, if not more so, than ill-conceived rushes to “do something.””

    That’s what I was wondering, because it really seems like epidemiology is really murky and hard to find straight answers, particularly concerning long term exposure. Look how long it took for people to admit that tobacco is carcinogenic.

    It seems like the main drawback to limiting possible carcinogenic exposure is money/political reasons. And environmental factors should receive a lot of attention even if they are small, because unlike genetics, it’s something we can actually address.

  18. bluedevilRA says:

    Dr. Hall, do you have any sources? Just to be clear, I am not being snarky (that was the theme of Friday). I struggle to find good science on the subject of BPA. I think everyone’s judgment has been clouded by the firestorm of fear that ripped through the populace.

    Someone actually came up to me randomly one day and criticized my use of an old Nalgene, which had BPA in it. I guess that is how smokers feel when they are publicly chastised.

  19. Harriet Hall says:

    bluedevilRA,

    My source was Steven Hentges on a blogger briefing call with Steve Novella and others. You can go to http://getbetterhealth.com/?s=bpa and scroll down to the “Are Plastic Products Safe? section where there is a link to the entire interview.

  20. Ash says:

    @SF Mom and Scientist – I agree with your comment about BPA exposures likely being associated with poor diet; while it doesn’t mean that BPA isn’t causing harm, it’s hard to make the case that adverse effects correlated with high BPA concentrations in urine are automatically caused by BPA.

    @Harriet – you’re generally correct that BPA is rapidly metabolized. There is, however, some evidence that it isn’t metabolized very well in baby rats, so it has been suggested that human babies also might not metabolize it. That’s why I’m generally supportive of phasing out BPA in baby bottles and baby formula, but don’t personally see a need to panic about it in everything else yet. Unfortunately BPA has become very politicized and it’s hard to sort out the good studies from the bad studies from the studies that may be good but are being used for the wrong purposes (e.g. environmental groups proposing exposure limits based on subcutaneous injection studies).

    Getting off the BPA issue, the point raised in the original post about childhood exposures to carcinogens is also very important. There are some data to suggest that, at least for some genotoxic carcinogens, fairly short-term exposures that occur early in life may be as potent as long-term exposures later in life. Regulatory agencies are starting to address this, but the traditional carcinogenicity studies don’t provide the data necessary to really look at how early life vs. adult effects differ.

  21. bluedevilRA says:

    Great! Thanks a lot. It’s hard to remember what life was like before I discovered SBM. I must have lived in a dark, boring, reading CNN in the morning cave. Nothing beats starting a day off with SBM, Orac, and Neurologica.

  22. JMB says:

    “The adoption of a new “precautionary, prevention-oriented approach” to replace our “current reactionary approaches in which human harm must be proven before action is taken to reduce or eliminate exposure.”

    To me, that sounds too much like,

    “The process with which our analysis was conducted represents an important advancement from evidence-based to evidence-informed medicine,” from the USPSTF.

    http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=hsevidsyn&part=A58706

    It is dangerous to mix science and politics. I would be very wary of any change in approach to our decision making advocated by a government funded panel. I still prefer the American Cancer Society response. If you want scientific consensus, you need a structure that will incorporate a larger number of scientists with a broader variety of expertise, but a core of scientists actively involved in treatment of patients. That structure is provided by the ACS. There are many mathematical/computer modeling techniques used in epidemiology that in my humble opinion, have not been adequately examined.

    Science should provide checks and balances to the political process, not a blank check for regulation.

    I do agree with greater precaution for food products for children, and greater caution for use of radiation in diagnostic procedures.

  23. TrevorButterworth says:

    Dr. Gorski, I would caution accepting the pump handle as an dispassionate source for information about BPA. As both Earl Gray, the EPA’s Senior Reproductive Toxicologist, and Richard Sharpe Chairman of the UK’s Endocrine Disruptor Expert Panel, have noted, the postings by Sarah Vogel, a historian allied with the position of Frederick vom Saal, about insensitive rats and failed positive controls rendering the regulatory research on BPA null are wrong.

    As Gray notes in a forthcoming letter in Toxicological Sciences:

    The insensitive strain argument “has been used for almost a decade in some quarters to try to dismiss every well-conducted rat study that obtained negative results with BPA. It is based on a failure to recognize the basic endocrinology underlying the cellular and molecular basis for tissue-specific responses to estrogens in different strains of rats… It is evident that the degree of estrogen sensitivity varies from tissue to tissue and no single rat strain is more or less sensitive than another for all traits…”

    “Several expert panels have addressed the ‘insensitive strain’ argument and dismissed this as being without “scientific merit” (Canada 2008; Chapin et al. 2008; National Toxicology Program 2008; Scientific Panel on food additives 2007).

    It goes on at considerable length. [http://toxsci.oxfordjournals.org/cgi/search?fulltext=vom+saal]. It is perhaps the most detailed exposition of the failure of research to prove that there’s any risk from BPA.

    Here’s what Sharpe told me in a recent interview when I asked him about Vogel calling him “simpleminded” and “theological” on the pump handle:

    “I consider the insensitive strain/lack of positive controls argument is an attempt to divert arguments away from important issues and down a sideline. In any case… these criticisms are spurious.”

    He also noted the problem with the ongoing failure to replicate the original studies advancing the hypothesis that low doses of BPA cause harm.

    “…if a study is not repeatable in a second lab then it is not robust. Even if there was some substance in the arguments about sensitive strains, then please will they show me the data that says that these are more appropriate models for humans – without recourse to the fallacious contraceptive pill argument. I do not have an axe to grind with BPA and I honestly remain open to being convinced that it poses a health risk to humans – but based on the present evidence for estrogenic effects, I just don’t see an issue. But I reiterate – I am completely open to being convinced otherwise, especially if any new data can at the same time explain away Earl Gray’s data and that of other large (negative) studies”

    If you want to read more about the war over BPA in the leading toxicology journal – click on this:

    http://stats.org/stories/2010/bpa_debate_apr7_10.html

    As for passionlessdrone’s comment that I should be ashamed at being praised by the ACSH, I am mystefied. On the issue of BPA, I have interviewed the scientists who undertook the regulatory assessments – from EFSA to the NTP, EPA and NSF International. All vehemently disagree with vom Saal. But why not click on the links to Sharpe in the original post, and Gray et al in this, and point out why they are wrong instead of attacking me for merely pointing this out with links to the studies?

    As for SF Mom and Scientist, the study you refer to is Melzer et al, which claims to have replicated a 2008 study by the same team at Exeter university (Lang et al) showing a link between BPA levels and heart disease.

    The original study, however, was dismissed by the European Food Safety Agency (Europe’s FDA) for being cross sectional and thus unable to prove causality, something the researchers were open about (but naturally the media covering it failed to give due emphasis to). “The cross sectional nature of the associations reported need to be treated with caution, as it is theoretically possible, for example, that those with cardiovascular disease change their diets in such a way as to increase BPA exposure.”

    There are some interesting problems with Melzer et al. Other endpoints the researchers had previously measured ended up losing statistical significance. Was this due to a decline in BPA urinary concentrations from 2003/4 to 2005/6 (the two NHANES datasets they used) – and more importantly, could the extent of the decline really be responsible for such differences? What of the problem of self-reporting accounting for such changes in outcome?

    Similarly, the lack of variance in BPA levels between individuals in each dataset also raises an interpretative problem: how could exposure differences so small between people result in health outcomes so different? The Exeter researchers speculate as to possible reasons for these outcomes, but the absence of biologically plausible explanations is glaring.

    The Exeter researchers also appear to have pooled results from both datasets to confirm the earlier findings. But you can’t statistically combine existing evidence with new evidence to support existing evidence. This requires an independent dataset.

    This study generated a lot of attention in the UK; I again point you to Sharpe’s view on the matter, this time from an interview in the Sun newspaper:

    ‘it is most likely that this association is diet related, ie those with the disorders have a diet containing more sugary drinks from bottles/cans containing the chemical. Recent animal studies have not shown that bisphenol-A exposure causes these problems under experimental conditions. Furthermore, we know that the main causes of these disorders in humans occur over a lifetime, so just finding an association at one point in life when the disease is present is unlikely to show cause and effect.”

  24. Ray Greek MD says:

    Hi David
    Nice article. Thanks for the summary!
    One question. You state: “the correlation between cell culture studies is even more unreliable than that of animal studies.” If you have the time, could you provide some references for that. As you know I am interested in the subject.
    Thanks!
    Ray

  25. ImperfectlyInformed says:

    Thanks for the informative article David. I’ve looked into the BPA issue quite a few times and it does seem fairly difficult to get to the bottom of it. The rat studies are odd, but the human studies are what worries me, and that’s ultimately what it comes down to. Not long ago an occupational study found increased risk of sexual dysfunction (http://humrep.oxfordjournals.org/cgi/content/abstract/dep381v1), and this comes after various other human studies. Notably the occupational-exposed group was exposed to more chemicals in general, but it’s still a suspicious result.

    I’m skeptical of Harriet’s source on testing BPA and an inactive metabolite. Why use as a source a blogger interview? My impression from the literature I’ve read is that most people do have actual, testable BPA in their urine, and that with a half-life of 6 hours and continuous exposure, most people carry a continuous BPA load in their bodies (http://ehp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info:doi/10.1289/ehp.0900604).

  26. ImperfectlyInformed says:

    For a decently detailed discussion on the testing for BPA issue and metabolization, see Does Rapid Metabolism Ensure Negligible Risk from Bisphenol A? (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2801165/).

  27. ImperfectlyInformed says:

    Err, turns out Harriet’s Halls’ source (http://getbetterhealth.com/are-plastic-products-safe-an-overview-of-the-science/2009.12.01), Steven Hentges, is just the PR guy for the American Chemistry Council. Note that the ACC is not the same as the American Chemistry Council. Huh. That interview is notably lacking anyone with qualifications in BPA who does not have a huge conflict of interest. Steve Novella is not an appropriate responder; should have got one of the numerous individuals who have published on BPA. I would have liked to hear a balanced discussion between two experts on either side of the issue. Did nobody in that call think the set up was a little odd?

    Anyway, I think it’s unfortunate that we’ve gotten to sidetracked on BPA since there’s probably a lot of other interesting issues on this topic.

  28. SD says:

    Govorit’ Cde. Gorski:

    “Thanks, all.

    Of course, I’m just waiting for SD to show up and do his radical Libertarian schtick. If he’s reading, I know he won’t be able to resist. It’s like red meat to a dog.

    Countdown 5…4…3…2…1…”

    Nah, this one wasn’t that good. You’re not in impressive form here, and the subject matter is basically background noise – basically just your garden-variety feel-good nannyism that will lead to no effect whatsoever other than to consume tax dollars by the hundred million. Yawn. Tell me something I didn’t know.

    Don’t worry, though; when you get particularly offensive, or say something interesting, I’ll be there.

    Nice to know you’re still thinking about me from time to time, though. >;->

    “priiiiiivate eyes *clap* they’re watching you *clap clap*”
    -SD

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