I would like to thank the ACSH for allowing me to republish this information. I have also added some additional information regarding the science behind using rodent testing as the determining factor in claims of carcinogenicity. RK
Until the 1960’s the standards used by the government to determine safety levels and manage risk were hopelessly imprecise and subjective.
To establish safe levels for substances in the air, water or soil, regulators needed to move from the black/white qualitative approach of either allowing or banning a substance to a quantitative approach of determining how much of each substance might be allowable in each environmental situation. As the health focus on cancer and the fears associated with chemicals escalated, noted University of California at Berkeley chemist Bruce Ames invented a quick, inexpensive test (now known as the Ames test) to evaluate toxicity. His test determines if any chemical of interest might cause mutations in the DNA of bacteria in vitro (in a controlled environment, such as in a test tube or Petri dish). If mutations were observed then that particular chemical was considered likely to be a carcinogen in lab animals.
The Ames test and the development of rodents modified to be cancer-prone led to an ultra-cautions toxicological evaluation and chemical regulatory process. Over the years, what many scientists believe is a convoluted multi-stage model has been developed to extrapolate animal risk to people:
1. Scientists do a biological assay (the Ames test) on some pesticide, food additive, preservative or other chemical to find out if it is mutagenic. It shows whether the DNA of the bacteria is altered in a significant way.Underscoring the relative arbitrariness of this process, the cutoff level is set differently by different agencies from country to country and even sometimes within a country. As in the case of the pesticide atrazine, these levels can vary as much as 100 times. (The European safety cutoff level is 1 part per billion, while the World Health Organization sets it at 100 ppb.)
2. If the chemical is confirmed as mutagenic, studies are then undertaken to determine what is called the “maximum tolerated dose” (MTD) of this chemical in rats of mice. The MTD is the amount of the chemical that almost kills a rodent (or almost achieves another parameter, such as suppressing body weight.) It is a dose that, depending on the particular chemical, can be thousands to millions of times higher than a human could ever ingest in a lifetime.
3. Next, the rodents are fed just 10 percent less than the maximum tolerated dose daily for their entire one to two year lifetime.
4. However, many chemicals cannot be fed to rodents because the substances are so noxious at the dosages given. So scientist often use gavage (forced feeding into the animal’s gut per day, often by injection), which is not how humans are exposed to the chemical, compromising the meaningfulness of the test.
5. After a year or two, the rodents are sacrificed and scientists count up the tumors the animals accumulated in various organs. Most of the rodents in the control group, fed a normal diet, will have tumors anyway because type have been bred to be cancer prone. So, if the test group of rodents fed-or more likely injected with-some 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 one tumor per animal, then the chemical being tested is said to increase cancer incidence by 300 percent. This does not mean that such a study proves a chemical will cause adverse effects in rats, let alone in humans exposed under more realistic conditions. Yet, this finding, designed as a first step in testing a hypotheses, often ends up in a headline or in a media release from one advocacy group or another attempting to use preliminary research to support a cause or movement.
6. Next and often under pressure from the energized media and environmental NGO’s, a political body, such as the European Parliament or the U.S. Congress, or a regulatory body, such as the EPA, will classify and/or confirm this chemical is a likely human carcinogen, as if rodents were nothing more than miniature humans.
7. These agencies then establish an “acceptable” level of the chemical – the EPA calls it “an upper estimate of the risk”- using what’s known as the “dose response curve”, which included a large margin of safety factor based on mathematical models. In moving to this new quantitative approach, government scientists began employing high-dose animal results and low exposure levels experienced by humans.
The result is that the scientific convention of setting one number to represent risk exaggerates the media and public perception of risk. Because only one number results for the assessment process, it is not surprising that, ignoring cautionary guidance by regulators, NGOs and the media select the country or agency with the tightest cutoff and then portray this number as exact, as the best estimate of risk and as predictive of cancer incidence. But that misstates what a cutoff number means. As the EPA notes,
“The actual risk [from exposure to a chemical] may be significantly lower and may indeed actually be zero. It is important to recognize that the use of this model results in risk estimates that are protective, but no predictive of cancer incidence.”Employing this model, a range of chemicals, including aminotriazole, DDT, cyclamates and Alar, at one time or another, have been in the crosshairs of environmental groups because of supposed cancer-causing effects on humans. Toxicology studies are important in public health because epidemiology is not very sensitive as you cannot conduct experiments on humans. They serve as a basis for potency estimates and offer the opportunity to compare risks. However, the advantages of these studies must be balanced with their potential to exaggerate risk. High-dose effects do not necessarily occur at low doses and effects that occur in test species do not necessarily occur in humans exposed to the same agents. Fear of the unknown and exaggerated precautions shouldn’t be invoked to impede scientific progress.
Editor’s notes: On August 23, 2005 the American Council on Science and Health petitioned the “Environmental Protection Agency (EPA) to eliminate "junk science" from the process by which it determines whether a substance is likely to cause cancer in humans.” Their petition “argues that current EPA guidelines violate the Information Quality Act (IQA) -- the law that requires the federal government to ensure the "equality, objectivity, utility, and integrity" of information it dispenses to the public.”
“Specifically, EPA routinely declares chemicals "carcinogens" -- implying a likelihood of a health threat to humans -- based solely on the creation of tumors in lab rodents by the administration of super high doses irrelevant to ordinary human exposure levels. Furthermore, effects in a single species may not be applicable to another species (rat tests do not even reliably predict effects in mice, which are closely related to rats, let alone effects in humans), though similar effects in multiple species might be an indicator of a genuine problem.”
Finally, after stalling for months the EPA responded by saying; “their Risk Assessment Guidelines are not statements of scientific fact -- and thus not covered by the IQA -- but merely statements of EPA policy.
I watched this as it played out and when they finally responded I had to ask; if EPA policy isn’t based on science what is it based on? The answer? The EPA is not now, nor has it ever been an agency based on science. It is a political entity created by Richard M. Nixon to carry out his political mandate to eliminate DDT, irrespective of the facts. Since then they have become filled with environmental activists who embrace an irrational misanthropic green concept whose goal is the elimination of pesticides, along with a host of other things that given us longer and healtheir lives than any time in history. This greenie philosophy is a secular religion that places mankind lower than the lowest species of plant or animal life.
We need to get that!