Posted by: Geoffrey Meadows | October 1, 2008

Just Keep Trying!: Cancer Studies and the Threshold Argument

There is an argument that goes something like this: Yes, we can continue to release toxins into the environment because at very low levels they do not produce cancer, and there are all kinds of chemicals in our environment anyway which at low levels do no harm at all.

This is what’s known as the threshold argument.  It argues that below a certain threshold no harm is done.  There is no proof that such a threshold exists, particularly for cancer.

A more popular theory, and the one which is used in actual science to determine risks (by the EPA and others) is the linear no-threshold theory.  It states that the incidence of cancers will go down in direct proportion to the amount of exposure (or dosage) until both the numbers of cancers and the threshold reach absolute zero.  It’s a straight slanted line on a graph.  Since the threshold in this theory is a straight line an is as close to zero as possible it is known as the linear no-threshold theory.  In this theory, any exposure, no matter how small could become a cancer, it’s just that at the low exposure levels the incidence of cancers will be small.

A third theory, which we might call the saturation theory, proposes that at low dosages (proportionately) more cancers occur, but at higher dosages, saturation occurs and not-as-many cancers (proportionately) will be the result.

Some evidence for this third theory comes from a study of radiation-caused cancers using an instrument called a charged-particle microbeam.(1)  This instrument can fire a single radioactive alpha particle with precision at a cell.  It can be pointed at either the cell’s nucleus where the DNA is, or outside the nucleus in the part of a cell that does not have the DNA (also called the cytoplasm).  Single alpha particles fired into the nucleus or into the cytoplasm both resulted in cancers.

It turns out that when 2, or 4, or 8 alpha particles were fired into a cell the number of cancers produced was not proportionate to the numbers of alpha particles.  The results seemed to suggest that the cell had reached saturation.  The greater effects (proportionately) in this experiment were experienced at the lower levels of radiation.

Now, it is a jump from radiation to toxins, but the possibility exists that cancer may react at low dosages even at a higher rate than the linear no-threshold argument would suggest.

So is there a threshold at which no cancers will be the result?  There may be – anything is possible – but there is no proof of it.  And there are reasons why we don’t have the proof.

Most of our experiments with exposure to toxins are done at high exposures with lab animals.  If a chemical is fed to lab animals at very high dosages and some of the animals develop cancers, we say there is a risk of cancer with this chemical.  All our data is high dosage data.

To test the cancer-causing ability of such a chemical at low dosages or over long periods of time would be much more difficult.  Since the exposures would produce less cancers statistically, we would have to use more animals, many more animals, to detect the difference.  A study of low dosage, long term exposures would involve the use of thousands of lab animals.  This makes such experiments costly and difficult to perform.

Molecular biology may one day make it possible to determine the exact chemical that caused a cancer.  But until that time comes, we have to make do with what is possible now.  That means making decisions about what is risky and what isn’t with very little data or proof.  Do we take a cautious approach or not?

There have been studies that have tried to make the connection between specific toxins in the environment and cancers such as breast cancer.  One notable study on breast cancer is the Silent Spring Institute’s Cape Cod Breast Cancer and Environment Study.

As it turns out, looking at cancer rates geographically reveals that some areas have higher rates of cancer than others.  No one is sure of all the factors involved.  When many cancers of a specific kind appear in a given area it may be called a cluster.  I won’t go into all the reasons why clusters are hard problems to solve.  Mainly, it is the problem of trying to account for the cancers statistically when there is so much chance variability to begin with.  It’s hard to know what’s chance and what’s the specific cause.

On Cape Cod in Massachusetts, breast cancer rates are higher than they are in the rest of the state.  At first it was thought that pesticides used in the cultivation of cranberries on the Cape was responsible, but, as often happens with these studies, the connection could not be proven.

It was thought that the pesticides used to protect the cranberry crop had leached into the ground water and that the people of Cape Cod were exposed to it mainly through the water supply.  Cancer can take 20 or more years to develop, and 20-year-old dosages of the pesticide in the water were impossible to determine retroactively, so the connection could not be made.  But the study is ongoing.

A more credible attempt to look at pesticides as a source of cancers and disease is the Agricultural Health Study (done by the National Cancer Institute, the National Institute of Environmental Health Sciences, and the EPA).  It studies farm workers who have worked with pesticides and have been much more exposed to them.

Farm workers, however, seem to have fewer than normal cancers.  It is believed this is because they are more seldom smokers and also presumably because they work out of doors and get plenty of exercise.  One would think then that if certain cancers show up more often among them that this would be an indicator of other sources of cancer or disease.

Because of the long germination times of cancer only preliminary results are in as yet.  It turns out that exposures to pesticides in farmers are correlated to higher rates of prostate and ovarian cancers among others.(2) Exposures to organophosphates was connected to higher rates of hearing loss.(3)  It has been shown that chlorpyrifos – an insecticide – correlated with depression and suicide.(4)  So what has been found already, albeit preliminary, shows to some extent how these chemicals may be affecting us when we come into contact with them.  The low levels of the general public’s exposures to these chemicals may protect us more than if we used these chemicals several times a year and came into close contact with them, but we may not be immune from them, even at a distance.  This could especially be the case with cancer.

My question is, why, when we already have evidence that these chemicals produce cancer in lab animals, we would continue to release them into the air, land, food supply, and water around us?  Is it simply because we don’t yet have the smoking gun at the genetic and molecular level that our hands are tied?  Our government still relies on studies done by the chemical companies themselves to determine if a certain chemical is safe.  We must rely more on independent research.  We have to fund it appropriately, and we have to do the research we are funding.

What happens when a chemical is found to be unsafe?  There has to be a clammoring of the public before it can be removed.  In Europe, many of the chemicals we use here have already been declared unsafe.

To conclude, there is a chemical, tributyltin, a toxic metal, that has been used in paints covering ships’ hulls to keep them clean of barnacles and algae.  This post is about cancer-causing toxins, but tributyltin didn’t cause cancer.  I’m using it here as an example of what can happen when we keep trying.  What happened was that in the course of coming into port some of the paint with tributyltin chipped off the ships or leached out from the paints and poisoned the fish and other living things in the port and along coasts.  The World Wildlife Fund (WWF) and some concerned shippers (Wallenius Wilhelmsen Logistics and the 2003 Group) got together and started to use other chemicals or hull-cleaning strategies.  Now due to a decade of efforts by the WWF there is a treaty to outlaw tributyltin.  Other strategies will be used now to keep ships’ hulls clean.  Business continues.  But it’s business with a conscience.  The fish and other living things of the ports and coasts are better off, and so are we.  Because we tried.  We did something.  We had the faith in ourselves and our ability to get the job done in a better way and we did it.  This is the essence of what I want to say about the toxics problem.

There is an old saying: If something is broke, fix it, and if it’s still broke, fix it again.  There are indeed many safe, or at least safer, chemicals out there.  If we find that a chemical causes cancer, let’s work on developing something else!  But let’s not just sit around waiting for the chemical companies to do it themselves.  Let’s get aware and press our government to keep studying these chemicals (with independent  studies).  And let’s keep pressing the chemical companies themselves to come up with something better.  Because we know it most likely will not happen unless they are pressured.  That’s just the system.

We’ll have made the world a better place to live in, and we’ll feel better about our footprint in it, too, if we — Just keep trying!

**********

(1)  For “targeted alpha radiation on cells” see The Proceedings of the National Academy of Sciences (U.S.A.), Cell Biology Section, vol. 94, pp. 3765-3770 (1997); vol. 96, pp. 4959-4964 (1999); and vol. 97, pp. 2099-2104 (2000).

(2)  Alavanja MCR, Sandler DP, Lynch CF, Knott C, Lubin JH, Tarone R, Thomas K, Dosemeci M, Barker J, Hoppin JA, Blair A. (2005). Cancer Incidence in the Agricultural Health Study. Scand J Work Environ Health, 31 (S1): 39–45.

(3)  Crawford JM, Hoppin JA, Alavanja MC, Blair A, Sandler DP, Kamel F. (2008 ) Hearing Loss Among Licensed Pesticide Applicators in the Agricultural Health Study. Journal of Occup Environ Med. Jul;50(7):817-826.

(4)  Lee WJ, Alavanja MCR, Hoppin JA, Rusiecki JA, Kamel F, Blair A, Sandler DP. (2007) Mortality among Pesticide Applicators Exposed to Chlorpyrifos in the Agricultural Health Study. Environmental Health Perspectives, 115(4): 528-534.

This whole post has been derived from a book on environmental health hazards that I highly recommend.  Especially if you don’t care for my rambling writing style, the book is very well written, and a great boon to anyone trying to understand the epidemiology and statistics of environmental hazards.  I think it is a must read for anyone in the environmental movement.  It’s straight science and very balanced and helpful.

How Much Risk?: A Guide to Understanding Environmental Health Hazards, by Inge F. Goldstein and Martin Goldstein. — Oxford: Oxford University Press, c2002.

The Silent Spring Institute’s Cape Cod Breast Cancer and Environment Study  –  http://s20428.gridserver.com/our-research/communities-high-breast-cancer-rates/cape-cod-breast-cancer-and-environment-study

The Agricultural Health Study  –  http://aghealth.nci.nih.gov/results.html , reading just the abstracts to these studies reinforces the idea that these chemicals have many effects, largely unknown; www.cancer.gov/cancertopics/factsheet/agricultural-health-study

For a recent article on the tributyltin solution, see www.sciencecentric.com/news/article.php?q=08091746 .

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Responses

  1. I had not heard of the saturation theory. Have you heard of hormesis? It’s a theory that very low levels of exposure can actually be beneficial. It was reportedly discovered because of radiation exposure.

    Personally I’m skeptical. If there is a demonstrated effect I wouldn’t be surprised if it’s because the immune system is reacting to the perceived threat.

    I had just recently stumbled across the Silent Spring Institute’s website myself.

    And here’s a final thought for you. Researchers are now looking at thirdhand (!) smoke exposure. It’s almost analogous to toxins that had been trapped being released from trees during forest fires and from melting glaciers and permafrost.

  2. I’m always skeptical myself when I read of plants that eat up toxins, etc. So now the toxins are in the plants; where do the toxins go when the plant dies and decomposes? (This is your “thirdhand” exposure.)

    It seems, short of actually chemically changing these toxins to forms that are not toxic, we’ll only be safe from these chemicals when they’re locked safe in rock and are buried underground – like mercury is in coal. But in coal’s case we’re burning the coal and bringing back the toxins!

    Thanks for your comments.

  3. There is a difference between chemicals that have been absorbed by trees over several decades or centuries (same for those deposited in glaciers) and intentionally using plants (or bacteria and other microbes) to absorb toxic chemicals and convert them to something else.

    With trees and glaciers the change in rate of release vs. rate of accumulation is extremely important. What were very small amounts have now accumulated such that rapid melting of glaciers (and death of trees, whether through forest fires, drought, etc.) results in much larger amounts being released over a much, much shorter period of time. (Which is one way in which global warming can actually affect people’s health.)

    Using bioremediation (I think that’s the term) to break down toxics into less toxic substances is much easier with organic compounds. Metals can be much more problematic, but if you figure out how to make a metallic substance less bioavailable you have reduced the chance that it will be absorbed by other plants or animals. Otherwise, yes, you’re absolutely right, when the plants where the materials are sequestered die, they will then decompose, releasing the toxics back into the environment.

    As examples of how metals might be handled, consider iron, chromium, and mercury. Iron is a necessary nutrient since it’s required for hemoglobin, yet people can suffer from iron poisoning. (The same is actually true of many vitamins. Certain doses can be toxic.) Hexavalent chromium is known to have very nasty effects. Trivalent chromium less so. And mercury’s bioavailability depends on whether it’s in an organic form (such as methylmercury), elemental mercury, or an inorganic compound. Some forms are much more toxic.

    The mercury in coal was deposited before the organic matter turned into coal over thousands and millions of years. In contrast, we’ve been releasing it by burning coal in significant quantities over at most a few hundred years.

    Aside: I’ve read recently that people are more likely to be exposed to BPA in a free state (that is, much more bioavailable) from receipts than from plastic bottles, where the rate of leaching is relatively low because the BPA is bound into the plastic.

    But with respect to burying toxic chemicals, one of the things that McDonough and Braungart discuss in “Cradle to Cradle” is that our approach to extracting materials from the earth, using them, in some cases “downcycling” them, and then burying them is not only unsustainable, but also extremely wasteful. (Which is why they advocate eliminating the concept of waste.)

    At some point, as in the movie “Wall-E,” we’re going to run out of room.


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