Shouldn’t the Dose Make the Poison?
Crop Duster
Are organics always less toxic than synthetics?

Editor’s Note: Why should a contrarian essay entitled “Chemophobia” be broadcast here? Because open debate is essential, and the author has many of his facts straight. The main point, toxicology’s foundation is dose equals poison, and this foundation is often ignored, is valid. Actuarial arguments, framed in actuarial terms, are not callous attempts to “use comparison to deprecate the risk,” they are essential to setting any rational strategy. A deadly poison that you would have to eat three barrels a day of for thirty years to have a 50% elevated risk of some disease, is not hazardous whatsoever if you merely eat three meals a week of it for thirty years.

If the risk of chemicals were put in perspective, Americans would have just gone in and cleaned up the superfund sites, instead of spending hundreds of billions in courtroom fees and salaries for bureaucrats, and done almost nothing. This should make anyone angry.

A distinguished chief scientist once told me his company was developing organic pesticides because that’s where it was easier to get public grants, the approvals were streamlined, and the marketing more effective. He asserted there are many extremely dangerous organic pesticides, that persist more and are far more toxic than available synthetic pesticides. Would DDT be safer and cheaper than current alternatives if it was properly applied? Dose definitely made the poison in the case of DDT, which was applied in doses 100 to 1,000 times higher than could have been effective.

Polemical, indignant, provocative, diametrically opposed points of view are difficult to take, but conventional wisdom should always be challenged. Are we making a mistake to not again use DDT? Wasn’t overuse, not toxicity, the issue with DDT? Isn’t it true that you shouldn’t apply the precautionary principle to everything? Exposing the absurdities that underlie anyone’s self-serving rhetoric helps us to distill what is valid. Are all GMOs really bad? What about vitamen A enriched rice that saved the eyesight of ten million children?

The dose makes the poison, not the label. Are we drowning in carcinogens, or are we just suffering from chemophobia? Read on for hard facts, and you decide. – Ed “Redwood” Ring

Paracelsus, a 16th century alchemist and physician, invented the science of toxicology.

Today, if you are a graduate student in toxicology at major university, you need answer only one question correctly during your final oral exam to get your PhD: The professor asks: what did Paracelsus have to say about potentially toxic chemicals? You answer, “umm, the dose makes the poison??” Huzzah! Here’s your PhD! “The dose makes the poison” means that of the thousands of various chemicals we ingest from breathing and eating, i.e. living, practically all of them are toxic if ingested at a high enough dose. For example, virtually all the various vitamins and minerals we need in order to survive can be toxic if taken in excess. But, excess may mean amounts far higher than one could possibly ingest on a daily basis during your lifetime, no matter how hard you tried.

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This brings us to the topic of chemical carcinogens. In 1958, Congress inserted the now infamous Delaney Clause into the Food, Drug and Cosmetic Act. It prohibited the presence in foods of any synthetic chemical (pesticide, food additive, etc.) in any amount if that chemical had been found to cause cancer in laboratory animals (1). Notice the law said synthetic chemical (more about that later). This law is still in effect (loosely, because even EPA regulators understand that zero is impossible), even though today’s analytical techniques enable chemists to detect any chemical of interest in food or water at levels a billion to a trillion times lower than was possible in 1958. Back then, if you put a gram of DDT into your backyard wading pool and sampled the water, you could detect the DDT using analytical techniques available at that time. Today, that same amount of DDT could be detected in a water sample from Lake Michigan!!

It was in 1959 that we had our first national cancer panic in the U.S. Traces of a synthetic herbicide that was a carcinogen in rodents were detected in cranberries, so nobody ate cranberries that Thanksgiving and the industry suffered mightily. This was OK with me because I never liked cranberries anyway. It was pointed out at the time that one would need to eat 15,000 pounds of cranberries every day of one’s life to match the dose rodents were given, but no one seemed to care. There have been many more such media and special interest group (including scientists who love grant money) inspired scares since then: dioxin everywhere, nitrites in bacon and sausage, alar in apples, cell phones causing brain cancer, etc. etc. When I was a kid in the 50s, sitting too close to those newly available “television sets” was widely believed to be a cancer risk because of exposure to the T.V. tube “rays”. Hey, cancer is scary, and very little was known at that time about the biochemical mechanisms involved in cancer etiology, and even less about how our immune system defends us against it.

So by 1959, the major tenet of toxicology, “the dose makes the poison,” was tossed out the window from 100 stories up, crushed like roadkill on the Jersey Turnpike.

After that, the man who got the carcinogen ball really rolling was the noted U.C. Berkeley chemist Bruce Ames. He invented a quick, easy, and cheap test (strangely, now called the “Ames test”) to determine if any chemical of interest can cause mutations in the DNA of bacteria in vitro. If mutations were observed, then that particular chemical was considered likely to be a carcinogen in lab animals (usually it is, but not always). Dr. Ames became a campaigner for environmental groups wanting to ban various pesticides and herbicides. Today, he has totally changed his position, but that’s another story for next time.

By the mid 1960s, rodents bred to be cancer prone (GMO rats and mice) became commercially available for carcinogen testing (it is very difficult to induce cancer in normal rats and mice).

Here’s how testing a chemical is done, then and now:

1) Do the Ames test on some pesticide, food additive, preservative, or whatever and find it to be mutagenic. This means the bacteria’s DNA in a gene is altered in some way or other.

2) Determine what is called the “maximum tolerated dose” (mtd) of this mutagenic chemical in your rats or mice. The mtd is the amount of the chemical that almost kills the rodents in a single dose. It is also a dose that, depending on the particular chemical, can be thousands to millions of times higher than a human could ever eat in a lifetime. Next, feed the rodents just 10% less than that dose daily for their entire lifetime, usually between one and two years. If you really care if your research might be relevant to reality (and if you have enough grant money because these tests are very expensive), you can also include groups of animals fed only the mtd and rarely even the mtd. Oops, I forgot to mention, if the test chemical is so noxious that the rodents won’t eat their food, use gavage, i.e., inject the chemical into their gut every day. This technique obviously mimics human exposure to pesticides, right?

3) After a year or two, sacrifice the animals and count up all the various tumors they might have in various organs. Most of the rodents in the control group, fed a normal diet, will have various tumors anyway because they have been bred to be cancer prone. So, if the test group of rodents fed some noxious chemical at the highest dose has an average of, say, four tumors per animal in a particular organ, and the control group has an average of only 1 tumor per animal, then the chemical being tested increases cancer incidence by 400% !!. Call the media!

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Next, the Food and Drug Administration (FDA) will classify this test chemical as a possible human carcinogen, as if rodents were nothing more than miniature humans, and establish acceptable levels of the chemical in foods using a HUGE margin of safety factor based on a very faulty mathematical model. Sometimes a test chemical will induce cancer in male rats but not in females, or visa versa. It doesn’t matter. Even if the test chemical caused cancer at the maximum tolerated dose (mtd), but did NOT result in ANY excess cancer at HALF the mtd (remember, the dose makes the poison?), the chemical will still be classified as a possible human carcinogen subject to government regulation. Remember, maximum tolerated dose is defined as an amount which will almost kill you with ONE exposure! Now, various “consumer safety groups” and professional fear mongers will launch scare attacks in all the “we love to report this kind of stuff” news media. The EPA will decide what levels are acceptable in the air, water, soil, etc., based on politics more than science, and the FDA will decide acceptable levels in foods based on politics and their faulty mathematical model.

Now let’s consider known human carcinogens. There are very few of these, but I will give you an example of how they came to be known, and it’s not because of rodent testing. About 60 years ago, a huge experiment was started in which millions of human volunteers, at their own expense, were exposed to really high daily doses of a suspected carcinogen over a period of at least 25 years. At the end of the test period, their cancer rates were compared to the rates found in a group of millions of people not exposed to that suspected carcinogen. It turns out that the exposure group had lung cancer incidence at least 10-15 times higher than the non-smoking group! Other types of cancers were also significantly increased. Oops, I forgot to say it was cigarette smoke that was the suspected carcinogen! Obviously, such controlled experiments using some chemical cannot be ethically conducted on humans in a laboratory setting. Because rodents go crazy if forced to breathe noxious stuff like cigarette smoke, it has never been shown that rats can get cancer from breathing it. So we have a situation where we know cigarette smoking causes cancer in humans, but we can’t be sure it does so in rats. Is there some irony here?

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There are only a few dozen known human carcinogens, and it takes long term exposure to them to increase cancer risks. Unarguable statistics (NOT rodent testing) have shown that the coal tar chimney sweeps are exposed to daily can cause cancer of the scrotum. If inhaled over a long period, asbestos fibers increase risk of lung cancer and lung disease. Ditto for uranium miners who inhaled lots of silica dust and radon down in the uranium mines in the 1950s and 60s. Mustard gas can cause cancer in doughboys (WW I) and Saddam victims, if the dose doesn’t kill them first. But the absolutely most dangerous, for sure, human carcinogen of all is something that each and every one of us is exposed to almost every day of our lives (unless you live in Seattle anytime or San Francisco in the summer). It’s called sunlight. You want some type of skin cancer? Hang out in the sun as much as possible all your life, don’t use sun block, and look really tanned and beautiful.

But let’s put this stuff in perspective. Asbestos fibers and silica dust need to be inhaled often over a period of many years to increase cancer risk. Asbestos sitting in your attic as a fire retardant insulation is no danger to anyone unless you insist on stirring it up and breathing it every day. Silica is sand, so are you afraid to go to the beach? You don’t inhale sand, but if you’re drilling down in a mine and stir up lots of silica dust and inhale it, you definitely increase lung cancer risk over the years. Even though long time smokers have a risk for lung cancer 10-15 times higher than non-smokers, 85 to 90% of those smokers never get lung cancer, although they may not be able to climb a flight of stairs without panting. And consider sunlight (the ultra violet portion of it). If the EPA could regulate our exposure to UV light using the same criteria it does for all the various pesticides and food preservatives that are carcinogens in rodents, we would all be mandated, like vampires, to stay indoors during daylight hours. We could not go out in daylight without using 200 power sun block, while wearing head to toe clothing and big floppy (government approved) hats! Hawaii would be off limits to humans! I’m not making this up, folks! So the next time you visit the tanning parlor or lie out on the beach, be absolutely sure to avoid eating any snacks containing those evil preservatives!

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You are still not convinced that the hundred-fifty or so chemicals found to be carcinogenic in rodents really shouldn’t be all that worrisome for us humans at levels of exposure that are related to real life?

Remember in paragraph two above how Congress mandated, with the Delaney clause (1958), that amounts of synthetic chemicals in foods must be zero if they caused cancer in rodents? It was not known then that virtually all the carcinogens in our environmental are natural, and that many (probably all) of the foods we eat contain thousands of different chemicals, some of which are rodent carcinogens. Apples, bananas, basil, cabbage, citrus fruits, mushrooms, turnips, and so many more foods we eat all contain chemicals that cause cancer at huge lifelong doses in laboratory rodents. Broccoli, for example, is known to be protective against cancer in humans when eaten at realistic levels over your lifetime, probably because it contains high levels of various natural antioxidants. It also contains at least four different possible human carcinogens based on the wonderful rodent testing I described above. If you ate 10 or 20 pounds of broccoli every day of your life, you just might increase your risk of some cancer or other. At an American Chemical Society meeting, where I chaired a Symposium (and gave a great talk myself, of course debunking the whole rat model), I had lunch with two FDA guys. As we ate our carcinogen loaded broccoli, I asked them “what if broccoli were a new food that no one had ever eaten before and you guys had to review it for approval as a food additive?” They admitted that it could not be approved under the present FDA rules for food use! I’m not making this up, as Dave Barry would say.

Plants have evolved defense mechanisms against attack by various bug, animal, and bacteria predators. They include, “natural” toxic chemicals and pesticides. For example, there are many mushrooms you do NOT want to eat. I know what some of you are thinking, because I’ve been through this with various friends and enemies who all refuse to listen to anything that goes against their green religion. You think that these “natural” chemicals in our foods are safe because us humans have developed an immunity, over hundreds of thousands of years, to these natural chemical toxins and carcinogens, but not to the relatively new synthetic food additives, herbicides and pesticides. That argument is unequivocally, without any doubt, completely wrong. “Artificial” food additives (preservatives) are chemically very similar to natural antioxidants and bioflavonoids found in vegetables, and everyone knows these chemicals are good for you. I know this because I am a brilliant biochemist who helped elucidate just how us humans metabolize chemicals that in the 1970s and 80′s we called “xenobiotics”, i.e., chemicals imbibed from eating, drinking, and breathing that are not native to our bodies.

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In the 1960s, very little was known about how all those thousands of xenobiotic chemicals we absorb into our bodies after we eat were metabolized. Now we know exactly how it’s done. All the foods we eat are broken down in the digestive tract into constituent chemicals that are then absorbed from the small intestine and dumped into our wondrous liver (of all our organs, only the brain is more wondrous). If our liver thinks we can use these chemicals (e.g., amino acids from proteins, sugars from starches, vitamins, etc.) they go into the bloodstream and travel to whatever part of the body that needs them. The thousands of other chemicals that our liver doesn’t think we need, such as drugs, all the chemicals responsible for the flavor and odors of foods, are subject to enzymatic activity that makes those chemicals ready to be eliminated from the bloodstream through the kidneys into the urine. If you feed a rodent or a human any chemical, “natural” or “artificial”, those chemicals will be metabolized in the same way. You can detect the metabolites in the urine, and that’s that.

We will finish this essay with two examples of carcinogen BS. They will either leave you thinking that I am a right wing extremist moron because you yourself are a left wing extremist moron, or your possession of normal common sense will convince you that I am absolutely right and you were really misinformed all your life about these matters:

Benzo-a-pyrene: This chemical is a potent carcinogen in rats. It is created in meats during roasting and grilling in the very tasty browned exterior of the meat. If you like BBQ and roasted meats of all kinds, you will ingest lots of rat carcinogen BaP over your lifetime (often sitting in the carcinogenic sunlight at an outdoor BBQ without any sunblock lotion). Should you never eat roasted meats ever again? Here is how research I did in the late 1970s helped make me feel the way I do today about all these so called carcinogens in the whole food supply and environment.

If you conduct an experiment in which rats are daily fed a diet containing BaP at levels talked about above, then cancer rates in those rats will be higher than a comparable group of rats fed a normal rat diet. But here’s the rub, unknown to biochemists in the 1960′s, a family of remarkable enzymes in the liver of the rodent, and in this case rat livers and human livers are similar, will chemically alter the BaP so that it is easily excreted from the bloodstream into the urine and out it goes harmlessly. One big problem for the poor lab rats, however, is that there is WAY too much of this altered BaP to be excreted all at once. So it then circulates around in the blood and goes through their liver a second time. It is chemically changed again, some goes out harmlessly, but we still have overload. This means un-excreted stuff goes through the liver a third time, and is chemically changed again, and then a fourth (still harmless) time! None of this would happen in a lifetime of you eating your beloved BBQ at extremely lower levels. Once and out is the story for BaP in our livers in real life exposure! But finally, for the overdosed rat, the fifth time through it’s overtaxed liver, a VERY potent carcinogen is created that can react with DNA and initiate the cancer process by mutating a susceptible gene in some organ or other. It you want to know, it is a diol epoxide (us chemists have to use some jargon sometime to sound intelligent. So, does common sense say anything about “the dose makes the poison”?

Finally, consider dioxin, the poster chemical of environmental contamination. The EPA once called dioxin the most potent carcinogen ever! It gained fame after the Viet Nam war because it was a contaminant in the herbicide “agent orange” widely sprayed for defoliation. Since then, there have been zillions of claims from veterans of that war (which I didn’t like at all, and I even marched against it as a good Berkeley hippie!) that exposure to it caused veterans to have increased risk of various diseases, including cancer. Subsequent studies have found no correlation with dioxin exposure and any disease, but many special interest groups still believe it is total environmental evil. What we didn’t know then, but know now, is that dioxin is a natural, ubiquitous chemical in the environment. Every time wood is burned in your fireplace, every time there is a forest fire, dioxin is created and spreads all over the place. If I specifically look for dioxin in virtually any food we eat, using today’s analytical techniques, I will find some. And it will be there at higher levels than the EPA considers safe. This is a really big “so what”, because the levels the EPA thinks is safe for humans are about a gazillion times lower than the level that might actually be dangerous, except to male rats. Remember, those EPA “safe” levels are based on rodent studies, and include a huge margin of safety.

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Here is real life example: In 1976, a catastrophic explosion occurred in a chemical plant in Seveso, Italy. Literally tons of noxious chemicals, including huge amounts of dioxin, were spewed into the air, only to settle into the soil and people’s bodies. Those workers who didn’t get killed by the explosion, but were heavily doused with dioxin, developed a severe form of acne that lasted for several weeks or months and then healed. That’s it! This is when various environmentalists were saying that a gram of dioxin could kill millions of people! Twenty-five years later, according to the most recent review of cancer mortality among Seveso residents, there have been no significant increases in overall cancers in the general population. In fact, it looks like dioxin protects against breast cancer in women. That is probably just a statistical fluke, but who knows when you are dealing with statistics? Ask Viktor Yushchenko, the new leader of Ukraine, how toxic dioxin is. Before the recent democratic elections in his country, his enemies tried to poison him by giving him a huge dose of dioxin. They believed the “conventional wisdom” of the world’s “green” groups that dioxin is really, really toxic. They could easily have killed him with traditional poisons such as arsenic, cyanide, ricin (a truly potent “natural” poison from castor beans) or whatever. Instead, they gave him a really bad case of acne from which he will recover, not need to worry about any future cancer, and be able to lead his nation on to greatness. There will be a part two of this carcinogen discussion in the future. Just keep visiting Ecoworld!

About the Author: Edward Wheeler, Ph.D, is a very old biochemist, who actually conducted pioneering cancer/nutrition research in the 1970′s and ’80′s for the U.S. Dept. of Agriculture. He authored some really, really good research papers in journals such as “Cancer research” and others. So he really, really knows what he’s talking about!!! Wheeler’s earlier essays from the “Monsters in the Closet” series are

Bring Back DDT?, and
GMOs, Salvation or Monsters?

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2 Responses to “Chemophobia”
  1. Roxaanne Jelinek says:

    Great article! Fun creative writing style to discuss serious business.
    The studies cited were helpful and I am better informed and armed against generalizing on toxic foods and chemicals. Hooray for the liver!!

  2. edward wheeler says:

    Thanks for the comment, Roxaanne. If I can convince even one person of the insanity of the carcinogen baloney (of course baloney contains carcinogens!) out there, then I am happy.


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