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Extension Toxicology Network

A Pesticide Information Project of Cooperative Extension Offices of Cornell University, Michigan State University, Oregon State University, and University of California at Davis. Major support and funding was provided by the USDA/Extension Service/National Agricultural Pesticide Impact Assessment Program.

  Toxicology
Information
Brief
Carcinogenicity

Publication Date: 9/93

INTRODUCTION

Although both natural and synthetic chemicals may cause a variety of toxic effects at high enough doses, the effect which is of most concern in the U.S. is cancer. This is not surprising considering the high incidence of this disease, its often fatal outcome and the overall cost to society. Unfortunately, the incidence of this disease seems to increase with age so that as people live longer, there will be more and more cases of cancer in our country.

Scientists do not yet understand exactly how cancer occurs or why some chemicals seem to cause cancer and others do not.

Chemicals which are known to cause cancer are called carcinogens and the process of cancer development is called carcinogenesis. Up to now, scientists have identified about two dozen chemicals or occupational exposures which appear to be definitely carcinogenic to humans. Some of the most familiar are tobacco smoke and asbestos. In addition, there are a number of chemicals which cause cancer in animals and are suspected of being human carcinogens. Since not all chemicals have been tested at present, it is possible that the number of known and suspect human carcinogens will increase in the future.

It must be remembered, however, that as with all toxic effects, the dose or amount of exposure is critical. Just as a small enough amount of cyanide will not lead to death, smoking one cigarette will not lead to lung cancer. Thus, in order to decide on the risk that a particular carcinogen poses, it is important to determine how much of the chemical will cause how many cases of cancer in a specified population. This value can then be compared to what is considered an acceptable risk. Currently, the generally accepted increase in risk of cancer is one additional cancer in one million people. A few exceptions to this criterion are made in the cases of food additives, including pesticides that are considered as food additives, where no amount of carcinogen is allowed (the Delaney Clause, as documented in the Federal Food, Drug and Cosmetic Act) and drinking water where a goal of zero contamination for carcinogens has been set.

CARCINOGEN TESTING

Once an acceptable risk for a carcinogen has been established (usually by the Environmental Protection Agency for environmental contaminants), there remains the problem of determining what dose or amount of chemical will lead to this risk. There are two types of studies which are used to make this determination: (1) investigations of human populations (epidemiology) and (2) experiments on laboratory animals. Each of these types of studies has its advantages and disadvantages and both have some degree of uncertainty, no matter how much evidence is gathered.

Epidemiological Studies in Human Populations

Investigations of human populations, in an attempt to establish the relationship between environmental factors and health, are called epidemiological studies. Scientists examine selected populations to single out particular exposures which might be related to toxic effects; in this case, cancer. Occupational groups, such as factory workers in a particular industry, are often studied for two reasons. One is that their exposures to the toxic compounds are generally higher than other people's so that a higher incidence of cancer is expected, if it occurs. A higher incidence is obviously easier to detect. The second reason is that their exposure to a specific chemical is often unique and can more easily be distinguished from exposures to many other chemicals which are used in daily life.

Through epidemiological studies among industrial worker populations, it was possible to show that asbestos is linked to lung cancer, vinyl chloride to a rare form of liver cancer, and benzene to leukemia. There have also been suggestions that pesticide exposure to farmers might lead to cancer but the results are not clear cut and there is still much controversy about the epidemiological studies which have been performed on these populations. Even in well documented cases, it is not possible to use epidemiology to establish the exact risk of exposure to specific levels (concentrations) of these chemicals.

Laboratory Animal Studies

Laboratory studies have several advantages over epidemiological studies. Studies on laboratory animals are often easier to interpret because chemicals can be studied one at a time; very high doses can be administered; other chemicals and environmental factors can be eliminated or controlled; and animals can be sacrificed during the course of the study. The disadvantages are that it is not known how to apply these high dose results to much lower dose exposures that happen in the real world. Equally perplexing is how animal results can be applied to human populations. In extrapolating from high to low doses and from animals to humans, regulatory agencies have taken the approach of trying to be as conservative as possible, i.e., of trying to leave a large margin of safety so that even if the studies are in error, human health (usually of the most sensitive groups in the population such as young children and pregnant women) will be protected.

As a result, the acceptable exposure levels (published in the Federal Register for each carcinogen) usually represent what is called the "worst case" exposure. An assumption made in the calculation of worst case exposure levels is that humans will be exposed to the same concentration of the chemical every day of their lives for seventy years. As a result, the published acceptable risk level does not necessarily represent the "safe level" but rather a target level with the expectation that the true risk to exposure is less than the published value. Remember that the exposure criteria are guidelines for the protection of sensitive elements of the population and are calculated with many factors of uncertainty (the relationship of animal toxicity to human toxicity for instance).

SUMMARY

Epidemiological investigations are used to establish links between a particular chemical and cancer in only a few cases and cannot be employed to determine the exact levels at which cancer will occur. On the other hand, laboratory animal studies provide a way of detecting the carcinogenicity of a large number of chemicals and can provide numerical values for cancer risks. However, the relevance of the animal high-dose results to low doses or to humans is not clear.

In light of these considerations, it is not possible to determine the exact cancer risk for any human population, much less any individual. Public policy makers have tried to use worst-case analyses to be as protective of human health as possible. To minimize cancer, regulations have been designed to reduce population exposure to known human carcinogens as much as possible. In the case of known animal carcinogens, minimizing exposure is also a regulatory goal. However, since many of these chemicals are also quite beneficial to society, there are questions as to how much exposure reduction can be achieved without eliminating the benefits of these chemicals. Achieving a balance of risk and benefit is especially difficult when the uncertainties involved in determining the actual risk to humans is considered.

At present, there are a number of pesticides known to be animal carcinogens. None have been shown absolutely to be human carcinogens. Exposure to pesticides which are probable human carcinogens can be minimized through proper protective equipment and proper storage, use and disposal of these pesticides. These measures not only protect the pesticide applicator but also the general public, which consumes foods treated with pesticides or spends time in buildings treated with these chemicals.