Stop banning products at the drop of a rat - criticism of use of rodents in testing possible carcinogens

0 Comments | Insight on the News, Dec 12, 1994 | by Elizabeth M. Whelan

Most Americans do not realize the extent to which rodents negatively influence our priorities when it comes to public-health expenditures. Spending on environmental regulations is affected along with the cost of goods and services, insurance premiums, employment opportunities and federal taxes. Mice and rats are interfering with our nation's pursuit of an improved standard of living and longer, healthier lives.

If prodded, you might recall something about the Food and Drug Administration want" to ban the sweeteners cyclamate and saccharin because they caused cancer in rodents. Or you may remember the Natural Resources Defense Council/60 Minutes debacle which caused parents around the nation to discard apple products to avoid Alar, a chemical purported to cause cancer.

But the phenomenon I call "mouse terrorism" - defined as a knee-jerk extrapolation from a high-dose animal study to a declaration of human cancer risk no matter how low human exposure - influences a vast array of federal and local regulations.

Using mouse terrorism, self-appointed "environmentalists" and their allies in regulatory agencies can ban a product or technology no matter what the cost involved and no matter how beneficial the technology compared to the minuscule risk. Their campaigns have been successful in dramatically inflating local, state and federal budgets to underwrite what is, in effect, a far-reaching, taxpayer-supported, chemical witch hunt.

Because of the enormous costs engendered by mouse terrorism and the clear implications for our country's economic future and health, the time is long overdue to consider the origins and major premises of the mouse-to-man extrapolation. The time has come for us to consider that mouse terrorism and policies that require chemicals to be banned literally "at the drop of a rat" pose a serious problem. Could we, for example, by elevating rodent testing to its current unchallengeable level, be reducing our food supply (by banning pesticides), raising taxes (to pay for the crusade against trace levels of chemicals) and siphoning money from more worthwhile avenues of medical research?

Animals long been have used as surrogates for humans in evaluating safety issues. But it was not until the late 1950s that researchers began to examine the possibility that cancer had its origins in environmental - or external - factors, rather than in differences in genetic susceptibility. It seemed a promising assumption that if carcinogens' could be identified and human exposure limited, the cancer toll could be reduced.

Some scientists and policymakers during the 1950s and 1960s limited their definition of "environment" almost exclusively to "chemicals." Overwhelmingly, scientists today define "environmental causes of cancer" not as trace chemical exposures but as lifestyle factors such as smoking. Back then, however, those who accepted the assumptions that carcinogens were only of synthetic origin and that dose was not a relevant factor set out to test a variety of industrial chemicals for animal carcinogenicity.

Intuition would dictate that if you want to know whether something causes cancer in humans, you should study people, not rats. And through epidemiology, human disease patterns are studied to detect factors that affect cancer risk. However, epidemiology suffers from several inherent limitations: First, it is difficult to observe small effects with statistical confidence by epidemiological means. Second, it frequently is difficult to find groups of people who have never been exposed to a factor under study (the so-called zero-exposure control group).

Thus, a traditional alternative (or supplement) to epidemiology is the animal test. Rats and mice generally are used because they are less expensive to maintain than other mammals. A standard test has been developed in which animals are exposed to a test substance at a very high dose to maximize the chance of detecting cancers during the animal's relatively short life span. The whole procedure for testing and evaluation of one chemical takes three or more years to complete - at about $1,500 per animal or $1 million for a typical test.

Large doses of the test chemical are used to detect the effects of even a weak carcinogen. The maximum-tolerated dose, or MTD, is the largest estimated dose that animals can tolerate without experiencing considerable (10 percent) weight loss compared to controls. These MTDs usually are orders of magnitude - thousands or millions of times - above the dose humans encounter.

While using the MTD is standard practice, this procedure is much in question. The central issue is whether dose levels that are nearly toxic in and of themselves can predispose an animal to develop cancer. It is very possible that physiological events occur in such stressed animals that would not occur at the much lower doses typical of human exposure. Thus, the lack of recognition of the sound toxicological principle "the dose makes the poison" seriously jeopardizes the scientific validity of animal cancer testing.